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Calcium: 141 Research Abstracts

1: J Nutr. 2003 Jul;133(7):22328. Appropriate calcium fortification of the food supply presents a challenge. JohnsonDown L, L'Abbe MR, Lee NS, GrayDonald K.

Fortification with calcium to increase dietary intakes of this mineral is currently under evaluation in Canada. To model the potential dietary consequences of food fortification, data from a large national survey of Canadians (n = 1543) were used. Food fortification scenarios were based on reference amounts for labeling requirements. Consumption of milk, cheese and other dairy products was associated with high calcium intakes, and there was a low prevalence of inadequacy in men < 50 y old; however, other agesex groups had lower intakes. The aim of the fortification modeling was to determine which scenario would most effectively reduce the proportion of the population with low intakes of calcium while minimizing the proportion of individuals who exceeded the tolerable upper intake level (UL). Given the correlation between energy and calcium (r = 0.60, P < 0.01), it appeared that any fortification scenario sufficient to increase the mean intake for women to near the adequate intake led to 67% of the men having calcium intakes above the UL. The results suggest that fortification of widely consumed foods is not a realistic way to address the issue of low calcium intakes and illustrate the need for concern about the growing use of fortification practices. PMID 12840185

2: Am J Kidney Dis. 2003 Mar;41(3 Suppl 2):S1047. Renal osteodystrophy: role of calcimimetics. Horl WH.

In patients with secondary hyperparathyroidism (HPT), increased parathyroid hormone (PTH) secretion is triggered by low plasma calcitriol levels, hypocalcemia, and hyperphosphatemia. Vitamin D analogues have been used successfully to reduce PTH levels, but increases in serum calcium, phosphorus, and calcium x phosphorus ion product levels may occur. Secondgeneration calcimimetics have been shown to suppress PTH levels and also reduce calcium x phosphorus ion product. Potential indications are patients with secondary HPT, particularly those who respond to calcitriol therapy with an increase in calcium x phosphorus ion product. Coadministration of active vitamin D compounds may be necessary to overcome intestinal malabsorption of calcium and maintain normocalcemia in patients on longterm treatment with calcimimetics.

3: J Fam Pract. 2003 Mar;52(3):234, 237. Do calcium supplements prevent postmenopausal osteoporotic fractures? Campbell BG, Ketchell D, Gunning K. Montana Family Practice Residency, Billings, MO, USA.

Calcium supplementation (10001200 mg daily) decreases menopauserelated bone loss and reduces the rate of vertebral and nonvertebral fractures. Calcium is more efficacious in conjunction with vitamin D (700800 IU daily), particularly in elderly patients, who have a high rate of vitamin D deficiency. PMID 12620181

4: S Afr Med J. 2003 Mar;93(3):2248. Calcium supplementation to prevent preeclampsiaa systematic review. Hofmeyr GJ, Roodt A, Atallah AN, Duley L.

BACKGROUND: Calcium supplementation during pregnancy may prevent high blood pressure and preterm labour. OBJECTIVE: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child adverse outcomes. DESIGN: A systematic review of randomised trials that compared supplementation with at least 1 g calcium daily during pregnancy with placebo. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register (October 2001) and the Cochrane Controlled Trials Register (Issue 3, 2001) were searched and study authors were contacted. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. Data were extracted and analysed. MAIN RESULTS: There was a modest reduction in the risk of preeclampsia with calcium supplementation (relative risk (RR) 0.68, 95% confidence interval (CI): 0.570.81). The effect was greatest for women at high risk of hypertension (RR 0.21, 95% CI: 0.110.39) and those with low baseline calcium intake (RR 0.32, 95% CI: 0.210.49). There was no overall effect on the risk of preterm delivery, although there was a reduction in risk among women at high risk of hypertension (RR 0.42, 95% CI: 0.230.78). There was no evidence of any effect of calcium supplementation on stillbirth or death before discharge from hospital. There were fewer babies with birthweight < 2,500 g (RR 0.83, 95% CI: 0.710.98). In one study, childhood systolic blood pressure > 95th percentile was reduced (RR 0.59, 95% CI: 0.390.91). CONCLUSIONS: Calcium supplementation appears to be beneficial for women at high risk of gestational hypertension and in communities with low dietary calcium intake. These benefits were confined to several rather small trials, and were not found in the largest trial to

5: Cancer Causes Control. 2003 Feb;14(1):112. Calcium, vitamin D, dairy products, and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States). McCullough ML, Robertson AS, Rodriguez C, Jacobs EJ, Chao A, Carolyn J, Calle EE, Willett WC, Thun MJ.

OBJECTIVE: Calcium, vitamin D, and dairy product intake may reduce the risk of colorectal cancer. We therefore examined the association between these factors and risk of colorectal cancer in a large prospective cohort of United States men and women. METHODS: Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed questionnaire on diet, medical history, and lifestyle in 199293. After excluding participants with a history of cancer or incomplete dietary information, 60,866 men and 66,883 women remained for analysis. During followup through 31 August 1997 we documented 421 and 262 cases of incident colorectal cancers among men and women, respectively. Multivariateadjusted rate ratios (RR) were calculated using Cox proportional hazards models. RESULTS: Total calcium intake (from diet and supplements) was associated with marginally lower colorectal cancer risk in men and women (RR = 0.87, 95% CI 0.671.12, highest vs lowest quintiles, p trend = 0.02). The association was strongest for calcium from supplements (RR = 0.69, 95% CI 0.490.96 for > or = 500 mg/day vs none). Total vitamin D intake (from diet and multivitamins) was also inversely associated with risk of colorectal cancer, particularly among men (RR = 0.71, 95% CI 0.510.98, p trend = 0.02). Dairy product intake was not related to overall risk. CONCLUSIONS: Our results support the hypothesis that calcium modestly reduces risk of colorectal cancer. Vitamin D was associated with reduced risk of colorectal cancer only in men. PMID 12708719

6: Clin Exp Rheumatol. 2003 JanFeb;21(1):1926. Calcium, vitamin D and etidronate for the prevention and treatment of corticosteroidinduced osteoporosis in patients with rheumatic diseases. Loddenkemper K, Grauer A, Burmester GR, Buttgereit F.

INTRODUCTION: Longterm glucocorticoid therapy, a major risk factor for the development of osteoporosis, is often necessary in chronically ill patients. At present there are no generally accepted guidelines for the prevention or treatment of steroidinduced osteoporosis. METHODS: In an open prospective study we investigated 99 patients with chronic rheumatic diseases receiving > or = 5 mg/day of prednisolone or the equivalent for at least one year. The objective was to identify osteoporosis risk factors in addition to glucocorticoid therapy and to evaluate the efficacy of prevention with calcium/vitamin D (group 1patients with osteopenia) and treatment with cyclical etidronate (group 2patients with osteoporosis). Biochemical markers of bone turnover, clinical parameters and bone mineral density (BMD) were measured. RESULTS: Increasing age and postmenopausal status were associated with more advanced manifestations of steroidinduced osteoporosis (p < 0.05). One year after the start of therapy parameters of bone metabolism increased significantly in group 1, while BMD did not change. In group 2, lumbar spine BMD increased significantly (p < 0.05) whereas femoral neck BMD and bone metabolism parameters remained constant. The intensity of back pain decreased in both groups (p < 0.05). There were fewer new fractures in group 2 than in group 1. CONCLUSION: Treatment with etidronate is effective in patients with glucocorticoidinduced osteoporosis.

7: Wei Sheng Yan Jiu. 2003 Jan;32(1):813. [Review of dietary risk factors for osteoporosis] Wang P, Zhang H.

Dietary factors are convenient but correctable factors in the pathogenesis of osteoporosis. The peak bone mass in the young can be increased and the rate of bone loss in the elderly possibly be reduced by dietary manipulation, which would be important and beneficial in the prevention of osteoporosis. Dietary risk factors for osteoporosis include low calcium intake, low or high protein intake, low vitamin intake, smoking, and high intake of alcohol, coffee, carbonated beverage and salt.

8: J Trop Pediatr. 2002 Dec;48(6):3513. Comparisons of oral calcium, high dose vitamin D and a combination of these in the treatment of nutritional rickets in children. Kutluk G, Cetinkaya F, Basak M.

Nutritional rickets remains a common child health problem in Turkey and many other developing countries. Although vitamin D deficiency is accepted as the basic problem underlying the disease, others postulate that a deficiency of dietary calcium, rather than vitamin D, is often responsible for the nutritional rickets in sunny countries. We conducted a placebocontrolled study to determine the best treatment regimen for nutritional rickets in children residing in lower socioeconomic regions of a sunny city, Istanbul. Fortytwo infants (aged 630 months) with rickets were divided into three groups and included in the study. In a randomized fashion vitamin D (300 000 units, intramuscularly), calcium lactate (3 g daily) or a combination of vitamin D and calcium were given to the children. Alkaline phosphatase, calcium, albumin, ionized calcium and phosphorus levels were measured each week. Xray examinations of the left wrist and left knee were undertaken at the beginning of the study and were repeated at the 2nd and 4th weeks and were scored in order to assess the response to treatment. Treatment produced an increase in serum calcium and a decrease in alkaline phosphatase concentration in all three groups, but the most important increase was reached in the vitamin D plus calcium group. We conclude that vitamin D deficiency appears to be the primary etiologic factor of rickets in our study group, but a better response to treatment with vitamin D or in combination with calcium was obtained than to treatment with calcium alone.

9: Urol Nurs. 2002 Dec;22(6):4059. OsteoporosisPart II: Dietary and/or supplemental calcium and vitamin D. Moyad MA.

Osteoporosis is a significant problem in women and men. As osteoporosis has garnered more attention there seems to be more attention than ever placed on the potential benefits of calcium and vitamin D. Health professionals need to inform patients that there are numerous healthy dietary sources of calcium and vitamin D. Several forms of calcium supplements are commercially available today and health professionals need to understand the similarities and differences between them. Calcium and vitamin D in moderation also have an excellent safety profile and may actually have benefits far beyond osteoporosis therapy. PMID 12593233

10: Dtsch Med Wochenschr. 2002 Oct 25;127(43):22512. [Disease prevention by vitamins and trace elements] Pfeiffer AF, Einig Ch.

SUMMARY: Vitamins and trace elements are largely provided by a balanced nutrition. In industrialized countries, though, frequent deficiencies occur e.g. in folic acid and vitamin D as well as iodide, iron and calcium. A short review of recommended daily intake is presented. PMID 12397538

11: Eur J Clin Invest. 2002 Sep;32(9):6939. Calcium affects biomarkers of colon carcinogenesis after right hemicolectomy. van Gorkom BA, van der Meer R, Karrenbeld A, van der Sluis T, Zwart N, Termont DS, Boersmavan Ek W, de Vries EG, Kleibeuker JH.

BACKGROUND: In Western societies colonic cancer most frequently develops in the distal colon, largely as a result of the composition of the diet. Modulation of dietary factors is therefore an attractive modality to reduce colorectal cancer risk. This study aims to evaluate the potentially protective effects of calcium in right hemicolectomy patients. MATERIALS AND METHODS: A randomized controlled crossover intervention trial was performed with 1000 mg of elemental calcium per day for 2 months in 15 right hemicolectomy patients. Primary endpoints were proliferative activity, determined by immunohistochemical detection of BrdUlabeled cells (LI) in rectal biopsies, and cytotoxicity and alkaline phosphatase activity of faecal water. Secondary endpoints were bile acid composition in faeces. RESULTS: Calciumreduced LI in the superficial onethird of the crypt (from 0.84 +/ 0.27% to 0.37 +/ 0.08%, P = 0.04) and a trend towards a lower total LI and LI in the mid onethird of the crypt was observed. Alkaline phosphatase activity was reduced from 6.2 +/ 2.6 U mL1 in the placebo period to 4.6 +/ 2.2 in the calcium period (P = 0.02), and a trend toward a lower cytotoxicity of faecal water was observed. No effect on total bile acids in faeces was observed, but calcium increased the percentage of deoxycholic acid (from 49.6 +/ 7.0% to 56.5 +/ 6.2%, P = 0.03) and decreased the percentages of cholic acid (from 10.3 +/ 4.7% to 5.8 +/ 2.7%, P = 0.05) and lithocholic acid (from 26.7 +/ 3.4% to 23.9 +/ 2.9%, P = 0.04). CONCLUSION: Calcium may have a protective effect against colorectal cancer risk in right hemicolectomy patients.

12: Am J Epidemiol. 2002 Jul 15;156(2):14857. Association of dairy products, lactose, and calcium with the risk of ovarian cancer. Goodman MT, Wu AH, Tung KH, McDuffie K, Kolonel LN, Nomura AM, Terada K, Wilkens LR, Murphy S, Hankin JH.

Epidemiologic findings have been inconsistent regarding the association of dietary fat, dairy products, and lactose with risk of ovarian cancer. The authors conducted a casecontrol study in Hawaii and Los Angeles, California, to examine several dietary hypotheses regarding the etiology of ovarian cancer in a population with a broad range of dietary intakes. A total of 558 patients with ovarian cancer diagnosed in 19931999 and 607 controls were interviewed regarding their diet. Consumption of all dairy products, all types of milk, and lowfat milk, but not consumption of whole milk, was significantly inversely related to the odds of ovarian cancer. Similar inverse gradients in the odds ratios were obtained for intakes of lactose and calcium, although these nutrients were highly correlated (r = 0.77). The odds ratio for ovarian cancer was 0.46 (95% confidence interval: 0.27, 0.76) among women in the highest quartile of dietary calcium intake versus the lowest (p for trend = 0.0006). The significant dietary association was limited to dairy sources of calcium (p for trend = 0.003), although a nonsignificant inverse gradient in risk was also found in relation to calcium supplement intake. These results suggest that intake of lowfat milk, calcium, or lactose may reduce the risk of ovarian cancer. PMID 12117706

13: Transfusion. 2002 Jul;42(7):93546. Controlled study of citrate effects and response to i.v. calcium administration during allogeneic peripheral blood progenitor cell donation. Bolan CD, Cecco SA, Wesley RA, Horne M, Yau YY, Remaley AT, Childs RW, Barrett AJ, Rehak NN, Leitman SF.

BACKGROUND: Leukapheresis procedures are generally performed at citrate anticoagulation rates extrapolated from shorter plateletpheresis procedures. However, neither the metabolic effects nor the management of associated symptoms have been critically evaluated during leukapheresis in healthy donors. STUDY DESIGN AND METHODS: Symptom assessments (n = 315) and laboratory analyses (n = 49) were performed during 244 procedures performed with and 71 without prophylactic calcium (Ca) chloride or Ca gluconate given at a dose linked to the citrate infusion rate (1.02.2 mg/kg/min). RESULTS: During leukapheresis of 12 to 25 L processed, ionized Ca and ionized magnesium (Mg) decreased as much as 35 and 56 percent, respectively, each exhibiting a tight negative correlation with marked increases in serum citrate levels. Significant increases in urinary Ca and Mg excretion accompanied the renal excretion of a large citrate load. Serum divalent cation levels remained depressed 24 hours after leukapheresis. Symptoms were more frequent in donors who were women, had low initial total Mg levels, and underwent procedures in which larger volumes were processed at higher citrate infusion rates. Ca infusions reduced clinically significant paresthesias by 96 percent and also attenuated decreases in serum potassium. Ca chloride maintained higher Ca levels than Ca gluconate. CONCLUSIONS: Prophylactic Ca infusions safely attenuate the marked metabolic effects of citrate administration and promote faster, more comfortable, leukapheresis procedures.

14: Toxicology. 2002 Jun 14;175(13):24755. Calcium supplementation during lactation blunts erythrocyte lead levels and deltaaminolevulinic acid dehydratase zincreactivation in women nonexposed to lead and with marginal calcium intakes. Pires JB, Miekeley N, Donangelo CM.

The purpose of this study was to evaluate the effect of calcium supplementation during lactation on changes in blood lead indices from late pregnancy to early lactation in women with low calcium intakes and low leadexposure. Fortyseven women, nonoccupationally exposed to lead and with habitually low calcium intake ( approximately 600 mg/d), participated in the study from 29 to 38 weeks of pregnancy to 78 weeks postpartum, nonsupplemented (n=25) and supplemented (n=22) with calcium (500 mg/d) during 6 weeks after delivery. Erythrocyte lead (PbRBC) and in vitro reactivation with zinc of blood deltaaminolevulinic acid dehydratase (ZndeltaALAD% reactivation) were used as lead indices. In the nonsupplemented group, PbRBC and ZndeltaALAD% reactivation increased significantly (P<0.001) from pregnancy (0.202+/0.049 microg Pb/g protein and 18.3+/6.0%) to lactation (0.272+/0.070 microg Pb/g protein and 22.7+/6.2%). No significant changes of these indices were observed in the calciumsupplemented group from pregnancy (0.203+/0.080 microg Pb/g protein and 15.8+/4.5%) to lactation (0.214+/0.066 microg Pb/g protein and 16.3+/4.1%). PbRBC levels and ZndeltaALAD% reactivation at lactation were lower (P<0.05) and hematocrit levels were higher (P<0.05) in the calciumsupplemented compared to the nonsupplemented women. Calcium supplementation during lactation appears to blunt the lactationinduced increase in maternal blood lead and its inhibitory effect on deltaALAD and possibly on maternal erythropoiesis.

15: J Am Soc Nephrol. 2002 Jun;13(6):160814. Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study. De Sevaux RG, Hoitsma AJ, Corstens FH, Wetzels JF.

A decrease in bone mineral density (BMD) is a major complication of renal transplantation (RTx), predominantly occurring within the first 6 mo after RTx. The most important causative factor is the use of corticosteroids, but persisting hyperparathyroidism and abnormalities in vitamin D metabolism play a role too. This study examines the effect of treatment with calcium and active vitamin D on the loss of BMD in the first 6 mo after RTx. A total of 111 renal transplant recipients (65 men, 46 women; age, 47 +/ 13 yr) were randomized to either treatment with active vitamin D (0.25 microg/d) plus calcium (1000 mg/d) (CaD group), or to no treatment (NoT group). Immunosuppressive therapy consisted of cyclosporine, prednisone, and mycophenolate mofetil. Laboratory parameters and BMD (lumbar spine and hip) were measured at 0, 1 (laboratory only), 3, and 6 mo after RTx. Lumbar BMD was nearly normal at the time of RTx. In both groups, a significant decrease in lumbar BMD was observed during the first 3 mo (CaD, 3.3 +/ 4.3%; P < 0.0001; NoT, 4.1 +/ 4.8%; P < 0.0001). Between the third day and sixth month, lumbar BMD slightly recovered in the CaD group, but it decreased further in the NoT group (total loss 0 to 6 mo: CaD, 2.6 +/ 5.0% [P < 0.001]; NoT, 5.0 +/ 4.7% [P < 0.0001]). As a result, the amount of bone loss at 6 mo was significantly lower in the CaD group (P = 0.02). Loss of BMD at the different femoral sites was also significantly reduced in the CaD group. Apart from a trend toward more frequent hypercalcemia in the CaD group, no clinical or biochemical differences existed between the groups. Treatment with a low dose of active vitamin D and calcium partially prevents bone loss at the lumbar spine and proximal femur during the first 6 mo after RTx.

16: Aliment Pharmacol Ther. 2002 May;16(5):91927. Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluoride. Abitbol V, Mary JY, Roux C, Soule JC, Belaiche J, Dupas JL, Gendre JP, Lerebours E, Chaussade S; Groupe D'etudes Therapeutiques des Affections Inflammatoires Digestives (GETAID).

BACKGROUND: Previous data have indicated low bone formation as a mechanism of osteoporosis in inflammatory bowel disease. Fluoride can stimulate bone formation. AIM: To assess the effect of fluoride supplementation on lumbar spine bone mineral density in osteoporotic patients with inflammatory bowel disease treated in parallel with calcium and vitamin D. METHODS: In this prospective, randomized, doubleblind, parallel and placebocontrolled study, 94 patients with inflammatory bowel disease (lumbar spine T score below 2 standard deviations, normal serum 25OH vitamin D), with a median age of 35 years, were included. Bone mineral density was measured by dualenergy Xray absorptiometry. Patients were randomized to receive daily either sodium monofluorophosphate (150 mg, n=45) or placebo (n=49) for 1 year, and all received calcium (1 g) and vitamin D (800 IU). The relative change in bone mineral density from 0 to 12 months was tested in each group (fluoride or placebo) and compared between the groups. RESULTS: Lumbar spine bone mineral density increased significantly in both groups after 1 year: 4.8 +/ 5.6% (n=29) and 3.2 +/ 3.8% (n=31) in the calciumvitamin Dfluoride and calciumvitamin Dplacebo groups, respectively (P < 0.001 for each group). There was no difference between the groups (P=0.403). Similar results were observed according to corticosteroid intake or disease activity. CONCLUSIONS: Calcium and vitamin D seem to increase lumbar spine density in osteoporotic patients with inflammatory bowel disease; fluoride does not provide further benefit.

17: J Bone Joint Surg Br. 2002 May;84(4):497503. Positive effects of anabolic steroids, vitamin D and calcium on muscle mass, bone mineral density and clinical function after a hip fracture. A randomised study of 63 women. Hedstrom M, Sjoberg K, Brosjo E, Astrom K, Sjoberg H, Dalen N.

A total of 63 women who had an operation for a fracture of the hip was randomly allocated to one year of treatment either with anabolic steroids, vitamin D and calcium (anabolic group) or with calcium only (control group). The thigh muscle volume was measured by quantitative CT. The bone mineral density of the hip, femur and tibia was assessed by quantitative CT and dualenergy xray absorptiometry and of the heel by quantitative ultrasound. Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did (p<0.01). There was less bone loss in the proximal tibia in the anabolic group than in the control group. The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months. Anabolic steroids, even in this moderate dose, given in combination with vitamin D and calcium had a beneficial effect on muscle volume, bone mineral density and clinical function in this group of elderly women.

18: Mutat Res. 2002 Apr 26;516(12):19. The protective effect of calcium against genotoxicity of lead acetate administration on bone marrow and spermatocyte cells of mice in vivo. AboulEla EI.

The protective effect of calcium given orally by gavage with two doses (40 and 80mg/kg body weight) was evaluated against clastogenecity induced by lead acetate with two concentrations (200 and 400mg/kg diet) on bone marrow and spermatocyte cells of mice in vivo. The parameter screened was percentage of chromosomal aberrations with and without gaps and sperm abnormalities. Statistical analyses indicated the protection efficacy of calcium with the high dose rather than the other in both types of mouse cells.The observation from the laboratory tests, dealing that lead acetate can be considered as an environmental genotoxic material. We recommended that it must be administered of calcium (as calcium chloride) as a protective agent to reduce the genotoxic effect of lead in the somatic and germ cells. PMID 11943604

19: Am J Clin Nutr. 2002 Apr;75(4):7739. Calcium intake influences the association of protein intake with rates of bone loss in elderly men and women. DawsonHughes B, Harris SS.

BACKGROUND: There is currently no consensus on the effect of dietary protein intake on the skeleton, but there is some indication that low calcium intakes adversely influence the effect of dietary protein on fracture risk. OBJECTIVE: The objective of the present study was to determine whether supplemental calcium citrate malate and vitamin D influence any associations between protein intake and change in bone mineral density (BMD). DESIGN: Associations between protein intake and change in BMD were examined in 342 healthy men and women (aged > or = 65 y) who had completed a 3y, randomized, placebocontrolled trial of calcium and vitamin D supplementation. Protein intake was assessed at the midpoint of the study with the use of a foodfrequency questionnaire and BMD was assessed every 6 mo by dualenergy Xray absorptiometry. RESULTS: The mean (+/SD) protein intake of all subjects was 79.1 +/ 25.6 g/d and the mean total calcium intakes of the supplemented and placebo groups were 1346 +/ 358 and 871 +/ 413 mg/d, respectively. Higher protein intake was significantly associated with a favorable 3y change in totalbody BMD in the supplemented group (in a model containing terms for age, sex, weight, total energy intake, and dietary calcium intake) but not in the placebo group. The pattern of change in femoral neck BMD with increasing protein intake in the supplemented group was similar to that for the total body. CONCLUSION: Increasing protein intake may have a favorable effect on change in BMD in elderly subjects supplemented with calcium citrate malate and vitamin D.

20: Cancer Causes Control. 2002 Apr;13(3):21320. Calcium, vitamin D, and risk of adenoma recurrence (United States). Martinez ME, Marshall JR, Sampliner R, Wilkinson J, Alberts DS.

OBJECTIVE: Few data exist regarding the association between calcium intake and adenoma recurrence, and no data exist for vitamin D. We investigated the role of dietary and supplemental sources of calcium and vitamin D in the etiology of adenoma recurrence. METHODS: Analyses were conducted among 1304 male and female participants in the Wheat Bran Fiber (WBF) trial of adenoma recurrence. Multiple logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In the fully adjusted multivariate model, the OR for participants with dietary calcium intake above 1,068 versus those with intake below 698 mg/day was 0.56 (95% CI = 0.390.80; ptrend = 0.007). Calcium supplementation at doses above 200 mg/day did not affect risk of recurrence. Although a borderline inverse association between dietary vitamin D and recurrence was observed after adjustment for age and gender, the association weakened in the fully adjusted model (OR = 0.78 for individuals in the upper compared to the lower quartile; 95% CI = 0.541.13). No association was shown for supplemental sources of vitamin D. CONCLUSIONS: Results of this study indicate that a higher intake of calcium decreases the risk of adenoma recurrence by approximately 45%, whereas vitamin D has no significant effect on recurrence rates. PMID 12020102

21: J Surg Res. 2002 Apr;103(2):24351. Ischemic preconditioning improves mitochondrial tolerance to experimental calcium overload. Crestanello JA, Doliba NM, Babsky AM, Doliba NM, Niibori K, Whitman GJ, Osbakken MD.

BACKGROUND: Ca(2+) overload leads to mitochondrial uncoupling, decreased ATP synthesis, and myocardial dysfunction. Pharmacologically opening of mitochondrial K(ATP) channels decreases mitochondrial Ca(2+) uptake, improving mitochondrial function during Ca(2+) overload. Ischemic preconditioning (IPC), by activating mitochondrial K(ATP) channels, may attenuate mitochondrial Ca(2+) overload and improve mitochondrial function during reperfusion. The purpose of these experiments was to study the effect of IPC (1) on mitochondrial function and (2) on mitochondrial tolerance to experimental Ca(2+) overload. METHODS: Rat hearts (n = 6/group) were subjected to (a) 30 min of equilibration, 25 min of ischemia, and 30 min of reperfusion (Control) or (b) two 5min episodes of ischemic preconditioning, 25 min of ischemia, and 30 min of reperfusion (IPC). Developed pressure (DP) was measured. Heart mitochondria were isolated at endEquilibration (endEQ) and at endReperfusion (endRP). Mitochondrial respiratory function (state 2, oxygen consumption with substrate only; state 3, oxygen consumption stimulated by ADP; state 4, oxygen consumption after cessation of ADP phosphorylation; respiratory control index (RCI, state 3/state 4); rate of oxidative phosphorylation (ADP/Deltat), and ADP:O ratio) was measured with polarography using alphaketoglutarate as a substrate in the presence of different Ca(2+) concentrations (0 to 5 x 10(7) M) to simulate Ca(2+) overload. RESULTS: IPC improved DP at endRP. IPC did not improve preischemic mitochondrial respiratory function or preischemic mitochondrial response to Ca(2+) loading. IPC improved state 3, ADP/Deltat, and RCI during RP. Low Ca(2+) levels (0.5 and 1 x 10(7) M) stimulated mitochondrial function in both groups predominantly in IPC. The Control group showed evidence of mitochondrial uncoupling at lower Ca(2+) concentrations (1 x 10(7) M). IPC preserved state 3 at high Ca(2+) concentrations. CONCLUSIONS: The cardioprotective effect of IPC results, in part, from preserving mitochondrial function during reperfusion and increasing mitochondrial tolerance to Ca(2+) loading at endRP. Activation of mitochondrial K(ATP) channels by IPC and their improvement in Ca(2+) homeostasis during RP may be the mechanism underlying this protection. PMID 11922741

22: Urology. 2002 Apr;59(4 Suppl 1):3440. Complementary therapies for reducing the risk of osteoporosis in patients receiving luteinizing hormonereleasing hormone treatment/orchiectomy for prostate cancer: a review and assessment of the need for more research. Moyad MA.

Osteoporosis in women has received a substantial amount of attention, but its impact in men is also significant and noteworthy. Those men who benefit from treatment for prostate cancer with androgen deprivation therapy (ADT) may also be at a higher risk for osteoporosis. Pharmacologic approaches to reduce this risk have received some attention. For example, agents such as bisphosphonates, estrogen receptorbinding drugs (diethylstilbestrol, tamoxifen, and raloxifene), calcitonin, and fluoride are some of the more promising interventions that have been previously outlined. In addition, statin drugs, or hepatic 3hydroxy3methylglutaryl coenzyme A reductase inhibitors, have recently been hypothesized to lower osteoporosis risk. However, complementary therapies, which may also have an impact on reducing osteoporosis risk, have not received attention. Dietary and supplemental calcium and vitamin D have been shown, in some preliminary investigations, to maintain bone density in women and men. Numerous healthy and affordable dietary sources of this mineral and vitamin exist, and large intakes can be realistically achieved through proper education. Similarly, the supplemental dosages required to impact risk have been moderate, appear to be safe, are of low cost, and thus may provide an additional route for reducing risk, especially if these interventions are initiated at the start of medical treatment. More studies in men receiving ADT are needed because the existing work has mostly focused on men without castrate levels of male hormone. Additionally, many studies with conventional and nonconventional agents have only focused on individuals with baseline osteoporosis, rather than normal bone mineral densities or osteopenia. Other promising complementary therapies, such as weightbearing exercise and abstaining from smoking, may also be of benefit. Newer estrogenictype supplements (eg, ipriflavone) appear interesting and have some preliminary data, but more research is desperately required to determine their actual impact and potential for adverse effects (such as lymphocytopenia from a recent trial). Simple, inexpensive, and potentially effective dietary and supplemental approaches to reduce the risk of osteoporosis in men exist, and they should be discussed with patients. Whether these approaches effectively reduce the risk of osteoporosis in men receiving androgen ablation remains to be determined. The possibility is intriguing, and future research is needed. In the meantime, it is important to keep in mind that these complementary approaches are, at the very least, an integral part of the conventional options used today to the reduce the risk of osteoporosis in men and women.

23: J Natl Cancer Inst. 2002 Mar 20;94(6):43746. Calcium intake and risk of colon cancer in women and men. Wu K, Willett WC, Fuchs CS, Colditz GA, Giovannucci EL.

BACKGROUND: Calcium has been hypothesized to reduce the risk of colon cancer, and in a recent randomized trial, calcium supplementation was associated with reduction in the risk of recurrent colorectal adenomas. We examined the association between calcium intake and colon cancer risk in two prospective cohorts, the Nurses' Health Study (NHS) and the Health Professionals Followup Study (HPFS). METHODS: Our study population included 87 998 women in NHS and 47 344 men in HPFS who, at baseline (1980 for NHS and 1986 for HPFS), completed a food frequency questionnaire and provided information on medical history and lifestyle factors. Dietary information was updated at least every 4 years. During the followup period (1980 to May 31, 1996 for the NHS cohort; 1986 to January 31, 1996 for the HPFS cohort), 626 and 399 colon cancer cases were identified in women and men, respectively. Pooled logistic regression was used to estimate relative risks (RRs), and all statistical tests were twosided. RESULTS: In women and men considered together, we found an inverse association between higher total calcium intake (>1250 mg/day versus < or =500 mg/day) and distal colon cancer (women: multivariate RR = 0.73, 95% confidence interval [CI] = 0.41 to 1.27; men: RR = 0.58, 95% CI = 0.32 to 1.05; pooled RR = 0.65, 95% CI = 0.43 to 0.98). No such association was found for proximal colon cancer (women: RR = 1.28, 95% CI = 0.75 to 2.16; men: RR = 0.92, 95% CI = 0.45 to 1.87; pooled RR = 1.14, 95% CI = 0.72 to 1.81). The incremental benefit of additional calcium intake beyond approximately 700 mg/day appeared to be minimal. CONCLUSIONS: Higher calcium intake is associated with a reduced risk of distal colon cancer. The observed risk pattern was consistent with a threshold effect, suggesting that calcium intake beyond moderate levels may not be associated with a further risk reduction. Future investigations on this association should concentrate on specific cancer subsites and on the doseresponse relationship.

24: Osteoporos Int. 2002 Mar;13(3):25764. Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study. Chapuy MC, Pamphile R, Paris E, Kempf C, Schlichting M, Arnaud S, Garnero P, Meunier PJ.

Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people. Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures, as proved by Decalyos I. Decalyos II is a 2year, multicenter, randomized, doublemasked, placebocontrolled confirmatory study. The intentiontotreat population consisted of 583 ambulatory institutionalized women (mean age 85.2 years, SD = 7.1) randomized to the calciumvitamin D3 fixed combination group (n = 199); the calcium plus vitamin D3 separate combination group (n = 190) and the placebo group (n = 194). Fixed and separate combination groups received the same daily amount of calcium (1200 mg) and vitamin D3 (800 IU), which had similar pharmacodynamic effects. Both types of calciumvitamin D3 regimens increased serum 25hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent, with levels returning within the normal range after 6 months. In a subgroup of 114 patients, femoral neck bone mineral density (BMD) decreased in the placebo group (mean = 2.36% per year, SD = 4.92), while remaining unchanged in women treated with calciumvitamin D3 (mean = 0.29% per year, SD = 8.63). The difference between the two groups was 2.65% (95% CI = 0.44, 5.75%) with a trend in favor of the active treatment group. No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis. The relative risk (RR) of HF in the placebo group compared with the active treatment group was 1.69 (95% CI = 0.96, 3.0), which is similar to that found in Decalyos I (RR = 1.7; 95% CI = 1.0, 2.8). Thus, these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women.

25: Osteoporos Int. 2002 Mar;13(3):2117. Association of physical activity and calcium intake with the maintenance of bone mass in premenopausal women. UusiRasi K, Sievanen H, Pasanen M, Oja P, Vuori I.

Altogether 92 initially 25 to 30yearold women of 132 original subjects participated in this 4year followup study, which evaluated the influence of physical activity and calcium intake on the bone mineral content (BMC) of premenopausal women. The subjects were originally selected for a crosssectional study according to their level of physical activity (high PA+ and low PA) and calcium intake (high Ca+ and low Ca), and the original groups were maintained in this followup study. The mean loss of BMC (95% CI) in the pooled data was 1.5% (0.7% to 2.4%) at the femoral neck, 0.6% (0.8% to 1.9%) at the trochanter and 6.0% (4.5% to 7.4%) at the distal radius during the 4year followup. According to repeated measures analyses of covariance neither physical activity nor physical fitness at baseline was associated with the rate of bone loss from the proximal femur. High calcium intake and the maintenance of body weight were both associated with a lower rate of bone loss from the proximal femur and distal radius. In addition, a long duration of breast feeding was associated with a higher rate of bone loss from the distal radius. PMID 11991440

26: Acta Neurol Scand. 2002 Feb;105(2):12831. Reversible peripheral neuropathy in idiopathic hypoparathyroidism. Goswami R, Bhatia M, Goyal R, Kochupillai N.

We describe a 40yearold male with idiopathic hypoparathyroidism presenting with tetany, proximal weakness, signs of hypocalcaemia including Chvostek and Trousseau's and diminished tendon reflexes in the upper and lower limbs. Electrophysiological studies revealed a sensorymotor neuropathy, predominantly axonal as evidenced by decreased CMAP amplitudes, with normal distal latenciesvelocites, except for median nerve where a prolonged distal latency was observed. Serial nerve conduction studies were performed at repeated intervals for 2 years, while he received treatment for hypoparathyroidism (calcium and vitamin D supplementation). A progressive improvement in neuropathy both clinical and on electrophysiological studies was observed. Occurrence of peripheral neuropathy in hypocalcaemic states such as hypoparathyroidism and its reversibility after normalization of calcium homeostasis lend proof to the role of critical Ca2+ ion concentration in the normal functioning of the peripheral axons. PMID 11903124

27: Eur J Endocrinol. 2002 Feb;146(2):21522. Wellbeing, mood and calcium homeostasis in patients with hypoparathyroidism receiving standard treatment with calcium and vitamin D. Arlt W, Fremerey C, Callies F, Reincke M, Schneider P, Timmermann W, Allolio B.

OBJECTIVE: Standard treatment in hypoparathyroidism consists of calcium and vitamin D (or vitamin D analogs) but does not employ replacement of the actual missing hormone. Only few studies have evaluated the efficacy of calcium/vitamin D treatment in hypoparathyroidism; the impact of chronic hypoparathyroid disease on wellbeing has not been investigated previously. DESIGN: Crosssectional, controlled study in 25 unselected women with postsurgical hypoparathyroidism since 6.4plus minus8.0 years (s.d.) on stable treatment with calcium and vitamin D (or analogs) and in 25 controls with a history of thyroid surgery but intact parathyroid function, who were matched for sex, age and time since surgery. METHODS: Assessment of wellbeing and mood using validated questionnaires (the revised version Symptom Checklist 90 (SCL90R); the Giessen Complaint List (GBB24); and the von Zerssen Symptom List (BL Zerssen)), serum and urinary calcium/phosphorus homeostasis, and in the hypoparathyroid patients also screening for secondary disease by kidney ultrasound, ophthalmological split lamp examination, and measurement of bone mineral density. RESULTS: Serum calcium was in the accepted therapeutic range in the majority of hypoparathyroid patients. However, calcium/phosphorus homeostasis as a whole was clearly nonphysiological. Nephrolithiasis was detected in 2 and cataracts in 11 of 25 hypoparathyroid patients. As compared with controls, hypoparathyroid patients had significantly higher global complaint scores in GBB24 (P=0.036), BL Zerssen (P=0.002) and SCL90R (P=0.020) with predominant increases in the subscale scores for anxiety, phobic anxiety and their physical equivalents. CONCLUSIONS: Current standard treatment in hypoparathyroidism is not only associated with an altered calcium/phosphorus homeostasis but also fails to restore wellbeing in these patients. Future studies need to address the impact of more physiological treatment options like parathyroid hormone(134) or parathyroid transplantation on wellbeing and mood in these patients. PMID 11834431

28: Int J Technol Assess Health Care. 2002 Fall;18(4):791807. The health economics of calcium and vitamin D3 for the prevention of osteoporotic hip fractures in Sweden. Willis MS.

OBJECTIVE: The objective of this study was to examine the economics of administering calcium and vitamin D3 to postmenopausal women in Sweden. We focus primarily on the costeffectiveness of treating older women for whom clear evidence of efficacy is available. We supplement this information, however, with estimates of the costeffectiveness of treating certain highrisk groups of younger women, while acknowledging the greater uncertainty involved. METHODS: We developed a Markov model for analyzing the occurrence and timing of hip fractures, based almost entirely on peerreviewed data from Sweden. In a 3year randomized clinical trial, the combination of calcium and vitamin D3 was shown to reduce the risk of hip fractures by 27%. Costs for treating hip fractures were based on 1,080 women who were hospitalized in Stockholm. RESULTS: Treatment of 70yearold women was cost saving at efficacy as low as twothirds that seen in the clinical trials, and upwards. Even at modest rates of efficacy, treatment of the highrisk 50 and 60yearold cohorts was generally costeffective and in some cases even cost saving. Particularly costeffective was treatment of women with identified osteoporosis or a maternal family history of hip fracture. CONCLUSION: Simulation results suggest a role for lifetime treatment of older women with calcium and vitamin D3 in Sweden. While there is more uncertainty underlying the treatment of younger women, our simulation results suggest that treatment may also be cost saving or at least costeffective for many cohorts of highrisk 50 and particularly 60yearold women, in particular those with osteoporosis or a maternal family history of hip fracture. PMID 12602080

29: Med Clin (Barc). 2001 Nov 17;117(16):6114. [Prevalence of hypovitaminosis D in elderly institutionalized residents: influence of a substitutive treatment] Larrosa M, Gratacos J, Vaqueiro M, Prat M, Campos F, Roque M.

BACKGROUND: Osteoporosis in the elderly is a common and severe disease, vitamin D deficiency being an important causative factor. Hypovitaminosis D is frequent in old people, particularly those living in nursing homes. SUBJECTS AND METHOD: We performed a crosssectional study of 100 randomly recruited elderly institutionalized subjects. The prevalence of hypovitaminosis D and its possible repercussion on the phosphocalcium metabolism were assessed. The degree of sun exposure and the existence of comorbidity were also recorded. Individuals with hypovitaminosis D were included in a longitudinal study (6 months' duration) aimed at assess the efficacy of treatment with calcium and two different therapeutic regimens with calcidiol (16,000 IU/week or 16,000 IU every 3 weeks). RESULTS: 87% of individuals had hypovitaminosis D; 21.8% of them had secondary hyperparathyroidism. The study population had a low degree of sun exposure and a high level of comorbidity. The two doses of calcidiol led to a normalization of 25OHD3 levels, increased calciuria and compensated secondary hyperparathyroidism, yet higher 25OHD3 levels were achieved with the weekly therapeutic scheme. CONCLUSIONS: Hypovitaminosis D prevalence appears to be very high In the elderly institutionalized population. Calcium and calcidiol supplementation normalized 25OHD3, improved calcium absorption and compensated secondary hyperparathyroidism. Calcium and vitamin D supplementation should be employed routinely in the elderly institutionalized population.

30: Ann Oncol. 2001 Nov;12(11):158993. Micronutrients and ovarian cancer: a casecontrol study in Italy. Bidoli E, La Vecchia C, Talamini R, Negri E, Parpinel M, Conti E, Montella M, Carbone MA, Franceschi S.

BACKGROUND: The role of selected micronutrients, vitamins and minerals in the aetiology of epithelial ovarian cancer was investigated using data from a casecontrol study conducted between 1992 and 1999 in five Italian areas. PATIENTS AND METHODS: Cases were 1,031 patients with histologically confirmed incident epithelial ovarian cancer. Controls were 2,411 subjects admitted for acute, nonneoplastic diseases to major hospitals in the same catchment areas. Dietary habits were elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed by quintiles of intake of nutrients. RESULTS: Inverse associations emerged for vitamin E (OR = 0.6; 95% CI: 0.50.8), betacarotene (OR = 0.8; 95% CI: 0.61.0), lutein/zeaxanthin (OR = 0.6; 95% CI: 0.50.8 for the highest vs. the lowest quintile of intake), and calcium intake (OR = 0.7; 95% CI: 0.61.0). When the combined effect of calcium and vitamin E was considered, the OR reached 0.4 (95% CI: 0.30.7) for subjects in the highest compared to those in the lowest intake tertile of both micronutrients. Results were consistent across strata of menopausal status, parity and family history of ovarian or breast cancer. CONCLUSIONS: The intake of selected micronutrients, which were positively correlated to a diet rich in vegetables and fruits, was inversely associated with ovarian cancer. PMID 11822759

31: Calcif Tissue Int. 2001 Jun;68(6):3527. Epub 2001 May 21. Acute effects in healthy women of oral calcium on the calciumparathyroid axis and bone resorption as assessed by serum betaCrossLaps. Zikan V, Haas T, Stepan JJ.

The purpose of this investigation was to test the hypothesis that the decrease in bone resorption after the calcium (Ca) load can be assessed by serum type 1 collagen crosslinked Ctelopeptide (Elecsys betaCrossLaps, Roche) (SCTX). Six young healthy women (2327 years of age) and six healthy late postmenopausal women (6369 years of age) with normal bone mineral density (BMD) received, after overnight fasting, 1 g of elemental Ca (in the form of calcium carbonate) dissolved in 250 ml of water or only plain water (fasting period). In addition, the late postmenopausal women were tested with an additional dose of 0.2 g of elemental Ca in 250 ml of water. Serum ionized Ca (SiCa), SCTX, plasma immunoreactive intact parathormone (PPTH) were measured before and during the 5 hours after the oral intake of Ca. Urine was collected at regular intervals, and urinary Ca and creatinine were analyzed. In both the young and late postmenopausal subjects, the load with Ca resulted in a significant increase in SiCa and urine Ca/creatinine ratio as well and a significant decrease of PPTH and SCTX compared with the fasting period. The comparison of the effects of 1 g Ca load between young and late postmenopausal women did not show any statistical significance in any measured parameters. In the late postmenopausal women, a significantly greater increase in SiCa concentrations and a significantly greater decrease in PPTH after 1 g were observed compared with those after a 0.2 g dose of Ca. During the first 3 hours, the load of both 1 g and 0.2 g of Ca induced a similar decrease in SCTX. After 5 hours, however, SCTX were significantly more suppressed after a 1 g dose than after a 0.2 g dose of Ca. In conclusion, a single oral morning dose of 1 g Ca suppresses bone resorption, as assessed by SCTX, to a similar degree in both young and late postmenopausal women with normal Ca absorption. In healthy late postmenopausal women the load of 0.2 g of Ca carbonate significantly suppresses bone resorption. PMID 11685423

32: J Clin Endocrinol Metab. 2001 Apr;86(4):16337. Effects of a shortterm vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. Pfeifer M, Begerow B, Minne HW, Nachtigall D, Hansen C.

Calcium supplementation is effective in reducing blood pressure in various states of hypertension, including pregnancyinduced hypertension and preeclampsia. In addition, calcitropic hormones are associated with blood pressure. The hypothesis is that shortterm therapy with calcium and vitamin D(3) may improve blood pressure as well as secondary hyperparathyroidism more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D(3) (cholecalciferol) and calcium on blood pressure and biochemical measures of bone metabolism were studied. The sample consisted of 148 women (mean +/ SD age, 74 +/ 1 yr) with a 25hydroxycholecalciferol (25OHD(3)) level below 50 nmol/L. They received either 1200 mg calcium plus 800 IU vitamin D(3) or 1200 mg calcium/day. We measured intact PTH, 25OHD(3), 1,25dihydroxyvitamin D(3), blood pressure, and heart rate before and after treatment. Compared with calcium, supplementation with vitamin D(3) and calcium resulted in an increase in serum 25OHD(3) of 72% (P < 0.01), a decrease in serum PTH of 17% (P = 0.04), a decrease in systolic blood pressure (SBP) of 9.3% (P = 0.02), and a decrease in heart rate of 5.4% (P = 0.02). Sixty subjects (81%) in the vitamin D(3) and calcium group compared with 35 (47%) subjects in the calcium group showed a decrease in SBP of 5 mm Hg or more (P = 0.04). No statistically significant difference was observed in the diastolic blood pressures of the calciumtreated and calcium plus vitamin D(3)treated groups (P = 0.10). Pearson coefficients of correlation between the change in PTH and the change in SBP were 0.49 (P < 0.01) for the vitamin D(3) plus calcium group and 0.23 (P < 0.01) for the calcium group. A shortterm supplementation with vitamin D(3) and calcium is more effective in reducing SBP than calcium alone. Inadequate vitamin D(3) and calcium intake could play a contributory role in the pathogenesis and progression of hypertension and cardiovascular disease in elderly women.

33: Public Health Nutr. 2001 Apr;4(2B):54759. Calcium and vitamin D nutrition and bone disease of the elderly. Gennari C.

Osteoporosis, a systemic skeletal disease characterized by a low bone mass, is a major public health problem in EC member states because of the high incidence of fragility fractures, especially hip and vertebral fracture. In EC member states the high incidence of osteoporotic fractures leads to considerable mortality, morbidity, reduced mobility and decreased quality of life. In 1995 the number of hip fractures in 15 countries of EC has been 382,000 and the estimated total care cost of about 9 billion of ECUs. Given the magnitude of the problem public health measures are important for preventive intervention. Skeletal bone mass is determined by a combination of endogenous (genetic, hormonal) and exogenous (nutritional, physical activity) factors. Nutrition plays an important role in bone health. The two nutrients essential for bone health are calcium and vitamin D. Reduced supplies of calcium are associated with a reduced bone mass and osteoporosis, whereas a chronic and severe vitamin D deficiency leads to osteomalacia, a metabolic bone disease characterized by a decreased mineralization of bone. Vitamin D insufficiency, the preclinical phase of vitamin D deficiency, is most commonly found in the elderly. The major causes of vitamin D deficiency and insufficiency are decreased renal hydroxylation of vitamin D, poor nutrition, scarce exposition to sunlight and a decline in the synthesis of vitamin D in the skin. The daily average calcium intake in Europe has been evaluated in the SENECA study concerning the diet of elderly people from 19 towns of 10 European countries. In about one third of subjects the dietary calcium intake results were very low, between 300 and 600 mg/day in women, and 350 and 700 mg/day in men. Calcium supplements reduce the rate of bone loss in osteoporotic patients. Some recent studies have reported a significant positive effect of calcium treatment not only on bone mass but also on fracture incidence. The SENECA study, has also shown that vitamin D insufficiency is frequent in elderly populations in Europe. There are a number of studies on the effects of vitamin D supplementation on bone loss in the elderly, showing that supplementations with daily doses of 400800 IU of vitamin D, given alone or in combination with calcium, are able to reverse vitamin D insufficiency, to prevent bone loss and to improve bone density in the elderly. In recent years, there has been much uncertainty about the intake of calcium for various ages and physiological states. In 1998, the expert committee of the European Community in the Report on OsteoporosisAction on prevention, has given the recommended daily dietary allowances (RDA) for calcium at all stage of life. For the elderly population, above age 65 the RDA is 700800 mg/day. The main source of calcium in the diet are dairy products (milk, yoghurts and cheese) fish (sardines with bones), few vegetables and fruits. The optimal way to achieve adequate calcium intake is through the diet. However, when dietary sources are scarce or not well tolerated, calcium supplementation may be used. Calcium is generally well tolerated and reports of significant sideeffects are rare. Adequate sunlight exposure may prevent and cure vitamin D insufficiency. However, the sunlight exposure or the ultraviolet irradiation are limited by concern about skin cancer and skin disease. The most rational approach to reducing vitamin D insufficiency is supplementation. In Europe, the RDA is 400800 IU (1020 microg) daily for people aged 65 years or over. This dose is safe and free of side effects. In conclusion, in Europe a low calcium intake and a suboptimal vitamin D status are very common in the elderly. Evidence supports routine supplementation for these people at risk of osteoporosis, by providing a daily intake of 700800 mg of calcium and 400800 IU of vitamin D. This is an effective, safe and cheap means of preventing osteoporotic fractures.

Publication Types: Review Review, Tutorial

34: Rheum Dis Clin North Am. 2001 Feb;27(1):10130. Calcium and vitamin D in osteoporosis. Morgan SL.

Calcium and vitamin D are useful adjunctive therapies in the prevention and treatment of osteoporosis. Peak BMD is optimally achieved with sustained optimal calcium and vitamin D intakes. Calcium and vitamin D intakes continue to be important after the third decade and into senescence. Although calcium and vitamin D are not therapies to be used alone to prevent early postmenopausal bone loss, they assume more prominent roles in late menopause and in the elderly to preserve bone health with advancing age. Calcium and vitamin D supplementation is an important adjunctive therapy to use together with antiresorptive therapies.

35: Calcif Tissue Int. 2000 Dec;67(6):4402. Inhibition of bone resorption by divideddose calcium supplementation in early postmenopausal women. Scopacasa F, Need AG, Horowitz M, Wishart JM, Morris HA, Nordin BE.

We have previously shown that a calcium (Ca) supplement of 1000 mg given in the evening reduces the overnight and early morning, but not the daytime, excretion of bone resorption markers in postmenopausal women within five years of the menopause. In the present study, we have looked at the effect of splitting the Ca into two doses of 500 mg each given in the morning and evening. We studied 19 healthy women (median age 53 years) who were all within 5 years of the menopause. On the 2 study days, urine was collected from 9 a.m. to 9 p.m. (day collection), and from 9 p.m. to 9 a.m. (night collection); a further fasting (spot) urine sample was obtained at 9 a.m. at the end of the night collection. The first day was a control day; on the second day the subjects ingested 500 mg Ca as the carbonate at 9 a.m. and 9 p.m. We measured pyridinoline crosslinks excretion in all the samples, as well as hydroxyproline in the fasting urine. The Ca supplements lowered urinary excretion of the markers during the day (P < 0.01), had only a marginal effect during the night, but reduced excretion significantly in the fasting urine (P < 0.001). In the whole 24hour period, the falls in resorption markers were small but comparable to those seen after the ingestion of 1 g of Ca in the evening. We conclude that the acute administration of 0.5 g Ca in the morning and evening reduced the markers of bone resorption in early postmenopausal women during the day but not during the following night, whereas the single 1 g supplement had the reverse effect. Over the 24hour period, there was nothing to choose between the two regimes. Women at this stage in their life cycle probably require a larger Ca supplement if they are not taking estrogen.

36: Med Wieku Rozwoj. 2000 OctDec;4(4):42330. [Current views on requirements for vitamin D, calcium and phosphorus, particularly in formula fed infants] Ksiazyk J.

Calcium (Ca) and phosphorus (P) absorption depends on vitamin D. Vitamin deficiency in children results in rickets and osteoporosis in adults. Prematurely born infants are at risk of osteopenia and rickets. Skin synthesis of vitamin D can obtain the level of 10 000 IU (250 ug) when the whole body is exposed to the sun. Recent opinion on vitamin D requirement establishes the level of more than 80 nmol/L of 25(OH)D. There are no recommendations for children but it seems that due to the risk of skin cancer, exposure to the sun in children will be limited and as a result higher dose of vitamin D will be needed. Calcium and phosphorus are the most common minerals of the human body. Calcium concentration in human milk is not related to the intake. Calcium intake of calcium in premature infants is 70140 mg/100 kcal. Phosphorus content in breast milk, even as low as 15 mg%, can maintain the optimal Ca/P ratio of 2/1. Prolonged breast feeding without additional Ca and P, may result in reduced bone mineralisation. Higher content of calcium in infant formula in comparison to human milk is due to the fact that Ca absorption from breast milk is 60% in comparison to 40% absorption from the formula.

37: Med Clin (Barc). 2000 Jun 10;115(2):4651. [Treatment of osteoporosis with calcium and vitamin D. Systematic review] Vallecillo G, Diez A, Carbonell J, Gonzalez Macias J.

BACKGROUND: Systematic review of the efficacy of calcium and vitamin D for the treatment of osteoporosis. MATERIAL AND METHOD: Review of the database MEDLINE between 1996 and may 1998, by the key words: osteoporosis, calcium, vitamin D (and related terms) and randomized clinical trial. Review of the electronic versions of Best Evidence, The Cochrane Library, congress abstracts and references from two main textbooks. Ascending review of the literature. All the reviews were performed independently by two of the authors. Design parameters and main results of the primary publications of the identified trials were tabulated. Two independent observers carried out methodological scoring of the studies. Results were tabulated and a judgement made for the results. RESULTS: Eleven studies on calcium, 8 of vitamin D and 12 about calcitriol and other hormone derivatives were included. Studies with calcium were mainly performed on nonclinical populations and in three antifracture efficacy was analyzed. Results were positive in population with low baseline intake and substantial supplementation. Trials on vitamin D were done in nonclinical and on institutionalized populations. Trials with calcitriol were developed mainly in osteoporotic fracture populations and reached poorer methodological validity scores. Heterogeneity of the studies precluded a metaanalysis of the different treatments. Studies on calcium showed clinical efficacy in a more consistent way. Interobserver score was good (kappa = 0.81) and there were no significant correlations between sample size and effect in the different studies. CONCLUSIONS: Calcium treatment is efficacious in populations with low intake receiving substantial supplementation. Vitamin D is efficacious associated with calcium mainly in deficient populations. Efficacy of calcitriol and other derivatives is more controversial.

38: Dev Med Child Neurol. 2000 Jun;42(6):4035. Effect of vitamin D and calcium on bone mineral density in children with CP and epilepsy in fulltime care. JekovecVrhovsek M, Kocijancic A, Prezelj J.

Atraumatic fractures are often seen in children and adolescents with cerebral palsy (CP) and epilepsy in fulltime care. Increased bone fragility was postulated to be due to osteopenia resulting from a combination of factors including immobilization and antiepileptic treatment. The aim of this study was to determine the effect of vitamin D and calcium substitution on bone mineral density (BMD) in a group of children with CP in fulltime care. Twenty children with the most severe form of CP (spastic quadriplegia) who had been treated with antiepileptic drugs for a relatively long period of time were included in the study. Physical examination and laboratory analyses excluded other possible causes of osteopenia. BMD was measured by dual Xray absorptiometry. Thirteen patients were treated for 9 months with 1,25dihydroxycholecalciferol vitamin D (0.25 mcg daily) and with calcium (500 mg daily). Seven control children were used for observation only. BMD greatly increased in the treated group, while children with CP in fulltime care who did not receive vitamin D and calcium substitution continued to lose their bone mass. It can be concluded that the addition of vitamin D and calcium increases BMD in children with the most severe form of CP, who are receiving antiepileptic drugs.

39: Nephrol Dial Transplant. 2000 Jun;15(6):87782. Changes in bone turnover after parathyroidectomy in dialysis patients: role of calcitriol administration. Mazzaferro S, Chicca S, Pasquali M, Zaraca F, Ballanti P, Taggi F, Coen G, Cinotti GA, Carboni M.

BACKGROUND: Available data on changes in serum levels of bone markers after parathyroidectomy (PTx) in dialysis patients are not uniform. Changes are thought to be due to either a reduction in PTH activity per se or to a direct effect of vitamin D therapy on bone cells. We aimed to verify whether treatment with vitamin D modifies serum levels of markers of bone synthesis (alkaline phosphatase (AP), osteocalcin (BGP), procollagen type I Cterminal peptide (PICP)) and resorption (collagen type I Cterminal peptide (ICTP)) within a period of 15 days in haemodialysis patients with severe secondary hyperparathyroidism following PTx. METHODS: We randomized two groups (A, treatment and B, placebo, 10 patients each) with comparable basal PTH values and measured bone markers 3, 7 and 15 days after surgery. All patients were treated with calcium supplements (i.v. and p.o.), and group A also received calcitriol (2.4+/1.0 microg/day, p.o.). RESULTS: In both groups, PTx induced significant changes in all the markers evaluated, except for BGP in group B. Compared to basal values, ICTP decreased from 481+/152 ng/ml in group A and 277+/126 ng/ml in group B to 267+/94 and 185+/71 ng/ml (M+/SD) respectively, and PICP increased from 307+/139 ng/ml in group A and 309+/200 ng/ml in group B to 1129+/725 and 1231+/1267 ng/ml (M+/SD) respectively, within 3 days of surgery. AP values increased after 15 days from 1115+/734 mU/ml in group A and 1419+/1225 mU/ml in group B to 1917+/1225 and 1867+/1295 mU/ml (M+/SD) respectively. On the contrary, mean values of BGP were never different from basal levels after PTx in either group. In the two groups, the pattern of changes of all the bone markers after PTx was almost identical. Group A patients predictably required lower doses of oral calcium supplements to correct hypocalcaemia (16. 9+/5.7 vs 22.1+/5.0 g/10 days; M+/SD, P<0.04). CONCLUSIONS: The opposite behaviour of serum PICP and ICTP after PTx, in both the treated and untreated groups suggests that quantitative uncoupling between bone synthesis and resorption is responsible for hypocalcaemia. This phenomenon, as reflected by the evaluated bone markers, is unaffected by calcitriol. Based on our data we conclude that immediately after parathyroid surgery, vitamin D therapy does not influence bone cell activity, but improves hypocalcaemia mainly through its known effect on intestinal calcium absorption.

40: Psychopharmacology (Berl). 2000 Jun;150(2):2205. The effects of an oral multivitamin combination with calcium, magnesium, and zinc on psychological wellbeing in healthy young male volunteers: a doubleblind placebocontrolled trial. Carroll D, Ring C, Suter M, Willemsen G.

RATIONALE: Vitamin and mineral supplements may be associated with improved psychological status. OBJECTIVE: The present study tested the effects of a multivitamin and mineral supplement (Berocca) on psychological wellbeing. METHODS: In a doubleblind randomisedcontrol trial, 80 healthy male volunteers were assigned to either Berocca or placebo. Questionnaires measuring psychological state were completed and a blood sample taken to determine plasma zinc concentration on day 1 (pretreatment) and again on day 28 (posttreatment), following 28 days of treatments, which were administered at a dosage of one tablet daily. At the end of the study, the acceptability of the treatment and participants' awareness of treatment condition were assessed, as was habitual dietary behaviour. RESULTS: Relative to placebo, treatment with Berocca was associated with consistent and statistically significant reductions in anxiety and perceived stress. Participants in the Berocca group also tended to rate themselves as less tired and better able to concentrate following treatment. In addition, participants registered more somatic symptoms following placebo than following Berocca. These effects cannot be attributed to differences in the acceptability of the two treatments or to participants guessing what treatment they received. CONCLUSION: These findings demonstrate that Berocca significantly reduces anxiety and perceived stress.

41: Ned Tijdschr Geneeskd. 2000 May 6;144(19):9003. [Hypocalcemia as a cause of reversible heart failure] Bolk J, Ruiter JH, van Geelen JA.

A 72yearold woman with therapy resistant congestive heart failure presented with severe hypocalcaemia due to hypoparathyroidism after strumectomy more than 25 years before. After suppletion of calcium her complaints resolved and there was considerable improvement in left ventricular function. Our case report suggests that hypocalcaemia induced cardiomyopathy should be considered in the differential diagnosis of therapy resistant heart failure and that myocardial impairment is reversible after administration of calcium.

42: Proc Nutr Soc. 2000 May;59(2):295301. Changing eating and physical activity patterns of US children. Johnson RK.

The number of US children who are overweight has more than doubled over the last decade. This change has broadened the focus of dietary guidance for children to address nutrient overconsumption and physical activity patterns. Total fat consumption expressed as a percentage of energy intake has decreased among US children. However, this decrease is largely the result of increased total energy intake in the form of carbohydrates and not necessarily due to decreased fat consumption. The majority of children aged 517 years are not meeting recommendations for Ca intakes. Much of this deficit is attributed to changing beverage consumption patterns, characterized by declining milk intakes and substantial increases in softdrink consumption. On average, US children are not eating the recommended amounts of fruits and vegetables. US adolescents become less active as they get older, and onequarter of all US children watch > or = 4 h television each day, which is positively associated with increased BMI and skinfold thickness. There is an urgent need in the USA for effective prevention strategies aimed at helping children grow up with healthful eating and physical activity habits to achieve optimal health.

43: Jpn J Physiol. 2000 Apr;50(2):20713. Involvement of Ca(2+) in antiarrhythmic effect of ischemic preconditioning in isolated rat heart. Hong K, Kusano KF, Morita H, Fujimoto Y, Nakamura K, Yamanari H, Ohe T.

We investigated the relationship between the effects of ischemic preconditioning (IPC) and Ca(2+) preconditioning (CPC) on reperfusioninduced arrhythmias. In the control group (noPC), Langendorffperfused rat hearts were subjected to 5min zeroflow global ischemia (I) followed by 15min reperfusion (I/R). In ischemic preconditioning groups (IPC), the hearts were subjected to three cycles of 3min global ischemia and 5min reperfusion. In the CPC group, the hearts were exposed to three cycles of 3min perfusion of higher Ca(2+) (2.3 mmol/l Ca(2+)) followed by 5min perfusion of normal 1.3 mmol/l Ca(2+), and the hearts were then subjected to I/R. Verapamil was administered in several hearts of the IPC group (VR+IPC). Ventricular arrhythmias upon reperfusion were less frequently seen in the IPC and CPC groups than in the noPC and VR+IPC groups. IPC and CPC could attenuate conduction delay and enhance shortening of the monophasic action potential duration during ischemia. The ventricular fibrillation threshold measured at 1min reperfusion was significantly higher in the IPC and CPC groups than in the noPC and VR+IPC groups. Verapamil completely abolished the salutary effects of IPC. These results demonstrate that Ca(2+) plays an important role in the antiarrhythmic effect of IPC during reperfusion. PMID 10880877

44: Ann Intern Med. 2000 Mar 7;132(5):34553. Low fractional calcium absorption increases the risk for hip fracture in women with low calcium intake. Study of Osteoporotic Fractures Research Group. Ensrud KE, Duong T, Cauley JA, Heaney RP, Wolf RL, Harris E, Cummings SR.

BACKGROUND: Decreased ability to absorb calcium with age limits adaptation to low calcium intake and is thought to lead to secondary hyperparathyroidism and increased risk for hip and other fractures. However, the associations between fractional calcium absorption, dietary calcium intake, and risk for fracture have never been studied. OBJECTIVE: To determine whether low fractional calcium absorption in women with low calcium intake increases the risk for subsequent hip and other nonspine fractures. DESIGN: Prospective cohort study. SETTING: Four clinical centers in Baltimore County, Maryland; Portland, Oregon; Minneapolis, Minnesota; and the Monongahela Valley, Pennsylvania. PARTICIPANTS: 5452 nonblack women 69 years of age or older participating in the fourth examination of the Study of Osteoporotic Fractures. MEASUREMENTS: Fractional calcium absorption was measured by using a 3hour single isotope (45Ca) technique. Incident fractures were identified prospectively and were confirmed by radiographic report. RESULTS: During an average of 4.8 years, 729 women (13%) experienced at least one nonspine fracture; 153 of these women had hip fractures. After adjustment for age, women with lower fractional calcium absorption were at increased risk for hip fracture (relative risk per 1SD [7.7%] decrease in fractional calcium absorption, 1.24 [95% CI, 1.05 to 1.48]). Women with low fractional calcium absorption and low calcium intake were at greatest risk for subsequent hip fracture; among women whose dietary calcium intake was less than 400 mg/d, those who had fractional calcium absorption at or below the median value of 32.3% had a 2.5fold (CI, 1.29fold to 4.69fold) increase in risk for hip fracture compared with those who had greater absorption efficiency. Fractional calcium absorption was not related to risk for other nonspine fractures (relative risk per 1SD [7.7%] decrease in fractional calcium absorption, 1.05 [CI, 0.96 to 1.14]). CONCLUSIONS: In elderly women, low fractional calcium absorption in the setting of low calcium intake increases the risk for hip fracture. Our findings support the hypothesis of type II osteoporosis, which postulates that decreased calcium absorption is an important risk factor for hip fracture in older persons.

45: Med Hypotheses. 2000 Mar;54(3):4323. How calcium from calcium carbonate and milk benefit peptic ulcer patients. Wang X.

Calcium from calcium containing antacids and milk enhance the integrity of gastrointestinal mucosa and mucus, as it is the natural linker agent of these structures, which strengthens their defense function. Copyright 2000 Harcourt Publishers Ltd. PMID 10783482

46: Cochrane Database Syst Rev. 2000;(2):CD000952. Calcium and vitamin D for corticosteroidinduced osteoporosis. Homik J, SuarezAlmazor ME, Shea B, Cranney A, Wells G, Tugwell P.

OBJECTIVES: To assess the effects of calcium and vitamin D compared to calcium alone or placebo in the prevention of bone loss in patients taking systemic corticosteroids. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal trials register, Cochrane Controlled Trials Register, EMBASE and Medline up to 1996. We also conducted a hand search of abstracts from various scientific meetings and reference lists of selected trials. SELECTION CRITERIA: All randomized trials comparing calcium and vitamin D to calcium alone or placebo in patients taking systemic corticosteroids. DATA COLLECTION AND ANALYSIS: Data was abstracted from trials by two investigators. Methodological quality was assessed in a similar manner. Analysis was performed using fixed effects models. MAIN RESULTS: Five trials were included, with 274 patients. The analysis was performed at two years after starting calcium and vitamin D. There was a significant weighted mean difference (WMD) between treatment and control groups in lumbar (WMD 2.6 (95% CI 0.7, 4.5), and radial bone mineral density (WMD 2.5 (95% CI 0.6, 4.4). The other outcome measures (femoral neck bone mass, fracture incidence, biochemical markers of bone resorption) were not significantly different. REVIEWER'S CONCLUSIONS: This metaanalysis demonstrated a clinically and statistically significant prevention of bone loss at the lumbar spine and forearm with vitamin D and calcium in corticosteroid treated patients. Because of low toxicity and cost all patients being started on corticosteroids should receive prophylactic therapy with calcium and vitamin D.

47: Kurume Med J. 2000;47(4):27983. Effectiveness of an educational trial to encourage sufficient calcium intake in women college students. Sueta K.

An educational trial to encourage sufficient calcium (Ca) intake was conducted on women college students who entered the college for dietitian either in 1993 or in 1994. The trial's effectiveness was assessed by a prospective cohort study. Two hundred and fifteen 18 or 19yearold students were assigned into two cohorts, i.e., a control cohort (CC) and an educated cohort (EC). Both groups received 3 surveys, i.e., at baseline, 1 week after, and 1 year after the Ca education, which was given only to the EC at baseline to encourage sufficient Ca intake. The amount of Ca taken by the CC did not significantly change in the 3 surveys. The EC took a significantly larger amount of Ca 1 week after and maintained relatively larger amount of Ca 1 year after the Ca education. These results suggest some effectiveness of Ca education on the women college students. PMID 11197149

48: Ann Pharmacother. 1999 Dec;33(12):13568. Calcium treatment for premenstrual syndrome. Ward MW, Holimon TD.

OBJECTIVE: To evaluate the use of calcium supplementation in the treatment of premenstrual syndrome. DATA SOURCES: Clinical literature accessed through MEDLINE (from January 1967 to September 1999). Key search terms included calcium, PMS, and premenstrual. DATA SYNTHESIS: Up to 50% of women experience some form of premenstrual syndrome. An evaluation of studies focusing on calcium in the management of premenstrual symptoms was conducted. CONCLUSIONS: Calcium supplementation of 12001600 mg/d, unless contraindicated, should be considered a sound treatment option in women who experience premenstrual syndrome. The supplemental dose of calcium can be adjusted downward in the few patients who routinely consume large quantities of calcium in their diet.

49: J Endocrinol Invest. 1999 Dec;22(11):8526. Importance of bioavailable calcium drinking water for the maintenance of bone mass in postmenopausal women. Costi D, Calcaterra PG, Iori N, Vourna S, Nappi G, Passeri M.

The aim of this research was to establish the importance of calcium intake through mineral water on vertebral bone density in women. To this purpose, we examined 255 women divided into two groups: those regularly drinking a high calcium content mineral water (group A; no.=175) and those using different type of water with a lower calcium content (group B; no.=80). Their dietary daily calcium intake was determined by means of a validated questionnaire (N.I.H. Consensus statement) and vertebral bone density was measured by DualEnergy Xray absorptiometry (Unigammaplus ACN densitometer). Women in group A ingested a significantly higher quantity of calcium in water than women in group B (mean difference 258 mg; 95% confidence limits: 147370 mg). The average bone density values were slightly but significantly higher in group A as compared to group B (mean+/SD: 1.044+0,15 vs 1.002+0,14; p=0.03). In addition to age, BMI and menopausal status, calcium intake was a significant predictor of spinal BMD. These 4 variables explained about 35% of the spinal BMD variance. When the analysis was repeated separately for pre and postmenopausal subjects, calcium remained a significant predictor in postmenopausal women (t=2.28; p=0.02), but not in premenopausal women. These results underline the importance of a lifelong daily calcium intake, resulting by the regular drinking of high bioavailable calcium water, in order to maintain bone mass after the menopause, in comparison to the use of a lower content calcium water. PMID 10710273

50: J Intern Med. 1999 Oct;246(4):35761. The effect of various hormonal preparations and calcium supplementation on bone mass in early menopause. Is there a predictive value for the initial bone density and body weight? Pines A, Katchman H, Villa Y, Mijatovic V, Dotan I, Levo Y, Ayalon D.

OBJECTIVES: To compare the effect of various oestrogen and oestrogen/progestin preparations on bone density over a 2year followup period in early postmenopausal women. SETTING: A retrospective study on 315 women followed in a menopause clinic. DESIGN: Anteroposterior lumbar spine bone densitometry was performed at baseline and between 18 and 24 months (mean 22 months) after initiation of hormone therapy. Participants were divided into six groups: women taking conjugated equine oestrogen (CEE) (n = 30); CEE plus sequential monthly medroxyprogesterone acetate (MPA) (n = 52); CEE plus sequential bimonthly MPA (n = 51); oral estradiol plus sequential monthly norethisterone acetate (n = 52); transdermal estradiol plus sequential monthly MPA (n = 30). A control group (n = 100) was composed of nonusers of hormones. RESULTS: Hormone users, as a whole (n = 215), increased their bone mineral density (BMD) by 2.9% (4.8) as compared to the controls who lost 3.5% (3.4; P < 0. 001). There were similar gains in BMD amongst the five study groups. Calcium supplementation was associated with better results in all women: users of hormones and calcium had a gain in BMD of 4.5% (4.8) compared to only 1.5% (4.5) in those on hormones but without calcium (P < 0.001); amongst the controls, women using calcium lost 1.4% (2. 4), whilst nonusers of calcium lost 3.7% (2.4; P < 0.001). A doseresponse curve was found between basal BMD and the effect of hormone therapy: women with osteoporosis (Tscore <75%) demonstrated the largest increase in BMD 6.3% (4.6), osteopenia (Tscore 7585%) was associated with a gain of 3.2% (5.6), lowborderline values (Tscore 86100%) gave a modest increase of 1.3% (4.3), and those with more than average BMD values (Tscore >100%) actually lost bone despite hormone treatment [2.1% (4.1)]. CONCLUSIONS: All hormone regimens had a similar bone conserving effect. Basal BMD value may serve as a predictor for the success of treatment. Calcium supplementation should be recommended in all postmenopausal women. PMID 10583706

51: J Assoc Physicians India. 1999 Sep;47(9):86973. Effect of protein and phosphate restricted and calcium and alphacalcidol supplemented diet on renal and parathyroid functions and protein status in chronic renal failure patients. Nand N, Aggarwal HK, Anupam, Sharma M.

OBJECTIVE: To assess the effect of low protein (0.6 g/kg/day), low phosphate (510 mg/kg/day) diet with calcium (600 mg/day) and alphaD3 (0.5 microgram/day) supplementation on renal and parathyroid functions in patients with chronic renal failure (CRF). METHODS: The study included 20 adult patients of CRF, maintained on diet therapy alone. The patients were followed up for renal and parathyroid functions and protein status for 6 months at monthly interval. RESULTS: There was symptomatic improvement in 88% patients. Blood urea and serum creatinine decreased significantly (p < 0.001 and < 0.01, respectively) and the slope of inverse serum creatinine against time changed to static or an upslope. Glomerular filtration rate (GFR) improved from a basal value of 29.35 +/ 18.2 ml/min to 39.25 +/ 27 ml/min after 6 months. Serum parathyroid hormone (PTH) level of 197.65 +/ 133.7 pg/ml and post treatment level of 254.55 +/ 217.19 after 6 months were not different (p > 0.05). Serum calcium remained stationary with a slight increase in serum phosphorus. Phosphorus had a negative correlation with calcium and GFR, whereas calcium had a negative correlation with PTH and phosphorus. PTH had a positive correlation with phosphorus and negative with GFR and calcium. CONCLUSION: There was an improvement in renal functions without any deleterious effect on the protein status of the patients of CRF. Also, there was halting of parathyroid dysfunction especially in those patients where there was no evidence of preexisting hyperparathyroidism. Hence, dietry management should be strictly enforced in CRF patients early in the course of disease.

52: Stroke. 1999 Sep;30(9):17729. Prospective study of calcium, potassium, and magnesium intake and risk of stroke in women. Iso H, Stampfer MJ, Manson JE, Rexrode K, Hennekens CH, Colditz GA, Speizer FE, Willett WC.

BACKGROUND AND PURPOSE: High intakes of calcium, potassium, and magnesium have been hypothesized to reduce risks of cardiovascular disease, but only a few prospective studies have examined intakes of these cations in relation to risk of stroke. METHODS: In 1980, 85 764 women in the Nurses' Health Study cohort, aged 34 to 59 years and free of diagnosed cardiovascular disease and cancer, completed dietary questionnaires from which we calculated intakes of calcium, potassium, and magnesium. By 1994, after 1.16 million personyears of followup, 690 incident strokes (129 subarachnoid hemorrhages, 74 intraparenchymal hemorrhages, 386 ischemic strokes, and 101 strokes of undetermined type) had been documented. RESULTS: Intakes of calcium, potassium, and magnesium were each inversely associated with age and smokingadjusted relative risks of ischemic stroke, excluding embolic infarction of nonatherogenic origin (n=347). Adjustment for other cardiovascular risk factors, including history of hypertension, attenuated these associations, particularly for magnesium intake. In a multivariate analysis, women in the highest quintile of calcium intake had an adjusted relative risk of ischemic stroke of 0.69 (95% CI, 0.50 to 0.95; P for trend=0.03) compared with those in the lowest quintile; for potassium intake the corresponding relative risk was 0.72 (95% CI, 0.51 to 1.01; P for trend=0.10). Further simultaneous adjustment for calcium and potassium intake suggested an independent association for calcium intake. The association of risk with calcium intake did not appear to be log linear; the increase in risk was limited to the lowest quintile of intake, and intakes > approximately 600 mg/d did not appear to reduce risk of stroke further. The inverse association with calcium intake was stronger for dairy than for nondairy calcium intake. Intakes of calcium, potassium, and magnesium were not related to risk of other stroke subtypes. CONCLUSIONS: Low calcium intake, and perhaps low potassium intake, may contribute to increased risk of ischemic stroke in middleaged American women. It remains possible that women in the lowest quintile of calcium intake had unknown characteristics that made them susceptible to ischemic stroke. PMID 10471422

53: N Engl J Med. 1999 Aug 19;341(8):5638. A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children. Thacher TD, Fischer PR, Pettifor JM, Lawson JO, Isichei CO, Reading JC, Chan GM.

BACKGROUND: Nutritional rickets remains prevalent in many tropical countries despite the fact that such countries have ample sunlight. Some postulate that a deficiency of dietary calcium, rather than vitamin D, is often responsible for rickets after infancy. METHODS: We enrolled 123 Nigerian children (median age, 46 months) with rickets in a randomized, doubleblind, controlled trial of 24 weeks of treatment with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of vitamin D and calcium. We compared the calcium intake of the children at enrollment with that of control children without rickets who were matched for sex, age, and weight. We measured serum calcium and alkaline phosphatase and used a 10point radiographic score to assess the response to treatment at 24 weeks. RESULTS: The daily dietary calcium intake was low in the children with rickets and the control children (median, 203 mg and 196 mg, respectively; P=0.64). Treatment produced a smaller increase in the mean (+/SD) serum calcium concentration in the vitamin D group (from 7.8+/0.8 mg per deciliter [2.0+/0.2 mmol per liter] at base line to 8.3+/0.7 mg per deciliter [2.1+/0.2 mmol per liter] at 24 weeks) than in the calcium group (from 7.5+/0.8 [1.9+/0.2 mmol per liter] to 9.0+/0.6 mg per deciliter [2.2+/0.2 mmol per liter], P<0.001) or the combinationtherapy group (from 7.7+/1.0 [1.9+/0.25 mmol per liter] to 9.1+/0.6 mg per deciliter [2.3+/0.2 mmol per liter], P<0.001). A greater proportion of children in the calcium and combinationtherapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphatase concentration of 350 U per liter or less and radiographic evidence of nearly complete healing of rickets (61 percent, 58 percent, and 19 percent, respectively; P<0.001). CONCLUSIONS: Nigerian children with rickets have a low intake of calcium and have a better response to treatment with calcium alone or in combination with vitamin D than to treatment with vitamin D alone. PMID 10451461

54: Gen Pharmacol. 1999 Aug;33(2):13741. Taurine and calcium interaction in protection of myocardium exposed to ischemic reperfusion injury. Oz E, Erbas D, Gelir E, Aricioglu A. Department of Physiology, Faculty of Medicine, Gazi University, Ankara, Turkey.

We aimed to investigate the cardioprotective role of taurine with low calcium level against reperfusion damage by adding taurine to extracellular fluid. Guineapig hearts were mounted on Langendorf perfusion apparatus and different compositions of perfusion solutions were prepared for each experimental group. After 20 min of normothermic ischemia the hearts were reperfused. Preischemic, postischemic and postreperfusion percentage changes of heart rate and contractile force were compared. Postreperfusion tissue weight, malondialdehyde (MDA) and prostaglandin Elike activity (PGElike activity) were assessed. Taurineadded lowcalcium perfusion solution significantly decreased the postischemic myocardial injury. PMID 10461851

55: Adv Nurse Pract. 1999 Jul;7(7):2631, 80. An expanding landscape. Osteoporosis. Treatment options today. Meiner SE.

Choices for osteoporosis therapy have expanded within the past 5 years. This article provides an overview of currently available therapy options. Exogenous estrogen can prevent and treat osteoporosis and is available in several delivery routes. Calcitonin is also designed to reduce bone loss in osteoporosis. Bisphosphonates such as alendronate prevent bone resorption by inhibiting osteoclasts and causing increased osteoclast cell death. Raloxifene is a selective estrogen receptor modulator and is the newest osteoporosis medication on the market. It may also have beneficial effects on breast cancer risk. All postmenopausal women should obtain 1,000 mg to 1,500 mg of calcium and 400 IU to 800 IU of vitamin D every dayregardless of any prescription therapy regimen for osteoporosis. They should also perform weightbearing exercise, such as walking, for 20 to 30 minutes every day or for 1 hour three times a week.

56: Clin Ther. 1999 Jun;21(6):105872. Supplemental calcium for the prevention of hip fracture: potential healtheconomic benefits. Bendich A, Leader S, Muhuri P.

We assessed the costeffectiveness of daily calcium supplementation for the prevention of primary osteoporotic hip fractures. The assessment was based on our metaanalysis of the published relativerisk estimates from 3 doublemasked, placebocontrolled, clinical trials and our analysis of raw data from the National Health and Nutrition Examination Survey 19881994 on the daily intake of calcium supplements by adults in the United States. These data were then used to estimate the preventable proportion of hip fractures. The 1995 National Hospital Discharge Survey database provided the number and demographic characteristics of patients discharged with a primary diagnosis of hip fracture, as well as their discharge destination. The 1990 itemized costs of hip fractures, as estimated by the US Congress Office of Technology Assessment, were inflated to 1995 dollars using the medical care component of the Consumer Price Index. Using these inflated itemized costs, we then estimated the weighted average expenditures, reflecting both the types of services associated with specific hospitaldischarge destinations and the demographic characteristics of discharged patients. The cost of supplements containing 1200 mg/d of elemental calcium for the mean duration (34 months) of the 3 clinical trials was calculated on the basis of 1998 unitprice and marketshare data for 6 representative products. For 1995, the data indicate that 290,327 patients aged > or =50 years were discharged from US hospitals with a primary diagnosis of hip fracture, at our estimated direct cost of $5.6 billion. Based on the risk reductions seen in the 3 trials, we estimated that 134,764 hip fractures and $2.6 billion in direct medical costs could have been avoided if individuals aged > or =50 years consumed approximately 1200 mg/d of supplemental calcium. Additional savings could be expected, because this intervention is also associated with significant reductions in the risk for all nonvertebral fractures. Comparing the cost of calcium with the expected medical savings from hip fractures avoided, it is costeffective to give 34 months of calcium supplementation to women aged > or =75 years in the United States. If, as the published studies suggest, shorter periods of supplementation result in an equivalent reduction in the risk of hip fractures, calcium supplementation becomes costeffective for all adults aged > or =65 years in the United States. The data support encouraging older adults to increase their intake of dietary calcium and to consider taking a daily calcium supplement. Even small increases in the usage rate of supplementation are predicted to yield significant savings and to reduce the morbidity and mortality associated with hip fracture at an advanced age. PMID 10440627

57: J Am Diet Assoc. 1999 May;99(5):5913. Calcium supplementation and exercise increase appendicular bone density in anorexia: a case study. Brooks ER, Howat PM, Cavalier DS. PMID 10333781

58: Scand J Clin Lab Invest. 1999 Apr;59(2):837. Short and longterm uses of calcium acetate do not change hair and serum zinc concentrations in hemodialysis patients. Hwang SJ, Chang JM, Lee SC, Tsai JH, Lai YH.

Calcium acetate (CaAc) acutely decreases absorption of concomitantly administered zinc gluconate (Hwang et al., AJKD 1992), but its longterm effect on zinc metabolism has not been studied. This study is intended to elucidate whether use of CaAc as phosphate binder on a daily basis affects zinc status in hemodialysis (HD) patients. Effects of CaAc on serum zinc were studied in 44 HD patients for 8 weeks (shortterm). In 10 of these patients, the changes of serum and hair zinc were followed for 8 months (longterm). The daily dose of CaAc contained 25.35 mmol elemental calcium. Serum and hair zinc concentrations were measured by atomic absorptiometry. Our results were as follows: (i) in the shortterm study, serum zinc concentrations did not show a significant difference compared to the baseline; (ii) in the longterm study, serum zinc concentrations showed no significant difference between different time points (11.0+/0.5 in the beginning, 11.9+/0.4 after 2 months, 11.4+/0.4 after 4 months and 11.3+/0.5 micromol/L after 8 months, n=10). However, these values were all significantly lower than in the normal controls (15.7+/0.5 micromol/L, n=16); (iii) hair zinc content was not significantly different from the baseline level (2.7+/0.1 in the beginning, 2.4+/0.1 after 2 months, 2.6+/0.2 after 4 months, 3.1+/0.1 micromol/g hair, and from that of normal controls, 2.7+/0.2 micromol/g hair). In conclusion, daily application of CaAc does not significantly interfere with zinc absorption and storage in HD patients. However, the comparable hair zinc content in the presence of decreased serum zinc concentrations indicates that the metabolic processing of zinc in HD patients is different from that of normal individuals. PMID 10353320

59: J Nutr. 1999 Mar;129(3):70711. Calcium does not inhibit iron absorption or alter iron status in infant piglets adapted to a high calcium diet. Wauben IP, Atkinson SA.

The purpose of this study was to investigate whether a dietary calcium:iron ratio similar to that often consumed by premature human infants inhibits iron absorption in infant piglets adapted to a high calcium diet. Male Yorkshire piglets were randomized at 3 to 4 d of age to a high calcium diet (4.67 g/L = HC) or a normal calcium diet (2.0 g/L = NC) and fed for 2 to 2.5 wk. An iron dextran injection was administered in amounts to achieve a marginal state of iron repletion to simulate iron status of premature infants. In vivo iron absorption from the diet was determined using the radiotracers 55Fe and 59Fe and whole body counting. Calcium:iron interactions at absorption sites in piglets fed HC and NC were investigated by measurements of timedependent 59Fe uptake in response to different calcium:iron ratios in vitro in brush border membrane vesicles (BBMV). In vivo iron absorption from the diet did not differ between NC and HC diet groups [57 +/ 8% versus 55 +/ 17% (mean +/ SD), respectively]. Iron status and iron contencentrations in spleen, liver, intestine, kidney and heart did not differ between diet groups. Iron uptake in BBMV was significantly reduced by calcium in both HC and NC (P < 0.001); but there were no significant differences in iron uptake in response to different calcium:iron ratios between HC and NC. With feeding a HC diet for 2 wk there may be an adaptive response to counteract the inhibitory effects of calcium on iron absorption, thus resulting in similar in vivo iron absorption and iron status irrespective of the 1.3fold difference in dietary calcium:iron ratio between piglet groups. However, future studies are needed to determine the specific sites of calcium:iron interactions and adaptation mechanisms. Since the calcium:iron ratios used in this study reflect the usual calcium:iron ratios in diets for premature infants, it is unlikely that interactive effects of calcium with iron will compromise iron status in this infant population when diets are supplemented with calcium.

60: Nutr Rev. 1999 Mar;57(3):848. The effects of potassium, magnesium, calcium, and fiber on risk of stroke. Suter PM.

Stroke mortality represents the third leading cause of death worldwide, after coronary artery disease and cancer. High blood pressure is a major risk factor for stroke. A recent study has identified potassium, magnesium, and fiber as significant modulators of stroke risk in men. The protective effects were particularly pronounced in hypertensive subjects. The observed protection may be due to direct and indirect effects of these nutrients on blood pressure and regulatory functions, such as endothelial function. A high intake of these nutrients, singularly or in combination, is associated with a more healthful overall lifestyle. The best strategy to achieve a high intake of these nutrients is a diet rich in fruits and vegetables.

61: Dis Colon Rectum. 1999 Feb;42(2):2127. Vitamin and calcium supplement use is associated with decreased adenoma recurrence in patients with a previous history of neoplasia. Whelan RL, Horvath KD, Gleason NR, Forde KA, Treat MD, Teitelbaum SL, Bertram A, Neugut AI.

INTRODUCTION: Although some have suggested that certain vitamins or calcium supplements may reduce adenoma recurrence, our own prior retrospective study found no such effects. The purpose of this casecontrol study was to further investigate whether regular vitamin or calcium supplement intake influenced the incidence of recurrent adenomatous polyps in patients with previous neoplasia who were undergoing followup colonoscopy. METHODS: This study enrolled 1,162 patients who underwent colonoscopy by one of three surgeons at ColumbiaPresbyterian Medical Center in New York City between March 1993 and February 1997. Of these patients 448 (250 males) had a previous diagnosis of colorectal neoplasia (cancer, adenomas, or dysplasia). Of these, 183 (40.8 percent) had an adenoma at the index colonoscopy. Information was collected on personal and family history of colonic diseases, cigarette smoking, medication, and vitamin and micronutrient supplement usage on a questionnaire that was completed by the patients before the colonoscopy. Odds ratios were obtained by unconditional logistic regression analysis, adjusting for age and gender, and used adenoma recurrence at index colonoscopy as the outcome. RESULTS: The mean interval between colonoscopic examinations was 37 months for the recurrent adenoma group and 38 months for the nonrecurrent group of patients (P = not significant). In this casecontrol study we found a protective effect for the use of vitamin supplements in general (any vitamin) on the recurrence of adenomas (odds ratio, 0.41; 95 percent confidence interval, 0.270.61). Specifically, this protective effect was observed for the use of multivitamins (odds ratio, 0.47; 95 percent confidence interval, 0.310.72), vitamin E (odds ratio, 0.62; 95 percent confidence interval, 0.390.98), and for calcium supplementation (odds ratio, 0.51; 95 percent confidence interval, 0.270.96). Nonsignificant protective effects were noted for carotene/vitamin A, vitamin D, and vitamin C. CONCLUSIONS: The use of multivitamins, vitamin E, and calcium supplements were found to be associated with a lower incidence of recurrent adenomas in a population of patients with history of previous colonic neoplasia. Prospective, randomized trials are needed to better assess the impact of these agents and to determine whether the use of these supplements is associated with a protective effect against recurrent adenomas. PMID 10211498

62: J Gynecol Obstet Biol Reprod (Paris). 1999 Feb;28(1):735. [Exanthematic pustulosis of pregnancy: favorable evolution using calcium and vitamin D2] Michel JL, Perrot JL, Varlet MN, Fond L, Seffert P, Cambazard F.

A 26yearold pregnant woman was hospitalized in an emergency setting for a skin eruption. She had developed pustules distributed on round patchlike areas of rash localized at the umbilicus and the larger skin folds. She was given calcitriol and calcium with good results. Systemic steroids are usually given for exanthematic pustulosis of pregnancy but with variable efficacy. Few cases of successful treatment with calcium and vitamin D have been reported. We suggest this alternative treatment could be useful in other cases.

63: Ann N Y Acad Sci. 1999;889:1207. Preclinical and early human studies of calcium and colon cancer prevention. Lipkin M.

Colorectal cancer continues to be a major cause of tumor mortality in the United States and other countries; despite attempts to improve the screening of highrisk populations, the incidence of this disease is still very high. Therefore, chemoprevention continues to be an important goal for the primary prevention of colorectal cancer. Among recent chemopreventive approaches, the administration of calcium and vitamin D continue to be evaluated in both preclinical and clinical studies. Many experimental findings described below have indicated associations between high calcium and vitamin D intake and decreased risk for colorectal cancer.

64: Ann N Y Acad Sci. 1999;889:13845. Calcium supplements and colorectal adenomas. Polyp Prevention Study Group. Baron JA, Beach M, Mandel JS, van Stolk RU, Haile RW, Sandler RS, Rothstein R, Summers RW, Snover DC, Beck GJ, Frankl H, Pearson L, Bond JH, Greenberg ER.

Experimental and observational findings suggest that calcium intake may protect against colorectal neoplasia. To investigate this hypothesis, we conducted a randomized, doubleblind trial of colorectal adenoma recurrence. Nine hundred thirty patients with a recent history of colorectal adenomas were randomly given calcium carbonate (3 gm daily; 1200 mg elemental calcium) or placebo, with followup colonoscopies one and four years after the qualifying examination. The main analysis focused on new adenomas found after the first followup endoscopy, up to (and including) the second followup examination. Risk ratios of at least one recurrent adenoma and ratios of the average numbers of adenomas were calculated as measures of calcium effect. There was a lower risk of recurrent adenomas in subjects assigned calcium. Eight hundred thirtytwo patients had two followup examinations and were included in the main analysis; the adjusted risk ratio of one or more adenomas was 0.81 (95% CI 0.67 to 0.99); the adjusted ratio of the average numbers of adenomas was 0.76 (95% CI 0.60 to 0.96). Among subjects who had at least one followup colonoscopy, the adjusted risk ratio of one or more recurrent adenomas was 0.85 (95% CI 0.74 to 0.98). The effect of calcium seemed independent of initial dietary fat and calcium intake. No toxicity was associated with supplementation. These findings indicate that calcium supplementation has a modest protective effect against colorectal adenomas, precursors of most colorectal cancers.

65: Am J Clin Nutr. 1998 Dec;68(6 Suppl):1394S1399S. Prevention of precancerous colonic lesions in rats by soy flakes, soy flour, genistein, and calcium. Thiagarajan DG, Bennink MR, Bourquin LD, Kavas FA.

The main purpose of this research was to determine whether diets containing soy products would inhibit the early stages of azoxymethaneinduced colon cancer in F344 rats. Additional objectives were to determine whether feeding starch instead of sucrose, feeding additional calcium (0.5% compared with 0.1%), or feeding a lowfiber powdered enteral formula would influence early colon carcinogenesis. Colon cancer was initiated with 2 injections of azoxymethane (15 mg/kg body wt) and a 12wk dietary treatment period was started 1 wk after the second injection. Precancerous colon lesions were assessed as foci with aberrant crypts (FAC). The mean numbers of FAC were 133 [soy concentrate (low concentration of phytochemicals)], 111 (starch substituted for sucrose), 98 [fullfat soy flakes (whole soybeans)], 87 (defatted soy flour), 77 (0.015% genistein), and 70 (0.5% Ca). The soy flour and fullfat soy flake diets contained 0.049% genistein derivatives (primarily glycosides), but were less effective in inhibiting the formation of FAC than the diet containing 0.015% genistein (as the aglycone). Eating soybeans and soy flour may reduce the early stages of colon cancer. PMID 9848506

66: J Clin Endocrinol Metab. 1998 Nov;83(11):381725. Calcium supplementation prevents seasonal bone loss and changes in biochemical markers of bone turnover in elderly New England women: a randomized placebocontrolled trial. Storm D, Eslin R, Porter ES, Musgrave K, Vereault D, Patton C, Kessenich C, Mohan S, Chen T, Holick MF, Rosen CJ.

Elderly women are at increased risk for bone loss and fractures. In previous crosssectional and longitudinal studies of women residing in northern latitudes, bone loss was most pronounced during winter months and in those consuming less than 1 g calcium per day. In this study we sought to test the hypothesis that calcium supplementation by either calcium carbonate or dietary means would prevent seasonal bone loss and preserve bone mass. Sixty older postmenopausal women without osteoporosis were randomized to one of three treatment arms: Dietary milk supplementation (D4 glasses of milk/day), Calcium carbonate (CaCO31000 mg/day in two divided doses), or placebo (P). After 2 yr, placebotreated women consumed a mean of 683 mg/day of calcium and lost 3.0% of their greater trochanteric (GT) bone mineral density (BMD) (P < 0.03 vs. baseline); Dietary supplemented women averaged a calcium intake of 1028 mg/day and sustained minimal loss from the GT (1.5%; P = 0.30), whereas CaCO3treated women (total Ca intake, 1633 mg/day) suffered no bone loss from the GT and showed a significant increase in spinal and femoral neck BMD (P < 0.05). Femoral bone loss occurred exclusively during the two winters of the study (i.e. total loss, 3.2%; P < 0.02 in placebotreated women) with virtually no change in GT BMD during summer. Serum 25OH vitamin D declined by more than 20% (P < 0.001) in all groups during the winter months but returned to baseline in summer; PTH levels rose approximately 20% (P < 0.001) during winter but did not return to baseline during the summers. Urine Ntelopeptide and osteocalcin levels increased significantly but only in the Ptreated women and only during winter. Serum insulin growth factor binding protein 4, an inhibitory insulin growth factor binding protein, rose 15% (P < 0.03) from summer to winter, but this increase was significant only in those women consuming <1000 mg/day of calcium. By multivariate analysis, total calcium intake was the strongest predictor of bone loss from the hip. Urinary Ntelopeptide also closely correlated with GT BMD but only during winter (P = 0.003). We conclude that calcium supplementation prevents bone loss in elderly women by suppressing bone turnover during the winter when serum 25OH vitamin D declines and serum PTH increases. The precise amount of calcium necessary to preserve BMD in elderly women requires further studies, although in this study, at least 1000 mg/day of supplemental calcium was adequate prophylaxis against femoral bone loss.

67: Aging (Milano). 1998 Oct;10(5):38594. Calcium, gammalinolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Kruger MC, Coetzer H, de Winter R, Gericke G, van Papendorp DH.

Recent animal work suggests that gammalinolenic acid (GLA) and eicosapentaenoic acid (EPA) enhance calcium absorption, reduce excretion and increase calcium deposition in bone. A pilot study was set up to test the interactions between calcium and GLA + EPA in humans. Sixtyfive women (mean age 79.5), taking a background diet low in calcium, were randomly assigned to GLA + EPA or coconut oil placebo capsules; in addition, all received 600 mg/day calcium as the carbonate. Markers of bone formation/degradation and bone mineral density (BMD) were measured at baseline, 6, 12 and 18 months. Twentyone patients were continued on treatment for a second period of 18 months, after which BMD (36 months) was measured. At 18 months, osteocalcin and deoxypyridinoline levels fell significantly in both groups, indicating a decrease in bone turnover, whereas bone specific alkaline phosphatase rose indicating beneficial effects of calcium given to all the patients. Lumbar and femoral BMD, in contrast, showed different effects in the two groups. Over the first 18 months, lumbar spine density remained the same in the treatment group, but decreased 3.2% in the placebo group. Femoral bone density increased 1.3% in the treatment group, but decreased 2.1% in the placebo group. During the second period of 18 months with all patients now on active treatment, lumbar spine density increased 3.1% in patients who remained on active treatment, and 2.3% in patients who switched from placebo to active treatment; femoral BMD in the latter group showed an increase of 4.7%. This pilot controlled study suggests that GLA and EPA have beneficial effects on bone in this group of elderly patients, and that they are safe to administer for prolonged periods of time.

68: Am J Vet Res. 1998 Aug;59(8):105562. Effect of intravenous calcium administration on gentamicininduced nephrotoxicosis in ponies. Brashier MK, Geor RJ, Ames TR, O'Leary TP.

OBJECTIVE: To determine whether supplemental i.v. calcium administration would attenuate or prevent gentamicininduced acute renal failure, defined as an increase in serum creatinine concentration > or = 50% above baseline. ANIMALS: 10 healthy pony mares. PROCEDURE: Pony mares were randomly assigned to receive calcium at a dosage of 20 mg/kg of body weight or saline solution i.v., twice daily for 14 days. All pony mares received gentamicin at a dosage of 20 mg/kg i.v. every 8 hours for 14 days. Gentamicin pharmacokinetic, serum biochemical, and urinalysis data were measured every other day for the 14day study period. Renal histologic examination was performed, and results were scored at the end of the 14day period. RESULTS: 4 of 5 mares not receiving calcium supplementation developed acute renal failure. Only 1 of the 5 mares receiving calcium supplementation developed acute renal failure. Over the course of the study, pony mares receiving calcium supplementation had significantly fewer changes in urinalysis variables, and significantly less microscopic renal damage. CONCLUSION: Daily i.v. administration of calcium attenuated gentamicininduced acute renal failure. CLINICAL RELEVANCE: Calcium supplementation may help diminish the risk of acute renal failure associated with aminoglycoside antibiotics.

69: Endocrinol Metab Clin North Am. 1998 Jun;27(2):38998. The roles of calcium and vitamin D in the prevention of osteoporosis. Reid IR.

Calcium supplementation produces small beneficial effects on bone mass throughout postmenopausal life and may reduce fracture rates by more than this change would predictpossibly by as much as 50%. There is little reason to use vitamin D in young populations that are replete in this compound, but in the elderly at risk of vitamin D deficiency, there is now evidence of significant reductions in nonvertebral fracture rates from physiologic replacement regimens. Some of the most substantial reductions in fracture rates have been found with combined therapy with calcium and vitamin D, and in these protocols it is not clear which is the principal active agent or whether, in fact, the combination is necessary for optimal antifracture efficacy.

70: Jpn Heart J. 1998 May;39(3):34753. Acute antihypertensive effects of calcium channel blockers are not affected by calcium supplementation in patients with essential hypertension. Sato K, Dohi Y, Miyagawa K, Kojima M.

The study was designed to investigate whether the acute antihypertensive effects of calcium channel blockers are affected by calcium supplementation in patients with essential hypertension. The antihypertensive effects of calcium channel blockers (oral manidipine or intravenous nicardipine) were studied before and during calcium supplementation (1200 mg/day for 8 weeks) in 30 hospitalized patients with essential hypertension. The averages of systolic and diastolic blood pressure during a 24hour period were not decreased by calcium supplementation. The acute antihypertensive effects of the calcium channel blockers nicardipine (0.25, 0.5, 1.5, 2.0 micrograms/kg/min, intravenous infusion) or manidipine (20 mg, once a day, orally) were not enhanced by calcium supplementation. Thus, calcium channel blockers can be safely combined with calcium supplementation in terms of blood pressure. PMID 9711186

71: Ann Thorac Surg. 1998 Apr;65(4):106570. Calcium preconditioning in human myocardium. Cain BS, Meldrum DR, Meng X, Shames BD, Banerjee A, Harken AH.

BACKGROUND: Ischemic stress and other protein kinase C (PKC)linked receptor stimuli can induce rapid cardiac protection against ischemiareperfusion injury. We and others have demonstrated that exogenous calcium (Ca2+) pretreatment confers PKCmediated cardiac functional and infarct protection in animal models, but it remains unknown whether Ca2+ preconditioning confers similar postischemic functional protection in human myocardium, and, if so, whether the mechanism is mediated by PKC. We postulated that Ca2+ preconditioning confers ischemic tolerance to human myocardium by a PKCdependent mechanism. METHODS: Human atrial trabeculae were suspended in organ baths and paced at 1 Hz, and force development was recorded. After 90 minutes of equilibration, all trabeculae were subjected to ischemia (45 minutes) and reperfusion (120 minutes). Exogenous CaCl2 (3.0 mmol/L for 5 minutes) or vehicle (saline solution) was administered before simulated ischemia, with or without concurrent PKC inhibition (bisindolylmaleimide I, 150 nmol/L). RESULTS: Ischemiareperfusion resulted in decreased postischemic developed force, Ca2+ preconditioning protected human myocardium against ischemiareperfusion injury (p < 0.05 versus control ischemiareperfusion), and concurrent PKC inhibition abolished the salutary effect of Ca2+ preconditioning in human myocardium (p < 0.05 versus Ca2+ preconditioning). CONCLUSIONS: Preconditioning with Ca2+ represents a potent means of accessing PKCmediated protection of the human myocardium against ischemiareperfusion injury. PMID 9564929

72: Cancer Epidemiol Biomarkers Prev. 1998 Apr;7(4):2915. Dietary and supplemental calcium and the recurrence of colorectal adenomas. Hyman J, Baron JA, Dain BJ, Sandler RS, Haile RW, Mandel JS, Mott LA, Greenberg ER.

The association between calcium intake and the risk of colorectal neoplasia remains controversial. This analysis prospectively investigated the association between dietary and supplemental calcium intake and recurrent colorectal adenomas. Participants were part of a multicenter, randomized clinical trial of antioxidant vitamins. The study endpoints were adenomas detected between surveillance colonoscopies conducted at approximately 1 year and 4 years after study entry. Baseline intake of energyadjusted calcium derived from a food frequency questionnaire was used as the main exposure of interest. Calcium supplement use was assessed by semiannual questionnaires. Logistic regression was used to compute odds ratios and 95% confidence limits, and Poisson regression was used to estimate rate ratios. Subjects in the fifth quintile of dietary calcium had an adjusted odds ratio of 0.72 (95% confidence interval, 0.431.22) compared to those in the lowest quintile. Investigation of the numbers of adenomas yielded stronger findings: the rate ratio for the fifth quintile versus the first was 0.63 (95% confidence interval, 0.391.02). Dietary calcium seemed to have a greater effect among individuals with a highfat diet than among those with a lowfat diet; however, the interaction was not statistically significant. Use of calcium supplements was not related to adenoma recurrence. These results suggest that a high calcium intake may be associated with a reduction in risk of recurrent adenomas, especially among individuals on a highfat diet.

73: Obstet Gynecol. 1998 Apr;91(4):58590. Prevention of preeclampsia by linoleic acid and calcium supplementation: a randomized controlled trial. Herrera JA, ArevaloHerrera M, Herrera S.

OBJECTIVE: To determine the effect of low doses of linoleic acid and calcium on prostaglandin (PG) levels and the efficacy of this treatment in the prevention of preeclampsia. METHODS: In a randomized, doubleblind, placebocontrolled study we treated 86 primigravidas with risk factors for preeclampsia (high biopsychosocial risk [above 3 points], positive rollover test, and high mean blood pressure [above 85 mmHg)] with daily doses of either 450 mg linoleic acid and 600 mg calcium (n=43) or 450 mg starch and 600 mg lactose placebo (n=43) during the third trimester of pregnancy. RESULTS: Four women in the experimental group (9.3%) developed preeclampsia compared with 16 (37.2%) controls (relative risk 0.25, 95% confidence interval 0.09, 0.69, P < .001). The median serum levels of PGE2 after 4 weeks of treatment increased by 106% in the experimental group (P=.03) and decreased by 33% in the control group (P=.02). The median ratio between thromboxane B2 and PGE2 decreased by 40% in the experimental group (P=.02) and increased by 18% in the control group (P=.14). No significant differences were observed in the median ratio between thromboxane B2 and 6keto PGF1alpha in either group. No serious maternal or neonatal side effects of treatment occurred in either group. CONCLUSION: The administration of low daily doses of linoleic acid and calcium during the third trimester of pregnancy reduced the incidence of preeclampsia significantly in women at high risk, possibly by correcting the PGE2 levels.

74: J Nutr. 1998 Mar;128(3):6405. Dietary restriction of energy and calcium alters bone turnover and density in younger and older female rats. Talbott SM, Rothkopf MM, Shapses SA.

To determine the influence of weight loss with or without adequate calcium intake on bone turnover and density, we examined the influence of dietary restriction of calcium or energy on body weight (BW), bone mineral density (BMD) and bone turnover in both younger (3 mo) and older (10 mo) female rats (n = 66). Diets were designed to allow feeding at two levels of calcium intake (normal = 78 mg/d and low = 15 mg/d) and two levels of energy intake (normal and 40% restriction) while keeping the intake of protein, fat, fiber, vitamins and other minerals equal between groups. Thus rats received either a control diet (CNTL), a diet restricted in calcium, energy or both for 9 wk. Energy restriction reduced BW 521% (P < 0.01) and elevated bone formation 1020% (P < 0.05) in both age groups. Bone resorption was 2040% above CNTL values (P < 0.05), in rats fed all three restricted diets. In younger rats, BMD increased over time in all groups (P < 0.05), but final BMD was lower in calcium restricted groups compared with CNTL (P < 0.01). In older rats, CNTL had a significantly greater final BMD (P < 0.05) than dietrestricted groups. These data indicate that, in both younger and older rats, dietary restriction of calcium or energy results in an elevated rate of bone turnover. BMD is compromised by calcium restriction in both younger and older rats, whereas only older rats were negatively influenced by dietary energy restriction. Thus the present study indicates a detrimental effect of lowenergy diets, as well as inadequate calcium intake, on bone density in mature rats. PMID 9482775

75: J Nutr Sci Vitaminol (Tokyo). 1996 Aug;42(4):31323. Effects of calcium gluconate on the utilization of magnesium and the nephrocalcinosis in rats fed excess dietary phosphorus and calcium. Chonan O, Takahashi R, Kado S, Nagata Y, Kimura H, Uchida K, Watanuki M.

The effects of calcium gluconate on the utilization of magnesium and nephrocalcinosis in male Wistar rats made magnesiumdeficient by adding excess dietary phosphorus (1.195 g of phosphorus/100 g of diet) and calcium (1.04 g of calcium/100 g of diet) were compared with the effects of calcium carbonate. The effects of dietary magnesium concentration on the magnesium status and nephrocalcinosis were also examined. Adding excess dietary phosphorus and calcium decreased the apparent magnesium absorption ratios and the concentrations of magnesium in the serum and femur and increased the deposition of calcium in the kidney, and the low magnesium condition (0.024 g of magnesium/100 g of diet) aggravated the deposition of calcium and the low magnesium status. The apparent magnesium absorption ratios and femur magnesium concentration in the rats fed a calcium gluconate diet (an equimolar mixture of calcium gluconate and calcium carbonate was used as a source of calcium) were significantly higher than in the rats fed a calcium carbonate diet (only calcium carbonate was used as a source of calcium), irrespective of dietary magnesium concentration. Dietary calcium gluconate lessened the accumulation of calcium in the kidney and increased the serum magnesium concentration compared with dietary calcium carbonate, when the rats were fed the normal magnesium diet (0.049 g of magnesium/100 g of diet) but not the low magnesium diet. We speculate that the increased utilization of magnesium by feeding the calcium gluconate diet to a limited extent prevented the low magnesium status and the severity of nephrocalcinosis caused by adding excess dietary phosphorus and calcium. PMID 8906632

76: Am J Clin Nutr. 1996 Jul;64(1):717. A followup study on the effects of calciumsupplement withdrawal and puberty on bone acquisition of children. Lee WT, Leung SS, Leung DM, Cheng JC.

Recent calcium supplementation trials in children have confirmed a positive but moderate effect of calcium intake on bone mineral accretion. However, the lasting effect of a higher bone mineral mass after calciumsupplement withdrawal is not known. This is an 18mo followup study conducted after an 18mo controlled calcium supplementation trial to study the persistent effect of higher bone mineral mass in children. Radial bone mineral mass was determined by singlephoton absorptiometry; lumbar spine and femoral neck bone mineral mass were evaluated by dualenergy Xray absorptiometry in 84 healthy Hong Kong children at age 8.5 y and these evaluations were repeated at age 10 y. Pubertal status was determined by Tanner staging. At the end of the followup, the differences in percentage gains in lumbar spine bone mineral content (12.1 +/ 8.2% compared with 14.9 +/ 10.05%, P = 0.24) and lumbar spine area (8.6 +/ 5.1% compared with 9.4 +/ 5.5%, P = 0.47) between the study and control groups disappeared. Dietary calcium intakes during followup were similar for the two groups (555 and 640 mg/d, P = 0.23). In multipleregression analyses, pubertal status was the strongest correlate of bone acquisition and linear growth in the study period. In conclusion, higher percentage gains in bone mineral mass in childhood by calcium supplementation for 18 mo were reversible. Our study showed that the benefits of calcium supplementation disappear after treatment is withdrawn. Longerterm calcium trials are necessary to determine whether peak bone mass can be modified through sustained supplementation so that appropriate calcium intakes can be determined. PMID 8669418

77: J Rheumatol. 1996 Jun;23(6):9951000. Vitamin D and calcium in the prevention of corticosteroid induced osteoporosis: a 3 year followup. Adachi JD, Bensen WG, Bianchi F, Cividino A, Pillersdorf S, Sebaldt RJ, Tugwell P, Gordon M, Steele M, Webber C, Goldsmith CH.

OBJECTIVE: To determine the efficacy and safety of vitamin D 50,000 units/week and calcium 1,000 mg/day in the prevention of corticosteroid induced osteoporosis. METHODS: A minimized double blind, placebo controlled trial in corticosteroid treated subjects in a tertiary care university affiliated hospital. The sample was 62 subjects with polymyalgia rheumatica, temporal arteritis, asthma, vasculitis, or systemic lupus erythematosus. The primary outcome measure was the percentage change in bone mineral density (BMD) of the lumbar spine in the 2 treatment groups from baseline to 36 mo followup. RESULTS: BMD of the lumbar spine in the vitamin D and calcium treated group decreased by a mean (SD) of 2.6% (4.1%) at 12 mo, 3.7% (4.5%) at 24 mo, and 2.2% (5.8%) at 36 mo. In the placebo group there was a decrease of 4.1% (4.1%) at 12 mo, 3.8% (5.6%) at 24 mo, and 1.5% (8.8%) at 36 mo. The observed differences between groups were not statistically significant. The difference at 36 mo was0.693% (95% CI 5.34, 3.95). CONCLUSION: Vitamin D and calcium may help prevent the early loss of bone seen in the lumbar spine as measured by densitometry of the lumbar spine. Longterm vitamin D and calcium in those undergoing extended therapy with corticosteroids does not appear to be beneficial.

78: J Clin Endocrinol Metab. 1996 May;81(5):1699703. Role of calcium intake in modulating agerelated increases in parathyroid function and bone resorption. McKane WR, Khosla S, Egan KS, Robins SP, Burritt MF, Riggs BL.

Serum parathyroid hormone (PTH) and bone resorption increase in elderly women and contribute to agerelated bone loss. Whether these abnormalities are caused by calcium deficiency resulting from agerelated decreases in absorption and renal conservation is unclear. We studied 28 normal elderly women (mean +/ SD, age 69.3 +/ 2.7 yr) who were maintained for 3 yr on usual calcium intake levels (20.4 +/ 7.2 mmol/day [815 +/ 289 mg/day]; n = 15) (known as the usual calcium group) or high calcium intake levels (60.4 +/ 6.5 mmol/day [2414+/260 mg/day]; n = 13) (known as the high calcium group) and a reference group of 12 normal young adult women (age 30.1 +/ 4.4 yr), whose calcium intake was 23.0 +/ 4.8 mmol/day (918 +/ 193 mg/day) (known as the young group). Serum PTH was measured every 2 h, and urinary excretion of deoxypyridinoline (Dpd), a new marker for bone resorption, was measured in 4 h collections. Parathyroid gland secretory capacity was assessed during induced hypocalcemia. The mean 24 h serum PTH was 40% lower (P < 0.001), and the mean 24 h urinary Dpd was 35% lower (P < 0.005) in the high than in the usual calcium group. Mean parathyroid gland secretory capacity also was 47% lower (P < 0.005) in the high calcium group than in the usual calcium group. However, the usual calcium group had a mean 24 h serum PTH level that was 70% higher (P < 0.001) and a mean 24 h urinary Dpd level that was 30% higher (P < 0.005) than the young group, whereas the high calcium group was indistinguishable from the young group. Thus, failure of elderly women to increase their calcium intake to offset agerelated increases in calcium requirement contributes substantially to their development of increased parathyroid activity and increased bone resorption, whereas a high calcium intake can reverse both abnormalities.

79: Maturitas. 1996 Apr;23(3):32732. Prophylaxis of osteoporosis with calcium, estrogens and/or eelcatonin: comparative longitudinal study of bone mass. PerezJaraiz MD, Revilla M, Alvarez de los Heros JI, Villa LF, Rico H.

OBJECTIVE: To evaluate three different therapeutic regimens for the prevention of osteoporosis in natural and surgical postmenopausal women who had been found to have rapid bone loss in analytical studies. METHODS: A total of 104 naturally or surgically postmenopausal women were studied, and subsequently followedup during 1 year for avoidance of the influence of seasonal variation on bone mass, a factor overlooked in several studies. They were randomized into four groups of 26 patients each: the untreated control group (mean age 50 +/ 5 years); the hormonal replacement treatment (HRT) group (mean age 48 +/ 6 years), which was treated for 24 days each month with transdermal 17 betaestradiol, 50 mg/day, together with medroxiprogesterone, 10 mg during 12 days; the calcium group (mean age 50 +/ 4 years), which was treated with elemental calcium, 1 g/day; and the calcitonin group (mean age 50 +/ 5 years), which was treated for 10 days each month with eel calcitonin, 40 IU/day and with elemental calcium, 500 mg/day. Fullbody bone densitometry, for measuring total body bone mineral content (TBBMC), was carried out in all the women at baseline and 1 year. TBBMC was corrected for body weight by dividing its value by body weight (TBBMC/W). RESULTS: After 1 year TBBMC/W was lower in every group: 2.14% (P < 0.001) in the control group; 0.14% (P = NS) in the HRT group (P < 0.05 vs. controls); 0.18% (P = NS) in the calcium group (P < 0.05 vs. controls); and 0.06% (P = NS) in the calcitonin group (P < 0.01 vs. controls; P < 0.05 vs. calcium and HRT). CONCLUSIONS: These findings show that all three treatments are effective in the prevention of postmenopausal loss of bone mass.

80: Am J Clin Nutr. 1996 Mar;63(3):3547. Bioavailability of calcium supplements and the effect of Vitamin D: comparisons between milk, calcium carbonate, and calcium carbonate plus vitamin D. Mortensen L, Charles P.

Our aim was to examine a regimen for calcium supplementation because various factors seem to be important for its bioavailability, and to examine the effect of adding vitamin D to the supplement. The participants were 20 healthy women aged 2859 y (chi: 38 y). During the 3d periods and 1 d before, the participants were consuming a calcium and energybalanced diet as similar to their usual daily diet as possible. The study was designed as a randomized, placebocontrolled, partly blinded crossover study divided into four periods of 3 d each: 1) three tablets containing 1000 mg CaCO3/d, 2) three tablets containing 1000 mg CaCO3 plus 5 micrograms (200 IU) vitamin D/d, 3)1 L more milk than in the usual daily diet, and 4) three placebo tablets daily. Bioavailability of the different calciumsupplement regimens were evaluated by changes in 24h urinary excretion of calcium, phosphate, and magnesium. A significant increase in urinary calcium excretion was found during all periods of supplementation compared with the placebo period (P<0.01). Excretion of calcium in the calcium carbonate period was not significantly higher that that in the milk period, but calcium carbonate plus vitamin D resulted in significantly higher calcium excretion compared with that in the milk period. We conclude that the examined calcium carbonate regimen is at least as good a calcium supplement as milk, and that addition of 600 IU vitamin D/d promptly resulted in an increase in urinary calcium excretion after an increase in calcium absorption, even in healthy women.

81: Hepatogastroenterology. 1996 JanFeb;43(7):1524. Calcium chemoprevention in colorectal cancer. Duris I, Hruby D, Pekarkova B, Huorka M, Cernakova E, Bezayova T, Ondrejka P.

BACKGROUND/AIMS: There are genetic, endoengenous, and exogenous factors responsible for colorectal cancer. Calcium may play a chemopreventive role in high risk groups. Binding fatty and biliary acids and their reduced absorbtion, with a consequent decrease of proliferative stimulation and reduction of secondary carcinogenic compounds, may explain this role. MATERIAL AND METHODS: 175 patients with adenomatous polyps after polypectomy and with calcium chemoprevention were evaluated for polyps recurrence. Another three groups of patients with colorectal cancer without chemoprevention (A,B) and with chemoprevention (group C) were followed concerning survival after surgery. RESULTS: The cumulative survival rate of patients after surgery due to colorectal carcinoma is significantly higher in a calcium chemopreventive group. Adenomatous polyps recurrences after polypectomy are lower (12.9%) in the chemoprevention group than in the group without prevention (55%) with a mean time of followup 3.1 yrs. CONCLUSIONS: Calcium is an important chemopreventive agent in adenomatous polyps after polypectomy and after colorectal surgery for colorectal cancer.

82: Osteoporos Int. 1996;6(4):3149. The effect of a short course of calcium and vitamin D on bone turnover in older women. Prestwood KM, Pannullo AM, Kenny AM, Pilbeam CC, Raisz LG.

Calcium and vitamin D (1200 mg/day + 800 IU) has been shown to reduce hip fracture incidence in older women living in longterm care facilities who had borderline low vitamin D levels. We examined the effect of a short course of calcium and vitamin D on biochemical markers of bone turnover in older communityliving women. Twelve communityliving women (mean age 75 years) in good general health, without diseases or on medications known to affect bone, were entered into the study. All women were treated with calcium citrate (1500 mg/day of elemental calcium) and vitamin D3 (1000 IU/day) (Ca + D) for 6 weeks. Biochemical markers of bone turnover were measured in serum and urine collected at baseline (two samples), 5 and 6 weeks on Ca + D, and 5 and 6 weeks after termination of Ca + D. Markers of bone formation were osteocalcin, bone alkaline phosphatase and type I procollagen peptide. Markers of bone resorption were urinary hydroxyproline, free pyridinoline and deoxypyridinoline crosslinks, and Ntelopeptides of type I collagen. Parathyroid hormone (PTH) and 25hydroxyvitamin D were also measured at baseline, 6 weeks on treatment and 6 weeks after termination of treatment. All markers of bone resorption decreased on Ca + D and returned to baseline after termination of Ca + D (p < 0.05). Markers of bone formation did not change with Ca + D treatment. PTH decreased on Ca + D and returned to baseline after treatment, and 25hydroxyvitamin D increased with treatment and remained elevated 6 weeks after the end of treatment. We conclude that Ca + D reduces bone resorption in older women, possibly by suppressing PTH levels.

83: Scand J Rheumatol Suppl. 1996;103:758; discussion 7980. Prevention of hip fractures by correcting calcium and vitamin D insufficiencies in elderly people. Meunier P.

For a 50year old caucasian woman today, the risk of a hip fracture over her remaining lifetime is about 17%. Tomorrow the situation will clearly be worse because the continual increase in life expectancy will cause a 3fold rise in worldwide fracture incidence over the next 60 years, particularly in women, but also in men. In addition, a secular increase in the incidence of hip fractures in individuals of the same age has been noted in both sexes by several investigators, and the cost of hip fractures is expected to dramatically increase in the next decades. Consequently, preventive strategies are urgently required. A great deal has been learned in recent years about the risk factors for hip fracture, the pathophysiology of this fracture, and the prediction of fracture risk, particularly through bone mass measurements on the hip and biochemical evaluations of parathyroid and vitamin D status. The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility. A substantial femoral bone loss continues throughout the old age, with a continuous and exponential increase in the risk of hip fracture, and any reduction or arrest of this loss will induce an important reduction in the incidence of hip fractures. A preventive effect on the risk of hip fracture may be partly achieved by using long term estrogen replacement therapy after menopause, but also by using vitamin D and calcium supplements for a late prevention in elderly people. Vitamin D insufficiency and deficit in calcium intake are very common in elderly people living either in institutions or at home, particularly in Europe where dairy products are not fortified with vitamin D. The cumulative response to this deficit in calcium intake and low vitamin D status is a negative calcium balance which stimulates parathyroid hormone secretion. In 300 residents of nursing homes, we recently found a significant negative correlation between serum 25 OHD and log serum PTH after ageadjustment. In addition, in 446 elderly women living at home in 5 French cities and selected from the voting lists, we also found an ageadjusted relationship between serum 25 OHD and PTH concentrations. This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements. We have shown in a 3year controlled prospective study that the daily use of these supplements (1.2 g of calcium and 800 IU of vitamin D3) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced of 23% (intentiontotreat analysis) the number of hip fractures and other non vertebral fractures. In parallel, serum perathyroid hormone concentration was reduced of 28% and low serum 25hydroxyvitamin D concentration returned to normal values. After 18 months of treatment the bone density of the total proximal femoral region had increased 2.7% the vitamin D3calcium group and decreased 4.6% in the placebo group (p < 0.001). This prevention is safe and can be recommended in people living in institutions. It could be also useful in other elderly subjects particularly at risk because of a low calcium intake, an absence of solar exposure and a previous history of falls. From the data of our study we assessed the economic consequences in terms of medical cost of this prevention. In case of treatment of all women living in nursing homes in France, this would saved FF 150000000 per year, the economic balance of prevention becoming positive as soon as the age of the beginning of the prevention reaches 73.5 years. It is now possible to partly stop bone loss in elderly people and it is never too late to prevent hip fractures with calcium and vitamin D supplements.

84: Nutrition. 1995 SepOct;11(5):40917. Optimal calcium intake. Sponsored by National Institutes of Health Continuing Medical Education. [No authors listed]

The National Institutes of Health Consensus Development Conference on Optimal Calcium Intake brought together experts from many different fields including osteoporosis and bone and dental health, nursing, dietetics, epidemiology, endocrinology, gastroenterology, nephrology, rheumatology, oncology, hypertension, nutrition and public education, and biostatistics, as well as the public, to address the following questions: 1) What is the optimal amount of calcium intake? 2) What are the important cofactors for achieving optimal calcium intake? 3) What are the risks associated with increased levels of calcium intake? 4) What are the best ways to attain optimal calcium intake? 5) What public health strategies are available and needed to implement optimal calcium intake recommendations? and 6) What are the recommendations for future research on calcium intake? The consensus panel concluded that: A large percentage of Americans fail to meet currently recommended guidelines for optimal calcium intake. On the basis of the most current information available, optimal calcium intake is estimated to be 400 mg/day (birth6 months) to 600 mg/day (612 months) in infants; 800 mg/day in young children (15 years) and 8001,200 mg/day for older children (610 years); 1,2001,500 mg/day for adolescents and young adults (1124 years); 1,000 mg/day for women between 25 and 50 years; 1,2001,500 mg/day for pregnant or lactating women; and 1,000 mg/day for postmenopausal women on estrogen replacement therapy and 1,500 mg/day for postmenopausal women not on estrogen therapy. Recommended daily intake for men is 1,000 mg/day (2565 years). For all women and men over 65, daily intake is recommended to be 1,500 mg/day, although further research is needed for this age group. These guidelines are based on calcium from the diet plus any calcium taken in supplemental form. Adequate vitamin D is essential for optimal calcium absorption. Dietary constituents, hormones, drugs, age, and genetic factors influence the amount of calcium required for optimal skeletal health. Calcium intake, up to a total intake of 2,000 mg/day, appears to be safe in most individuals. The preferred source of calcium is through calciumrich foods such as dairy products. Calciumfortified foods and calcium supplements are other means by which optimal calcium intake can be reached in those who cannot meet this need by ingesting conventional foods. A unified public health strategy is needed to ensure optimal calcium intake in the American population. PMID 8748190

85: Med Hypotheses. 1995 Jul;45(1):6872. Calcium supplementation prevents pregnancyinduced hypertension by increasing the production of vascular nitric oxide. LopezJaramillo P, Teran E, Moncada S.

Pregnancyinduced hypertension (PIH) remains a common cause of maternal and fetal morbidity and mortality. During the past 7 years, some progress has been made in the prevention of PIH. Specifically, clinical studies have shown that supplementation with calcium can significantly reduce the frequency of PIH, specially in populations with a low calcium intake. We have suggested that, in such a population, calcium supplementation is a safe and effective measure for reducing the frequency of PIH. Thus, the purpose of this article is to advance a hypothesis about the mechanism by which calcium supplementation reduces the risk of PIH. We propose that dietary calcium supplementation reduces the frequency of PIH by maintaining the serum ionized calcium level which is crucial for the production of endothelial nitric oxide, the increased generation of which maintains the vasodilatation that is characteristic of normal pregnancy.

86: Am J Med. 1995 Apr;98(4):3315. Longterm effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial. Reid IR, Ames RW, Evans MC, Gamble GD, Sharpe SJ.

PURPOSE: To determine the longterm effects of calcium supplements or placebo on bone density in healthy women at least 3 years postmenopause. PATIENTS AND METHODS: Eightysix women from our previously reported 2year study agreed to continue on their doubleblind treatment allocation (1 g elemental calcium or placebo) for a further 2 years, with 78 women (40 on placebo) reaching the 4year end point. Median (interquartile range) dietary calcium intakes for the whole group were 700 mg (range 540 to 910) per day at baseline, 670 mg (range 480 to 890) per day at 2 years, and 640 mg (range 460 to 880) per day at 4 years. The bone mineral density (BMD) of the total body, lumbar spine, and proximal femur was measured every 6 months by dualenergy, xray absorptiometry. RESULTS: There was a sustained reduction in the rate of loss of total body BMD in the calcium group throughout the 4year study period (P = 0.002), and bone loss was significantly less in the calciumtreated subjects in years 2 through 4 also (difference between groups 0.25% +/ 0.11% per year, P = 0.02). In the lumbar spine, bone loss was reduced in the calcium group in year 1 (P = 0.004), but not subsequently. There was, however, a significant treatment effect at this site over the whole 4year period (P = 0.03). In the proximal femur, the benefit from calcium treatment also tended to be greater in the first year and was significant over the 4year study period in the femoral neck (P = 0.03) and the trochanter (P = 0.01). Nine symptomatic fractures occurred in 7 subjects in the placebo group and 2 fractures in 2 subjects receiving calcium (P = 0.037). CONCLUSIONS: Calcium supplementation produces a sustained reduction in the rate of loss of total body BMD in healthy postmenopausal women.

87: J Pediatr. 1995 Apr;126(4):5516. Effects of dairy products on bone and body composition in pubertal girls. Chan GM, Hoffman K, McMurry M.

OBJECTIVE: To study the effect of calcium supplementation with dairy products on the bone and body composition of pubertal girls. DESIGN: Randomized control study with 12month followup. SETTING: General community. SUBJECTS: Fortyeight white girls whose mean age was 11 years and sexual development at Tanner stage 2. INTERVENTION: One group's diet was supplemented with dairy products to the recommended dietary allowance of 1200 mg calcium daily. The other group ate their usual diet. MAIN OUTCOME MEASURES: Bone mineral content and density were measured at the radius, femoral neck, lumbar spine, and total body bone mineral by singlephoton and dualenergy xray absorptiometry at the start of the study and after 3, 6, 9, and 12 months. Body composition (lean body mass and body fat) was measured by dualenergy xray absorptiometry at the same intervals. Serum calcium, phosphate, 25hydroxyvitamin D, 1,25dihydroxyvitamin D, alkaline phosphatase, magnesium, and albumin concentrations were determined at the start and end of the study. The urinary calcium/creatinine ratio and hydroxyproline concentration were also determined. RESULTS: The dairy group had higher intakes of calcium, phosphate, vitamin D, and protein than control subjects. The dairy group had significantly greater increases during the 1year study in bone mineral density at the lumbar spine bones (22.8% +/ 6.9% vs 12.9% +/ 8.3%) and in total body bone mineral (14.2% +/ 7.0% vs 7.6% +/ 6.0%) than control subjects. Dietary calcium, phosphate, vitamin D, and protein intakes were associated with the lumbar bone density and total body bone calcium. There were no differences in serum or urinary biochemical values between the two groups at the start or end of the study. CONCLUSIONS: Young girls whose dietary calcium intake was provided primarily by dairy products at or above the recommended dietary allowances had an increased rate of bone mineralization. Increased intake of dairy foods did not increase overall total or saturated fat intake and was not associated with excessive weight gain or increased body fat.

88: Chin Med J (Engl). 1995 Jan;108(1):579. Calcium supplementation during pregnancy for reducing pregnancy induced hypertension. Cong K, Chi S, Liu G.

Pregnancy induced hypertension (PIH) is a common complication in pregnancy and prenatal stage. Because the direct and indirect relationship between low calcium intake and many diseases, such as rachitis, young age myopia and hypertension, calcium supplementation has been a hot topic among nutritionists. Randomized trials of calcium supplementation during pregnancy were conducted in 212 healthy primipara. They were divided into 4 groups and gave 120mg, 240mg, 1g or 2g of calcium daily from 20 to 28 wks of gestation up to delivery respectively. As a result, the incidence of PIH was 8.9%, 7.5%, 8% and 4% respectively in these groups. The control group (106 pregnant women) who did not receive calcium gave an incidence of 18%. Supplementation of 2g of calcium daily showed significant results in lowering the incidence of PIH (P < 0.05) without any adverse effects. In 1992 calcium supplementation was widely used in antenatalclinic. 200 cases with intake of 2g calcium were compared with corresponding noncalcium supplementation cases, and the incidence of PIH was 7.5% and 16.5% (P < 0.005) respectively. Mediating parathyroid hormone and renin activity are thought to be the effect of calcium on decreasing the incidence of PIH.

89: J Cell Biochem Suppl. 1995;22:6573. Calcium and the prevention of colon cancer. Lipkin M, Newmark H.

Chemoprevention studies utilizing calcium have now progressed from basic measurements to clinical trials. Calcium's effects on epithelial cells have demonstrated decreased proliferation and induced cell differentiation with increasing levels of calcium in vitro, similar in vivo effects in rodent and human colon, and decreased carcinogeninduced colonic tumor formation in rodents. Current studies are attempting to inhibit colonic adenoma formation in human subjects. Most but not all epidemiologic studies also link increased dietary calcium with a decreased risk of colon cancer. In animal models, supplemental dietary calcium has decreased mammary epithelial cell hyperplasia and hyperproliferation and colonic cell hyperproliferation when the latter was induced by bile acids, fatty acids, and partial resection of the small intestine. Supplemental dietary calcium also decreased carcinogeninduced colonic tumors in several rodent models. In normal mice, and in mice carrying a targeted apc gene mutation, we recently increased colonic polypoid hyperplasias by a Westernstyle diet containing low calcium and vitamin D. In human subjects at increased risk for colon cancer, oral calcium supplementation significantly reduced colonic epithelial cell proliferation in most of the studies, including four randomized clinical trials. These studies have now progressed to shortterm human clinical trials, including trials that measure the regrowth of transformed adenoma cells. Shortterm adenomaregrowth clinical trials, however, are limited in their ability to measure whether chemopreventive agents inhibit early genotoxic events, abnormal cellular metabolic activities involved in tumor promotion over many years, or the progression of adenoma cells to carcinoma.

90: Miner Electrolyte Metab. 1995;21(13):23641. Calcium, why and how much? Palmieri GM.

Although calcium (Ca) is pivotal for the prevention of osteoporosis, its role in the prevention of other unrelated diseases such as arterial hypertension, cancer of the colon and nephrolithiasis is perplexing. No unitarian hypothesis explaining these unrelated effects of Ca has been postulated. Cytosolic Ca concentration is 10,000fold lower than in the extracellular space, and this gradient is tightly maintained. Abnormal elevation of cytosolic Ca causes cell damage and death. Parathyroid hormone is a Ca agonist and the suppression of its secretion by Ca could explain the beneficial role of Ca intake in multiple diseases. Thus, parathyroid ablation improves hypertension in rats and cardiomyopathy in hamsters. Since anthropologic data suggests a higher Ca intake, of approximately 1,600 1,600 mg/day, in preneolithic than in modern diets, it is likely that our levels of PTH on genetically predisposed subjects with a loose cellular Ca control may aggravate frequent modern diseases and the process of aging. A higher Ca intake in both sexes should be one of the goals of preventive medicine of our time.

91: Headache. 1994 NovDec;34(10):5902. Alleviation of migraines with therapeutic vitamin D and calcium. ThysJacobs S.

Two postmenopausal migraineurs who developed frequent and excruciating migraine headaches (one following estrogen replacement therapy and the other following a stroke) were treated with combination vitamin D and calcium. Therapeutic replacement with vitamin D and calcium resulted in a dramatic reduction in the frequency and duration of their migraine headaches. PMID 7843955

92: Int J Gynaecol Obstet. 1994 Nov;47(2):11520. Prevention of preeclampsia with calcium supplementation and vitamin D3 in an antenatal protocol. Ito M, Koyama H, Ohshige A, Maeda T, Yoshimura T, Okamura H.

OBJECTIVES: Using an angiotensin sensitivity test we carried out a prospective study in an attempt to predict the possible onset of preeclampsia and to prevent it by calcium supplementation (elemental calcium 156 or 312 mg/day per os) and treatment with vitamin D3 (0.5 micrograms/3 day per os). METHOD: We used a study design in which 666 singleton pregnant women were managed with conventional antenatal care and 210 singleton pregnant women were managed with a protocol, together with conventional antenatal care. RESULT: Of the 666 women managed conventionally, 113 (16.9%) developed preeclampsia. However, the incidence of preeclampsia in the 210 women managed on the protocol was lower, at 10.9%. CONCLUSION: Our findings indicate that this protocol for the prediction and prevention of preeclampsia is useful for pregnant women at high risk of developing preeclampsia.

93: Headache. 1994 Oct;34(9):5446. Vitamin D and calcium in menstrual migraine. ThysJacobs S.

Two premenopausal women with a history of menstruallyrelated migraines and premenstrual syndrome were treated with a combination of vitamin D and elemental calcium for late luteal phase symptoms. Both cited a major reduction in their headache attacks as well as premenstrual symptomatology within 2 months of therapy. These observations suggest that vitamin D and calcium therapy should be considered in the treatment of migraine headaches. PMID 8002332

94: J Paediatr Child Health. 1994 Oct;30(5):4446. Oral calcium treatment in vitamin Ddependent rickets type II. Wong GW, Leung SS, Law WY, Cheung NK, Oppenheimer SJ.

Vitamin Ddependent rickets type II is a rare hereditary disease that results from target organ resistance to the action of 1,25dihydroxyvitamin D3. There is a great heterogeneity in the clinical presentation of this condition. The affected patients usually present early in childhood with clinical and biochemical evidence of rickets. Physiological replacement dosage of 1,25dihydroxyvitamin D3 has no therapeutic effect. Responses to pharmacological doses of vitamin D metabolites or longterm calcium infusion have been variable. A case is reported here of an 8 year old girl, of consanguineous parents with vitamin Ddependent rickets, type II, in whom treatment with high dose oral calcium resulted in marked biochemical and radiological improvement. It is concluded that high dose oral calcium treatment is an effective treatment option for patients with vitamin Ddependent rickets type II. PMID 7833085

95: J Clin Endocrinol Metab. 1994 Sep;79(3):7305. The effect of calcium supplementation on the circadian rhythm of bone resorption. Blumsohn A, Herrington K, Hannon RA, Shao P, Eyre DR, Eastell R.

Bone resorption shows a circadian rhythm in human subjects, but the physiological mechanisms underlying this rhythm are unknown. We compared the circadian rhythm of bone collagen degradation in 18 premenopausal women before and after oral calcium supplementation (1000 mg calcium for 14 days). Subjects were randomized to receive calcium at either 0800 h or 2300 h. Continuous 48h urine collections and 1 day of 4h urine collections were obtained before and after the 14day supplementation period. We measured urinary deoxypyridinoline (Dpd) and the crosslinked Ntelopeptide of type I collagen (NTx) as biochemical markers of bone resorption. There was a significant effect of time of day on excretion of Dpd and NTx (analysis of variance, P < 0.001) with peak excretion between 03000700 h and a nadir between 15001900 h. The mean amplitude (peak to trough) was similar for Dpd and NTx (70.3% and 63.3%, respectively). Evening calcium supplementation resulted in marked suppression of the nocturnal increase in Dpd and NTx and reversed the usual nocturnal increase in the level of parathyroid hormone. In contrast, morning calcium supplementation had no significant effect on the circadian rhythm of Dpd or NTx. Evening calcium supplementation suppressed overall daily excretion of Dpd by 20.1% (P = 0.03) and NTx by 18.1% (P = 0.03). Morning calcium supplementation had no significant effect on overall daily excretion of either Dpd or NTx. We conclude that evening calcium supplementation suppresses the circadian rhythm of bone resorption. The daily rhythm of PTH secretion or calcium intake is likely to be an important determinant of this rhythm. Experimental protocols designed to investigate the effect of calcium supplementation on bone mineral density should take the timing of supplementation into account.

96: Obstet Gynecol. 1994 Sep;84(3):34953. Prevention of pregnancyinduced hypertension by calcium supplementation in angiotensin IIsensitive patients. SanchezRamos L, Briones DK, Kaunitz AM, Delvalle GO, Gaudier FL, Walker CD.

OBJECTIVE: To evaluate the efficacy of oral supplemental calcium in reducing the incidence of pregnancyinduced hypertension (gestational hypertension or preeclampsia) in angiotensinsensitive nulliparas. METHODS: Sensitivity to intravenously infused angiotensin was determined at 2428 weeks' gestation in 281 nulliparous women who had positive rollover tests. Angiotensinsensitive women were given 2 g/day of oral elemental calcium or placebo in a randomized, doubleblind clinical trial. The tablets were dispensed by the hospital pharmacy in serially numbered computerized pill bottles so as to assess compliance. Repeat angiotensin sensitivity test was performed at 3436 weeks' gestation. RESULTS: Sixtythree of 67 angiotensinsensitive nulliparas were evaluable; 29 received calcium and 34 received placebo tablets. Four of 29 calciumtreated subjects (13.8%, 95% confidence interval [CI] 432%) developed preeclampsia, compared to 15 of 34 (44.1%, 95% CI 2762%) in the placebo group (relative risk [RR] 0.37, 95% CI 0.150.92; P = .01). The incidence of any type of hypertension was nine of 29 (31%, 95% CI 1551%) with calcium treatment, compared to 22 of 34 (64.7%, 95% CI 4680%) with placebo (RR 0.46, 95% CI 0.250.86; P = .01). CONCLUSION: Calcium supplementation given in pregnancy to highrisk nulliparas reduces the incidence of pregnancyinduced hypertension.

97: Osteoporos Int. 1994 Sep;4(5):24552. Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitaminDreplete elderly patients. Chevalley T, Rizzoli R, Nydegger V, Slosman D, Rapin CH, Michel JP, Vasey H, Bonjour JP.

The efficacy of calcium (Ca) in reducing bone loss is debated. In a randomized placebocontrolled doublemasked study, we investigated the effects of oral Ca supplements on femoral shaft (FS), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD), and on the incidence of vertebral fracture in vitaminDreplete elderly. Ninetythree healthy subjects (72.1 +/ 0.6 years) were randomly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months. Sixtythree patients (78.4 +/ 1.0 years) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo. FS BMD changes in Casupplemented nonfractured women were significantly different from those in the placebo group (+0.6 +/ 0.5% v 1.2 +/ 0.7%, p < 0.05). There was no difference in effect between the two forms of Ca. The changes of +0.7 +/ 0.8% v 1.7 +/ 1.6% in FN BMD of Casupplemented women and the placebo group did not reach statistical significance. In fractured patients, FS, FN and LS BMD changes were 1.3 +/ 0.8, +0.3 +/ 1.6 and +3.1 +/ 1.2% (p < 0.05 for the last). The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patientyears in Casupplemented nonfractured subjects and in the placebo group, respectively, and 144.0 in Casupplemented fractured patients. Thus, oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly.

98: Am J Respir Crit Care Med. 1994 Aug;150(2):3947. Therapy of steroidinduced bone loss in adult asthmatics with calcium, vitamin D, and a diphosphonate. Worth H, Stammen D, Keck E.

In a prospective, controlled, and randomized clinical trial, we examined the effects of treatment with vitamin D (1,000 IU/d), calcium (1 g/d), and ethane1hydroxy1,1diphosphonate (EHDP; 7.5 mg/kg body weight) on vertebral bone mass in fourteen asthmatics undergoing longterm treatment with systemically applied corticosteroids. The extent of steroidinduced bone loss was judged by vertebral bone density of the lumbar spine measured by dualphoton absorptiometry as well as by vertebral crush fracture incidence examined by conventional Xray. Results of the measurements before treatment and after six mo were compared with those of an untreated control group of nineteen asthmatics. Bone density increased during the observation period by 5% in the treated group, compared with a decrease of 4.3% in the untreated control group (p < 0.01). Moreover, in the treated group no radiologically visible new fractures occurred; in the control group new fractures were observed in four patients. There were no serious side effects of the applied drugs during the 6mo period. Therefore, the combination of EHDP, calcium, and vitamin D appears to be a useful regimen for the management of steroidinduced bone loss in adult asthmatics.

99: J Dairy Sci. 1994 May;77(5):115560. ADSA Foundation Lecture. Low calcium intake: the culprit in many chronic diseases. Heaney RP, BargerLux MJ.

Calcium is the fifth most abundant element in the earth's crust and is necessary for both plant and animal life today. Moreover, the natural diets of all mammals are rich in calcium. The diet of Stone Age human adults is estimated to have contained from 50 to 75 mmol of calcium (2000 to 3000 mg)/d, three to five times the median calcium intake of presentday US adults. Human physiology has adapted to this environmental abundance with an intestinal absorptive barrier and inefficient renal conservation of calcium. Although mammalian physiology contains mechanisms by which organisms can adjust to temporary environmental shortages, chronic calcium retention has a number of health consequences, most notably bone fragility, high blood pressure, and colon cancer. Evidence indicates that improvement in calcium intake (or in vitamin D status) prevents some portion of each of these multifactorial problems. At least 14 intervention studies have established the skeletal benefit of increased calcium intake during growth and among women in the late postmenopause. Other evidence suggests that adequate calcium may protect against saltsensitive and pregnancyassociated hypertension and that high intakes of both dietary calcium and vitamin D reduce development of precancerous changes in colonic mucosa.

100: Clin Exp Pharmacol Physiol. 1994 Mar;21(3):1738. Augmentation of baroreceptor reflex function by oral calcium supplementation in essential hypertension. Dazai Y, Iwata T, Hiwada K.

1. We studied the effect of oral calcium supplementation (1.0 g/day) for 1 week on baroreceptor reflex function and the lability of blood pressure in association with the changes in autonomic nervous activity in 14 hospitalized patients with mild to moderate essential hypertension (nine males and five females, mean age of 56 +/ 11.2 (s.d.) years). 2. Baroreceptor reflex sensitivity (BRS) was determined by the change in RR intervals in response to the pressor response induced by phenylephrine injection. We measured coefficient of variation of RR interval (CVRR) and urinary excretion of catecholamines to evaluate the mechanism of change in BRS. We also used coefficient of variation of blood pressure (CVBP) and error of single cosinor analysis as parameters for lability of 24h blood pressure. 3. The means of 24h systolic and diastolic blood pressures showed no significant changes after calcium supplementation for 1 week. BRS and CVRR were significantly increased by calcium supplementation. Daily excretions of norepinephrine and epinephrine corrected by creatinine were unchanged. Both CVBP and error of 24h systolic blood pressure showed a significant decrease after calcium treatment. 4. These results indicate that oral calcium supplementation augments baroreceptor reflex function, in part through an enhancement of parasympathetic nervous activity, resulting in reduction of the lability of blood pressure in patients with mild to moderate essential hypertension.

101: J Rheumatol. 1994 Mar;21(3):5305. Effects of nutritional supplementation on bone mineral status of children with rheumatic diseases receiving corticosteroid therapy. Warady BD, Lindsley CB, Robinson FG, Lukert BP.

OBJECTIVE. Because children with rheumatic disease receiving longterm corticosteroids are at high risk for developing osteoporosis, we attempted to determine whether nutritional supplementation would improve bone status in this group of children. METHODS. In a crossover design study, 10 corticosteroid treated children with rheumatic disease and osteoporosis received calcium and vitamin D supplementation for 6 months to determine their effect on bone density. They were then studied for 6 months without added nutrition supplements. The mean age was 13.1 years with a mean duration of disease of 4.2 years. Six patients had juvenile rheumatoid arthritis, 2 had systemic lupus erythematosus and 2 had mixed connective tissue disease. These children obtained a minimum of 1 g of calcium and 400 IU of vitamin D daily from diet and added supplements. Dual photon absorptiometry, laboratory and dietary data were obtained at baseline, 6 months, and one year. RESULTS. Spinal bone density significantly improved with supplementation. Osteocalcin values remained low throughout the study. CONCLUSION. Our results suggest some children with rheumatic disease receiving corticosteroids would benefit from calcium and vitamin D supplementation. PMID 8006898

102: Am J Hypertens. 1993 Nov;6(11 Pt 1):9337. Augmentation of the renal tubular dopaminergic activity by oral calcium supplementation in patients with essential hypertension. Dazai Y, Iwata T, Hiwada K.

We studied the effect of oral calcium supplementation on renal tubular dopaminergic activity in patients with mild to moderate essential hypertension. Fifteen patients aged 45 to 68 years (nine men and six women, mean age 59 +/ 7 [SD]) participated in the study. We orally administered calcium (1.0 g per day for 1 week) during hospitalization. The change in 24h blood pressure (BP), measured by ambulatory BP monitoring, and excretions of electrolytes and catecholamines were investigated before and after 1 week of oral calcium supplementation. The mean values of 24h systolic and diastolic BP showed no significant changes by calcium loading. Daily urinary excretion of free dopamine, sodium clearance (CNa), fractional excretion of sodium (FENa), and urinary volume were significantly increased by oral calcium supplementation. Urinary excretions of epinephrine and norepinephrine and creatinine clearance showed no significant changes by oral calcium treatment. CNa and FENa showed significant correlations with urinary excretion of free dopamine. These results suggest that oral calcium supplementation induces natriuresis partly through augmentation of renal tubular dopaminergic activity. PMID 8305167

103: Calcif Tissue Int. 1993 Nov;53(5):3046. Comparison of the suppressive effect of two doses (500 mg vs 1500 mg) of oral calcium on parathyroid hormone secretion and on urinary cyclic AMP. Guillemant J, Guillemant S.

The respective effects of the ingestion of two different doses of calcium (500 and 1500 mg) on serum ionized calcium, intact parathyroid hormone (PTH 184), and the urinary excretion of 3',5'cyclic adenosine monophosphate (cyclic AMP) were evaluated in 15 young male adults. Ionized serum calcium and PTH 184 were measured before and 1 hour, 2 hours and 3 hours (P1, P2, and P3) after the oral intake of calcium. Cyclic AMP was measured in 2hour urine samples collected before and during 4 hours after the ingestion of calcium. Similar increments in serum ionized calcium (delta Ca2+) were observed except at P3 where the delta Ca2+ was significantly (P < 0.02) higher after 1500 mg (0.088 mmol/liter) than after 500 mg of (0.062 mmol/liter). In the same way, the comparison of the PTH 184 concentrations showed no statistical difference except at P3 (P < 0.002). When expressed as a percentage of P0, the P1 and P2 PTH 184 values were more suppressed after 1500 mg than after 500 mg of calcium (P1: 69% vs 59%; P < 0.02; P2: 66% vs 50%; P < 0.02). However, the simultaneous cyclic AMP responses (24% vs 19%) were not significantly different. The results show that the respective maximal effects on PTH secretion and on urinary cyclic AMP of two very different oral doses of calcium are only slightly different.

104: Zhonghua Fu Chan Ke Za Zhi. 1993 Nov;28(11):6579, 700. [Calcium and pregnancy induced hypertension] Cong KJ.

In this paper the relationship between calcium and pregnancy induced hypertension (PIH) was prospectively studied. 150 normal pregnant women were divided into 3 groups: group A with supplement of calcium element 1g/day, group B 2g/day and group C with no calcium supplement. 8%, 4% and 18% of each group had developed PIH respectively. It seems that supplement of 2 gram calcium per day gave the best result. Furthermore the study was expanded: 200 cases with supplement of calcium element 2 g/day from 2028th week of pregnancy, another 200 pregnant women without calcium supplement. The occurrence of PIH was 7.5% and 16.5% respectively. There was no adverse effect with 2 g calcium supplement. The metabolism of calcium in normal pregnancy and PIH was discussed. Supplement of calcium during pregnancy may benefit by reduction of PIH incidence.

105: J Thorac Cardiovasc Surg. 1993 Sep;106(3):5119. Duration of asystolic reperfusion and reperfusate electrolyte composition influence postcardioplegia ventricular fibrillation. Holman WL, Spruell RD, Pacifico AD.

The conditions of postcardioplegia reperfusion that influence cardiac electrophysiologic recovery have not yet been fully elucidated. Studies of postcardioplegia electrophysiologic recovery and reperfusioninduced arrhythmias, particularly reperfusioninduced ventricular fibrillation, are useful for improving our understanding of reperfusion injury since reperfusioninduced arrhythmias are sensitive indicators for reperfusion injury. The purpose of this study was to determine the effects of asystolic reperfusion and reperfusate electrolyte composition on postcardioplegia electrophysiologic recovery of the heart. The hypothesis tested is that the duration of asystolic reperfusion produced by a hyperkalemic reperfusate is a primary determinant for the return of cardiac electrical activity without reperfusioninduced ventricular fibrillation and that reperfusion with a hypocalcemichyperkalemic solution further reduces the prevalence of reperfusioninduced ventricular fibrillation by limiting myocyte calcium exposure during initial postischemic recovery. Fiftysix pigs were supported by cardiopulmonary bypass and subjected to identical conditions of hypothermic cardioplegic arrest. Reperfusion was initiated with unmodified pump blood, a hypocalcemicnormokalemic cardioplegic solution, a hyperkalemicnormocalcemic cardioplegic solution, or a hyperkalemichypocalcemic cardioplegic solution. The hyperkalemicnormocalcemic solution was administered at a dose of 500 ml/m2 or 1500 ml/m2. The hyperkalemichypocalcemic and hypocalcemicnormokalemic solutions were given only at a dose of 500 ml/m2. All cardioplegic reperfusion solutions were followed by infusion of unmodified pump blood for the remainder of the 15minute period of controlled reperfusion. Reperfusioninduced ventricular fibrillation was less prevalent in the highdose hyperkalemic solution group (4/12) than in the lowdose hyperkalemic solution (9/10) or unmodified pump blood (12/12) groups (p < 0.05). The transmyocardial lactate gradient at the time of initial postreperfusion electrical activity was positive (0.21 +/ 0.04 mmol/L) in the highdose hyperkalemic group and negative (0.05 +/ 0.09 mmol/L) in the lowdose hyperkalemic group (p < 0.05). Fibrillation was less prevalent in the hypocalcemichyperkalemic group (8/12) than in the other groups reperfused with cardioplegic solution at a dose of 500 ml/m2 (hypocalcemicnormokalemic, 10/10; hyperkalemicnormocalcemic, 9/10) or in the group reperfused with unmodified pump blood (12/12) (p < 0.05, hypocalcemichyperkalemic group versus other reperfusate groups). Reperfusioninduced ventricular fibrillation is an indicator of reperfusion injury, and in this study the conditions of reperfusion influenced the prevalence of reperfusioninduced ventricular fibrillation. Recovery of aerobic metabolism during hyperkalemiainduced asystolic reperfusion was associated with a lower prevalence of reperfusioninduced ventricular fibrillation. Combining hypocalcemia with hyperkalemia decreased the prevalence of reperfusioninduced ventricular fibrillation. PMID 8361195

106: J Cardiovasc Pharmacol. 1993 Aug;22(2):2739. Administration of intravenous calcium before verapamil to prevent hypotension in elderly patients with paroxysmal supraventricular tachycardia. Miyagawa K, Dohi Y, Ogihara M, Sato K.

The aim of this study is to evaluate the effects on blood pressure and heart rate of i.v. calcium before the administration of verapamil during the treatment of paroxysmal supraventricular tachycardia (PSVT) in elderly patients. Administration of i.v. verapamil with or without preceding i.v. calcium administration was performed in elderly patients with PSVT. Verapamil (1.0 mg/min) was administered i.v. in 10 patients (Group A) and calcium (3.75 mg/kg for 5 min) followed by verapamil (1.0 mg/min), which was administered i.v. in seven patients (Group B). Blood pressure and heart rate were measured during the study every 5 minutes. Verapamil was effective in suppressing PSVT in both groups. In Group A, i.v. verapamil caused sustained decreases in blood pressure and heart rate over 25 min. In Group B, systolic blood pressure transiently fell immediately after administration of i.v. verapamil, but reversed to the baseline level in 5 min. The absolute and percentage decreases in blood pressure were significantly smaller in Group B than in Group A, whereas changes in heart rate were identical in both groups. Thus, i.v. calcium was effective in preventing hypotension during the treatment of PSVT with verapamil. This regimen was beneficial for elderly patients, since a sufficient dose of verapamil for suppressing PSVT could be administered without causing hypotension. PMID 7692169

107: N Engl J Med. 1993 Jun 17;328(24):174752. Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol, and calcitonin. Sambrook P, Birmingham J, Kelly P, Kempler S, Nguyen T, Pocock N, Eisman J.

BACKGROUND. Prolonged corticosteroid therapy increases the risk of osteoporosis and fracture. We studied whether corticosteroidinduced osteoporosis could be prevented by treatment with calcium, calcitriol (1,25dihydroxyvitamin D3), and calcitonin. METHODS. One hundred three patients starting longterm corticosteroid therapy were randomly assigned to receive 1000 mg of calcium per day orally and either calcitriol (0.5 to 1.0 microgram per day orally) plus salmon calcitonin (400 IU per day intranasally), calcitriol plus a placebo nasal spray, or double placebo for one year. Data on treatment efficacy were available for 92 of these patients. Bone density was measured every four months for two years by photon absorptiometry. There were no significant differences between groups with respect to age, underlying disease, initial bone density, or corticosteroid dose during the first year. RESULTS. Calcitriol (mean dose, 0.6 microgram per day), with or without calcitonin, prevented more bone loss from the lumbar spine (mean rates of change, 0.2 and 1.3 percent per year, respectively) than calcium alone (4.3 percent per year, P = 0.0035). Bone loss at the femoral neck and distal radius was not significantly affected by any treatment. In the second year, lumbar bone loss did not occur in the group previously treated with calcitonin plus calcitriol (+0.7 percent per year), but it did occur in the group given calcium alone (2.3 percent per year). The calcitriol group also lost lumbar bone (3.6 percent per year) but received more corticosteroid in the second year than the other two groups. CONCLUSIONS. Calcitriol and calcium, used prophylactically with or without calcitonin, prevent corticosteroidinduced bone loss in the lumbar spine.

108: J Pediatr. 1993 May;122(5 Pt 1):7618. Effect of parenteral calcium and phosphorus therapy on mineral retention and bone mineral content in very low birth weight infants. Prestridge LL, Schanler RJ, Shulman RJ, Burns PA, Laine LL.

HYPOTHESIS: If calcium and phosphorus are administered to very low birth weight infants in amounts larger than those currently used in standard parenteral nutrition solutions, apparent retention of calcium and phosphorus (intake minus urinary excretion) will increase and bone mineralization will improve. DESIGN: Randomized, controlled, doubleblind trial. SETTING: Neonatal intensive care unit. PATIENTS: Twentyfour very low birth weight infants (< 1.2 kg) expected to receive parenteral nutrition exclusively for approximately 3 weeks beginning 3 days after birth. INTERVENTIONS: Infants received parenteral nutrition solutions, either the standard mixture containing 1.25 mmol calcium and 1.5 mmol phosphorus per deciliter (group STAND: n = 12, birth weight 921 +/ 171 gm, gestational age 27 +/ 2 weeks (mean +/ SD)) or 1.7 mmol calcium and 2.0 mmol phosphorus per deciliter (group HIGH: n = 12, 857 +/ 180 gm, 27 +/ 2 weeks). MAIN OUTCOME MEASURES: Intake, urinary excretion, and apparent retention of calcium, phosphorus, and magnesium every 3 days during parenteral nutrition therapy. Serum indexes of mineral status twice during therapy. Bone mineral content of the distal segment of the left radius at 1, 4, 8, and 26 weeks. RESULTS: Apparent calcium retention (1.2 +/ 0.2 vs 1.6 +/ 0.2 mmol.kg1.d1) and phosphorus retention (1.4 +/ 0.2 vs 1.8 +/ 0.4 mmol.kg1.d1) differed significantly (p < 0.01) between groups STAND and HIGH, respectively; neither changed with the duration of parenteral nutrition therapy. Serum calcium, magnesium, parathyroid hormone, 25hydroxyvitamin D, and osteocalcin concentrations were similar in both groups. Serum phosphorus concentration was significantly higher in group HIGH than in group STAND (p = 0.025). The absolute bone mineral content and the rate of increase in bone mineral content between 1 and 4, 1 and 8, and 1 and 26 weeks were significantly greater in group HIGH than in group STAND. CONCLUSIONS: Increased parenteral intakes of calcium and phosphorus resulted in greater retention of these minerals during parenteral nutrition therapy and in greater bone mineral content after therapy.

109: J Card Surg. 1993 Mar;8(2 Suppl):32931. Calcium and stunned myocardium. Mazer CD.

Calcium administration during ischemia or at the onset of reperfusion is generally considered to be deleterious because cytosolic calcium is elevated at this time. In contrast, the administration of calcium antagonists before or during ischemia is protective. While calcium antagonists may not be beneficial when given after reperfusion, calcium administration during this period has been found to enhance the recovery of systolic and diastolic function of stunned myocardium.

110: N Engl J Med. 1993 Feb 18;328(7):4604. Effect of calcium supplementation on bone loss in postmenopausal women. Reid IR, Ames RW, Evans MC, Gamble GD, Sharpe SJ.

BACKGROUND. The use of calcium supplements slows bone loss in the forearm and has a beneficial effect on the axial bone density of women in late menopause whose calcium intake is less than 400 mg per day. However, the effect of a calcium supplement of 1000 mg per day on the axial bone density of postmenopausal women with higher calcium intakes is not known. METHODS. We studied 122 normal women at least three years after they had reached menopause who had a mean dietary calcium intake of 750 mg per day. The women were randomly assigned to treatment with either calcium (1000 mg per day) or placebo for two years. The bone mineral density of the total body, lumbar spine, and proximal femur was measured every six months by dualenergy xray absorptiometry. Serum and urine indexes of calcium metabolism were measured at base line and after 3, 12, and 24 months. RESULTS. The mean (+/ SE) rate of loss of totalbody bone mineral density was reduced by 43 percent in the calcium group (0.0055 +/ 0.0010 g per square centimeter per year) as compared with the placebo group (0.0097 +/ 0.0010 g per square centimeter per year, P = 0.005). The rate of loss of bone mineral density was reduced by 35 percent in the legs (P = 0.02), and loss was eliminated in the trunk (P = 0.04). Calcium use was of significant benefit in the lumbar spine (P = 0.04), and in Ward's triangle the rate of loss was reduced by 67 percent (P = 0.04). Calcium supplementation had a similar effect whether dietary calcium intake was above or below the mean value for the group. Serum parathyroid hormone concentrations tended to be lower in the calcium group, as were urinary hydroxyproline excretion and serum alkaline phosphatase concentrations. CONCLUSIONS. Calcium supplementation significantly slowed axial and appendicular bone loss in normal postmenopausal women. PMID 8421475

111: J Hum Hypertens. 1993 Feb;7(1):435. Effect of oral calcium supplementation on blood pressure in patients with previously untreated hypertension: a randomised, doubleblind, placebocontrolled, crossover study. Galloe AM, Graudal N, Moller J, Bro H, Jorgensen M, Christensen HR.

It has been claimed that calcium lowers BP. The present randomised, doubleblind, placebocontrolled crossover study is the first to investigate the effect on BP of a high oral dose of calcium given for a long period to patients with previously untreated hypertension. Elemental calcium (2 g) was administered for 12 weeks interchanging with a period of 12 weeks of placebo. Twenty patients completed the protocol. There was no significant difference in change of BP during the period of additional calcium intake when compared with placebo (P = 0.33). The risk of not detecting a real BPlowering effect of calcium of at least 3 mmHg was < 5%. No evidence for the existence of a subgroup of 'responders' was found. It is concluded that a high daily dose of calcium supplementation given for 12 weeks does not decrease BP in previously untreated patients with mild to moderate hypertension.

112: N Engl J Med. 1992 Dec 3;327(23):163742. Vitamin D3 and calcium to prevent hip fractures in the elderly women. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ.

BACKGROUND. Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. METHODS. We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/ SD] age, 84 +/ 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. RESULTS. Among the women who completed the 18month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the baseline value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the baseline value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3calcium group and decreased 4.6 percent in the placebo group (P < 0.001). CONCLUSIONS. Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

113: Am J Clin Nutr. 1992 Dec;56(6):10458. Calcium supplementation and plasma ferritin concentrations in premenopausal women. Sokoll LJ, DawsonHughes B.

The effect of calcium supplement use on iron stores was examined in a randomized controlled study in freeliving, healthy, premenopausal women. Of 109 women who completed the study, 52 were in the control group and 57 took two tablets containing 250 mg Ca as the carbonate with each of two meals daily for 12 wk. In all subjects at baseline, plasma ferritin concentrations were positively correlated with hemeiron intake (r = 0.21, P = 0.04), serum iron concentration (r = 0.19, P = 0.04), transferrin saturation (r = 0.31, P = 0.001), and hemoglobin concentration (r = 0.22, P = 0.02), and negatively correlated with total ironbinding capacity (TIBC, r = 0.42, P < 0.001). No significant differences in absolute or percent changes in plasma ferritin concentrations, serum iron concentrations, TIBC, transferrin saturation, hemoglobin concentrations, or hematocrit were observed between the treatment and control groups. Thus, over a 12wk period, use of 1000 mg Ca as the carbonate daily with meals does not appear to be detrimental to iron stores in healthy, freeliving, premenopausal women.

114: CMAJ. 1987 Mar 15;136(6):58793. Osteoporosis, calcium and physical activity. Martin AD, Houston CS.

Sales of calcium supplements have increased dramatically since 1983, as middleaged women seek to prevent or treat bone loss due to osteoporosis. However, epidemiologic studies have failed to support the hypothesis that larger amounts of calcium are associated with increased bone density or a decreased incidence of fractures. The authors examine the evidence from controlled trials on the effects of calcium supplementation and physical activity on bone loss and find that weightbearing activity, if undertaken early in life and on a regular basis, can increase the peak bone mass of early adulthood, delay the onset of bone loss and reduce the rate of loss. All of these factors will delay the onset of fractures. Carefully planned and supervised physical activity programs can also provide a safe, effective therapy for people who have osteoporosis. PMID 3545420

115: Nutr Rev. 1992 Nov;50(11):3357. Maximizing peak bone mass: calcium supplementation increases bone mineral density in children. [No authors listed]

Attaining peak skeletal bone mass during childhood may reduce the incidence of osteoporosis in later life. A recent study in six to 14yearold identical twins showed that calcium supplementation increased bone mineral density. The effects of supplementation were especially pronounced in prepubertal children. PMID 1488160

116: Nutr Rev. 1992 Aug;50(8):2336. Calcium supplementation prevents hypertensive disorders of pregnancy. [No authors listed]

Preeclampsia, a hypertensive disorder of pregnancy, is a major cause of fetal and maternal morbidity and mortality. Epidemiologic studies have shown an inverse relationship between dietary calcium intake and gestational hypertension. A recent largescale, randomized, doubleblind, placebocontrolled clinical trial has shown that supplementation of pregnant women with 2 g calcium per day from the twentieth week of gestation to term can significantly lower the incidence of hypertensive disorders of pregnancy. The beneficial effect of calcium supplementation was apparent as early as the twentyeighth week of gestation. The mechanism responsible for the effects of calcium on gestational hypertension is unknown. PMID 1345035

117: Zhonghua Xin Xue Guan Bing Za Zhi. 1992 Aug;20(4):2434, 261. [Protective effects of gradual restoring of calcium on working rat hearts with ischemiareperfusion injury] Xie SP.

The effects of gradually restoring calcium concentration in initiating reperfusion on cardiac function, coronary blood flow and myocardial calcium content during reperfusion following global ischemia have been observed in isolated working rat hearts. The results showed that gradually restoring calcium reperfusion facilitated the recovery of the contracting relaxing and pump functions as well as coronary blood flow, and decreased the occurrence of arrhythmias during reperfusion and myocardial calcium content after reperfusion. The mechanism of the protective effect of gradual calcium restoration on the hearts was probably due to the inhibition of calcium overload in cardiac cells. However high calcium reperfusion deteriorated cardiac function.

118: Gastroenterology. 1992 Jul;103(1):927. Calcium supplementation decreases rectal epithelial cell proliferation in subjects with sporadic adenoma. Wargovich MJ, Isbell G, Shabot M, Winn R, Lanza F, Hochman L, Larson E, Lynch P, Roubein L, Levin B.

The results of three small clinical trials examining the effect of calcium carbonate supplementation on the proliferation cytokinetics of the rectal epithelium in subjects with a current history of sporadic adenoma are reported. In six subjects, a daily administration of 1500 mg of calcium carbonate for 90 days failed to significantly suppress thymidine labeling in normalappearing mucosa of the rectum. However, a daily dose of 2000 mg of calcium significantly (P = 0.008) altered mucosal proliferation in a second set of six subjects after a 30day trial. Finally, a placebocontrolled trial of calcium (2000 mg) was conducted in which 20 subjects were randomized to groups receiving a 4week intervention with calcium (or placebo), followed by the alternative treatment (placebo or calcium). The results of the study show a marked suppression of rectal proliferation during the calcium phase of the study but not during the placebo phase. This study adds to accumulating evidence showing that calcium supplementation regulates the proliferative behavior of colonic epithelium in the individual at high risk for colon cancer. Longer term trials of calcium supplementation will ascertain whether a continuing benefit from increasing dietary calcium translates into inhibition of adenoma recurrence.

119: Radiology. 1992 Jul;184(1):15964. Amelioration of cardiodepressive effects of gadopentetate dimeglumine with addition of ionic calcium. Muhler A, Saeed M, Brasch RC, Higgins CB.

Doses of gadopentetate dimeglumine of 0.10.5 mmol/kg cause cardiodepressive effects when injected as a rapid central bolus into the left jugular vein. This study evaluated the hemodynamic effects of this magnetic resonance imaging contrast medium with and without calcium supplementation in a rat model. Also, the potential of gadopentetate dimeglumine to bind ionized serum calcium was investigated in vitro. Addition of calcium ions resulted in dosedependent attenuation of the hemodynamic depression induced by gadopentetate dimeglumine alone. The cardiodepressive response was negated for a 0.1mmol/kg dose of the contrast agent by addition of 6 mumol/kg of calcium, for a 0.3mmol/kg dose by addition of 12 mumol/kg of calcium, and for a 0.5mmol/kg dose by addition of 18 mumol/kg of calcium. Concentrations of 2 and 4 mmol/L of gadopentetate dimeglumine were found to bind 5.1% and 10.1% of the ionized calcium in rat serum under in vitro conditions, respectively. PMID 1609076

120: Acta Physiol Scand. 1992 Jun;145(2):938. Calcium supplementation and thyroid hormone protect against gentamicininduced inhibition of proximal tubular Na+,K(+)ATPase activity and other renal functional changes. Fukuda Y, Eklof AC, Malmborg AS, Aperia A.

Gentamicin can cause proximal tubule necrosis. We have shown that inhibition of PT Na+,K(+)ATPase activity is rapidly induced by gentamicin. We have now investigated whether manipulations known to attenuate the negative effects of gentamicin on renal excretory capacity, i.e. high calcium intake and Lthyroxine treatment, will also attenuate gentamicininduced inhibition of Na+,K(+)ATPase activity and ameliorated signs of proximal tubule damage. Rats were gentamicin or vehicletreated for 7 days. Subgroups were given 4% calcium (Ca) supplements or Lthyroxine 20 micrograms 100 g1 body weight daily. Gentamicin significantly reduced the glomerular filtration rate and increased the urinary excretion of the proximal tubule lysosomal enzyme, NacetylbetaDglucosaminidase. Gentamicin significantly reduced proximal tubule Na+,K(+)ATPase activity, measured in single permeabilized proximal tubule segments. Sodium excretion was inversely correlated to proximal tubule Na+,K(+)ATPase activity. Both calcium and Lthyroxine alleviated all gentamicininduced sideeffects on renal function as well as on proximal tubule Na+,K(+)ATPase activity. Calcium and Lthyroxine had no significant effect on renal function. Lthyroxine, but not calcium, increased proximal tubule Na+,K(+)ATPase activity in control rats. Renal cortical tissue gentamicin concentration was not influenced by calcium but was significantly lowered by Lthyroxine. Two procedures which, via different mechanisms, afford protection from gentamicininduced changes in renal function also give protection from gentamicininduced inhibition of Na+,K(+)ATPase activity. This suggests that loss of integrity of the Na+,K(+)ATPase enzyme contributes to gentamicininduced nephrotoxicity. PMID 1322021

121: Vnitr Lek. 1992 Apr;38(4):3526. [Diabetic osteopathy. Favorable effect of treatment of osteomalacia with vitamin D and calcium on high blood glucose levels] Kocian J.

A group of 61 diabetics (incl. 35 treated by diet alone and 26 who were treated also by oral antidiabetics) with associated osteomalacia were treated with vitamin D (dosage 42,000 to 85,000 i. u. per day) and calcium (470700 mg/day). After six weeks of this treatment the serum calcium level rose on average by 0.15 mmol/l and the blood sugar level declined on average by 1.68 mmol/l. A linear negative correlation was proved between these two parameters. The fasting blood sugar level declined in 53 subjects (86.88%) and only in five patients (8.19%) the blood sugar level increased, in three subjects (4.91%) it did not change. Possible explanations of this phenomenon include the influence of an increased calcium concentration on insulin secretion and release from pancreatic betacells on the one hand and enhanced glucose utilization in the periphery on the other hand.

122: N Engl J Med. 1992 Feb 6;326(6):35762. Treatment of postmenopausal osteoporosis with calcitriol or calcium. Tilyard MW, Spears GF, Thomson J, Dovey S.

BACKGROUND AND METHODS. Osteoporosis is a common problem whose management is controversial. To evaluate the efficacy and safety of calcitriol (1,25dihydroxyvitamin D3) in the treatment of postmenopausal osteoporosis, we conducted a threeyear prospective, multicenter, singleblind study in 622 women who had one or more vertebral compression fractures. The women were randomly assigned to receive treatment with calcitriol (0.25 micrograms twice a day) or supplemental calcium (1 g of elemental calcium daily) for three years. New vertebral fractures were detected by means of lateral roentgenography of the spine each year, and calcium absorption was measured in 392 of the women. RESULTS. The women who received calcitriol had a significant reduction in the rate of new vertebral fractures during the second and third years of treatment, as compared with the women who received calcium (second year, 9.3 vs. 25.0 fractures per 100 patientyears; third year, 9.9 vs. 31.5 fractures per 100 patientyears; P less than 0.001). This effect was evident only in women who had had five or fewer vertebral fractures at base line (second year, 5.2 vs. 25.3 fractures per 100 patientyears; third year, 4.2 vs. 31.0 fractures per 100 patientyears; P less than 0.0001). The groups also differed significantly in the number of peripheral fractures; 11 such fractures occurred in 11 women in the calcitriol group, whereas 24 occurred in 22 women in the calcium group (P less than 0.05). There was no significant difference between the groups in the incidence of side effects requiring withdrawal of treatment (8.6 percent in the calcitriol group vs. 6.5 percent in the calcium group). CONCLUSIONS. Continuous treatment of postmenopausal osteoporosis with calcitriol for three years is safe and significantly reduces the rate of new vertebral fractures in women with this disorder.

123: Clin Nephrol. 1992 Jan;37(1):148. Reduction of urinary oxalate by combined calcium and citrate administration without increase in urinary calcium oxalate stone formers. Ito H, Suzuki F, Yamaguchi K, Nishikawa Y, Kotake T.

Oxalic acid seems to play a far greater role in the formation of calcium oxalate stone than calcium. Three grams of calcium lactate and 3 g of sodium potassium citrate were administered to 46 urolithiasis patients, whose stones were mainly composed of calcium oxalate. Urinary oxalate level was reduced significantly without raising urinary calcium level by the administration of the two drugs for two weeks. The reduction of urinary oxalic acid was particularly remarkable in patients without hypercalciuria. The mechanism of action of these drugs was discussed. PMID 1541059

124: N Engl J Med. 1991 Nov 14;325(20):1399405. Calcium supplementation to prevent hypertensive disorders of pregnancy. Belizan JM, Villar J, Gonzalez L, Campodonico L, Bergel E.

BACKGROUND. Calcium supplementation has been reported to reduce blood pressure in pregnant and nonpregnant women. We undertook this prospective study to determine the effect of calcium supplementation on the incidence of hypertensive disorders of pregnancy (gestational hypertension and preeclampsia) and to determine the value of urinary calcium levels as a predictor of the response. METHODS. We studied 1194 nulliparous women who were in the 20th week of gestation at the beginning of the study. The women were randomly assigned to receive 2 g per day of elemental calcium in the form of calcium carbonate (593 women) or placebo (601 women). Urinary excretion of calcium and creatinine was measured before calcium supplementation was begun. The women were followed to the end of their pregnancies, and the incidence of hypertensive disorders of pregnancy was determined. RESULTS. The rates of hypertensive disorders of pregnancy were lower in the calcium group than in the placebo group (9.8 percent vs. 14.8 percent; odds ratio, 0.63; 95 percent confidence interval, 0.44 to 0.90). The risk of these disorders was lower at all times during gestation, particularly after the 28th week of gestation (P = 0.01 by lifetable analysis), in the calcium group than in the placebo group, and the risk of both gestational hypertension and preeclampsia was also lower in the calcium group. Among the women who had low ratios of urinary calcium to urinary creatinine (less than or equal to 0.62 mmol per millimole) during the 20th week of gestation, those in the calcium group had a lower risk of hypertensive disorders of pregnancy (odds ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09) and less of an increase in diastolic and systolic blood pressure than the placebo group. The pattern of response was similar among the women who had a high ratio of urinary calcium to urinary creatinine during the 20th week of gestation, but the differences were smaller. CONCLUSIONS. Pregnant women who receive calcium supplementation after the 20th week of pregnancy have a reduced risk of hypertensive disorders of pregnancy.

125: Am J Hypertens. 1991 Oct;4(10 Pt 1):8369. Calcium treatment of essential hypertension in elderly patients evaluated by 24 H monitoring. Takagi Y, Fukase M, Takata S, Fujimi T, Fujita T.

We used 24h monitoring of blood pressure (BP) to evaluate the effect of calcium supplementation on mild to moderate essential hypertension in elderly hospitalized patients for the first time in a controlled crossover study. The mean systolic and diastolic BP over a period of 24 h declined by 13.6 mm Hg (P less than .005) and 5.0 mm Hg (P less than .05) respectively in patients whose diet was supplemented with 1 g of elemental calcium in the form of oystershell electrolysate (AA calcium). Serum ionized calcium and urinary calcium and sodium excretion increased (serum Ca2+ 0.16 +/ 0.03 mEq/L, P less than .05; FECa 0.5 +/ 0.2%, P less than .05; FENa 0.4 +/ 0.1%, P less than .05) and plasma parathyroid hormone was suppressed (12.2 +/ 2.3 pg/mL, P less than .005). These data suggest that supplementation of dietary calcium may contribute to a reduction of BP in elderly patients with essential hypertension.

126: Hinyokika Kiyo. 1991 Oct;37(10):110710. [Combined administration of calcium and citrate reduces urinary oxalate excretion] Ito H.

Three grams of calcium lactate and 3 g of uralyt U were administered to 39 calcium oxalate stone formers. Urinary oxalate level was reduced significantly without raising urinary calcium level by the administration of the two drugs for two weeks. The mechanism of action of these drugs and the diet which might produce a similar effect were discussed.

127: J Clin Endocrinol Metab. 1991 Sep;73(3):53340. Calcium supplementation reduces vertebral bone loss in perimenopausal women: a controlled trial in 248 women between 46 and 55 years of age. Elders PJ, Netelenbos JC, Lips P, van Ginkel FC, Khoe E, Leeuwenkamp OR, Hackeng WH, van der Stelt PF.

To study the effect of calcium supplementation on perimenopausal bone loss, 295 women were randomized into a control group and 2 supplementation groups receiving, respectively, 1000 and 2000 mg elemental calcium/day for a period of 2 yr. We observed a significant decrease in lumbar bone loss in relation to the calcium supplementation (mean loss after 2 yr of 3.5% in the control group vs. 1.3% and 0.7% in the 1000 and 2000 mg groups, respectively), a significant increase in urinary calcium excretion, and a significant decrease in the urinary hydroxyproline/creatine ratio, serum alkaline phosphatase, osteocalcin, and 1,25dihydroxyvitamin D. The effect of calcium supplementation on lumbar bone loss was significant in the first year of supplementation, but not in the second. However, the urinary hydroxyproline/creatinine ratio and the serum alkaline phosphatase level remained significantly decreased in the treatment groups at the end of the study; this was not the case for serum osteocalcin. Calcium supplementation did not have a significant effect on metacarpal cortical bone loss. The difference in biochemical parameters between the 2 supplementation groups was small. No significant interaction was observed between the menopausal status of the subjects and the effect of calcium supplementation. We conclude that calcium supplementation retards lumbar bone loss in the first year of calcium supplementation by reducing bone turnover. However, the effect on lumbar bone loss over a longer time span is still uncertain.

128: Am J Clin Nutr. 1991 Aug;54(2):4258. Influence of calcium intake and growth indexes on vertebral bone mineral density in young females. Sentipal JM, Wardlaw GM, Mahan J, Matkovic V.

This crosssectional study examined the relationship between current calcium intake and vertebral bone mineral density (VBMD) in 49 healthy Caucasian adolescent females aged 818 y. The ability of current calcium intake to account for the variance in VBMD in this population was compared with that seen with weight, height, maturational age (determined by the Tanner Sexual Maturity Rating), chronological age, and total energy expenditure. Calcium intake was determined from the mean of 4d, foodintake records. Average vertebral bone mineral density from L1L4 was measured by dual xray absorptiometry. A multipleregression model revealed that 81% of the variance in VBMD was described by maturational age, chronological age, and calcium intake, with all representing significant predictors of bone mineral density (P less than 0.0001, 0.005, 0.04, respectively). This study supports the hypothesis that better calcium nutrition during adolescence may optimize, within genetic boundaries, peak bone mass. PMID 1858707

129: Bol Oficina Sanit Panam. 1991 Feb;110(2):12635. [Use of calcium for the prevention of pregnancyinduced hypertension] LopezJaramillo P, de Felix M.

The Andean population of Ecuador is exposed to major risk factors associated with pregnancyinduced hypertension (PIH). The disease is very frequent, and perinatal and maternal death rates are high. Recently a causal relationship has been suggested between dietary calcium deficiency and PIH, with the proposal that calcium supplements be given throughout pregnancy in order to prevent the disease. This article reviews a series of clinical tests carried out over a sixyear period which have demonstrated that calcium supplementation is an effective lowcost measure for reducing the frequency of PIH in women whose intake of the mineral is low. It is not yet known how calcium reduces the risk of PIH. It is suggested that adequate intake of the mineral keeps serum levels of calcium within its narrow physiological limits; these are crucial for the synthesis of nitric oxide in the vascular endothelium, a substance that appears to be responsible for maintaining the vasodilatation that characterizes normal pregnancy. However, before the general use of calcium supplements can be recommended, it will be necessary to conduct epidemiological studies on larger numbers of women.

130: Clin Ter. 1990 Oct 31;135(2):95103. [Calcium folinate in old age] Baroni MC, Delsignore R, Cuzzupoli M, Candelora P, Passeri M.

The authors report the results obtained in a group of 60 elderly patients (age greater than or equal to 65 years) treated with a 15 mg tablet of calcium folinate per day for 60 days. The drug was very well tolerated and it significantly improved the blood chemistry and clinical parameters considered.

131: Am J Obstet Gynecol. 1990 Oct;163(4 Pt 1):112431. Calcium supplementation during pregnancy may reduce preterm delivery in highrisk populations. Villar J, Repke JT.

Results are presented of a randomized, doubleblinded controlled clinical trial of calcium supplementation (2.0 gm of elemental calcium as calcium carbonate) and a placebo. All participants were 17 years of age or less and clinically healthy. Patients were enrolled by the twenty third week of gestation. The mean duration of calcium supplementation or placebo was approximately 14 weeks. Treatment consisted of 2.8 (+/ 1.5) tablets per day in the placebo group (N = 95) and 3.0 (+/ 1.4) tablets per day in the calcium group (N = 94). Dietary calcium intake was similar in both groups at about 1200 mg/day. The calcium group had a lower incidence of preterm delivery (less than 37 weeks; 7.4% vs 21.1%; p = 0.007); spontaneous labor and preterm delivery (6.4% vs 17.9%; p = 0.01); and low birth weight (9.6% vs 21.1%; p = 0.03). This effect was also present after stratified analysis by level of treatment compliance, urinary tract infection, and chlamydial infection. Lifetable analysis demonstrated an overall shift to a higher gestational age in the calcium group compared with the placebo group (logrank test, p = 0.02). As suggested previously, the observed effect could be mediated by a reduction in uterine smooth muscle contractibility. If confirmed by future research, these results could represent an important preventive intervention for prematurity in highrisk populations.

132: N Engl J Med. 1990 Sep 27;323(13):87883. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. DawsonHughes B, Dallal GE, Krall EA, Sadowski L, Sahyoun N, Tannenbaum S.

Background. The effectiveness of calcium in retarding bone loss in older postmenopausal women is unclear. Earlier work suggested that the women who were most likely to benefit from calcium supplementation were those with low calcium intakes. Methods. We undertook a doubleblind, placebocontrolled, randomized trial to determine the effect of calcium on bone loss from the spine, femoral neck, and radius in 301 healthy postmenopausal women, half of whom had a calcium intake lower than 400 mg per day and half an intake of 400 to 650 mg per day. The women received placebo or either calcium carbonate or calcium citrate malate (500 mg of calcium per day) for two years. Results. In women who had undergone menopause five or fewer years earlier, bone loss from the spine was rapid and was not affected by supplementation with calcium. Among the women who had been postmenopausal for six years or more and who were given placebo, bone loss was less rapid in the group with the higher dietary calcium intake. In those with the lower calcium intake, calcium citrate malate prevented bone loss during the two years of the study; its effect was significantly different from that of placebo (P less than 0.05) at the femoral neck (mean change in bone density [+/ SE], 0.87 +/ 1.01 percent vs. 2.11 +/ 0.93 percent), radius (1.05 +/ 0.75 percent vs. 2.33 +/ 0.72 percent), and spine (0.38 +/ 0.82 percent vs. 2.85 +/ 0.77 percent). Calcium carbonate maintained bone density at the femoral neck (mean change in bone density, 0.08 +/ 0.98 percent) and radius (0.24 +/ 0.70 percent) but not the spine (2.54 +/ 0.85 percent). Among the women who had been postmenopausal for six years or more and who had the higher calcium intake, those in all three treatment groups maintained bone density at the hip and radius and lost bone from the spine. Conclusions. Healthy older postmenopausal women with a daily calcium intake of less than 400 mg can significantly reduce bone loss by increasing their calcium intake to 800 mg per day. At the dose we tested, supplementation with calcium citrate malate was more effective than supplementation with calcium carbonate.

133: Arzneimittelforschung. 1990 Sep;40(9):9847. [Reduction of reactivity to allergic rhinitis with intravenous administration of calcium. Clinicalexperimental study on the effect of changes of local airway resistance after nasal allergen provocation] Bachert C, Drechsler S, Keilmann A, Seifert E, Schmidt R, Welzel D.

The antiallergic activity of calcium was investigated in 25 patients with allergic rhinitis by nasal provocation with increasing doses of phleum pratense during a symptom free interval. Prior to that provocation, the patients received 9 mmol calcium (CalciumSandoz) i.v. or placebo respectively (double blind crossover design). The concentration of serum calcium increased after calcium injection by 0.45 +/ 0.055 mmol/l. Calcium exerted a significant protective effect as compared to placebo: higher allergen doses, (p = 0.021) i.e. 20433 biological units/ml vs. 7494 biological units/ml, were required in order to induce a defined allergic reaction (50% decrease of nasal air flow). The data thus furnish evidence that intravenous calcium reduces the allergic response in type I allergy.

134: Am Heart J. 1990 Aug;120(2):3816. Hypocalcemic myocardial dysfunction: short and longterm improvement with calcium replacement. Wong CK, Lau CP, Cheng CH, Leung WH, Freedman B.

The effects of short and longterm calcium replacement on myocardial function in six asymptomatic patients (age 48 +/ 3, mean +/ SEM) with hypocalcemia complicating surgical hypoparathyroidism were studied. Cardiac output was determined by ascending aortic continuous wave Doppler assessment and was measured as minute distance. During intravenous calcium replacement at rest, ascending aortic minute distance increased from 6.75 +/ 1.10 to 9.17 +/ 1.29 m as the calcium level rose from 1.76 +/ 0.08 to 2.06 +/ 0.19 mmol/L without changes in heart rate and blood pressure (p less than 0.01). The peak velocity and acceleration of blood flow derived from Doppler measurement showed a similar rise during calcium infusion. Symptomlimited cycle ergometry was performed before and 3 months after normalization of calcium by longterm oral therapy. Although the resting cardiac output was unchanged, the maximum cardiac output at peak exercise also increased from a minute distance of 11.58 +/ 1.84 to 15.37 +/ 2.28 m (p less than 0.05), together with an increase of maximum heart rate from 136 to 149 beats/min (p less than 0.05). Exercise duration was also prolonged from 11.9 +/ 2.9 to 13.0 +/ 2.8 minutes. Thus hypocalcemia impairs cardiac performance, but this impairment is reversible with calcium replacement. PMID 2382615

135: J Nutr. 1990 Aug;120(8):87681. Effect of calcium citratemalate on skeletal development in young, growing rats. Kochanowski BA.

It has been previously demonstrated that calcium from calcium citratemalate (CCM), a mixture of calcium, citric acid and malic acid, is betterabsorbed than calcium from calcium carbonate (CaCO3) in humans and in rats. It was of interest to determine if this differential in absorption would result in differences in bone development under chronic feeding conditions. The present study was designed to compare CCM with CaCO3 for effects on bone development in weanling female C/D rats fed either CCM or CaCO3 at 0.3 or 0.6% dietary Ca for 4 or 12 wk. There was a nonsignificant trend for rats fed CCM to weigh more and have larger bones than rats fed CaCO3. Histologic evaluation of cortical and trabecular bone revealed normal bone formation in all rats. Trabecular bone was significantly affected by calcium level and source. The 0.3% Ca diets (either source) resulted in reduced trabecular bone volumes in tibias. After 4 wk, rats fed CCM had 2325% more trabecular bone than rats fed CaCO3. By 12 wk, the difference was even greater; rats fed CCM had 4447% more trabecular bone than rats fed CaCO3. Dietary calcium source did not affect cortical bone. It is concluded that because of its positive effects on bone, CCM is a more bioavailable calcium source than CaCO3. PMID 2380795

136: Chest. 1990 May;97(5):11069. Shortterm control of supraventricular tachycardia with verapamil infusion and calcium pretreatment. Barnett JC, Touchon RC.

Nineteen consecutive patients with atrial fibrillation/flutter or other types of supraventricular tachycardia were given intravenous (IV) calcium salts (1 g) followed by verapamil infusion at a rate of 1 mg/min. Successful treatment was defined as control of ventricular response to less than or equal to 100 beats per minute (bpm) or conversion to sinus mechanism in patients with atrial arrhythmias: 11 patients had atrial fibrillation; three had atrial flutter; four had reentrant supraventricular tachycardias (SVT); and one had paroxysmal SVT. Therapy was successful in all patients. The mean dose of verapamil required to achieve desired outcome was 20 mg. Heart rate showed no significant change as a result of calcium pretreatment (160 bpm v 151 bpm). However, heart rate was significantly decreased, to 95 bpm, after treatment with verapamil. Blood pressure showed no change from baseline with either calcium or verapamil therapy. Verapamil infusion following IV calcium successfully treats atrial fibrillation/flutter or SVTs without depressing systemic blood pressure. PMID 2331904

137: J Clin Endocrinol Metab. 1990 Jan;70(1):26470. Dietary modification with dairy products for preventing vertebral bone loss in premenopausal women: a threeyear prospective study. Baran D, Sorensen A, Grimes J, Lew R, Karellas A, Johnson B, Roche J.

The effect of dietary calcium on vertebral bone mass in women is controversial. In a randomized study we have investigated the effect of dietary modification in the form of dairy products on vertebral bone mass in 30 to 42yrold premenopausal women over a 3yr period. Twenty women increased their dietary calcium intake by an average of 610 mg/day (P less than 0.03) for 3 yr, while 17 age and weightmatched women served as controls. Calcium intake was monitored by 3day diet histories and 24h urinary calcium excretion. The consumption of the dairy products did not alter serum calcium or PTH levels or the fasting urinary calcium to creatinine ratio. Twentyfourhour urinary calcium excretion increased by 28% (P less than 0.03) in the supplemented women. Dairy product intake was accompanied by increased dietary fat intake, but there were no statistically significant changes in serum cholesterol, low density lipoprotein cholesterol, or high density lipoprotein cholesterol levels. The vertebral bone density in the women consuming increased calcium did not change over the 3yr period (0.4 +/ 0.9%). In contrast, the vertebral bone density in the control women declined (2.9 +/ 0.8%; P less than 0.001) and was significantly lower than that in the supplemented group at 30 and 36 months. The study suggests that dietary modification in the form of dairy products retards vertebral bone loss in premenopausal women. Therefore, increased calcium intake in estrogenreplete premenopausal women may prevent agerelated bone loss.

138: Zentralbl Gynakol. 1989;111(21):14414. Zinc, magnesium and copper in serum of women given a calcium supplement. Jendryczko A, Tomala J, Drozdz M.

Earlier investigators have demonstrated in animal studies interrelationships between mineral elements. Serum zinc, magnesium and copper were monitored over a two year period in 120 women between the ages of 40 and 55 years. One group (65 women) was supplemented with calcium, the other served as a control. We concluded that calcium supplementation at a level of 1,500 mg Ca mainly does not affect serum zinc, magnesium and copper, however, serum copper concentration is elevated in women taking medication for hypertension. PMID 2603586

139: Magnes Res. 1988 Dec;1(34):14753. Consequences of low dietary magnesium and high dietary calcium on pregnancy outcome and tissue mineralization in rats. Pinkham CS, Kubena KS.

Weanling female SpragueDawley rats were fed purified diets to determine the influence of excess dietary calcium upon tissue content of magnesium and calcium, and reproductive outcome. Two levels of calcium (5000 and 16,000 ppm) and magnesium (200 and 1200 ppm) in a 2x2 factorial design (adequate magnesium and calcium = C; low magnesium adequate calcium = L; high calcium adequate magnesium = CHC; and high calcium low magnesium = LHC) were used during the study which included growth and breeding (10 weeks), and gestation and lactation (6 weeks). Depressed weight gain during growth and gestation occurred in response to calcium excess. Renal calcium accumulation was reduced in LHC dams as compared to L dams. In dams fed excess calcium, magnesium concentrations of bone, serum, and kidney were depressed while serum alkaline phosphatase activity increased. The adverse effects of high calcium seen in the dams were not apparent in LHC pups. These pups were heavier and more viable during lactation than pups in the L group. High dietary calcium in combination with low dietary magnesium during one reproductive cycle resulted in altered mineral levels in tissues and improved growth and viability of pups when compared to magnesiumdeficient animals. PMID 3275202

140: Scand J Gastroenterol. 1988 Dec;23(10):123740. Treatment of chronic diarrhoea: loperamide versus ispaghula husk and calcium. Qvitzau S, Matzen P, Madsen P.

Twentyfive patients with chronic diarrhoea were included in an open, randomized crossover trial comparing the effect of loperamide with ispaghula and calcium. Nineteen patients completed both treatments. Before treatment the median number of daily stools was 7 (range, 413), stool consistency was loose in all, and urgency was present in 16 out of 19 patients. Both treatments halved stool frequency, but with regard to urgency and stool consistency ispaghula and calcium was significantly better. A combination of ispaghula and calcium seems to be a cheap and effective alternative to conventional treatment of chronic diarrhoea. Moreover, side effects were minimized.

141: Drug Intell Clin Pharm. 1988 JulAug;22(78):5756. Verapamil preceded by calcium in supraventricular tachycardia. Stringer KA, Hicks P, Royal SH, Branconi JM, Sloan R.

Verapamil has been shown to be effective in the management of supraventricular tachycardia (SVT). However, the utility of verapamil may be limited because of adverse effects, specifically hypotension. Several clinical observations have shown that the intravenous administration of calcium is effective in reversing the myocardial depressant effects of verapamil. We report the case of a patient with SVT and a systolic blood pressure of 80 mm Hg in which the administration of calcium chloride prior to that of verapamil may have negated verapamilinduced hypotension. PMID 3416743