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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 a