Estrogen replacement may be an alternative to parathyroid surgery for the treatment of osteoporosis in elderly postmenopausal women presenting with primary hyperparathyroidism: a preliminary report.

Diamond T, Ng AT, Levy S, Magarey C, Smart R. Department of Endocrinology, St. George Hospital, Sydney, Australia.

Osteoporos Int 1996;6(4):329-33

Parathyroid surgery is indicated in patients presenting with primary hyperparathyroidism (PHPT) and osteoporosis (defined as bone mineral density more than 2 standard deviations below normal). Many are elderly women with complex medical problems, either unwilling or considered unfit for surgery. Estrogen replacement therapy (ERT) may potentially be an alternative form of therapy in this group. We studied 15 consecutive postmenopausal women presenting with PHPT and osteoporosis. Group 1 comprised 5 women who elected to be treated with ERT (conjugated equine estrogen, 0.3-0.625 mg/day). The other 10 women underwent successful parathyroidectomy. These 10 patients were randomly subdivided into group 2 (5 patients who received calcitriol 0.25 micrograms b.i.d. for 12 months following surgery) and group 3 (5 patients who received elemental calcium 1 g/day for 12 months following surgery). Lumbar spine and femoral neck bone mineral density (BMD) were measured prior to and after 12 months of therapy, using a dual-energy X-ray absorptiometer (Lunar DPX-L). The three groups did not differ with respect to their ages (group mean 71.8 years), or baseline serum calcium (group mean 2.77 mmol/l), serum parathyroid hormone (group mean 11.0 pmol/l), lumbar spine BMD (group mean 0.93 g/cm2) and femoral neck BMD (group mean 0.73 g/cm2). Serum calcium normalized in all patients who underwent surgery and none developed hypoparathyroidism. A non-significant decrease in serum calcium was seen in patients treated with ERT only. Lumbar spine (+5.3% per year; 95% CI, 1.1% to 9.6%) and femoral neck BMD (+5.5% per year; 95% CI, -2.1% to 13.2%) increased significantly after 12 months of ERT (< 0.001 compared with pre-therapy values). These increases in BMD did not differ significantly from those in patients who underwent successful parathyroidectomy followed by either calcitriol therapy or calcium replacement (lumbar spine BMD increase of +6.2% per year, 95% CI 3.1% to 9.4%; and femoral neck BMD increase of +3% per year, 95% CI 0 to 6%). In summary, increases in lumbar spine and femoral neck BMD occur following treatment of PHPT. ERT appeared as effective as parathyroidectomy (combined with either calcitriol or calcium supplements) for the treatment of osteoporosis in elderly postmenopausal women presenting with PHPT.

Review of Medical Physiology 1995.

Ganong, W.F.

Norwalk, CT: Appleton & Lange.

Effect of hormone replacement therapy on bone mineral density in postmenopausal women with mild primary hyperparathyroidism. A randomized, controlled trial.

Grey AB, Stapleton JP, Evans MC, Tatnell MA, Reid IR. University of Auckland, New Zealand.

Ann Intern Med 1996 Sep 1;125(5):360-8

BACKGROUND: Most patients with primary hyperparathyroidism are postmenopausal women. The presence of osteopenia in persons with mild primary hyperparathyroidism is considered an indication for parathyroidectomy. No prospective, controlled trials have assessed medical therapies for osteopenia in primary hyperparathyroidism.

OBJECTIVE: To examine the effects of estrogen-progestin therapy (hormone replacement therapy) on bone mineral density and biochemical indices in postmenopausal women with mild primary hyperparathyroidism.

DESIGN: Double-blind, randomized, placebo-controlled trial.

SETTING: University teaching hospital.

PATIENTS: 42 postmenopausal women with mild primary hyperparathyroidism.

INTERVENTION: Patients were randomly assigned to receive either conjugated estrogens, 0.625 mg/d, and medroxyprogesterone, 5 mg/d, or placebo.

MEASUREMENTS: Bone mineral densities of the total body, lumbar spine, proximal femur (femoral neck, Ward triangle, trochanter), and proximal forearm were measured every 6 months using dual-energy x-ray absorptiometry. Biochemical indices of bone turnover and calcium metabolism were measured at baseline, 6 months, and 2 years.

RESULTS: In the placebo group, bone mineral densities of the total body and the proximal forearm decreased significantly from baseline (mean +/- SE, -2.3% +/- 0.7% [p = 0.005] and -3.5% +/- 1.2% [p = 0.01], respectively). At the other sites, bone mineral density also tended to decline. In the hormone replacement therapy group, bone mineral density increased from baseline in the total body (1.3% +/- 0.4%; P = 0.004), lumbar spine (5.2% +/- 1.4%; p = 0.002), and femoral neck (3.4% +/- 1.5%; p = 0.05). The between-group differences in bone mineral density at the end of the study ranged from 3.6% to 6.6% and were significant at all sites (< 0.001 and < 0.05) except for the Ward triangle (p = 0.06). In the hormone replacement therapy group, serum alkaline phosphatase levels decreased by 22% (p = 0.0004 compared with baseline), urinary hydroxyproline excretion decreased by 42% (p = 0.0004), urinary N-telopeptide excretion decreased by 54% (p = 0.001), and urinary calcium excretion decreased by 45% (p = 0.007). Hormone replacement therapy did not change levels of serum ionized calcium or intact parathyroid hormone.

CONCLUSIONS: Although hormone replacement therapy has little effect on serum calcium levels, it suppresses bone turnover, reduces urinary calcium excretion, and increase bone mineral density throughout the skeleton in postmenopausal women with mild primary hyperparathyroidism. This therapy is thus an important management option for these patients.

Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women.

Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW Jr. Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, USA. spotter@protein.com

Am J Clin Nutr 1998 Dec;68(6 Suppl):1375S-1379S

The effects of soy protein (40 g/d) containing moderate and higher concentrations of isoflavones on blood lipid profiles, mononuclear cell LDL receptor messenger RNA, and bone mineral density and content were investigated in 66 free-living, hypercholesterolemic, postmenopausal women during a 6-mo, parallel-group, double-blind trial with 3 interventions. After a control period of 14 d, during which subjects followed a National Cholesterol Education Program Step I low-fat, low-cholesterol diet, all subjects were randomly assigned to 1 of 3 dietary groups: Step I diet with 40 g protein/d obtained from casein and nonfat dry milk (CNFDM), Step I diet with 40 g protein/d from isolated soy protein containing 1.39 mg isoflavones/g protein (ISP56), or Step I diet with 40 g protein/d from isolated soy protein containing 2.25 mg isoflavones/g protein (ISP90). Total and regional bone mineral content and density were assessed. Non-HDL cholesterol for both ISP56 and ISP90 groups was reduced compared with the CNFDM group (< 0.05). HDL cholesterol increased in both ISP56 and ISP90 groups (< 0.05). Mononuclear cell LDL receptor mRNA was increased in subjects consuming ISP56 or ISP90 compared with those consuming CNFDM (< 0.05). Significant increases occurred in both bone mineral content and density in the lumbar spine but not elsewhere for the ISP90 group compared with the control group (< 0.05). Intake of soy protein at both isoflavone concentrations for 6 mo may decrease the risk factors associated with cardiovascular disease in postmenopausal women. However, only the higher isoflavone-containing product protected against spinal bone loss.

Exposure of infants to phyto-oestrogens from soy-based infant formula.

Setchell KD, Zimmer-Nechemias L, Cai J, Heubi JE. Clinical Mass Spectrometry Center, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.

Lancet 1997 Jul 5;350(9070):23-7

BACKGROUND: The isoflavones genistein, daidzein, and their glycosides, found in high concentrations in soybeans and soy-protein foods, may have beneficial effects in the prevention or treatment of many hormone-dependent diseases. Because these bioactive phyto-oestrogens possess a wide range of hormonal and non-hormonal activities, it has been suggested that adverse effects may occur in infants fed soy-based formulas.

METHODS: To evaluate the extent of infant exposure to phyto-oestrogens from soy formula, the isoflavone composition of 25 randomly selected samples from five major brands of commercially available soy-based infant formulas were analysed, and the plasma concentrations of genistein and daidzein, and the intestinally derived metabolite, equol, were compared in 4-month-old infants fed exclusively soy-based infant formula (n = 7), cow-milk formula (n = 7), or human breast-milk (n = 7).

FINDINGS: All of the soy formulas contained mainly glycosides of genistein and daidzein, and the total isoflavone content was similar among the five formulas analysed and was related to the proportion of soy isolate used in their manufacture. From the concentrations of isoflavones in these formulas (means 32-47 micrograms/mL), the typical daily volume of milk consumed, and average bodyweight, a 4-month-old infant fed soy formula would be exposed to 28-47 per day, or about 4.5-8.0 mg/kg bodyweight per day, of total isoflavones. Mean (SD) plasma concentrations of genistein and daidzein in the seven infants fed soy-based formulas were 684 (443) ng/mL and 295 (60) ng/mL, respectively, which was significantly greater (< 0.05) than in the infants fed either cow-milk formulas (3.2 [0.7] and 2.1 [0.3] ng/mL), or human breast-milk (2.8 [0.7] and 1.4 [0.1] ng/mL), and an order of magnitude higher per bodyweight than typical plasma concentrations of adults consuming soy foods.

INTERPRETATION: The daily exposure of infants to isoflavones in soy infant-formulas is 6-11 fold higher on a bodyweight basis than the dose that has hormonal effects in adults consuming soy foods. Circulating concentrations of isoflavones in the seven infants fed soy-based formula were 13000-22000 times higher than plasma oestradiol concentrations in early life, and may be sufficient to exert biological effects, whereas the contribution of isoflavones from breast-milk and cow-milk is negligible.

Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety.

Vieth R. Department of Laboratory Medicine and Pathobiology, University of Toronto, Mount Sinai Hospital, Ontario, Canada. rvieth@mtsinai.on.ca

Am J Clin Nutr 1999 May;69(5):842-56

For adults, the 5-microg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20-50 microg (800-2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations < 140 nmol/L, which require a total vitamin D supply of 250 microg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of < or = 1000 microg (40000 IU)/d. Because vitamin D is potentially toxic, intake of < 25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2000 IU)/d is too low by at least 5-fold.

Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism.

Zimmermann E, Wassmer S, Steudle V.

Miner Electrolyte Metab 1996;22(1-3):196-9

Calcium-alpha-ketoglutarate (Ca-ket) is known as a highly effective phosphate (P) binder in hemodialysis (HD) patients. In addition, alpha-ketoglutarate has been shown to improve metabolic alterations. We investigated the effect of long-term P-binding therapy with Ca-ket to determine whether P accumulation is the main reason of secondary hyperparathyroidism (HPT) in HD patients or not. Ca-ket was prescribed to 14 HD patients as a soluble preparation in a mean dosage of 4.5 g/day (0.975 g elemental Ca) for a period of 36 months. Serum P continuously dropped from prestudy 2.6 +/- 0.1 (mean +/- SEM) to 1.9 +/- 0.07 mmol/l (< 0.001), whereas serum Ca increased from 2.2 +/- 0.1 to 2.47 +/- 0.08 mmol/l (< 0.05). Thus, Ca/P ratio in serum converted significantly from 0.91 +/- 0.02 (prestudy) to 1.28 +/- 0.01 (< 0.001). Intact parathyroid hormone (iPTH) continuously normalized in all patients from 29 +/- 5 to 8 +/- 2 pmol/l (< 0.001). The present data show that long-term treatment with Ca-ket normalizes secondary HPT by simultaneously P binding and correcting Ca/P ratio in serum without vitamin D treatment.

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Vitamin D3 and calcium to prevent hip fractures in the elderly women.

Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ Institut National de la Sante et de la Recherche Medicale (INSERM), Unite 234, Hopital Edouard Herriot, Lyon, France.N Engl J Med 1992 Dec 3;327(23):1637-42

BACKGROUND. Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known.

METHODS. We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women.

RESULTS. Among the women who completed the 18-month study, the number of hip fractures was 43% lower (P = 0.043) and the total number of nonvertebral fractures was 32% lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44% from the base-line value at 18 months (< 0.001) and the serum 25(OH)D concentration had increased by 162% over the base-line value (< 0.001). The bone density of the proximal femur increased 2.7% in the vitamin D3-calcium group and decreased 4.6% in the placebo group (< 0.001).

CONCLUSIONS. Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

Hyperparathyroidism.

Rude RK Division of Endocrinology/Diabetes/Hypertension, University of Southern California, Los Angeles, USA.Otolaryngol Clin North Am 1996 Aug;29(4):663-79

Primary hyperparathyroidism is the most prevalent cause of hypercalcemia. Although renal stone disease and osteitis fibrosis were prominent complications of this disorder in the past, the advent of biochemical screening has resulted in earlier detection. This has changed the clinical presentation of primary hyperparathyroidism, so that as many as 80% of patients do not have any sign or symptom that can be attributed solely to the disease. Improvement in assays for PTH has allowed for accurate bio-chemical diagnosis in over 90% of cases. Neck exploration is the treatment of choice for any patient who presents with signs, symptoms, or complications of hypercalcemia or hyperparathyroidism. Medical therapy is indicated in patients who either cannot undergo surgery because of medical contraindication, failed prior neck surgery, unresectable parathyroid carcinoma or simply refuse surgery. Medical therapy is not optimal, although sex steroid replacement therapy in the postmenopausal woman has met with some success. Calcitonin, phosphate, and bisphosphonates may be used, but their long-term efficacy is not clear. Recent studies have suggested that a large proportion of patients with asymptomatic primary hyperparathyroidism do not demonstrate progression of disease in terms of renal dysfunction, bone disease, or biochemical changes in calcium or PTH. Guidelines have been established for medical follow-up of such patients. If any such patient develops signs or symptoms during medical follow-up, surgery is then indicated.

Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly.

Chel VG; Ooms ME; Popp-Snijders C; Pavel S; Schothorst AA; Meulemans CC; Lips P Psychogeriatric Center Marienhaven, Warmond, The Netherlands.

J Bone Miner Res (United States) Aug 1998, 13 (8) p1238-42

The objective of this study was to compare the effect of ultraviolet radiation (UV) and oral vitamin D3 on the vitamin D status and parathyroid hormone (PTH) concentration in elderly nursing home patients. The design of the study was a randomized clinical trial. The setting was a psychogeriatric nursing home. Subjects included 45 female psychogeriatric patients with a mean age of 85 years. Exclusion criteria were going outdoors more than once a week and the presence of actinic or cancer skin lesions. Intervention was random allocation of UV-B irradiation at half the minimal erythemal dose of the lower back, three times per week during 12 weeks (UV-B), or oral vitamin D3 400 IU/day during 12 weeks (VIT-D), or no treatment (CONTR). Main outcome measures were change in fasting serum levels of vitamin D metabolites at 0, 2, 4, 8, and 12 weeks in the treatment groups, compared with the control group. PTH(1-84) was measured at 0 and 12 weeks. Baseline serum 25-hydroxyvitamin D (25(OH)D) was lower than 30 nmol/l in 95% of the participants. It increased to a median value of around 60 nmol/l after 12 weeks both in the UV-B and VIT-D groups, whereas there was no change in the CONTR group. Serum 1,25-dihydroxyvitamin D increased significantly in the UV-B group. Serum calcium increased significantly in both treatment groups. Serum PTH decreased more than 30% in both treatment groups (< 0.001), whereas there was no significant change in the control group. Irradiation with UV-B in the very elderly for a few minutes per day leads to adequate improvement of the vitamin D status. It is as effective as oral vitamin D3 in increasing serum 25(OH)D and suppressing secondary hyperparathyroidism .

Clinical profile of primary hyperparathyroidism in adolescents and young adults.

Loh KC; Duh QY; Shoback D; Gee L; Siperstein A; Clark OH Department of Medicine, University of California at San Francisco, USA.

Clin Endocrinol (Oxf) (England) Apr 1998, 48 (4) p435-43

OBJECTIVE: Primary hyperparathyroidism (PHPT) is an uncommonly diagnosed condition among adolescents and young adults. We review the clinical characteristics of these patients based on our institutional experience.

SUBJECTS: Patients aged 12-28 years treated for PHPT at our institution from 1990 to 1996 were evaluated by a review of medical records and current follow-up data. This consisted of 22 patients (8M:14F), constituting approximately 3% of all patients operated for PHPT during this period.

MEASUREMENTS: Serum and urinary calcium concentrations, renal function, and serum intact parathyroid hormone (IPTH) levels were measured in all patients. After biochemical confirmation of diagnosis, the patients completed a questionnaire to evaluate the presence of symptoms and/or conditions associated with PHPT. All the patients underwent parathyroidectomy and their tumour characteristics were evaluated. Surgical outcome was determined by measurements of serum calcium and IPTH levels postoperatively and during long-term follow-up.

RESULTS: A third of the patients were diagnosed by routine serum chemistry whereas two-thirds presented with symptoms or conditions associated with hypercalcaemia. Non-specific complaints such as fatigue or exhaustion, and weakness or lethargy constitute the most common findings on questionnaire review. A family history of PHPT was present in only 2 patients. The preoperative peak serum calcium levels ranged from 2.67 to 4.19 mmol/l (norm: 2.10-2.54 mmol/l), with a median of 3.07 mmol/l. Surgical pathologies revealed 59% solitary adenoma, 27% hyperplasia, 9% multiple adenomas and 5% carcinoma. Comparison between the adolescents (aged 12-18 years) and young adults (aged 19-28 years) revealed no differences in the clinical, pathological or laboratory profiles, except for a male predominance in adolescent patients. Fifteen patients had resection of one or more adenomas while 7 underwent subtotal parathyroidectomy. Six patients (27%) were reoperated cases, all received primary treatment elsewhere. All patients with benign PHPT were cured surgically, with a median follow-up of 47 months (range 3-77 months). One reoperated patient developed permanent hypocalcaemia. One patient with carcinoma underwent several operations for recurrence; he is now eucalcaemic despite persistent disease at 80 months from diagnosis.

CONCLUSIONS: We found a high incidence of multiglandular disease and relatively non-specific symptomatology in our adolescent and young adult patients with primary hyperparathyroidism . In view of the heterogeneous clinical expression noted in young patients, one should consider primary hyperparathyroidism in the differential diagnosis of unexplained non-specific complaints, and perform serum calcium estimations more readily in these subjects. Our experience suggests that primary hyperparathyroidism can be a serious disease with significant morbidity if left untreated, whereas parathyroidectomy provides successful results.

Different effects of PTH on erythrocyte calcium influx

Vezzoli G.; Reina M.C.; Cusi D.; Soldati L.; Zerbi S.; Spaventa R.; Baragetti I.; Bianchi G. P.L. Bedani, Divisione di Nefrologia, Azienda Ospedale S. Anna, Corso Giovecca 203, 44100 Ferrara Italy

Italian Journal of Mineral and Electrolyte Metabolism (Italy), 1996, 10/3-4 (149-152)

Since Caions mediate cellular response to parathyroid hormone (PTH), the effect of PTH on cell membrane Ca influx was studied by measuring erythrocyte passive Sr influx. Two different experiments have been performed:

1) Sr influx was determined in erythrocytes from 10 patients with primary hyperparathyroidism and 14 controls either in the absence and in the presence of nitrendipine, a dihydropiridine (DHP) Ca channel blocker; the results were compared in the two patient groups;

2) Sr influx was measured in erythrocytes from 4 normal subjects after incubation with and without PTH and the results in the presence of the hormone were compared with those in its absence. In the first experiment erythrocyte Sr influx was lower in patients with primary hyperparathyroidism when measured without nitrendipine (total Sr influx), but did not differ with controls when measured in presence of the inhibitor (DHP- independent Sr influx), Erythrocyte Sr uptake inhibited by nitrendipine (DHP- dependent Sr influx) was calculated by the difference between total and DHP- independent Sr influx values and was decreased in hyperparathyroid patients. In the second experiment Sr influx was increased after incubation of erythrocytes with PTH. We hypothesize that in primary hyperparathyroidism the high plasma levels of PTH may induce a downregulation of the erythrocyte Ca influx, mediated by the increase in cellular Ca content. These events may sustain the desensitization to physiological effects of PTH that has been reported in patients with primary hyperparathyroidism and after prolonged PTH infusion.

Hypercalcemia due to constitutive activity of the parathyroid hormone (PTH)/PTH-related peptide receptor: Comparison with primary hyperparathyroidism

Parfitt A.M.; Schipani E.; Rao D.S.; Kupin W.; Han Z.-H.; Juppner H. UAMSH, 4301 West Markham Street, Little Rock, AR 72205-7199 USA

Journal of Clinical Endocrinology and Metabolism (USA), 1996, 81/10 (3584-3588)

In Jansen's disease (JD), the hypercalcemia found in about half the cases is the result of a mutant, constitutively overactive, form of the PTH/PTHrP receptor, which in these cases also causes the skeletal dysplasia. The subject of the present report was first seen in 1956 and is still under treatment at the same medical center. We report the clinical course and a detailed study of calcium and bone metabolism carried out in 1976 and compare the results with those of six typical patients with mild primary hyperparathyroidism in whom exactly the same studies were carried out. In the patient with JD, the hypercalcemia was of early onset; chronic and nonprogressive; refractory to the administration of phosphate, glucocorticoid, and calcitonin; and accompanied by suppressed PTH levels as determined by two different immunoassays, an undetectable PTHrP level, increased excretion of nephrogenous cAMP (an in vivo bioassay of endogenous PTH production), decreased tubular reabsorption of phosphate, increased tubular reabsorption of calcium, increased biochemical indexes of bone turnover, and increased histological indexes of bone turnover on iliac bone histomorphometry after double tetracycline labeling. There was exaggerated loss of cortical bone and preservation of cancellous bone. All the results in JD relating to renal or skeletal effects of PTH excess were within or close to the ranges found in the hyperparathyroid patients, except that tubular reabsorption of phosphate was more depressed. Because PTH secretion was suppressed, any effects mediated by putative alternative receptors would have been diminished. We conclude that 1) the hypercalcemia due to constitutive overactivity of the PTH/PTHrP receptor is indistinguishable from that of mild primary hyperparathyroidism in clinical characteristics and renal tubular and skeletal features; and 2) the classic laboratory manifestations of primary hyperparathyroidism, with the possible exception of osteitis fibrosa cystica, can all be accounted for by overactivity of a single receptor.

Osteoclast cytomorphometry in patients with femoral neck fracture

Chappard D.; Basle M.F.; Audran M.; Benhamou C.L.; Rebel A. LHEA-Lab. d'Histologie-Embryologie, Faculte de Medecine, 49045 Angers Cedex France

Pathology Research and Practice (Germany), 1996, 192/6 (573-578)

In patients with femoral neck fracture, nutritional deficiencies have been shown to be common. A low calcium diet and/or a reduced vitamin D intake have been suspected to cause secondary hyperparathyroidism responsible for increased bone turn over and bone loss. Parathyroid hormone (PTH) levels are increased in these patients, data which are in accordance with the pronounced changes observed on bone biopsies reflecting a true hyperparathyroidism. We have used a cytomorphometrical approach to characterize PTH-induced changes on the osteoclastic population. Osteoclasts were detected histochemically (by tartrate resistant acid phosphatase staining) on bone biopsies from 10 control subjects, 8 patients with primary hyperparathyroidism and 10 patients with a femoral neck fracture of osteoporotic origin. The maximum Feret's diameter of each osteoclast (Oc.Le) was determined with a semiautomatic image analyzer. In all groups, the frequency distribution of Oc.Le appeared positively skewed. In both hip fractured patients and primary hyperparathyroid patients, the mode of the distribution was higher (25-30 microm) than in controls (20-25 microm). When graphically converted on a probability graph, the osteoclastic populations appeared homogeneous and well described by a lognormal distribution in the three groups. However osteoclasts appeared similarly enlarged in the groups of patients with primary hyperparathyroidism and with femoral neck fracture. PTH has been shown to increase both the recruitment of mononucleated precursors and their fusion into larger osteoclasts than controls. In the present study, a cytomorphometric method appeared able to identify the border line hyperparathyroidism in the hip fractured patients.

Combined therapy with salmon calcitonin and high doses of active vitamin D3 metabolites in uremic hyperparathyroidism

Matuszkiewicz-Rowinska J.; Niemczyk S.; Puka J.; Sawicki A.; Switalski M. ; Talalaj M.; Pacocha E.; Marusza W.; Ostrowski K. Klinika Chorob Wewnetrznych, Akademia Medyczna, ul. Banacha 1a, Warszawa Poland

Polskie Archiwum Medycyny Wewnetrznej (Poland), 1996, 96/1 (23-31)

Active vitamin D3 pulse therapy effectively suppress parathormon (PTH) synthesis in uremic hyperparathyroidism but high serum levels of calcitriol achieved can induce direct osteoclastic resorption and block bone formation. Therefore we found it interesting to examine whether an addition of the osteoclast inhibitor, calcitonin (CT), could reduce those unwanted effects. 75 hemodialysis patients with at least 5-fold 1-84 PTH serum level elevation were divided into 4 treatment groups; I (n = 19) - CT and 1alpha-OH-D3; II (n = 20) - CT; III (n = 19) - 1alpha-OH-D3 (n = 10) or 1,25(OH)2D3 (n = 9) alone; IV (n = 17) - none of these drugs. CT (200 IU) and 1alpha-OH-D3/1,25(OH2D3 (up to 5 microg) were given 3 times a week. Dialysate Ca was 1.40-1.45 (Group I, III) or 1.95-2.00 mmol/l (Group II, IV). Within 8 months serum 1-84 PTH fell by 75% (< 0.001) in Group I and by 77% (< 0.001) in Group II, serum Ca increased by 0.22 plus or minus 0.05 mmol/l in Group I (< 0.005) and by 0.25 plus or minus 0.05 mmol/l in Group III (< 0.005), alkaline phosphatase activity decreased by 35% in Group I (< 0.01) and 31% in Group III (< 0.005) whereas in Groups II and IV no significant changes were noted. In Group III no differences between patients taking 1alpha-OH-D3 or 1,25(OH)2D3 were observed. The significant reduction of serum hydroxyproline (37%, < 0.001) was seen only in Group I. The increase in bone mineral density (BMD) measured by dual-energy X-ray absorptiometry was greater in Group I than in Group III (< 0.05). In Group II the effect was mostly insignificant, whereas in Group IV a substantial decrease (< 0.001) in BMD was observed. These data suggest that combined therapy with CT and oral 1alpha-OH-D3 pulses is more effective than pulses alone in inhibiting bone resorption and in increasing BMD in hemodialysis patients with uremic hyperparathyroid bone disease.

The PTH-calcium relationship curve in secondary hyperparathyroidism, an index of sensitivity and suppressibility of parathyroid glands

Caligara F.; Giangrande A.; Allaria P.; Castiglioni A. USL 3, Provincial General Hospital, Nephrology and Dialysis Department, Piazza Solaro 3, 21052 Busto Arsizio Italy

Nephrology Dialysis Transplantation (United Kingdom), 1996, 11/Suppl. 3 (136-141)

A sigmoidal relationship, fitting a four-parameter model, has been demonstrated in in who and in vitro studies to link the parathyroid hormone (PTH) secretion rate and calcium concentration changes. In uraemic patients different patterns of calcium-mediated PTH secretion were reported in different types of renal bone diseases and a shift to the right and a steeper slope has been observed in secondary hyperparathyroidism. To gain more information that could predict indexes for successful medical therapy we investigated the calcium-PTH sigmoidal relationship in 42 hyperparathyroid patients with different degrees of secondary hyperparathyroidism; we classified as moderate those patients presenting basal PTH (PTH(bas)) < 600 pg/ml and bone alkaline phosphatase (AP) < 500 U/l, and severe those with a PTH(bas) less than or equal to 600 pg/ml and bone AP less than or equal to 500 U/l. Changes in ionized calcium (iCa) were induced by calcium-free dialysis on the first day, to induce hypocalcaemia up to serum iCa 3.5 mEq/l, and calcium 8 mEq/l dialysis on the third day, to induce hypercalcaemia. The moderate hyperparathyroidism patients had PTH(max), PTH(min) and slope, calculated in absolute values and relative values, lower than severe hyperparathyroidism patients but they did not differ in the minimal to maximal PTH ratio. In the moderate group the PTH(bas) correlated with all the curve parameters except PTH(min), calculated both in absolute and percentage values, while in the severe group PTH(min) was the only parameter correlating to the PTH(bas). In conclusion, by performing the dynamic test, we found that some glands were not suppressible among moderate hyperparathyroidism patients.

Severe acute pancreatitis as a first symptom of primary hyperparathyroid adenoma: A case report

Shimizu H.; Kodama A. Division of Developmental Genetics, Centre for Biochemical Science, Chiba University School of Medicine, Inohana 1-8-1, Chuo-Ku, Chiba 260 Japan

Journal of Laryngology and Otology (United Kingdom), 1996, 110/6 (602-603)

We present a case of severe acute pancreatitis in a 14-year-old boy that may have been caused by hyperparathyroidism. The clue to finding the parathyroid adenoma was the hypercalcaemia. Although the patient did have acute pancreatitis, no therapy had been effective until the discovery of the parathyroid adenoma. After the excision of the parathyroid adenoma, the function of the pancreas and serum calcium returned to normal. This result suggests a certain cause and effect relationship between hyperparathyroidism and acute pancreatitis.

24,25 dihydroxyvitamin D supplementation corrects hyperparathyroidism and improves skeletal abnormalities in X-linked hypophosphatemic rickets - A clinical research center study

Carpenter T.O.; Keller M.; Schwartz D.; Mitnick M.; Smith C.; Ellison A.; Carey D.; Comite F.; Horst R.; Travers R.; Glorieux F.H.; Gundberg C.M.; Poole A.R.; Insogna K.L. Department of Pediatrics, Yale University School of Medicine, P.O. Box 208064, New Haven, CT 06520-8064 USA

Journal of Clinical Endocrinology and Metabolism (USA), 1996, 81/6 (2381-2388)

Therapy for X-linked hypophosphatemia (XLH) only partially corrects skeletal lesions and is often complicated by hyperparathyroidism. 24,25(OH)2 D3 improves skeletal lesions in a murine model of XLH and suppresses PTH secretion in animals. Therefore, we undertook a placebo-controlled trial of 24,25(OH)2 D3 supplementation to standard treatment in patients with XLH to improve bone disease and reduce hyperparathyroid complications. Fifteen subjects with XLH receiving standard treatment (1,25(OH)2 D3 or dihydrotachysterol plus phosphate) were evaluated, supplemented with placebo, and reevaluated one yr later. 24,25(OH)2 D3 supplementation was then begun and studies repeated after another year. Each patient underwent a detailed evaluation of calcium homeostasis over a 24-h period. Rachitic abnormalities were assessed radiographically in children. Adults underwent bone biopsies. 24,25(OH)2 D3 normalized PTH values in nine subjects (peak PTH was 46.5 plus or minus 6.6 pmol/L at entry, 42.3 plus or minus 5.9 pmol/L after placebo, and 23.3 plus or minus 5.4 pmol/L after 24,25(OH)2 D3). Nephrogenous cAMP decreased at night, coincident with the decrease in PTH, and serum phosphorus was slightly greater with 24,25(OH)2 D3. Radiographic features of rickets improved during 24,25(OH)2 D3 supplementation in children, and osteoid surface decreased in adults. 24,25(OH)2 D3 is a useful adjunct to standard therapy in XLH by effecting correction of hyperparathyroidism and improvement of rickets and osteomalacia.

1-alpha-hydroxyvitamin D3 treatment decreases bone turnover and modulates calcium-regulating hormones in early postmenopausal women

Chen J.-T.; Shiraki M.; Hasumi K.; Tanaka N.; Katase K.; Kato T.; Hirai Y.; Nakamura T.; Ogata E. Dr. J.-T. Chen, Department of Gynecology, Cancer Institute Hospital, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo 170 Japan

Bone (USA), 1997, 20/6 (557-562)

50 Japanese women within 10 years after menopause (mean age 52.5 years) were studied to determine the effects of 0.75 microg of 1-alpha-hydroxyvitamin D3 (1-alpha-(OH)D3) with calcium (150 mg/day) (treated group: N = 25) and calcium only (control group: N = 25) for 12 months on bone mass and metabolism. Their L2-4 BMD measurements were 1.5 SD below the mean value of Japanese young, normal women, L2-4 BMDs increased significantly in the treated group (+2.1%; < 0.01), but decreased significantly in controls (-2.l%; < 0.01). Although serum calcium and creatinine remained unchanged in both groups, phosphorus levels increased significantly in the treated group (< 0.01). Urinary calcium/creatinine (Cr) increased in both groups. Urinary pyridinoline/Cr and deoxypyridinoline/Cr decreased significantly in the treated group (< 0.05), but not in the control group. Serum osteocalcin levels remained unchanged in both groups, Intact parathyroid hormone levels decreased significantly (< 0.05) and calcitonin levels significantly increased in the treated group (< 0.05), but these changes were not observed in the control group. These data clearly demonstrate that 0.75 microg of 1-alpha-(OH)D3 maintained bone mass by reducing bone resorption by modulation of calcium-regulating hormones. Temporarily increased urinary calcium excretion was observed in control group, but did not appear to be effective in modulating bone turnover.

Role of parathyroid hormone-related peptide (PTHrP) in hypercalcemia of malignancy and the development of osteolytic metastases

De Vernejoul M.-C. M.-C. De Vernejoul, INSERM U349, Clinique de Rhumatologie, Hopital Lariboisiere, 6 Rue Guy Patin, 75475 Paris Cedex 10 France

Journal of Clinical Rheumatology (USA), 1997, 3/2 Suppl. (S109-S113)

Hypercalcemia of malignancy carries an extremely grim prognosis. The most common mechanism underlying hypercalcemia of malignancy is production by the tumor cells of cytokines responsible for osteoclastic differentiation and, therefore, lysis of the bone adjacent to the tumor. A minority of cases are attributable to increased renal reabsorption of calcium caused by a humoral factor, termed parathyroid hormone-related peptide, which is produced by some primary tumors. These two mechanisms can be involved in conjunction, particularly in patients with breast cancer. The development of osteolytic metastases initiates a vicious cycle in which bone degradation products, especially growth factors, stimulate the growth of the tumor cells located at the bone-tumor interface. Parathyroid hormone-related peptide is produced by many malignant tumors, most notably those of the breast. In addition to its endocrine effect on the kidney, it may have a paracrine effect consisting of enhancement of osteoclastic differentiation with osteolysis of the bone adjacent to the tumor. Other factors produced by primary tumor cells, such as proteases, intercellular adhesion molecules, or bone matrix proteins, may influence the propensity for the tumor to produce bone metastases. Bisphosphonates are usually effective in inducing a remission of hypercalcemia of malignancy and in improving the clinical manifestations of osteolytic metastases. Elucidation of the factors that influence the propensity for malignancies to metastasize to bone would improve our ability to use bisphosphonates optimally as adjuncts to tumor therapy.

Experimental study of glucocorticoid-induced rabbit osteoporosis

Chen N.; Tian L.-Y.; Liu Z.-X.; Zhang B.-H.; Zhang S.-T. N. Chen, Department of Pediatrics, First Affiliated Hospital, Hubei Medical University, Wuhan 430060 China

Chinese Pharmacological Bulletin (China), 1996, 12/6 (540-542)

To study the effect of variant administration and cumulative dose of glucocorticoid on the skeleton, thirty male rabbits were divided into 5 groups, serum calcium, phosphorus, alkaline phosphatase and N-terminal fragment of parathyroid hormone (PTH) and bone mineral content (BMC) were determined, The results showed no significant differences were observed between supplement calcium group and control group at the level of BMC and PTH (< 0.05), but there were significantly decreased BMC and elevated PTH in other groups (< 0.01), especially in the high-dose group. The results indicated that glucocorticoid-induced osteoporosis is associated with the steroid dose, and the pathogenesis is concerned with the development of secondary hyperparathyroidism. Alternate-day therapy can't prevent bone loss. Supplementation of calcium and vitamin D is an effective method for the prevention and treatment.

Medical parathyroidectomy - The value of vitamin D

Traindl O.; Reading S. Division of Nephrology, Department of Internal Medicine III, University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna Austria

Acta Chirurgica Austriaca (Austria), 1996, 28/Suppl. 124 (8-10)

Background: The lack of active vitamin D(1,25(OH)2D3, calcitriol) in uremic patients causes a decrease in intestinal resorption. The resulting chronic hypocalcemia (plus the uremic hyperphosphatemia) stimulates increased parathyroid hormone (PTH) release and is accompained by a hyperplasia of the parathyroid glands.

Methods: Reviewing the recent literature we intended to answer the following questions: (a) Is there any optimal time point to initiate vitamin D therapy? (b) Is intravenous application more effective than the oral route? (c) Is vitamin D therapy effective and safe? (d) Does vitamin D decrease PTH secretion in patients with manifest secondary hyperparathyroidism (SHPT)?

Results: Vitamin D therapy should be initiated in uremic patients in the pre-dialysis period to prevent SHPT. Severe hypercalciemia must be considered as possible side effect. Given orally or intravenously calcitriol has been shown to normalize intestinal calcium resorption, by increasing serum calcium levels and an additional suppressive effect upon the parathyroid glands calcitriol has been shown to decreas PTH-production in SHPT.

Conclusions: In uremic patients vitamin D therapy may prevent the development of SHPT in the predialysis period. In patients SHPT it has the potential to reduce PTH secretion. Severe hypercalcemia has been reported as possible side effect.

Oral vitamin D or calcium carbonate in the prevention of renal bone disease?

Argiles A.; Mourad G.; Mion C. UDSA-AIDER, 746 Rue Croix de Lavit, 34192 Montpellier Cedex 5 France

Curr Opin Nephrol Hypertens 1996 Jul;5(4):329-36

It is well known that hyperparathyroidism begins early in renal failure and progresses, probably not linearly, throughout the natural course of renal diseases and dialysis therapy. Recent progress in basic medical science has improved our understanding of the mechanisms by which the classically known stimuli for parathyroid hormone synthesis and secretion may act, including hypocalcaemia, hyperphosphataemia and vitamin D3 metabolism disturbances. In the treatment of hyperparathyroidism, although some authors stress the benefit of treating one of these stimuli, it is probably more effective to combine the treatment of them all. There is conclusive recent work showing the efficacy of using both CaCO3 and vitamin D3, either in chronic renal failure or in dialsis patients at every stage of hyperparathyroidism. Therefore, the treatment of hyperparathyroidism should start early, long before dialysis, and it should aim to correct any of the causal factors. Both CaCO3 and vitamin D3 derivatives may be used in the prevention and treatment of renal bone disease. The limits of this association are the increasingly often reported adynamic bone disease, which in our experience has not yet given major clinical problems, and hyperphosphataemia. Uncontrolled serum phosphate levels would counterbalance the beneficial effect of vitamin D3 derivatives on hyperparathyroidism.

A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures

Francis R.M.; Boyle I.T.; Moniz C.; Sutcliffe A.M.; Davis B.S.; Beastall G.H.; Cowan R.A.; Downes N. Musculoskeletal Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN United Kingdom

Osteoporosis International (United Kingdom), 1996, 6/4 (284-290)

Although vitamin D supplementation in the frail elderly improves calcium absorption, suppresses parathyroid hormone, decreases bone loss and reduces the risk of fractures, such treatment may be ineffective in patients with vertebral osteoporosis, because of impaired vitamin D metabolism or resistance to the action of vitamin D metabolites on the bowel. We have therefore performed a randomized, single masked study comparing the effects of alfacalcidol treatment (0.25 microg twice daily) and vitamin D2 supplementation (500-1000 units daily) on calcium absorption and bone turnover in 46 elderly women (median age 69 years, range 64-79 years) with radiological evidence of vertebral fractures. Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of treatment with vitamin D2 (< 0.001), but was unchanged in the group receiving alfacalcidol. Serum 1,25-dihydroxyvitamin D did not change significantly in either group over the study period. Fractional 45Ca absorption increased after 3 months of treatment with alfacalcidol (< 0.05), but was unchanged with vitamin D2. There was also a reduction in plasma intact parathyroid hormone and serum alkaline phosphatase after 6 months of treatment with alfacalcidol (< 0.05) which was not seen in the group receiving vitamin D2. Our study shows that vitamin D2 supplementation is ineffective in stimulating calcium absorption in elderly women with vertebral osteoporosis. By increasing calcium absorption in such patients, alfacalcidol may prove more effective than vitamin D in the management of vertebral osteoporosis.

Comparison of effects of calcitriol and calcium carbonate on secretion of interleukin-1beta and tumour necrosis factor-alpha by uraemic peripheral blood mononuclear cells

Tsukamoto Y.; Nagaba Y.; Izumida I.; Morishita T.; Saitoh M. Division of Nephrology, Department of Medicine, Kitasato Univ School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228 Japan

Nephrology Dialysis Transplantation (United Kingdom), 1996, 11/Suppl. 3 (15-21)

We studied 26 non-dialysed patients with chronic renal failure (creatinine clearance (CCr) 32.6 plus or minus 12.7 ml/min). They were divided into three groups according to their CCr and serum intact parathyroid hormone (PTH) and were given 0.5 microg/day oral calcitriol (calcitriol group, n = 8), 3 g/day calcium carbonate (CaCO3 group, n = 10), or neither (control uraemic group, n = 8). Serum intact PTH decreased from 154 plus or minus 75 to 90 plus or minus 43 pg/ml in the calcitriol group (< 0.01) and from 162 plus or minus 97 to 77 plus or minus 62 pg/ml in the CaCO3 group (< 0.001). Calcium carbonate was also effective in suppressing serum tartrate-resistant acid phosphatase, alkaline phosphatase and intact osteocalcin levels, while calcitriol did not suppress serum osteocalcin. Secretion of interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) by phytohaemagglutinin A (PHA)-activated peripheral blood mononuclear cells (PBMC) was greater in uraemic patients than in age-matched healthy controls (n = 8). Calcitriol was effective in suppressing secretion of both cytokines, while calcium carbonate was capable of suppressing only TNF-alpha secretion. CCr decreased from 37.4 plus or minus 15.4 to 33.0 plus or minus 11.8 ml/min (< 0.05) in the CaCO3 group, while it did not decrease in either the calcitriol group or the control uraemic group during a 6 month period. These results suggest that supplementation with calcitriol is necessary to maintain bone formation and normalize IL-1beta and TNF-alpha secretion by activated PBMC in uraemic patients.

24,25 dihydroxyvitamin D supplementation corrects Intradialytic calcium balances with different calcium dialysate levels. Effects on cardiovascular stability and parathyroid function

Carpenter T.O.; Keller M.; Schwartz D.; Mitnick M.; Smith C.; Ellison A.; Carey D.; Comite F.; Horst R.; Travers R.; Glorieux F.H.; Gundberg C.M.; Poole A.R.; Insogna K.L. Department of Pediatrics, Yale University School of Medicine, P.O. Box 208064, New Haven, CT 06520-8064 USA

Nephron (Switzerland), 1996, 72/4 (530-535)

It has been shown that calcium carbonate (CaCO3) is an effective phosphate binder which is less toxic than Al(OH)3. However, given that its use with standard calcium dialysate (CaD) levels may lead to hypercalcemia, a decrease in CaD levels has been proposed. The aim of the present study was to evaluate the acute clinical and biochemical consequences of a lowering of CaD in HD patients. Dialysate composition was otherwise the same. (1) Blood pressure levels (BP) during short hemodialysis were measured in a group of 12 patients who underwent alternate hemodialyses with dialysate calcium of 1.75 and 1.25 mmol/l. (2) Ca2+ and PTH kinetics during short hemodialysis were studied in a group of 6 patients who were sequentially treated with 1.75 and 1.25 mmol/l CaD. The results show: (1) that cardiovascular stability in chronic HD patients during short HD sessions with low CaD (LCaD) may be good; (2) that a single treatment with standard CaD (SCaD) produces positive calcium balances (JCa2+) with Ca2+ plasma increase and PTHi inhibition at the end of HD sessions; during HD with LCaD there were neutral mean JCa2+ and no changes in post-dialysis mean Ca2+ and PTHi plasma levels; furthermore 2 patients showed a small PTHi increase during HD with LCaD and neutral JCa2+ because of a high positive bicarbonate balance during HD. In conclusion, as with several aspects of dialysis treatment, dialysate calcium levels should also be individualized to avoid hypercalcemic crises or PTHi stimulation.

Influence of ovariectomy on bone metabolism in very old rats

Gaumet N.; Seibel M.J.; Brailion P.; Giry J.; Lebecque P.; Davicco M.J.; Coxam V.; Rouffet J.; Delmas P.D.; Barlet J.P. INRA Clermont-Theix, F 63122 Ceyrat France

Calcified Tissue International (USA), 1996, 58/4 (256-262)

Twenty-five 30-month-old Lou rats fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi were divided into five groups. Four groups were surgically ovariectomized. From day 2 until day 29 after ovariectomy, they were S.C. injected either with 17 beta estradiol (E2; 10 microg/kg BW/48 hours) or progesterone (P; 140 microg/kg BW/48 hours), or 17 beta estradiol + progesterone (E2P) at the same doses, or solvent alone (OVX). The fifth group was sham operated (SH) and injected with solvent. Urine was collected in metabolic cages from day 24 to 29 after OVX, and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion (markers of bone resorption) was measured by HPLC. All animals were killed 30 days after ovariectomy. Serum was then collected for measurement of osteocalcin (OC), alkaline phosphatase (ALP), parathyroid hormone (PTH), and calcitonin (CT). At necropsy, the success of ovariectomy was checked by marked atrophy of the uterine horns. Left and right femur were harvested for densitometric and mineral analysis, respectively. Ovariectomy had no significant effect upon plasma calcium and PTH concentrations. E2 or E2P treatment significantly increased plasma PTH and calcitonin concentrations. Plasma OC concentration and ALP were not different in any of the groups. In contrast, urinary excretion of PYD and DPD was higher in OVX than in SH rats. Bone mineral density (BMD) of the distal femur was decreased by OVX, but was not different in the E2P and SH groups. A similar pattern was observed for the mineral or Ca content of whole femur. Thus, OVX decreased BMD and bone mineral content (BMC) in very old female rats. Plasma OC concentration and ALP activity failed to demonstrate any significant effect of OVX, whereas PYD and DPD were elevated. These results suggest that bone resorption is increased in OVX rats, even when supplemented with E2 or P alone. However, no significant difference was observed between SH and OVX rats treated with supplementation of both E2 and P. Thus, in very old rats, a combination of E2 and P is much more effective than E2 or P alone to prevent bone loss following ovariectomy.

Biochemical effects of calcium and vitamin D supplementation in elderly, institutionalized, vitamin D-deficient patients

Chapuy M.-C.; Chapuy P.; Thomas J.-L.; Hazard M.-C.; Meunier P.-J. Service de Rhumatologie, Pavillon F, Hopital Edouard Herriot, Place d'Arsonval, 69437 Lyon Cedex 3 France

Revue du Rhumatisme (English Edition) (France), 1996, 63/2 (135-140)

Forty-five subjects (41 women and 4 men) in long-stay and medium-stay facilities, aged 74 to 95 years (mean 86.4 years), with 25-hydroxy-vitamin D levels less than 12 ng/ml, were treated for six consecutive months with two tablets per day of a preparation containing vitamin D3 (800 IU/day) and calcium carbonate (1 g elemental calcium/day). Serum levels of 25-hydroxy-vitamin D were very low at baseline (5.6 plus or minus 0.4 ng/ml) and rose significantly under treatment, to normal values, 33.2 plus or minus 1.2 and 40.9 plus or minus 2.1 ng/ml after three and six months, respectively (< 0.001 for both comparisons). Serum calcium increased significantly, by 4.5% (< 0.001) during the first three months, and remained at a plateau thereafter. Corrected serum calcium rose by 8.9% (< 0.001) during the trial. No patient developed hypercalcemia. Serum parathyroid hormone levels, which were elevated at baseline (71.6 plus or minus 5.8 pg/ml; normal, 12 to 54 pg/ml), decreased gradually and significantly throughout the treatment period, by 43.0% and 67.1% after three and six months, respectively (< 0.001 for both comparisons). Serum alkaline phosphatase activity fell concomitantly, by 9.9% after three months (< 0.01) and 36.5% after six months (< 0.001). In conclusion, the preparation used in our study is effective in correcting both the vitamin D deficiency that is prevalent in elderly institutionalized patients and the resultant increase in bone turnover.

Long-term effect of intravenous calcitriol on the treatment of severe hyperparathyroidism, parathyroid gland mass and bone mineral density in haemodialysis patients.

Huraib S; Abu-Aisha H; Abed J; Al Wakeel J; Al Desouki M; Memon N Department of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia.

Am J Nephrol (Switzerland) 1997, 17 (2) p118-23

We conducted this study on 15 chronic haemodialysis patients to evaluate the efficacy of i.v. calcitriol over a 1-year period in the treatment of severe secondary hyperparathyroidism (HPT), in particular its effect on bone mineral density (BMD) and parathyroid gland mass. Mean age was 39 +/- 11.9 (20-65) years and dialysis duration was 58 +/- 3 (19-130) months. i.v. calcitriol was given at a dose of 1 microg post-dialysis 3 times/week for 3 weeks; the dose was then adjusted to maintain the total serum calcium at less than 2.88 mmol/l. The maximum dose was 3 microg 3 times/week. Serum calcium (Ca) and phosphorus (P) were determined prior to treatment, then weekly for 6 weeks and every 2 weeks thereafter. Skeletal survey, dual photon densitometry and parathyroid ultrasound (US) were done prior to treatment and after 1 year. Bone biopsy was done in 10 patients at the beginning of treatment. There was a significant reduction (< 0.01) in pre-treatment mid-region serum parathyroid hormone (PTH) from 1,476 +/- 895 to 489 +/- 485 P mol/l, as well as alkaline phosphatase (< 0.04) from 236.5 +/- 221 to 116.3 +/- 49 U/l. This was without a significant increase in serum Ca (2.15 +/- 0.25 to 2.44 +/- 0.26 mmol/l, p = 0.08). Three patients had recurrent hypercalcaemia which responded to reduction of Ca in dialysate. There was a significant increase in BMD over the spine from 1.071 +/- 0.25 to 1.159 +/- 0.22 g/cm2 (< 0.003) with a percent increase of 9.3 +/- 8.9% as well as over the femoral neck from 0.834 +/- 0.002 to 0.89 +/- 0.09 g/cm2 (< 0.001) with a percent increase of 7.45 +/- 6.81%. Five patients had enlarged parathyroid glands by US and in 3 of these, there was a significant reduction to normal with treatment. Bone biopsy was done in 10 patients. Six patients had predominant hyperparathyroid bone disease and 4 had mixed uraemic osteodystrophy. In conclusion, long-term i.v. treatment with calcitriol is effective in the treatment of severe secondary HPT. PTH decreased without a significant increase in serum Ca. BMD also increases during this therapy.

Calcitriol in the management of secondary hyperparathyroidism of renal failure.

Daisley-Kydd RE; Mason NA Procter & Gamble Pharmaceuticals, Cincinnati, Ohio, USA.

Pharmacotherapy (United States) Jul-Aug 1996, 16 (4) p619-30

Secondary hyperparathyroidism (HPT) is characterized by persistent hypersecretion of parathyroid hormone (PTH), and produces characteristics of hyperparathyroid bone disease and a variety of biochemical and hormonal derangements. Management of uremic secondary HPT involves both prevention and treatment. Among preventive measures are attempts to control serum phosphate and serum calcium concentrations through dietary restriction, administration of phosphate binders, and calcium supplementation. Treatment with a vitamin D analog such as calcitriol returns plasma calcium concentrations toward normal and suppresses PTH secretion. The availability of a parenteral formulation of calcitriol, and new information regarding alternative routes of administration and regimens employing oral pulse dosing have renewed interest in calcitriol for the management of uremic secondary HPT. (64 Refs.)

Parathyroid hormone increases bone formation and improves mineral balance in vitamin D-deficient female rats.

Toromanoff A; Ammann P; Mosekilde L; Thomsen JS; Riond JL University of Zurich, Institute of Animal Nutrition, Switzerland toro@vetphys.unizh.ch

Endocrinology (United States) Jun 1997, 138 (6) p2449-57

The present study was designed to investigate whether enhanced bone formation due to intermittent PTH administration is dependent on vitamin D metabolites. Forty-eight female Sprague-Dawley rats were randomized into four groups: 1) vitamin D-sufficient, saline-injected (+D Sal); 2) vitamin D-sufficient, human (h) PTH-(1-38)-treated (+D PTH); 3) vitamin D-deficient, saline-injected (-D Sal); and 4) vitamin D-deficient, hPTH-(1-38)-treated (-D PTH) animals. The -D diet contained 2% calcium (Ca), 1.25% phosphorus (P), and 20% lactose to maintain normocalcemia and normophosphatemia despite vitamin D deficiency. The +D diet contained 0.8% Ca, 0.5% P, 20% lactose, and 1000 IU/kg vitamin D. After 45 days of either diet, the rats were injected with 50 microg/kg BW PTH or saline, s.c., daily for 2 weeks. Serum Ca, Mg, P, albumin, and creatinine were similar in all groups. PTH administration decreased endogenous PTH concentrations in the -D PTH compared with those in the - D Sal group. Serum alkaline phosphatase activity, bone mass measurements, dual energy x-ray absortiometric analysis of mineral density, and mechanical testing values in vertebrae and femora of the -D Sal animals did not significantly differ from those in +D Sal animals. Moreover, in both diet groups, PTH improved bone biochemical activity (as assessed by serum alkaline phosphatase), bone mass, mineral density, and biomechanical properties. These results indicate that mineral supply, more than vitamin D itself, may be important for normal bone mineralization and to enable PTH to enhance bone formation. A balance study performed during the last 3 days of the experiment revealed that PTH increased apparent intestinal magnesium absorption in the +D group only. Ca and P retention, however, were augmented in both diet groups after PTH treatment. In conclusion, in normocalcemic and normophosphatemic -D rats, PTH treatment reduced the increased endogenous hormone concentration and improved Ca and P retention. Furthermore, PTH may have a vitamin D-dependent influence on intestinal magnesium absorption. Finally, short term PTH treatment is anabolic in bone of vitamin D-deficient rats when adequate mineral amounts are provided in the diet.

Effects on bone mineral density of low-dosed oral contraceptives compared to and combined with physical activity.

Hartard M; Bottermann P; Bartenstein P; Jeschke D; Schwaiger M Department of Preventive and Rehabilitative Sports Medicine, Technical University of Munich, Klinikum rechts der Isar, Germany.

Contraception (United States) Feb 1997, 55 (2) p87-90

A cross-sectional study was designed to examine the influence of exercise compared to and in combination with low-dosed oral contraceptives (OCs) on bone mineral density (BMD). One hundred twenty-eight women (20 to 35 years of age) were assigned to four groups with respect to the years of exercise and OC intake. Influence factors were determined by a detailed questionnaire and interview. BMD for L2-4 and the femoral neck was assessed by DXA. The highest BMD values were found in the group of women characterized by long-term exercise (9.45 +/- 4.32 yr) and short use of OC (1.6 +/- 1.69 yr). No beneficial effect of exercise on BMD was found in the group with a long exercise period (10.4 +/- 4.14 yr) and long-term intake of OC (8.2 +/- 4.14 yr). Differences in mean BMD values between the two groups were significant in all regions assessed (< 0.05). No differences in mean BMD were found in the groups with short-term exercise but long or brief histories of OC. The question arises as to whether active women taking low-dosed OC at an earlier age will develop an adequate BMD.

The importance of genetic and nutritional factors in responses to vitamin D and its analogs in osteoporotic patients.

Nakamura T Department of Orthopedic Surgery, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-Ku, Kitakyushu, Japan 807.

Calcif Tissue Int (United States) Jan 1997, 60 (1) p119-23

The effects of vitamin D and its analogs on fractures and bone mass have been clarified by clinical observations for more than 10 years. Reviewing the results of six clinical trials on osteoporotic fractures using activated vitamin D analogs, there appeared to be a negative correlation between basal levels of calcium intake and the incidence of vertebral fractures in the control groups. For example, when daily calcium intake was about 600 mg, there were approximately 800 vertebral fractures per 1000 persons a year in the controls. When daily calcium intake was above 1000 mg, the incidence was less than 400 fractures per 1000 persons a year. The incidence of fractures decreased by about half in the activated vitamin D-treated group compared with the control group, but the most marked preventive effects of activated vitamin D on fractures were obtained in clinical studies, with daily calcium intakes of 400-800 mg. The effects of vitamin D analogs on bone mass were reported in the clinical studies, but the results are not consistent. However, these studies suggest that the effects of both 1,25(OH)2D3 and 1-alpha(OH)D3 on bone mass were dose dependent, and the doses were low in clinical studies in which good results were not obtained. Significant effects on bone mass were obtained when more than 0.6 micro;g of 1,25(OH)2D3, or more than 0.75 micro;g of 1-alpha(OH)D3 was administered, with increase in the urinary calcium level being within the acceptable range. Reported data indicate that both nonactivated vitamin D and activated vitamin D reduce the serum parathyroid hormone level. However, activated vitamin D administration is more effective, and is able to reduce bone resorption in postmenopausal, osteoporotic patients with a vitamin D-sufficient status. Recent studies concerning the polymorphism of the vitamin D-receptor gene emphasize that sensitivity to active vitamin D varies between genotypes. In the bb type, sensitivity to active vitamin D is high, and calcium absorption efficiency in the intestine under low calcium conditions increases with increase in the serum 1,25(OH)2D level. A significant increase in lumbar bone mineral density was obtained after administration of activated vitamin D to osteoporotic patients of bb type. However, in the genotype with the B factor, sensitivity to active vitamin D was low, and the rate of increase of bone density was low. These data suggest that nutritional and genetic factors are critical when using active vitamin D and its analogs in the treatment of osteoporosis. (38 Refs.)

Effective suppression of parathyroid hormone by 1 alpha-hydroxy-vitamin D2 in hemodialysis patients with moderate to severe secondary hyperparathyroidism.

Tan AU Jr; Levine BS; Mazess RB; Kyllo DM; Bishop CW; Knutson JC; Kleinman KS; Coburn JW Medical Service, West Los Angeles Veterans Affairs Medical Center (Wadsworth Division), California, USA.

Kidney Int (United States) Jan 1997, 51 (1) p317-23

Calcitriol, as used for treating secondary hyperparathyroidism, has a low therapeutic index. The safety and efficacy of the vitamin D analog, 1 alpha (OH)-vitamin D2, (1 alpha D2), which has less toxicity in animals than 1 alpha (OH)-vitamin D3, was tested in a multicenter study of 24 hemodialysis patients with secondary hyperparathyroidism [serum intact (i) PTH < 400 pg/ml]. Calcium-based phosphate binders alone were used to maintain serum phosphorus < or = 6.9 mg/dl. After eight weeks without calcitriol (washout), oral 1 alpha D2, 4 micrograms/day or 4 micrograms thrice weekly, was started, with the dose adjusted over 12 weeks to maintain serum iPTH between 130 and 250 pg/ml. Pre-treatment serum iPTH fell from 672 +/- 70 pg/ml (SEM) to 289 +/- 36 after treatment (< 0.05). The maximal decrease in serum iPTH was 48 to 96%, with 87.5% of patients reaching target iPTH levels. The final dose of 1 alpha D2 average 14.2 micrograms/week. Pre-treatment serum calcium rose modestly from 8.8 +/- 0.2 mg/dl to 9.5 +/0 0.2 after treatment (< 0.001). Only once did modest hypercalcemia (serum Ca < 11.2 mg/dl) necessitate stopping treatment. Neither the average serum P level, the incidence of hyperphosphatemia, nor the dose of phosphate binders changed from washout to treatment. Thus, oral 1 alpha D2 is highly efficacious in suppressing secondary hyperparathyroidism in hemodialysis patients and is safe despite exclusive use of calcium-based phosphate-binders. Future studies should clarify the optimal dosage regimen.

The rise and fall of primary hyperparathyroidism: a population-based study in Rochester, Minnesota, 1965-1992.

Wermers RA; Khosla S; Atkinson EJ; Hodgson SF; O'Fallon WM; Melton LJ 3rd Mayo Clinic, Rochester, Minnesota, USA.

Ann Intern Med (United States) Mar 15 1997, 126 (6) p433-40

BACKGROUND: The introduction of routine measurement of serum calcium levels led to a sharp increase in the incidence of primary hyperparathyroidism in the early 1970s.

OBJECTIVE: To evaluate the trends in the incidence of primary hyperparathyroidism since the mid-1970s.

SETTING: Rochester and Olmsted County, Minnesota.

DESIGN: Population-based descriptive study.

PATIENTS: All residents of Rochester, Minnesota, who received an initial diagnosis of primary hyperparathyroidism between 1965 and 1992 were identified through the medical records linkage system of the Rochester Epidemiology Project. Included as persons having definite cases (92% of the total) were patients with pathologically confirmed hyperparathyroidism, hypercalcemia with inappropriately elevated parathyroid hormone levels, or hypercalcemia that had lasted for more than a year and had no cause other than primary hyperparathyroidism.

MEASUREMENTS: Incidence rates were calculated and directly standardized to the population structure of white persons in the United States in 1990.

RESULTS: From 1965 to June 1974 (the prescreening era), the age- and sex-adjusted incidence of primary hyperparathyroidism in Rochester was 15 cases per 100,000 person-years. After measurement of calcium levels was added to the automated serum chemistry panel in July 1974, the incidence increased to 112 per 100,000 person-years in 1975 and then decreased somewhat, reflecting a sweeping effect. Despite improved case ascertainment, however, the incidence rate has continued to decrease; in 1992, the incidence was 4 per 100,000 person-years. A few patients had complications that might have been caused by hyperparathyroidism (22% between 1965 and June 1974 and 6% thereafter), and survival was not impaired in either period. The maximum serum calcium levels did not change (P = 0.15).

CONCLUSIONS: The progressive decrease in the incidence of primary hyperparathyroidism is unexpected and suggests a significant change in the epidemiology of this disease.

Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study.

Hansen TB; Brixen K; Vahl N; Jorgensen JO; Christiansen JS; Mosekilde L; Hagen C Department of Endocrinology, Odense University Hospital, Denmark.

J Clin Endocrinol Metab (United States) Sep 1996, 81 (9) p3352-9

The effects of GH substitution on skeletal mass, bone turnover, and calcium metabolism were investigated in 29 patients with GH deficiency who were randomized to sc injections with GH (2 IU/m2 day) or placebo for 12 months. During GH treatment, serum insulin-like growth factor I increased 263 +/- 98% (< 0.001). Serum osteocalcin, bone a alkaline phosphatase, and procollagen type I C-terminal propeptide increased by 376 +/- 78% (< 0.005), 128 +/- 17% (< 0.005), and 100 +/- 17% (< 0.005), respectively. Serum type I collagen telopeptide and urinary levels of pyridinoline, deoxypyridinoline, and hydroxyproline rose by 158 +/- 39% (< 0.005), 170 +/- 48% (< 0.005), 156 +/- 78% (< 0.005), and 161 +/- 50% (< 0.005), respectively. Serum ionized calcium rose by 1.7 +/- 0.6% (< 0.05), whereas serum PTH decreased insignificantly. Vitamin D metabolites remained unaltered. Urinary calcium/creatinine increased and phosphate/creatinine decreased transiently, returning to baseline values at 9 months. When measured by dual energy x-ray absorptiometry, whole body bone mineral density (BMD) and (BMD) of the radius decreased 2.4 +/- 0.6% (< 0.05) and 3.5 +/- 1.0% (< 0.005), respectively, whereas no significant changes were observed in BMD of the femur or spine. Our results indicate that long term GH treatment activates bone remodeling in patients with GH deficiency. The observed slight decrease in BMD may be explained by expansion of the remodeling space and reduced mean age of bone tissue. IT remains unclear whether long term treatment with GH will lead to an increase in bone mass and improved skeletal biomechanical competence.

Acute biochemical effects of growth hormone treatment compared with conventional treatment in familial hypophosphataemic rickets.

Patel L; Clayton PE; Brain C; Pelekouda E; Addison GM; Price DA; Mughal MZ Department of Child Health, University of Manchester, UK.

Clin Endocrinol (Oxf) (England) Jun 1996, 44 (6) p687-96

OBJECTIVE: Conventional treatment of familial hypophosphaiaemic rickets with oral phosphate and 1 alpha-hydroxycholecalciferol (1 alpha HCC) does not satisfactorily correct the metabolic or physical defects of the disease and can have adverse effects, such as nephrocalcinosis. Hyperoxaluria from increased oral phosphate intake may contribute to nephrocalcinosis. Growth hormone enhances renal tubular phosphate reabsorption and 1,25-dihydroxy-cholecalciferol production in normal and in GH deficient individuals, and may thus be of benefit to patients with familial hypophosphataemic rickets.

PATIENTS: We have assessed the acute effects of GH on phosphate and calcium metabolism in 6 children (age 4-14 years) with familial hypophosphataemic rickets.

DESIGN: Each patient served as his/her own control and received the following in a sequential non-randomized design: conventional treatment with oral phosphate 1.0-3.4 mmol/kg/day in 3-6 divided doses and 1 alpha HCC 18-31 ng/kg/day-no treatment-GH 0.05 mg/kg daily-GH and 1 alpha HCC-and GH with phosphate and 1 alpha HCC. Each treatment was given for 7 days with 7 day periods of no treatment in between.

MEASUREMENTS AND RESULTS: Glomerular filtration rate, tubular maximum rate of phosphate reabsorption per litre of glomerular filtrate (TmP/GFR) and serum 1,25-dihydroxycholecalciferol increased with GH. Mean 24-hour plasma phosphate concentrations did not increase with GH but were higher in the treatment phases which included phosphate and 1 alpha HCC (P = 0.002). Serum PTH was higher when GH was given in combination with phosphate and 1 alpha HCC compared to other phases. Urine oxalate excretion did not differ between the treatment phases.

CONCLUSIONS: GH seemed to partially correct the defects in renal tubular phosphate transport and 1 alpha-hydroxylation of 25-hydroxycholecalciferol. We speculate that the net effect of GH treatment was an increase in body phosphate, although this was not reflected in a change in plasma phosphate. Therefore, GH in combination with 1 alpha HCC may act as a phosphate sparing agent, permitting treatment with lower and less frequent doses of oral phosphate and reducing adverse effects such as nephrocalcinosis.

Calcium, phosphate, vitamin D, and the parathyroid

Marks K.H.; Kilav R.; Naveh-Many T.; Silver J. Nephrology Services, PO Box 12000, Jerusalem il-91120 Israel

Pediatric Nephrology (Germany), 1996, 10/3 (364-367)

The main factors which regulate parathyroid hormone (PTH) production are calcium, phosphate, vitamin D, and estrogens. Hypocalcemia leads to increased PTH secretion in seconds and minutes, gene expression in hours, and parathyroid (PT) cell number in weeks and months. Hypercalcemia leads to a decrease in PTH secretion by its action on the PT cell calcium receptor and no decrease in PTH mRNA levels. There is now convincing evidence that phosphate regulates the PT, independent of its effect on serum calcium and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). In vivo in rats hypophosphatemia markedly decreases PTH mRNA and serum intact PTH levels, independent of its effect on serum calcium and 1,25(OH)2D3. Clinical studies also indicate that phosphate regulates the PT independent of its effect on calcium and 1,25(OH)2D3; 1,25(OH)2D3 itself has a marked effect on the PT, where it decreases PTH gene transcription by a direct action on the PT. The application of basic science findings of how calcium, phosphate, and 1,25(OH)2D3 regulate the PT has led to an efficient and safe prescription for the management of the secondary hyperparathyroidism of chronic renal failure, which is the maintenance of a normal serum calcium and phosphate and the careful use of 1,25(OH)2D3.

Vitamin D metabolism in chronic childhood hypoparathyroidism: Evidence for a direct regulatory effect of calcium

Carpenter T.O.; Insogna K.L.; Boulware S.D.; Mitnick M.A. Department of Pediatrics (Endocrinology), Yale University School of Medicine, PO Box 3333, New Haven, CT 06510 USA

J. Pediatr. (USA), 1990, 116/2 (252-257)

We noted the presence of elevated levels of circulating 1,25-dihydroxyvitamin D (83 pg/ml (200 pmol/L)), with low total serum calcium concentration (6.5 mg/dl (1.88 mmol/L)), in an untreated adolescent boy with hypoparathyroidism. Furthermore, an inverse relationship between total serum calcium and circulating 1,25-dihydroxyvitamin D levels was evident during treatment with 1,25-dihydroxyvitamin D3. We examined this relationship with a 33-hour intravenous infusion of calcium gluconate in the absence of exogenous 1,25-dihydroxyvitamin D3 therapy. The infusion was accompanied by a gradual increase of both total serum calcium and blood ionized calcium concentration for hypocalcemic to normocalcemic ranges, and produced a 50% reduction in circulating 1,25-dihydroxyvitamin D values, with minimal changes in circulating phosphorus, magnesium, and 25-hydroxyvitamin D values. These results suggest that calcium-dependent, parathyroid hormone-independent regulation of 1,25-dihydroxyvitamin D production may exist in human beings.

Determinants for serum 1,25-dihydroxycholecalciferol in primary hyperparathyroidism

Mosekilde L.; Charles P.; Lindegreen P. University Department of Endocrinology, Aarhus County Hospital, DK-8000 Aarhus C Denmark

Bone Miner. (Netherlands), 1989, 5/3 (279-290)

Serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) 25-hydroxyvitamin D3 (25(OH)D3), C-terminal immunoreactive PTH (iPTH), calcium and phosphate, and endogenous creatinine clearance (Cl(cr)) were measured in 34 patients with primary hyperparathyroidism. Cl(cr) ranged from 13 to 161 ml/min (mean 72). S-iPTH was elevated in 82% of the patients and correlated positively to serum calcium (r = 0.74, < 0.001) and inversely to Cl(cr) (r = -0.50, < 0.02). S-25(OH)D3 was reduced in 28% of the patients and depended on regular multivitamin supplementation (< 0.005). S-1,25(OH)2D3 was increased in 26% of the patients and decreased in 9%. It was positively correlated to S-25(OH)D3 (r = 0.39, < 0.05) and Cl(cr) (r = 0.42, < 0.02) and inversely to serum levels of calcium (r = -0.39, < 0.05), phosphate (r = -0.42, < 0.02) and iPTH (r = -0.40, < 0.05). Multiple regression analysis revealed a positive correlation to 25(OH)D3 when Cl(cr) was taken into account and to Cl(cr) when S-25(OH)D3 was taken into account. When both variables were considered no significant partial correlations were found between S-1.25(OH)2D3 and serum calcium, phosphate and PTH, respectively. It is concluded that serum levels of 25(OH)D3 and renal function are the main determinants for S-1,25(OH)2D3 in primary hyperparathyroidism.

Magnesium hormonal regulation and metabolic interrelations

Ferment O.; Touitou Y. Laboratoire de Biochimie Medicale, Faculte de Medecine Pitie-Salpetriere, F 75634 Paris Cedex 13 France

Presse Med. (France), 1988, 17/12 (584-587)

Magnesium ion is of great importance in physiology by its intervention in 300 enzymatic systems, its role in membrane structure and its function in neuromuscular excitability. The skeleton is the first pool of magnesium in the body. Intestinal absorption, renal metabolism, bone accretion and resorption of magnesium are very similar to those of calcium. Magnesium metabolism is accurately controlled, in particular by parathyroid hormone, 25 - dihydroxy vitamin D3, calcitonin, catecholamine and estrogens. The main regulation mechanisms of magnesium metabolism are located in the kidney which is the principal excretory organ.

Treatment with active vitamin D (alphacalcidol) in patients with mild primary hyperparathyroidism

Lind L.; Wengle B.; Sorensen O.H.; Wide L.; Akerstrom G.; Ljunghall S. Department of Internal Medicine, Gavle Hospital, Gavle Sweden

Acta Endocrinol. (Denmark), 1989, 120/2 (250-256)

The parathyroid gland possesses receptors for 1,25-dihydroxyvitamin D3, the active metabolite of the vitamin D system, and in vitro experiments have shown that 1,25-dihydroxyvitamin D3 can inhibit the secretion of PTH. In this study 31 subjects who had displayed persistent mild hypercalcemia for 14 years and presumably had mild primary hyperparathyroidism (HPT) were challenged with 1.0 microg alphacalcidol (1alpha-(OH)-vitamin D3) over 6 months in a double-blind, placebo-controlled study. Before initiation of therapy, the hyperparathyroid subjects showed lower serum levels of 1,25-dihydroxyvitamin D in relation to PTH or calcium when compared with age- and sex-matched controls. Treatment induced a slight rise in serum calcium (0.05 mmol/l), but no sigificant decrease of the PTH levels. Eighteen of the subjects thereafter entered open study with a higher dose of alphacalcidol (2.0 microg) over 1 year. Although this high dose induced a marked rise in serum calcium (0.17 mmol/l), there was only a transient reduction of the PTH levels. Thus, during long-term condition there was an escape from the suppressive action of the elevated calcium concentrations and no evidence of a specific inhibition of PTH secretion by a small oral dose of active vitamin D. Eleven patients on chronic haemodialysis treatment thrice weekly received 1 microg 1,25(OH)2D3 i.v. after each dialysis for 3 weeks. Phosphate binders were mainly CaCO3, supplemented in a few patients by moderate amounts of Al(OH)3. Ionised calcium was measured by ion-selective electrode, normal values being 1.28-1.42 mmol/l. PTH was estimated by an N-terminal-sensitive assay; normal values are < 0.25 ng/ml. Results before and after 1,25(OH)2D3 were: ionised calcium before haemodialysis, 1.19 plus or minus 0.12 and 1.17 plus or minus 0.14; ionised calcium after haemodialysis, 1.33 plus or minus 0.07 and 1.30 plus or minus 0.09; PTH before haemodialysis, 1.39 plus or minus 0.71 and 1.38 plus or minus 0.69; PTH after haemodialysis, 0.64 plus or minus 0.22 and 0.60 plus or minus 0.17; phosphate before haemodialysis, 1.85 plus or minus 0.48 and 2.18 plus or minus 0.43 (< 0.05). No change of PTH concentration and ionised calcium before and after haemodialysis treatment could be documented after i.v. 1,25(OH)2D3 treatmetn. Mild and severe hyperparathyroidism were indistinguishable. Increased serum calcium concentrations therefore appear to be required for the suppression of PTH secretion by i.v. 1,25(OH)2D3 therapy.