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To determine the effects of 1α,25-dihydroxyvitamin D [1,25(OH)D] on the renal metabolism of 25-hydroxyvitamin D [25(OH)D], the influence of 1,25(OH)D and 24,25-dihydroxyvitamin D [24,25(OH)D] was compared in vitamin D-deficient rats. Serum calcium (Ca), serum immunoreactive parathyroid hormone (iPTH) and the specific activities (SA) of renal 25(OH)D: 24-hydroxylase (24-hydroxylase) and 25(OH)D: 1α-hydroxylase (1-hydroxylase) were measured. In vitamin D-deficient rats, mean serum Ca was low, serum iPTH was increased, renal 1-hydroxylase was increased, and renal 24-hydroxylase was below the limit of detection. Treatment with either 1,25(OH)D or 24,25(OH)D, 50 ng/d for 2 days, significantly increased mean serum Ca but did not change serum iPTH, renal 1-hydroxylase SA, or renal 24-hydroxylase SA. 1,25(OH)D, 50 ng/d for 7 days, returned serum Ca and iPTH to normal, lowered renal 1-hydroxylase SA, and induced renal 24-hydroxylase activity. In contrast, 24,25(OH)D, 50 ng/d for 7 days, similarly lowered renal 1-hydroxylase SA but did not induce renal 24-hydroxylase activity. Thyroparathyroidectomy of vitamin D-deficient rats resulted in a rapid decline in 1-hydroxylase SA. The results indicate that in vitamin D-deficient rats a) 1,25(OH)D reduces renal 1-hydroxylase SA and increases renal 24-hydroxylase SA and b) 24,25(OH)D reduces renal 1-hydroxylase SA and does not alter renal 24-hydroxylase SA. Inhibition of renal 1-hydroxylase by the two metabolites is apparently mediated through changes in serum Ca and circulating iPTH, whereas stimulation by 1,25(OH)D of renal 24-hydroxylase activity is direct. [ABSTRACT FROM AUTHOR]

For 2 weeks 27 patients with hypercalcemia received a standard oral treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) as the sole agent. Results were grouped according to causes of hypercalcemia and compared with effects of APD in 13 normocalcemic patients with Paget's disease of bone and 7 with osteoporosis. In 12 hypercalcemic patients with osteolytic bone lesions and in the 20 normocalcemic patients, the mean serum calcium decreased to final levels that were subnormal and significantly lower than those obtained after treatment of 8 patients with primary hyperparathyroidism. In 3 patients with myeloma and in 4 tumor patients without bone lesions, serum calcium did not always decrease to the normal range. Implications of these observations for the mechanism of hypercalcemia are discussed. [ABSTRACT FROM AUTHOR]

This work was conducted to estimate the replacement dose of the synthetic bovine parathyroid hormone [PTH(1-34)] that is required for maintenance of serum calcium (Ca) in parathyroidectomized (PTX) rats. Male rats were PTX and used in this study only if serum Ca was reduced to at least 7 mg/dl. We found that a solution of 2% cysteine, 150 mM NaCl, and 1 mM HCl was superior to 20 mM acetic acid for maintenance of biological activity of PTH (1-34) in situ during the period of hormone infusion studied. The PTH dose-calcemic response relationship was investigated using PTH in doses of 0.6, 1, and 3 U/h. The infusion of 1 U PTH per hour raised Ca to the normal level, whereas rats infused with 0.6 U/h were hypocalcemic and 3 U/h resulted in marked hypercalcemia. To extend this observation we carried out an infusion of 1 U PTH per hour for 14 days. We found that this infusion rate of bovine PTH (1-34) provided a relatively stable level of serum calcium with modest fluctuation from normocalcemic to somewhat hypercalcemic levels for the entire 14-day period of PTH infusion. Serum calcitonin was also elevated during the infusion period and then returned to the initial level when PTH treatment was stopped. After the minipumps containing PTH were removed, the serum Ca dropped rapidly to 5 mg/dl, which was significantly lower than the control (vehicle-infused) or initial values of serum Ca (7 mg/dl). Infusion of PTH at 3 U/h for 4 days did not produce this rebound hypocalcemia after the pumps were removed. Serum Ca in those experiments returned to the initial level after hormone treatment was discontinued. [ABSTRACT FROM AUTHOR]