Abstract There is increasing evidence that pamidronate and related compounds are effective in the prevention and treatment of osteoporosis. It is therefore of relevance to document the time course and mechanism of bis-phosphonate action in this condition. To this end, the present study describes the biochemical responses to prophylactic treatment with oral pamidronate (APD, 150 mg/day) in 16 glucocorticoid-treated patients and contrasts them with those in 19 steroid-treated control subjects. Measurements were made over a period of 12 months. The treated patients showed a fall in urine hydroxyproline excretion at 6 weeks associated with a reduction in serum ionized calcium concentration, a rise in serum 1,25-(OH)2D3, and a nonsignificant rise in serum bone gla protein (BGP). In contrast to BGP, serum alkaline phosphatase activity declined at 6 weeks, falling further at 3 months. Between 3 and 12 months, BGP levels paralleled those of alkaline phosphatase and hydroxyproline, all these being significantly below their initial values, and the other parameters returned to baseline. There was a gradual increase in plasma phosphate concentrations in the treated group over the 12 month period. It is concluded that pamidronate produces an acute and sustained inhibition of bone resorption followed by a more gradual reduction in bone formation. This transient dissociation results in a reduction in serum calcium, leading to a rise in serum 1,25-(OH)2D3, which in turn stimulates BGP production. Thereafter, indices of bone turnover remain subnormal but serum calcium and 1,25-(OH)2D3 return to baseline.
Abstract Changes in serum and urine biochemical indices have been studied in ten normal subjects in the four hours following the ingestion of four proprietary calcium supplements. Each was taken in a dose containing 1 gram of elemental calcium. The four preparations were ranked according to the amount of calcium absorbed in the order Spar‐Cal and Calcium Sandoz> Os‐Cal> Ossopan. There were no significant differences between the four preparations in the changes in parathyroid hormone (PTH) and urine hydroxyproline levels. For this reason, the four results from each subject were averaged. Following the calcium load there was a reduction in mean PTH from 0.16 ± 0.01 to 0.10 ± 0.02 μg/l ( p <0.001) and a decline in urine hydroxyproline/creatinine ratio from 20 ± 1 to 17 ± 1 ( p <0.02), suggesting that bone resorption responds immediately to dietary calcium intake. There was a rise in urine sodium excretion which correlated with the indices of calcium absorption ( r = 0.63, p <0.01) but not with the sodium content of the calcium preparations. This effect could be important, particularly in elderly patients on borderline sodium intakes.
Blacks are known to have a higher bone mass than whites and have recently been found to have significantly different levels of calcitropic hormones and other biochemical indices of calcium metabolism. To assess the possible significance of these biochemical differences to interracial differences in bone mass, we have undertaken an assessment of indices of calcium metabolism in Polynesian subjects, since they also have a higher bone mass than whites. Serum concentrations of 25-hydroxyvitamin D were slightly lower in Polynesians than in whites (65 ± 5 vs. 95 ± 10 nmol/L; P < 0.02), but there were no differences between the groups in serum levels of calcium (total and ionized), phosphate, magnesium, 1,25-dihydroxyvitamin D, PTH, calcitonin, alkaline phosphatase activity, and bone gla-protein. Furthermore, urinary excretion of hydroxyproline, calcium, phosphate, magnesium, sodium, and potassium and the tubular maximum for the reabsorption of phosphate were not different between whites and Polynesians. Intestinal strontium absorption was similar in the two groups. In contrast, distal forearm bone mineral content was higher in Polynesians (P < 0.01) and midupper arm muscle area was also increased in this group (P < 0.005). It is concluded that the higher bone mass of Polynesians cannot be attributed to alterations in the basal levels of calcitropic hormones, but may be related to their greater muscle mass. It is probable that the previously observed black-white differences in the vitamin D endocrine system are secondary to the effects of skin color on vitamin D synthesis and are not contributory to the lower bone mass of whites.
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