1,25-Dihydroxyvitamin D3: short- and long-term effects on bone and calcium metabolism in patients with postmenopausal osteoporosis.

Abstract

We evaluated the effects of therapy with a small dose (0.5 Iug/day) of 1,25-dihydroxyvitamin D3 in 12 previously untreated patients with postmenopausal osteoporosis. Combined radiocalcium kinetic and balance studies showed that at base line, net calcium absorption (mean ± SEM) was low (7 + 3%), calcium balance was negative (-59 ± 22 mg/day), and bone resorption rate (297 ± 40 mg/day) exceeded bone formation rate (239 ± 36 mg/day). After short-term therapy (6-8 months), calcium absorption was normal (27 ± 3%, P < 0.001 for difference from base line), calcium balance had improved (+2 + 26 mg/day, P < 0.05), and bone resorption rate (195 ± 35 mg/day, P < 0.01) had decreased more than bone formation rate (197 ± 26 mg/day, NS). Compared with base-line values, after long-term therapy (2 years) the increased level of calcium absorption was maintained (27 ± 3%, P < 0.001), but calcium retention declined to a level intermediate (-27 ± 24 mg/day, NS) between base-line and shortterm treatment values, and both bone resorption rate (294 ± 33 mg/day, NS) and bone formation rate (267 + 34 mg/day, NS) increased. Urinary hydroxyproline excretion was lower than before treatment (26.3 ± 2.0 mg/day) after both short-term (21.1 ± 1.6 mg/day, P < 0.001) and long-term (22.0 ± 1.8 mg/day, P < 0.01) treatments. Trabecular bone volume was 11.3 ± 1.0% at base line and increased to 16.0 ± 1.2% (P < 0.01) after long-term treatment. By contrast, the eight patients studied before and after 6-8 months of placebo treatment had no significant change in any variable.Many investigators have found that a substantial proportion of patients with postmenopausal osteoporosis have impaired intestinal calcium absorption as assessed either by metabolic balance or by absorption ofradiocalcium (1-6). We have previously reported (6) that patients with postmenopausal osteoporosis have a significant decrease in mean serum 1,25-dihydroxyvitamin D [1,25(OH)2D], the major hormonal factor controlling calcium absorption. Some (7-9) but not all (10) investigators also have found that serum 1,25(OH)2D was low normal or low in patients with osteoporosis. Another group (11) reported that, when patients with osteoporosis were stratified on the basis of calcium absorption, those with calcium malabsorption had serum 1,25(OH)2D levels that were significantly lower than normal. In that same study, the women with osteoporosis had no change in serum 1,25(OH)2D levels in response to a low-calcium diet, whereas the normal control subjects had significant increases.It is not known whether the impaired calcium absorption contributes to the negative calcium balance characteristic of osteoporosis. We have previously reported that treatment with a small dose of 1,25(OH)2D3 for 7 days normalizes calcium absorption in patients with this disorder (6). The current study was undertaken to determine whether this result could be maintained with continued treatment and, if so, whether it would have a beneficial effect on abnormal bone and calcium metabolism characteristic of untrea...

Impaired vitamin D metabolism with aging in women. Possible role in pathogenesis of senile osteoporosis.

“…Senile osteoporosis traditionally has been attributed to bone cell senescence and, thus, has been considered not to be amenable to therapy. We have documented a potentially treatable (28) abnormality of vitamin D metabolism, which could contribute to age-related bone loss. It is now appropriate to determine whether impaired calcium absorption in elderly women can be corrected by treatment with a small dose of 1,25(0H)2D and, if so, whether this reduces their bone loss.…”

Curative Effect of Combined Treatment With Alendronate and 1 α-Hydroxyvitamin D3 on Bone Loss by Ovariectomy in Aged Rats

“…1a (OH)D3 has been reported to prevent bone loss and increase the mechanical properties in ovariectomized rats, although its mechanism is still controversial (30 -32). 1a (OH)D3 as well as 1,25(OH) 2 D 3 increases bone mass possibly by up-regulating the intestinal absorption of calcium or modulating bone turnover (33).…”

Effect of 1 .ALPHA.-Hydroxyvitamin D3 on Loss of Bone Mineral Density Immediately after Artificial Menopause.

“…These results may indicate that 1a(OH)D3 has a suppressive effect on In earlier studies, a decrease in excretion following active vitamin D analogue was reported [6][7][8][9][10]. In ovariectomized animals, the inhibitory effect of 1, 25 (OH)2D3 on bone resorption has been demonstrated [3,4].…”

“…Taking into account the fact that the loss of L2-4 BMD measured by DXA was as much as 8% per year as demonstrated in the control group of the preventive trial, L2-4 BMD measured by DXA is a good endpoint for the evaluation of the agent in early menopausal subjects. The endpoints used in other studies in the literature are L2.4 BMD as measured by dual photon absorptiometry [6][7][8]12] and the incidence of fractures [7,8,12,13]. The percent change in these parameters was not more than 5% in one year, because the subjects studied were more than 60 years old.…”

“…High-dose vitamin D analogue causes toxicity such as hypercalcemia and hypercalciuria [8]. Lowcalcium intake, however, allows the administration of high doses without side effects [11].…”