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...