Long Term 25-Hydroxyvitamin D₃ Therapy in Postmenopausal Osteoporosis: Demonstration of Responsive and Nonresponsive Subgroups

Previous studies from our laboratory have demonstrated that 25-hydroxyvitamin D³ (25OHD³) therapy is effective in raising the impaired intestinal calcium absorption (α) associated with postmenopausal osteoporosis. In the present study we have assessed the effects of long term 25-OHD³ therapy (50 ¼g/day; mean treatment period, 1.3 yr) in 12 women with postmenopausal osteoporosis (mean age, 62.5 yr). Our results indicate that there was a significant increase in a for the group during therapy. However, we found that the patients could be divided into 2 groups based upon their ability to raise a in response to 25OHD³ therapy. In those who responded (n = 7), a increased from 0.36 ± 0.05 to 0.49 ± 0.08 (±SD; P < 0.005) while no significant change was observed for the nonresponders (0.44 ± 0.03 to 0.48 ± 0.07). During therapy, there were significant increases in serum 25OHD and 24, 25-dihydroxyvitamin D [24, 25-(OH)²D] for both groups. Serum 1, 25-(OH)²D significantly increased in the responders (21 ± 8 to 39 ± 13 pg/ml; P < 0.01), but not in nonresponders (25 ± 11 to 28 ± 8 pg/ml). Betweengroup comparisons for responders vs. nonresponders before therapy disclosed significant reductions in 24, 25-(OH)²D (0.4 ± 0.3 vs. 2.2 ± 0.8 ng/ml; P < 0.005) and α (0.36 ± 0.05 vs. 0.44 ± 0.03; P < 0.01). During therapy, there were no significant differences in any parameter between the two groups, except for serum 1, 25-(0H)²D which was significantly higher in the responders (39 ± 13 vs. 28 ± 8 pg/ml; P < 0.05). These data would suggest that in postmenopausal osteoporosis, the ability to raise a in response to 25OHD³ therapy is due in part to increases in serum 1, 25-(0H)²D during therapy. This suggests that in some patients with postmenopausal osteoporosis, renal 25OHD3-la-hydroxylase may be impaired.