Efficacy and safety of doxercalciferol (1α hydroxyvitamin D2) on spine and femur bone mineral density in postmenopausal osteopenic women
Background The use of small doses of vitamin D 3 analogs or metabolites is common in the prevention of renal osteodystrophy. Their use in the treatment of osteoporosis has been limited by their potent adverse effects, causing hypercalcemia and hypercalciuria. We evaluated a vitamin D 2 analog, i.e., 1α-hydroxyvitamin D 2 (doxercalciferol), that has a lower incidence of adverse effects. Methods In a 1-year pilot randomized double-blind, placebo-controlled study, 55 postmenopausal women (aged 60–71 years) with osteopenia were treated for a year with either doxercalciferol or placebo, and 41 women completed an optional second year. The dose of 1 µg was increased by 1 µg at weekly intervals to a maximum of 5 µg. The daily dose of doxercalciferol averaged 4.1 µg after 12 months and 3.6 µg after 24 months. Bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry (DEXA) of the spine and femoral neck were obtained at 6-month intervals for 24 months. The serum and urine calcium levels were measured frequently for safety. Results In the primary intention-to-treat (ITT) analysis at 12 months, there was no significant difference between the two groups for femoral neck and spine BMD. At 24 months, there was a significant difference in favor of doxercalciferol for femoral neck BMD, with the treatment/placebo difference being 1.70% ( p < 0.047); for spine BMD, the treatment/placebo difference was 1.1% ( p = 0.36). In the per-protocol analysis at 12 months, the doxercalciferol/placebo difference for femoral neck was 0.5% ( p = 0.497) and for spine BMD was 1.6% ( p = 0.071). At 24 months, the doxercalciferol/placebo difference for femoral neck BMD was 2.2% ( p < 0.017) and for spine BMD was 2.4% ( p < 0.041). Over 24 months, there were five mild hypercalcemia events, 2.54 mmol/L (>10.2 mg/dl), in five patients. The mean 24-h urine calcium increased by 3.75 mmol (150 mg), with 16 episodes of hypercalciuria, 10 mmol (>400 mg), in 12 patients. Conclusions The results show that doxercalciferol treatment showed no difference from the placebo group on bone loss at 12 months; however, at 24 months, doxercalciferol showed significant prevention of bone loss from the femoral neck and spine. Clinical Trial Registration https://clinicaltrials.gov/ , identifier NCT07660536.