Vitamin D supplementation is recommended whenever patients are given therapeutic drugs for
osteoporosis, to make their
calcium (Ca) balance positive.
Vitamin D is converted to
25-hydroxyvitamin D in the liver, and then activated to become 1α,25-dihydroxyvitamin D in the kidneys. The active
vitamin D acts in the intestine to stimulate Ca absorption and maintain the Ca balance. 2β-(3-Hydroxypropyloxy)-1α,25-dihydroxyvitamin D3 (
eldecalcitol) and 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD) are newly developed
vitamin D analogs, with a substitution at the 2 position of 1α,25-dihydroxyvitamin D3 (
calcitriol).
Eldecalcitol and 2MD share common structural and
biological characteristics. Both compounds increase serum Ca levels more markedly than
calcitriol, increase bone mineral density (BMD), and improve bone strength in ovariectomized (OVX) rats. In a randomized, placebo-controlled, double-blind, 1 year clinical trial,
eldecalcitol dose-dependently increased lumbar and hip BMD and suppressed bone turnover markers in patients with
osteoporosis. Whereas, 2MD markedly increased the bone turnover markers, but it did not change the BMD of postmenopausal women with
osteopenia in a 1 year clinical trial. After a randomized, double-blind, 3 year fracture-prevention trial comparing it with
alfacalcidol,
eldecalcitol was approved for the treatment of
osteoporosis in Japan. On the other hand, the manufacturer discontinued the clinical development of 2MD. In this review, we discuss the similarities and differences between these 2 compounds, and the reasons why different outcomes resulted from their clinical trials.