Vitamin D3 analogs for the treatment of osteoporosis

Abstract

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.