The vitamin D analogue 2MD increases bone turnover but not BMD in postmenopausal women with osteopenia: Results of a 1‐year phase 2 double‐blind, placebo‐controlled, randomized clinical trial

Most osteoporosis drugs act by inhibiting bone resorption. A need exists for osteoporosis therapies that stimulate new bone formation. 2‐Methylene‐19‐nor‐(20S)‐1α,25‐dihydroxyvitamin D3 (2MD) is a vitamin D analogue that potently stimulates bone formation activity in vitro and in the ovariectomized rat model. In this randomized, double‐blind, placebo‐controlled study of osteopenic women, the effect of daily oral treatment with 2MD on bone mineral density (BMD), serum markers of bone turnover, and safety were assessed over 1 year. Volunteers were randomly assigned to three treatment groups: placebo (n = 50), 220 ng of 2MD (n = 54), and 440 ng of 2MD (n = 53). In general, 2MD was well tolerated. Although 2MD caused a marked increase in markers of bone formation, it did not significantly increase BMD. Since 2MD also shows marked activity on bone resorption (as revealed by dose‐dependent increases in serum C‐telopeptide cross‐links of type I collagen in this study), 2MD likely stimulated both bone formation and bone resorption, thereby increasing bone remodeling. © 2011 American Society for Bone and Mineral Research.