title: 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.
abstract: 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 D(3) (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.
authors.affiliation: Deltanoid Pharmaceuticals and the Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA. deluca@biochem.wisc.edu.
authors.forename: Hector F
authors.initials: HF
authors.lastname: DeLuca
authors.forename: Wendy
authors.initials: W
authors.lastname: Bedale
authors.forename: Neil
authors.initials: N
authors.lastname: Binkley
authors.forename: J Chris
authors.initials: JC
authors.lastname: Gallagher
authors.forename: Michael
authors.initials: M
authors.lastname: Bolognese
authors.forename: Munro
authors.initials: M
authors.lastname: Peacock
authors.forename: John
authors.initials: J
authors.lastname: Aloia
authors.forename: Margaret
authors.initials: M
authors.lastname: Clagett-Dame
authors.forename: Lori
authors.initials: L
authors.lastname: Plum
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D016723:Bone Remodeling / Q000187:drug effects*; D002117:Calcitriol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002118:Calcium / Q000097:blood; D003710:Demography; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010919:Placebos; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D051381:Rats; D014807:Vitamin D / Q000031:analogs & derivatives*
chemical_list: C519954:2-methylene-19-nor-(20S)-1alpha,25-dihydroxyvitamin D3; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D010281:Parathyroid Hormone; D010919:Placebos; D014807:Vitamin D; D002117:Calcitriol; D002118:Calcium