title: A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures--a randomized, active comparator, double-blind study.
abstract: BACKGROUND
  Eldecalcitol is an analog of 1,25-dihydroxyvitamin D(3) that improves bone mineral density; however, the effect of eldecalcitol on the risk of fractures is unclear. The objective of this study is to examine whether eldecalcitol is superior to alfacalcidol in preventing osteoporotic fractures. This trial is registered with ClinicalTrials.gov, number NCT00144456.
  
  
  RESULTS
  This 3 year randomized, double-blind, active comparator, superiority trial tested the efficacy of daily oral 0.75 μg eldecalcitol versus 1.0 μg alfacalcidol for prevention of osteoporotic fractures. 1054 osteoporotic patients 46 to 92 years old were randomly assigned 1:1 to receive eldecalcitol (n=528) or alfacalcidol (n=526). Patients were stratified by study site and serum 25-hydroxyvitamin D level. Patients with low serum 25-hydroxyvitamin D levels (<50 nmol/L) were supplemented with 400 IU/day vitamin D(3). Primary end point was incident vertebral fractures. Secondary end points included any non-vertebral fractures and change in bone mineral density and bone turnover markers. Compared with the alfacalcidol group, the incidence of vertebral fractures was lower in eldecalcitol group after 36 months of treatment (13.4 vs. 17.5%; hazard ratio, 0.74; predefined 90% confidence interval [CI], 0.56-0.97). Eldecalcitol reduced turnover markers and increased bone mineral density more strongly than alfacalcidol. Eldecalcitol reduced the incidence of three major non-vertebral fractures, which was due to a marked reduction in wrist fractures by a post-hoc analysis (1.1 vs. 3.6%; hazard ratio, 0.29; 95% CI, 0.11-0.77). Among the adverse events, the incidence of increase in serum and urinary calcium was higher in the eldecalcitol group, without any difference in glomerular filtration rate between the two groups.
  
  
  CONCLUSIONS
  Eldecalcitol is more efficacious than alfacalcidol in preventing vertebral and wrist fractures in osteoporotic patients with vitamin D sufficiency, with a safety profile similar to alfacalcidol.
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medical Sciences, Tokushima 770-8503, Japan. toshimat@clin.med.tokushima-u.ac.jp
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Masako
authors.initials: M
authors.lastname: Ito
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Takako
authors.initials: T
authors.lastname: Hirota
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanigawara
authors.forename: Teruki
authors.initials: T
authors.lastname: Sone
authors.forename: Masao
authors.initials: M
authors.lastname: Fukunaga
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D002762:Cholecalciferol / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D012307:Risk Factors; D016103:Spinal Fractures / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D006728:Hormones; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D; C547512:eldecalcitol