title: Changes in bone mineral density, bone turnover markers, and vertebral fracture risk reduction with once weekly teriparatide.
abstract: OBJECTIVE
  We aimed to evaluate the surrogacy of bone mineral density and bone turnover markers for incident vertebral fracture using data from 237 patients treated with once weekly 56.5 μg teriparatide or placebo.
  
  
  METHODS
  This analysis was conducted using data from the Teriparatide Once-Weekly Efficacy Research trial, a randomized, double-blind, placebo-controlled trial for patients with severe osteoporosis in Japan. A total of 237 subjects (placebo group, n = 130; teriparatide group, n = 107) were assessed at baseline and at 72 weeks. Main outcome measures included estimation of the treatment effects of once weekly teriparatide on vertebral fracture risk reduction using percentage changes in lumbar bone mineral density and bone turnover markers.
  
  
  RESULTS
  The percentage change in lumbar bone mineral density was 6.69% in the teriparatide group compared with 0.28% in the placebo group (p < 0.01). One incident vertebral fracture occurred in the teriparatide group compared with 16 in the placebo group. The unadjusted and adjusted hazard ratios of the teriparatide group compared with the placebo group were 0.07 (95% confidence interval: 0.01 to 0.56) and 0.64 (95% confidence interval: 0.06 to 6.36), respectively. The proportion of treatment effect explained by changes in lumbar bone mineral density was 83% (Freedman's method) and 66% (Chen's method). There were no notable changes in hazard ratios if we adjusted for bone turnover markers.
  
  
  CONCLUSIONS
  Most of the vertebral fracture risk reduction with once weekly 56.5 μg teriparatide is explained by changes in lumbar bone mineral density rather than changes in bone turnover markers.
authors.affiliation: Graduate School of Medicine and Public Health, Kyoto University , Kyoto , Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kuroda
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016103:Spinal Fractures / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019379:Teriparatide / Q000008:administration & dosage*
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D019379:Teriparatide