title: Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial.
abstract: BACKGROUND
  Odanacatib, a cathepsin K inhibitor, increases spine and hip areal bone mineral density (BMD) in postmenopausal women with low BMD and cortical thickness in ovariectomized monkeys.
  
  
  OBJECTIVE
  The objective of the study was to examine the impact of odanacatib on the trabecular and cortical bone compartments and estimated strength at the hip and spine.
  
  
  METHODS
  This was a randomized, double-blind, 2-year trial.
  
  
  METHODS
  The study was conducted at a private or institutional practice.
  
  
  METHODS
  PARTICIPANTS included 214 postmenopausal women with low areal BMD.
  
  
  METHODS
  The intervention included odanacatib 50 mg or placebo weekly.
  
  
  METHODS
  Changes in areal BMD by dual-energy x-ray absorptiometry (primary end point, 1 year areal BMD change at lumbar spine), bone turnover markers, volumetric BMD by quantitative computed tomography (QCT), and bone strength estimated by finite element analysis were measured.
  
  
  RESULTS
  Year 1 lumbar spine areal BMD percent change from baseline was 3.5% greater with odanacatib than placebo (P < .001). Bone-resorption marker C-telopeptide of type 1 collagen was significantly lower with odanacatib vs placebo at 6 months and 2 years (P < .001). Bone-formation marker procollagen I N-terminal peptide initially decreased with odanacatib but by 2 years did not differ from placebo. After 6 months, odanacatib-treated women had greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD and estimated strength at the hip (P < .001). At the cortical envelope of the femoral neck, bone mineral content, thickness, volume, and cross-sectional area also increased from baseline with odanacatib vs placebo (P < .001 at 24 months). Adverse experiences were similar between groups.
  
  
  CONCLUSIONS
  Over 2 years, odanacatib decreased bone resorption, maintained bone formation, increased areal and volumetric BMD, and increased estimated bone strength at both the hip and spine.
authors: Department of Endocrinology, Institute of Clinical Research, University of Southern Denmark, DK-5000 Odense C., Denmark. kbrixen@health.sdu.dk
authors: Kim
authors: K
authors: Brixen
authors: Roland
authors: R
authors: Chapurlat
authors: Angela M
authors: AM
authors: Cheung
authors: Tony M
authors: TM
authors: Keaveny
authors: Thomas
authors: T
authors: Fuerst
authors: Klaus
authors: K
authors: Engelke
authors: Robert
authors: R
authors: Recker
authors: Bernard
authors: B
authors: Dardzinski
authors: Nadia
authors: N
authors: Verbruggen
authors: Shabana
authors: S
authors: Ather
authors: Elizabeth
authors: E
authors: Rosenberg
authors: Anne E
authors: AE
authors: de Papp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000000981:diagnostic imaging / Q000188:drug therapy*; D017698:Postmenopause; D011859:Radiography; D016896:Treatment Outcome
chemical_list: D001713:Biphenyl Compounds; D050071:Bone Density Conservation Agents; C527128:odanacatib