title: Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate.
abstract: Strontium ranelate is a new anti-osteoporotic treatment. On bone biopsies collected from humans receiving long-term treatment over 5 yr, it has been shown that strontium ranelate has good bone safety and better results than placebo on 3D microarchitecture. Hence, these effects may explain the decreased fracture rate.
  
  
  BACKGROUND
  Strontium ranelate's mode of action involving dissociation of bone formation and resorption was shown in preclinical studies and could explain its antifracture efficacy in humans.
  
  
  METHODS
  One hundred forty-one transiliac bone biopsies were obtained from 133 postmenopausal osteoporotic women: 49 biopsies after 1-5 yr of 2 g/d strontium ranelate and 92 biopsies at baseline or after 1-5 yr of placebo.
  
  
  CONCLUSIONS
  Histomorphometry provided a 2D demonstration of the bone safety of strontium ranelate, with significantly higher mineral apposition rate (MAR) in cancellous bone (+9% versus control, p = 0.019) and borderline higher in cortical bone (+10%, p = 0.056). Osteoblast surfaces were significantly higher (+38% versus control, p = 0.047). 3D analysis of 3-yr biopsies with treatment (20 biopsies) and placebo (21 biopsies) using microCT showed significant changes in microarchitecture with, in the strontium ranelate group, higher cortical thickness (+18%, p = 0.008) and trabecular number (+14%, p = 0.05), and lower structure model index (-22%, p = 0.01) and trabecular separation (-16%, p = 0.04), with no change in cortical porosity. The changes in 3D microarchitecture may enhance bone biomechanical competence and explain the decreased fracture rate with strontium ranelate.
authors.affiliation: INSERM, Université Lyon 1, Lyon, France. Monique.Arlot@sante.univ-lyon1.fr
authors.forename: Monique E
authors.initials: ME
authors.lastname: Arlot
authors.forename: Yebin
authors.initials: Y
authors.lastname: Jiang
authors.forename: Harry K
authors.initials: HK
authors.lastname: Genant
authors.forename: Jenny
authors.initials: J
authors.lastname: Zhao
authors.forename: Brigitte
authors.initials: B
authors.lastname: Burt-Pichat
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Roux
authors.forename: Pierre D
authors.initials: PD
authors.lastname: Delmas
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Meunier
mesh_terms: D000368:Aged; D001706:Biopsy; D016723:Bone Remodeling / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007085:Ilium / Q000187:drug effects* / Q000473:pathology; D008875:Middle Aged; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000000981:diagnostic imaging / Q000188:drug therapy*; D017698:Postmenopause; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013995:Time; D014057:Tomography, X-Ray Computed / Q000295:instrumentation / Q000379:methods
chemical_list: D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate