Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate

J Bone Miner Res. 2008 Feb;23(2):215-22. doi: 10.1359/jbmr.071012.

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.

Introduction: 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.

Materials and 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.

Results and 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.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biopsy
  • Bone Remodeling / drug effects
  • Double-Blind Method
  • Female
  • Histocytochemistry
  • Humans
  • Ilium / drug effects*
  • Ilium / pathology
  • Middle Aged
  • Organometallic Compounds / adverse effects
  • Organometallic Compounds / therapeutic use*
  • Osteoblasts / drug effects
  • Osteoblasts / pathology
  • Osteogenesis / drug effects
  • Osteoporosis, Postmenopausal / diagnostic imaging
  • Osteoporosis, Postmenopausal / drug therapy*
  • Postmenopause
  • Thiophenes / adverse effects
  • Thiophenes / therapeutic use*
  • Time
  • Tomography, X-Ray Computed / instrumentation
  • Tomography, X-Ray Computed / methods

Substances

  • Organometallic Compounds
  • Thiophenes
  • strontium ranelate