title: Strontium ranelate treatment improves trabecular and cortical intrinsic bone tissue quality, a determinant of bone strength.
abstract: Beside its influence on determinants of bone strength (geometry, microarchitecture), which is likely to be related to a cellular effect, strontium ranelate improves bone tissue quality as evaluated by nanoindentation, increasing elastic modulus, hardness, and dissipated energy in vertebrae of rats treated for 104 wk with daily dose from 0 to 900 mg/kg.
  
  
  BACKGROUND
  We previously showed that strontium ranelate treatment improves the mechanical properties of the vertebral body and long bone midshaft in intact rats. The increased energy to failure obtained with strontium ranelate is essentially caused by an increase in plastic energy, suggesting that bone formed during treatment can withstand greater deformation before fracture. In the bone mineral phase, strontium is mainly located in the hydrated shell and could thus potentially influence intrinsic bone tissue quality.
  
  
  METHODS
  To study whether strontium ranelate treatment could positively influence intrinsic bone tissue quality (elastic modulus, hardness, and dissipated energy), nanoindentation tests were performed at the level of trabecular nodes and cortex under physiological or dry conditions in vertebrae of rats treated for 104 wk with strontium ranelate at a daily dose of 0, 225, 450, or 900 mg/kg (n = 12 per group). Ex vivo microCT measurements and axial compression tests of adjacent vertebral bodies were also performed. Significance of difference was evaluated using ANOVA.
  
  
  RESULTS
  In agreement with previous results, strontium ranelate (900 mg/kg/d) [corrected] increased versus controls in maximal load (+23%), total energy (+71%), and plastic energy (+143%). At the level of trabecular bone, strontium ranelate treatment resulted in a significant increase in elastic modulus (+15.1%, p < 0.01), hardness (+11.5%, p < 0.05), and dissipated energy (+16.2%, p < 0.001) versus controls in physiological, but not in dry, conditions. The effect was less pronounced in cortex.
  
  
  CONCLUSIONS
  These results show for the first time a direct action of strontium ranelate on bone tissue quality. Beside its shown influence on classical determinants of bone strength (geometry, microarchitecture), which is likely to be related to a cellular effect, strontium ranelate improves bone tissue quality. This could contribute to the increase in bone strength and thus be involved in the reduction of fracture risk in postmenopausal osteoporotic patients treated with strontium ranelate.
authors.affiliation: Division of Bone Diseases, WHO Collaborting Centre for Osteoporosis Prevention, Department of Rehabilitation and Geriatrics, University Hospitals, Geneva, Switzerland. Patrick.Ammann@medicine.unige.ch
authors.forename: Patrick
authors.initials: P
authors.lastname: Ammann
authors.forename: Isabelle
authors.initials: I
authors.lastname: Badoud
authors.forename: Sébastien
authors.initials: S
authors.lastname: Barraud
authors.forename: Romain
authors.initials: R
authors.lastname: Dayer
authors.forename: René
authors.initials: R
authors.lastname: Rizzoli
mesh_terms: D000818:Animals; D005260:Female; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013131:Spine / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D013876:Thiophenes / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed
chemical_list: D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate