Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants.
CONCLUSIONS
Treatment of adult ovariectomized (OVX) rats with strontium ranelate prevented vertebral biomechanics degradation as a result of the prevention of bone loss and micro-architecture deterioration associated to an effect on intrinsic bone material quality. Strontium ranelate influenced the determinants of bone strength by prevention of ovariectomy-induced changes which contribute to explain strontium ranelate antifracture efficacy.


BACKGROUND
Strontium ranelate effects on the determinants of bone strength in OVX rats were evaluated.


METHODS
Adult female Sprague-Dawley rats were OVX, then treated daily for 52 weeks with 125, 250, or 625 mg strontium ranelate/kg. Bone strength, mass, micro-architecture, turnover, and intrinsic quality were assessed.


RESULTS
Strontium ranelate prevented ovariectomy-induced deterioration in mechanical properties with energy necessary for fracture completely maintained vs. SHAM at 625 mg/kg/day, which corresponds to the clinical dose. This was related to a dose-dependent effect on bone volume, higher trabeculae number, and lower trabecular separation in strontium ranelate vs. OVX. Load and energy required to induce lamella deformation were higher with strontium ranelate than in OVX and in SHAM, indicating that the bone formed with strontium ranelate is able to withstand greater damage before fracture. Bone formation was maintained high or even increased in strontium ranelate as shown by mineralizing surfaces and alkaline phosphatase while strontium ranelate led to reductions in deoxypyridinoline.


CONCLUSIONS
Strontium ranelate administered at 625 mg/kg/day for 52 weeks prevented OVX-induced biomechanical properties deterioration by influencing the determinants of bone strength: it prevented bone loss and micro-architecture degradation in association with an effect on intrinsic bone quality. These beneficial effects on bone contribute to explain strontium ranelate antifracture efficacy.
Bain
S D
SD
Department Orthopaedics/Sports Medicine, University of Washington, Washington, USA. sdbain@u.washington.edu
Jerome
C
C
Shen
V
V
Dupin-Roger
I
I
Ammann
P
P
D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D019245:Compressive Strength; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D010024:Osteoporosis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013324:Strontium / Q000097:blood; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*; D055114:X-Ray Microtomography
D000596:Amino Acids; D050071:Bone Density Conservation Agents; D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase; D013324:Strontium