Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants

• Published in: Osteoporosis international 2009-08, Vol.20 (8), p.1417-1428
• Main Authors: Bain, S. D, Jerome, C, Shen, V, Dupin-Roger, I, Ammann, P
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - blood; Amino Acids - urine; Animals; Biological and medical sciences; Biomechanics. Biorheology; Bone biomechanics; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - therapeutic use; Bone intrinsic quality; Bone micro-architecture; Bone Remodeling - drug effects; Bones; Compressive Strength; Disease Models, Animal; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical - methods; Drug therapy; Endocrinology; Female; Fundamental and applied biological sciences. Psychology; Lumbar Vertebrae - drug effects; Lumbar Vertebrae - pathology; Lumbar Vertebrae - physiopathology; Medical sciences; Medicine; Medicine & Public Health; Organometallic Compounds - administration & dosage; Organometallic Compounds - therapeutic use; Original Article; Orthopedics; Osteoporosis - pathology; Osteoporosis - physiopathology; Osteoporosis - prevention & control; Osteoporosis. Osteomalacia. Paget disease; Ovariectomized rat; Ovariectomy; Rats; Rats, Sprague-Dawley; Rheumatology; Rodents; Strontium - blood; Strontium ranelate; Thiophenes - administration & dosage; Thiophenes - therapeutic use; Tissues, organs and organisms biophysics; X-Ray Microtomography
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-008-0815-8

Summary 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. Introduction 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. Conclusion 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.