Bain S D, Jerome C, Shen V, Dupin-Roger I, Ammann P
Department Orthopaedics/Sports Medicine, University of Washington, Washington, USA.
Osteoporos Int. 2009 Aug;20(8):1417-28. doi: 10.1007/s00198-008-0815-8. Epub 2008 Dec 19.
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.
Strontium ranelate effects on the determinants of bone strength in OVX rats were evaluated.
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.
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.
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.
雷奈酸锶对成年去卵巢（OVX）大鼠的治疗可预防椎体生物力学性能的退化，这是由于其预防了与对骨内在材料质量的影响相关的骨质流失和微结构恶化。雷奈酸锶通过预防去卵巢诱导的变化来影响骨强度的决定因素，这有助于解释雷奈酸锶的抗骨折疗效。
评估了雷奈酸锶对OVX大鼠骨强度决定因素的影响。
成年雌性Sprague-Dawley大鼠接受去卵巢手术，然后每天用125、250或625mg雷奈酸锶/千克治疗52周。评估骨强度、质量、微结构、周转率和内在质量。
雷奈酸锶可预防去卵巢诱导的机械性能恶化，在625mg/千克/天（相当于临床剂量）时，骨折所需能量与假手术组完全相同。这与对骨体积、更高的小梁数量和雷奈酸锶组相对于OVX组更低的小梁间距的剂量依赖性效应有关。诱导薄片变形所需的负荷和能量在雷奈酸锶组高于OVX组和假手术组，表明用雷奈酸锶形成的骨在骨折前能够承受更大的损伤。如矿化表面和碱性磷酸酶所示，雷奈酸锶组的骨形成维持在高水平甚至增加，而雷奈酸锶导致脱氧吡啶啉减少。
每天给予625mg/千克的雷奈酸锶治疗52周可通过影响骨强度的决定因素来预防OVX诱导的生物力学性能恶化：它预防了骨质流失和微结构退化，并对骨内在质量产生影响。这些对骨的有益作用有助于解释雷奈酸锶的抗骨折疗效。
