Ozasa Ryosuke, Saito Mitsuru, Ishimoto Takuya, Matsugaki Aira, Matsumoto Yoshihiro, Nakano Takayoshi
Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Department of Orthopaedic Surgery, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.
Bone. 2022 Apr;157:116309. doi: 10.1016/j.bone.2021.116309. Epub 2022 Jan 5.
Combination therapy with bisphosphonates and vitamin D analogs has been frequently used for the treatment of osteoporosis. However, its effects on bone anisotropies, such as orientations of collagen and apatite at the nanometer-scale, which is a promising bone quality index, and its trabecular architecture at the micrometer scale, are not well understood despite its important mechanical properties and its role in fracture risk. In the present study, we analyzed the effects of ibandronate (IBN), eldecalcitol (ELD), and their combination on the collagen/apatite orientation and trabecular architectural anisotropy using an estrogen-deficiency-induced osteoporotic rat model. Estrogen deficiency caused by ovariectomy (OVX) excessively increased the degree of collagen/apatite orientation or trabecular architectural anisotropy along the craniocaudal axis in the lumbar vertebra compared to that of the sham-operated group. The craniocaudal axis corresponds to the direction of principal stress in the spine. The excessive material anisotropy in the craniocaudal axis contributed to the enhanced Young's modulus, which may compensate for the reduced mechanical resistance by bone loss to some extent. The solo administration of IBN and ELD prevented the reduction of bone fraction (BV/TV) determined by μ-CT, and combination therapy showed the highest efficacy in BV/TV gain. Furthermore, the solo administration and combination treatment significantly decreased the degree of collagen/apatite orientation to the sham level. Based on the results of bone mass and collagen/apatite orientation, combination treatment is an effective strategy. This is the first report to demonstrate the efficacy of IBN, ELD, and combination treatment with IBN and ELD relative to the bone micro-architectural anisotropy characterized by collagen/apatite orientation.
双膦酸盐和维生素D类似物的联合疗法已被频繁用于治疗骨质疏松症。然而，尽管其具有重要的力学性能且在骨折风险中起作用，但其对骨各向异性的影响，如纳米级胶原蛋白和磷灰石的取向（这是一个有前景的骨质量指标）以及微米级小梁结构的影响，仍未得到充分了解。在本研究中，我们使用雌激素缺乏诱导的骨质疏松大鼠模型，分析了伊班膦酸钠（IBN）、 eldecalcitol（ELD）及其组合对胶原蛋白/磷灰石取向和小梁结构各向异性的影响。与假手术组相比，卵巢切除术（OVX）导致的雌激素缺乏使腰椎沿头尾轴的胶原蛋白/磷灰石取向程度或小梁结构各向异性过度增加。头尾轴对应于脊柱主应力的方向。头尾轴上过度的材料各向异性导致杨氏模量增加，这可能在一定程度上补偿因骨质流失而降低的机械阻力。单独给予IBN和ELD可防止通过μ-CT测定的骨分数（BV/TV）降低，联合治疗在增加BV/TV方面显示出最高疗效。此外，单独给药和联合治疗均显著降低了胶原蛋白/磷灰石取向程度至假手术组水平。基于骨量和胶原蛋白/磷灰石取向的结果，联合治疗是一种有效的策略。这是第一份证明IBN、ELD以及IBN与ELD联合治疗相对于以胶原蛋白/磷灰石取向为特征的骨微结构各向异性的疗效的报告。
