State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Bone. 2013 Apr;53(2):340-9. doi: 10.1016/j.bone.2012.12.044. Epub 2013 Jan 2.
Osteoporosis (OP) and osteoarthritis (OA) are major health problems in the increasing elderly population, particularly in postmenopausal women, but their relationship remains unclear. The present study investigated whether alendronate (ALN), a potent inhibitor of bone resorption, could protect articular cartilage from degeneration in a combined animal model of OP and OA induced by ovariectomy (OVX). Seventy-eight seven-month-old female Sprague-Dawley rats were assigned into five experimental groups: (1) sham-operated with vehicle treatment, (2) sham-operated with ALN treatment, (3) OVX with vehicle treatment, (4) ALN treatment starting at OVX, and (5) ALN treatment starting at eight weeks after OVX. Histological and micro-CT analyses, together with urine collagen degradation markers, indicated that early ALN treatment completely prevented both subchondral bone loss and cartilage surface erosion induced by OVX. Although late ALN treatment also inhibited subchondral bone loss and significantly reduced cartilage erosion in the OVX rats, these tissues did not completely recover even after 10-weeks of ALN treatment. Quantitative RT-PCR analyses showed that the protective effect of ALN correlated with increased ratio of OPG/RANKL in both subchondral bone and cartilage. Moreover, whereas OVX caused upregulation of expression of matrix metalloproteinases MMP-13 and MMP-9 in the articular cartilage and chondrocytes in the interface between the articular cartilage and subchondral bone, respectively, early ALN treatment blocked whereas late ALN treatment attenuated the upregulation of these catabolic enzymes in the corresponding tissues. Together, these data indicate that the subchondral bone loss plays an important role in OA pathogenesis in the combined OP and OA model and suggest that treatment timing is an important factor for the effectiveness of anti-resorptive drug therapy of combined OP and OA.
骨质疏松症（OP）和骨关节炎（OA）是老年人口增长中主要的健康问题，尤其是绝经后妇女，但它们之间的关系尚不清楚。本研究探讨了骨吸收抑制剂阿仑膦酸钠（ALN）是否可以在去卵巢（OVX）诱导的 OP 和 OA 联合动物模型中保护关节软骨免受退变。将 78 只 7 月龄雌性 Sprague-Dawley 大鼠分为 5 个实验组：（1）假手术+ vehicle 处理组，（2）假手术+ ALN 处理组，（3）OVX+ vehicle 处理组，（4）OVX 时开始 ALN 处理组，（5）OVX 后 8 周开始 ALN 处理组。组织学和 micro-CT 分析以及尿胶原降解标志物表明，早期 ALN 处理完全阻止了 OVX 引起的软骨下骨丢失和软骨表面侵蚀。尽管晚期 ALN 处理也抑制了 OVX 大鼠的软骨下骨丢失并显著减少了软骨侵蚀，但即使在 10 周的 ALN 处理后，这些组织也没有完全恢复。定量 RT-PCR 分析表明，ALN 的保护作用与软骨下骨和软骨中 OPG/RANKL 比值的增加有关。此外，OVX 导致关节软骨和软骨下骨交界处的软骨细胞中基质金属蛋白酶 MMP-13 和 MMP-9 的表达上调，而早期 ALN 处理阻断了这些蛋白的上调，而晚期 ALN 处理则减弱了这些蛋白的上调。总之，这些数据表明，软骨下骨丢失在联合 OP 和 OA 模型中的 OA 发病机制中起重要作用，并提示治疗时机是抗吸收药物治疗联合 OP 和 OA 的有效性的重要因素。
