Fernández-Martín Silvia, Permuy María, López-Peña Mónica, Muñoz Fernando, González-Cantalapiedra Antonio
Department of Anatomy, Animal Production and Veterinary Clinical Sciences, Veterinary Faculty, Universidad de Santiago de Compostela, Lugo, Spain.
Front Vet Sci. 2020 Nov 2;7:576212. doi: 10.3389/fvets.2020.576212. eCollection 2020.
Osteoarthritis (OA) is the most prevalent degenerative joint disease in animals and humans. It is characterized by pain, articular cartilage damage and joint stiffness. It has been suggested that the status of the subchondral bone compartment plays an important role in the initiation and progression of OA. Bisphosphonates have been proposed as a potential disease-modifying treatment for OA, however their effectiveness is not yet clear. Twenty-four male adult New Zealand rabbits were used to evaluate the effects of risedronate on the subchondral bone quality and cartilage degradation in a long-term model of experimentally induced OA. Animals underwent an anterior cruciate ligament transection and partial medial meniscectomy or sham operation in only one knee, which was randomly chosen, using the contralateral as healthy control. Animals were divided into three groups ( = 8): untreated control group and sham surgery control group; both groups received only vehicle; and risedronate group, treated with 2.5 mg orally weekly for 24 weeks. Stifle joints were harvested and scanned using a high-resolution micro-CT to evaluate the subchondral plate and trabecular bone changes. The macroscopic evaluation and histological analysis were determined using an adapted Osteoarthritis Research Society International scoring scheme to assess the cartilage degeneration. The lateral and medial femoral condyle and tibial plateau were evaluated. Additionally, the histological synovial membrane assessment was carried out. Sample analysis showed that the experimental model induced osteoarthritic changes in the operated joints, whereas in sham-operated rabbits, almost no histological changes were observed on articular cartilage surfaces. In terms of macroscopic and histological analyses, risedronate-treated animals did not show improved cartilage health compared with untreated operated rabbits, but a slightly anti-inflammatory activity was observed in the synovial membrane. Risedronate administration showed a slight tendency to increase subchondral bone plate thickness in lateral compartments but, it did not show conservation of periarticular bone and was not be able to suppress the osteophyte formation. In conclusion, long-term risedronate use did not demonstrate a positive effect on reducing the cartilage damage, and failed to prevent the subchondral bone changes and osteophytogenesis in an experimental rabbit model of OA.
骨关节炎（OA）是动物和人类中最常见的退行性关节疾病。其特征为疼痛、关节软骨损伤和关节僵硬。有研究表明，软骨下骨腔室的状态在OA的发生和发展中起着重要作用。双膦酸盐已被提议作为一种潜在的改善OA病情的治疗方法，但其有效性尚不清楚。本研究使用24只成年雄性新西兰兔，在长期实验性诱导OA模型中评估利塞膦酸盐对软骨下骨质量和软骨降解的影响。动物仅在一侧膝关节进行前交叉韧带切断术和部分内侧半月板切除术或假手术，随机选择一侧膝关节，对侧作为健康对照。动物分为三组（每组n = 8）：未治疗对照组和假手术对照组，两组均仅给予赋形剂；利塞膦酸盐组，每周口服2.5 mg，持续24周。采集膝关节并使用高分辨率微型计算机断层扫描（micro-CT）进行扫描，以评估软骨下板和小梁骨的变化。采用国际骨关节炎研究学会改良评分方案进行宏观评估和组织学分析，以评估软骨退变情况。对股骨内外侧髁和胫骨平台进行评估。此外，还进行了组织学滑膜评估。样本分析表明，实验模型在手术关节中诱导了骨关节炎变化，而在假手术兔中，关节软骨表面几乎未观察到组织学变化。在宏观和组织学分析方面，与未治疗的手术兔相比，利塞膦酸盐治疗的动物软骨健康状况并未改善，但在滑膜中观察到轻微的抗炎活性。利塞膦酸盐给药显示外侧腔室软骨下骨板厚度有轻微增加的趋势，但未显示关节周围骨的保存，也无法抑制骨赘形成。总之，在实验性兔OA模型中，长期使用利塞膦酸盐对减少软骨损伤未显示出积极作用，也未能预防软骨下骨变化和骨赘形成。
