Data_Sheet_3_Histomorphometric Quantitative Evaluation of Long-Term Risedronate Use in a Knee Osteoarthritis Rabbit Model.PDF

Osteoarthritis (OA) treatment is a major orthopedic challenge given that there is no ideal drug capable to reverse or stop the progression of the OA. In that regard, bisphosphonates have been proposed as potential disease-modifying drugs due to their possible chondroprotective effect related to obtaining a greater subchondral bone quality. However, their effectiveness in OA is still controversial and additionally, there is little evidence focused on their long-term effect in preclinical studies. The aim of this study was to evaluate the risedronate quantitative effect on articular and subchondral periarticular bone by histomorphometry, in an experimental rabbit model in an advanced stage of OA. Twenty-four adult New Zealand rabbits were included in the study. OA was surgically induced in one randomly chosen knee, using the contralateral as healthy control. Animals were divided into three groups (n = 8): placebo control group, sham surgery group and risedronate-treated group. After 24 weeks of treatment, cartilage and subchondral femorotibial pathology was evaluated by micro-computed tomography (micro-CT) and undecalcified histology. The research results demonstrated that the experimental animal model induced osteoarthritic changes in the operated joints, showing an increased cartilage thickness and fibrillation associated with underlying subchondral bone thinning and decreased trabecular bone quality. These changes were especially highlighted in the medial tibial compartments as a possible response to surgical instability. Regarding the trabecular analysis, significant correlations were found between 2D histomorphometry and 3D imaging micro-CT for the trabecular bone volume, trabecular separation, and the trabecular number. However, these associations were not strongly correlated, obtaining more precise measurements in the micro-CT analysis. Concerning the long-term risedronate treatment, it did not seem to have the capacity to reduce the osteoarthritic hypertrophic cartilage response and failed to diminish the superficial cartilage damage or prevent the trabecular bone loss. This study provides novel information about the quantitative effect of long-term risedronate use on synovial joint tissues.

骨关节炎（Osteoarthritis, OA）的治疗一直是骨科领域的重大难题，目前尚无理想药物能够逆转或阻断OA的病情进展。鉴于此，双膦酸盐（bisphosphonates）因可能通过提升软骨下骨质量发挥软骨保护作用，被视为潜在的OA疾病修饰药物。然而，其用于OA治疗的有效性仍存在争议，且目前临床前研究中针对其长期疗效的相关证据较为匮乏。本研究旨在通过组织形态计量学（histomorphometry）方法，在OA晚期实验兔模型中评估利塞膦酸钠（risedronate）对关节及软骨下骨周围组织的量化作用。本研究共纳入24只成年新西兰兔，通过手术在其中一侧随机选取的膝关节诱导OA模型，并以对侧膝关节作为健康对照。将实验兔随机分为3组（每组n=8）：安慰剂对照组、假手术组及利塞膦酸钠给药组。给药24周后，通过显微计算机断层扫描（micro-computed tomography, micro-CT）及非脱钙组织学方法，评估股骨胫骨关节的软骨及软骨下骨病理变化。研究结果显示，手术造模组的膝关节出现了OA病理改变：软骨厚度增加、出现纤维样变，同时伴随下方软骨下骨骨质变薄及骨小梁质量下降。此类病理改变在胫骨内侧间室尤为显著，这可能与手术导致的关节不稳定相关。在骨小梁分析中，二维组织形态计量学与三维显微CT成像在骨小梁体积、骨小梁间距及骨小梁数量这三项指标上存在显著相关性，但此类关联并未达到强相关程度，且显微CT分析可获得更为精准的测量结果。关于长期利塞膦酸钠给药的疗效，结果显示其既无法减轻OA所致的软骨肥厚反应，也未能缓解表层软骨损伤或阻止骨小梁骨质丢失。本研究为长期使用利塞膦酸钠对滑膜关节组织的量化影响提供了全新的研究数据。