The Role of Bone in Osteoarthritis Progression

描述(申请人提供)：关节周围骨的解剖和生物力学特性在整个关节的负荷力分散中起主要作用。事实上，膝关节上30%-50%的负荷被关节周围的骨骼吸收，相比之下，关节软骨只吸收了1%-3%。在保护关节软骨免受损伤方面，关节周围骨对负荷力的减弱起着至关重要的作用。然而，软骨下骨的增厚和关节周围骨小梁结构的破坏在骨性关节炎(OA)早期就发生了，甚至可能早于软骨损伤。这些改变，再加上软骨下骨的严重病理性破坏，如“囊肿”、磨损和骨小梁塌陷(在骨性关节炎中常见)，可能会削弱关节周围骨减弱压力的能力，并进一步易于进展。临床研究进一步证实，关节周围骨的病理过程影响骨性关节炎的病程。有异常关节周围核素扫描表现或MRI上软骨下骨髓病变的OA膝关节，进展的风险更大。衡量全身骨健康的指标，如骨密度(BMD)和维生素D，也强烈影响骨性关节炎进展的风险。这表明，骨关节炎关节周围骨反应的性质预示着稳定或进展，这可能受到全身骨因素的影响，如骨密度和维生素D。这些观察迫使我们研究关节周围骨在骨关节炎中的纵向作用，以增加对进展机制的理解，完善预测模型，并提出组织靶向干预建议。对双X射线骨密度仪(DXA)和磁共振成像(MRI)方案的技术改进为关节周围骨密度和骨小梁形态的测量提供了有吸引力的方法。骨关节炎倡议(OAI)队列提供了一个无与伦比的机会，可以在大样本中研究关节周围和全身骨因素在膝骨性关节炎进展中的作用，大样本的综合评估包括通过3-TESLA MRI每年测量软骨体积。拟议的辅助研究将部署在进展子队列中，并将增加双膝和右侧股骨颈的纵向DXA骨密度测量、使用高分辨率MRI的膝关节周围小梁形态测量、骨髓病变、囊肿和半月板损伤评分、血清25-羟基维生素D、甲状旁腺激素(PTH)和维生素D受体基因分型。所有这些数据都将在特定的时间点加入和丰富OAI公共数据集。

DESCRIPTION (provided by applicant): The anatomic and biomechanical properties of peri-articular bone play a primary role in the dispersion of loading forces across the joint. Indeed, 30-50% of a load across a knee is absorbed by peri-articular bone compared to only 1-3% by articular cartilage. The attenuation of loading forces by peri-articular bone is critical in protecting articular cartilage from damage. However, thickening of subchondral bone and disruption of peri-articular trabecular architecture occur early in osteoarthritis (OA), and may even antedate cartilage damage. These changes, together with the later development of gross pathological disruption of subchondral bone by 'cysts', attrition and trabecular collapse (common in OA), are likely to impair the capability of peri-articular bone to attenuate compressive forces and further predispose to progression. Clinical studies provide further evidence that pathological processes in peri-articular bone influence the course of OA. OA knees with abnormal peri-articular scintigraphic appearances, or subchondral bone marrow lesions on MRI, have greater risk for progression. Measures of systemic bone health such as bone density (BMD) and vitamin D also strongly influence the risk of OA progression. This suggests that the nature of the peri-articular bone response in OA predicates stabilization or progression, and that this may be influenced by systemic bone factors such as BMD and vitamin D. These observations compel us to study the longitudinal role of peri-articular bone in OA to increase understanding of the mechanisms of progression, refine predictive models, and suggest tissue-targeted interventions. Technical modifications to dual x-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) protocols offer appealing approaches to measurement of BMD and trabecular morphology of peri-articular bone. The Osteoarthritis Initiative (OAI) cohort provides an unequalled opportunity to study the role of peri- articular and systemic bone factors in the progression of knee OA in a large sample whose comprehensive evaluations include annual measurement of cartilage volume by 3-Tesla MRI. The proposed ancillary study would be deployed in the progression subcohort and would add longitudinal DXA BMD measurement of both knees and right femoral neck, knee peri-articular trabecular morphometry using high-resolution MRI, bone marrow lesion, cyst and meniscal damage scores, serum 25-hydroxy vitamin D, parathormone (PTH), and vitamin D receptor genotyping. All these data will join and enrich the OAI public data set at specified time points.