The Role of Bone in Osteoarthritis Progression

描述（由申请人提供）：关节周围骨的解剖学和生物力学特性在关节载荷力的分散中起主要作用。事实上，与关节软骨仅吸收1-3%相比，膝关节上30-50%的载荷被关节周围骨吸收。关节周围骨对载荷力的衰减对于保护关节软骨免受损伤至关重要。然而，软骨下骨增厚和关节周围骨小梁结构破坏发生在骨关节炎（OA）的早期，甚至可能先于软骨损伤。这些变化，以及后来由“囊肿”、磨损和小梁塌陷（常见于OA）引起的软骨下骨的大体病理性破坏，可能会损害关节周围骨减弱压缩力的能力，并进一步倾向于进展。临床研究进一步证明关节周围骨的病理过程影响OA的病程。膝关节骨性关节炎伴关节周围MRI异常或MRI显示软骨下骨髓病变的患者，其进展风险更大。全身骨骼健康的指标，如骨密度（BMD）和维生素D也强烈影响OA进展的风险。这表明OA等同器械中关节周围骨反应的性质是稳定或进展，这可能受到全身骨因素（如BMD和维生素D）的影响。这些观察结果迫使我们研究关节周围骨在OA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措施。对双能X线骨密度仪（DXA）和磁共振成像（MRI）方案的技术改进为测量关节周围骨的BMD和骨小梁形态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，在大样本中研究膝关节和全身骨因素在膝关节OA进展中的作用，其综合评价包括每年通过3特斯拉MRI测量软骨体积。拟定的辅助研究将部署在进展子队列中，并将增加双膝和右股骨颈的纵向DXA BMD测量、使用高分辨率MRI的膝关节周围骨小梁形态测定、骨髓病变、囊肿和骨小梁损伤评分、血清25-羟基维生素D、甲状旁腺素（PTH）和维生素D受体基因分型。所有这些数据将在特定时间点加入和丰富审调处的公共数据集。

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.