A Systems View of Risk Factors for Knee Osteoarthritis Reveals Insights into the Pathogenesis of the Disease
A Systems View of Risk Factors for Knee Osteoarthritis Reveals Insights into the Pathogenesis of the Disease
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DOI：
10.1007/s10439-014-1117-2
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发表时间：
2015-02-01
影响因子：
3.8
通讯作者：
Chu, Constance R.
中科院分区：
文献类型：
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作者：
Andriacchi, Thomas P.;Favre, Julien;Chu, Constance R.
骨关节炎（OA）的早期检测仍然是一个关键但尚未解决的多方面问题。为了解决骨性关节炎的多面性，我们开发了一个系统模型，以整合骨性关节炎的生物学、力学和结构组成部分的许多观察结果，并确定骨性关节炎的主要危险因素（衰老、肥胖和关节创伤）的共同特征，这些特征在临床骨性关节炎发展之前就存在。该分析支持OA发病机制的统一观点，即当疾病的一个组成部分（例如，机械性）变得异常时，发生OA的风险就出现了，而与其他组成部分（例如，生物和/或结构）的相互作用影响了最终的软骨破裂和进展为临床OA。该模型以刺激-反应形式应用，结果表明，在5年随访中，基线机械刺激可以提高生物标志物预测膝关节OA患者软骨变薄的敏感性。系统方法提供了对疾病发病机制的新认识，并为开展多学科研究提供了基础，以便在疾病改造最有可能取得成功的阶段解决早期发现和治疗问题。
Early detection of osteoarthritis (OA) remains a critical yet unsolved multifaceted problem. To address the multifaceted nature of OA a systems model was developed to consolidate a number of observations on the biological, mechanical and structural components of OA and identify features common to the primary risk factors for OA (aging, obesity and joint trauma) that are present prior to the development of clinical OA. This analysis supports a unified view of the pathogenesis of OA such that the risk for developing OA emerges when one of the components of the disease (e.g., mechanical) becomes abnormal, and it is the interaction with the other components (e.g., biological and/or structural) that influences the ultimate convergence to cartilage breakdown and progression to clinical OA. The model, applied in a stimulus-response format, demonstrated that a mechanical stimulus at baseline can enhance the sensitivity of a biomarker to predict cartilage thinning in a 5 year follow-up in patients with knee OA. The systems approach provides new insight into the pathogenesis of the disease and offers the basis for developing multidisciplinary studies to address early detection and treatment at a stage in the disease where disease modification has the greatest potential for a successful outcome.