Center for Musculoskeletal Regeneration, Houston Methodist Academic Institute, Houston, TX 77030, USA.
Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX 77030, USA.
Int J Mol Sci. 2023 Jun 20;24(12):10386. doi: 10.3390/ijms241210386.
Osteoarthritis (OA) is one of the most common degenerative diseases of articular cartilage. During OA, all the elements that contribute to the joint undergo physiological and structural changes that impair the joint function and cause joint pain and stiffness. OA can arise naturally, with the aging population witnessing an increase in diagnoses of this pathology, but the root causes of OA have yet to be identified, and increasing interest is arising towards investigating biological sex as a risk factor. Clinical studies show increased prevalence and worse clinical outcomes for female patients, yet most clinical and preclinical studies have disproportionately focused on male subjects. This review provides a critical overview of preclinical practices in the context of OA, highlighting the underlying need for taking biological sex as both a risk factor and an important component affecting treatment outcome. A unique insight into the possible reasons for female underrepresentation in preclinical studies is offered, including factors such as lack of specific guidelines requiring the analysis of sex as a biological variable (SABV), research-associated costs and animal handling, and wrongful application of the reduction principle. Additionally, a thorough investigation of sex-related variables is provided, stressing how each of them could add valuable information for the understanding of OA pathophysiology, as well as sex-dependent treatment strategies.
骨关节炎（OA）是关节软骨最常见的退行性疾病之一。在 OA 中，所有导致关节的因素都会发生生理和结构变化，从而损害关节功能并引起关节疼痛和僵硬。OA 可能是自然发生的，随着人口老龄化，这种病理学的诊断有所增加，但 OA 的根本原因尚未确定，人们越来越关注将生物性别视为一个风险因素。临床研究表明，女性患者的患病率增加，临床结局更差，但大多数临床前和临床研究都不成比例地侧重于男性受试者。本综述在 OA 背景下对临床前实践进行了批判性概述，强调了将生物性别作为风险因素和影响治疗结果的重要因素的必要性。本文还提供了对女性在临床前研究中代表性不足的可能原因的独特见解，包括缺乏要求将性别作为生物学变量进行分析的具体指南、与研究相关的成本和动物处理、以及错误应用简化原则等因素。此外，还对与性别相关的变量进行了彻底调查，强调了它们中的每一个如何为理解 OA 病理生理学以及基于性别的治疗策略提供有价值的信息。
