Department Orthopaedic Surgery, Stanford University, Stanford, California, USA.
Department of Surgery, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA.
J Orthop Res. 2021 Aug;39(8):1585-1595. doi: 10.1002/jor.25045. Epub 2021 Apr 29.
Osteoarthritis (OA) is a leading cause of pain and disability for which disease-modifying treatments remain lacking. This is because the symptoms and radiographic changes of OA occur after the onset of likely irreversible changes. Defining and treating earlier disease states are therefore needed to delay or to halt OA progression. Taking this concept a step further, studying OA pathogenesis before disease onset by characterizing potentially reversible markers of increased OA risk to identify a state of "pre-osteoarthritis (pre-OA)" shifts the paradigm towards OA prevention. The purpose of this review is to summarize the 42 studies comprising the 2019 Kappa Delta Elizabeth Lanier Award where conceptualization of a systems-based definition for "pre-osteoarthritis (pre-OA)" was followed by demonstration of potentially reversible markers of heightened OA risk in patients after anterior cruciate ligament (ACL) injury and reconstruction. In the process, these efforts contributed a new magnetic resonance imaging method of ultrashort echo time (UTE) enhanced T2* mapping to visualize joint tissue damage before the development of irreversible changes. The studies presented here support a transformative approach to OA that accounts for interactions between mechanical, biological, and structural markers of OA risk to develop and evaluate new treatment strategies that can delay or prevent the onset of clinical disease. This body of work was inspired by and performed for patients. Shifting the paradigm from attempting to modify symptomatic radiographic OA towards monitoring and reversing markers of "pre-OA" opens the door for transforming the clinical approach to OA from palliation to prevention.
骨关节炎(OA)是导致疼痛和残疾的主要原因,但目前仍缺乏针对这种疾病的治疗方法。这是因为 OA 的症状和影像学改变发生在可能发生不可逆变化之后。因此,需要定义和治疗更早的疾病状态,以延迟或阻止 OA 的进展。更进一步,通过描述增加 OA 风险的潜在可逆标志物,在疾病发生前研究 OA 的发病机制,以确定“前骨关节炎(pre-OA)”状态,将范式转变为 OA 的预防。本综述的目的是总结 2019 年 Kappa Delta Elizabeth Lanier 奖的 42 项研究,这些研究提出了一种基于系统的“前骨关节炎(pre-OA)”概念,随后在 ACL 损伤和重建后的患者中证明了潜在的可逆的 OA 风险标志物。在此过程中,这些努力提出了一种新的磁共振成像方法——超短回波时间(UTE)增强 T2* 映射,以在不可逆变化发生之前可视化关节组织损伤。这里介绍的研究支持了一种对 OA 的变革性方法,该方法考虑了 OA 风险的机械、生物和结构标志物之间的相互作用,以开发和评估可以延迟或预防临床疾病发生的新治疗策略。这项工作的灵感来自于患者,并为患者而开展。将试图改变有症状的放射影像学 OA 的范式转变为监测和逆转“pre-OA”标志物,为 OA 的临床治疗从缓解转向预防打开了大门。