Steps Towards OA Prevention

预防 OA 的步骤

• 批准号: 10642327
• 负责人: Caroline M Lisee
• 金额: $ 12.09万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642327
• 关键词: Affect; Animal Model; Biology; Biomechanics; Cartilage; Clinical Research; Clinical Trials; Collagen; Cross-Sectional Studies; Data; Degenerative polyarthritis; Development; Frequencies; Funding; Future; Goals; Health; Individual; Intervention; Joints; K-Series Research Career Programs; Knee Osteoarthritis; Knee joint; Knowledge; Laboratories; Limb structure; Link; Magnetic Resonance Imaging; Measures; Mechanics; Medial; Mentors; Mission; Observational Study; Participant; Persons; Physical activity; Pilot Projects; Population; Pre-Post Tests; Prevention; Prevention Research; Prevention strategy; Principal Investigator; Productivity; Proteoglycan; Public Health; Quality of life; Randomized, Controlled Trials; Recommendation; Reconstructive Surgical Procedures; Relaxation; Research; Research Design; Research Personnel; Rest; Risk; Risk Factors; Risk Reduction; Series; Sports Medicine; Standardization; Surrogate Endpoint; Testing; Thick; Time; Training; Traumatic Arthropathy; United States; United States National Institutes of Health; Walking; anterior cruciate ligament injury; anterior cruciate ligament reconstruction; arm; career; career development; clinical trial implementation; density; disability; disorder prevention; efficacy evaluation; health assessment; high risk; high risk population; human subject; improved; in vivo; innovation; joint loading; mechanical load; novel; physical inactivity; pilot test; preventive intervention; reconstruction; resilience; response; risk mitigation; skill acquisition; skills; theories

PROJECT SUMMARY/ABSTRACT Osteoarthritis (OA) is a leading cause of disability. Identifying modifiable mechanisms of poor knee joint health development for disease prevention strategies are critical to improving long-term health. Aberrant mechanical loading has been theorized as a primary risk factor for knee OA. Most studies primarily focus on mechanical mechanisms of excessive joint loading in OA development. However, recent evidence suggests that joint underloading may also play a role. The effects of low loading frequency assessed via daily steps in real world settings on knee joint health is an understudied parameter of aberrant mechanical loading in individuals at risk for OA. Individuals with anterior cruciate ligament (ACL) injury who undergo ACL reconstruction (ACLR) surgery are a representative population to assess the effects of low loading frequency on knee joint health because they are at elevated risk for posttraumatic OA development and demonstrate low daily steps compared to uninjured individuals. Therefore, the overall study objective is to determine the mechanistic links between joint loading frequency and comprehensive magnetic resonance imaging (MRI) measures of knee joint cartilage health in individuals post-ACLR. The central hypothesis is that individuals post-ACLR who take low daily steps will demonstrate deconditioned, less resilient cartilage characterized by poor tibiofemoral cartilage composition and greater cartilage strain which represent equally important, but independent measures of cartilage health. Furthermore, increasing daily steps using a 16-week daily step promotion paradigm in individuals post-ACLR who underload (<7000 daily steps which is predictive of physical inactivity) will recondition cartilage by improving tibiofemoral cartilage composition and strain. The proposed study aims to determine: 1) associations between daily steps with tibiofemoral cartilage composition and strain in ACLR individuals (n=56) using an observational cross-sectional study design, and 2) the effects of increasing daily steps over 16-weeks on tibiofemoral cartilage composition and strain in ACLR individuals with low daily steps (n=28) using a single arm, longitudinal pre-test post-test study design. The proposed study is innovative because it builds on observational studies linking underloading with poor knee joint health and will be the first study to mechanistically determine how altering loading frequency (i.e., increasing daily steps) affects comprehensive in vivo measures of cartilage health in individuals at risk for OA. Successful completion of the proposed study will provide foundational evidence for the development of a future randomized controlled trial to determine the efficacy of an adaptive daily step promotion intervention to reduce the risk of OA development in high-risk individuals. The proposed K01 Career Development Award will provide the investigator with protected time to advance analysis and interpretation of MRI measures of cartilage biology and mechanics as well as develop skills in clinical trial implementation. The comprehensive training plan is vital to the investigator’s long-term career development in establishing an independent research line to develop novel interventions for OA prevention and promote long-term quality of life.

项目概要/摘要 骨关节炎 (OA) 是导致残疾的主要原因。确定膝关节健康状况不佳的可改变机制。 制定疾病预防策略对于改善机械异常的长期健康至关重要。 理论上，负荷被认为是膝关节 OA 的主要危险因素。 然而，最近的证据表明关节过度负荷在 OA 发展中的机制。 通过现实世界中的日常步数评估的低负荷频率的影响也可能发挥作用。 膝关节健康设置是处于危险中的个体异常机械负荷的一个未经充分研究的参数 适用于患有前交叉韧带 (ACL) 损伤并接受 ACL 重建 (ACLR) 手术的患者 是评估低负荷频率对膝关节健康影响的代表性人群，因为他们 发生创伤后骨关节炎的风险较高，并且与未受伤者相比每日步数较低 因此，总体研究目标是确定关节载荷之间的机械联系。 膝关节软骨健康的频率和综合磁共振成像（MRI）测量 中心假设是，ACLR 后每日步数较低的个体会出现这种情况。 表现出状况不佳、弹性较差的软骨，其特征是胫股软骨成分较差，并且 更大的软骨应变代表着同样重要但独立的软骨健康指标。 此外，对于 ACLR 后的个体，使用 16 周每日步数提升范例来增加每日步数 负荷不足的人（每日步数<7000 步，这预示着身体活动不足）将通过改善软骨状况来修复软骨 胫股软骨成分和应变本研究旨在确定：1) 之间的关联。 使用观察性方法对 ACLR 个体 (n=56) 的胫股软骨成分和应变进行每日步数 横断面研究设计，2) 16 周内每天增加步数对胫股软骨的影响 使用单臂纵向预测试对每日步数较低的 ACLR 个体 (n=28) 进行成分和应变分析 所提出的研究是创新的，因为它建立在观察性研究的基础上。 膝关节健康状况不佳导致负荷不足，这将是第一项机械地确定如何改变的研究 负荷频率（即增加每日步数）影响软骨健康的综合体内测量 成功完成拟议的研究将为有 OA 风险的个体提供基础证据。 开发未来的随机对照试验，以确定适应性每日步数提升的功效 旨在降低高危人群发生 OA 风险的干预措施 拟议的 K01 职业。 发展奖将为研究者提供受保护的时间来推进分析和解释 软骨生物学和力学的 MRI 测量以及临床试验实施技能的培养。 全面的培训计划对于研究者的长期职业发展至关重要 独立研究线开发预防 OA 的新型干预措施并提高长期生活质量。