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.

项目总结/文摘