Body composition, bone structure, and joint damage in rheumatoid arthritis

类风湿性关节炎的身体成分、骨骼结构和关节损伤

• 批准号: 8794427
• 负责人: JOSHUA F. BAKER
• 金额: --
• 依托单位: PHILADELPHIA VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8794427
• 关键词: Accounting; Address; Adipose tissue; Adrenal Cortex Hormones; Adult; Affect; Appointment; Arthritis; Biometry; Body Composition; Body Weight; Body mass index; Bone Density; Cachexia; Caring; Cartilage; Cells; Center for Translational Science Activities; Cessation of life; Characteristics; Chronic; Chronic Disease; Clinical; Clinical Investigator; Clinical Research; Cohort Studies; Conduct Clinical Trials; Data; Databases; Dedications; Deterioration; Development; Development Plans; Disease; Disease Outcome; Epidemiologic Studies; Epidemiology; Fatty acid glycerol esters; Fracture; Funding; Future; General Population; Glucocorticoids; Goals; Growth Factor; Health; Inflammation; Inflammatory; Innovative Therapy; Insulin-Like Growth Factor I; Intervention; Intramuscular; Joints; Knowledge; Laboratories; Long-Term Effects; Magnetic Resonance Imaging; Measures; Mechanical Stimulation; Mechanics; Mentors; Mentorship; Methods; Morbidity - disease rate; Muscle; Nursing Faculty; Obesity; Osteoclasts; Osteoporosis; Outcome; Participant; Pathway interactions; Patients; Philadelphia; Physical Function; Population; Prevalence; Prevention; Production; Recording of previous events; Registries; Research; Research Personnel; Resources; Rheumatism; Rheumatoid Arthritis; Rheumatology; Risk; Role; Serological; Severities; Severity of illness; Structure; Synovitis; Thick; Time; Training; United States National Institutes of Health; Veterans; Weight; Woman; Work; adiponectin; adverse outcome; arthritic pain; arthritis registry; arthropathies; bone; bone health; bone loss; bone metabolism; career; career development; clinical epidemiology; cytokine; density; disability; experience; improved; interest; joint injury; multidisciplinary; muscle form; myostatin; novel; osteoporosis with pathological fracture; patient oriented research; prevent; programs; prospective; skills; substantia spongiosa; success; ward

DESCRIPTION (provided by applicant): The candidate is a junior investigator in rheumatology with advanced training in clinical epidemiology and a focus on patient-oriented research in chronic rheumatic diseases. He has a long history of clinical work within the Philadelphia VA and has recently been appointed here as clinical faculty. Throughout his training he has shown dedication to the care of veterans and proposes to develop his career within the VA. The candidate proposes a comprehensive interdisciplinary career development plan that will provide him with the skills and experience for his development into an independent clinical investigator. His co-mentors are NIH K24-funded senior investigators from the UPENN and VA, who have expertise in bone and joint health in varied chronic diseases. His multidisciplinary team includes additional NIH-funded leaders in biostatistics, epidemiology, bone metabolism, body composition, and rheumatic disease, each of whom is dedicated to a coordinated effort to ward the success of his career. He will draw on outstanding resources, including the VA Rheumatoid Arthritis national registry as well as the CTSA-supported Center for Clinical and Translational Research, and the Center for Clinical Epidemiology and Biostatistics at nearby UPENN. He will also complete additional formal didactic training in methods relevant to this proposal. The proposed project will build on his epidemiology training and prior research experience to promote his transition to independence. His long-term goals are to conduct clinical trials to improve body composition, bone health, and related outcomes in rheumatoid arthritis (RA). The study proposed here is the necessary first step to inform these trials. Osteoporotic fractures and joint damage account for significant morbidity in RA, resulting in billions of dollars in national costs.1 Recent studies suggest a greater prevalence and severity of arthritis in US veterans, compared with non-veterans.2 Furthermore, the VA identified arthritis, pain, obesity, and osteoporosis as priority conditions in women; each of these is addressed in this application. Low body weight has been associated with many adverse outcomes in RA, including fractures, joint damage, and death. However, the dynamic effect of the disease itself on BMI has not been characterized nor have the effects of altered body composition on RA outcomes. The long-term effects of this chronic inflammatory disease on body weight have not been clarified and may help explain these associations. Similarly, low BMI is associated with low lean mass. The applicant demonstrated that low lean mass and greater fat mass are associated with cortical thinning of bone among healthy adults. Given that 1) rheumatoid cachexia is characterized by reduced lean mass with normal or increased fat mass and 2) low lean mass is associated with thinning of cortical bone, loss of lean mass in RA likely contributes to the excess fracture risk in this population. The critical knowledge gaps are 1) whether associations between bone and BMI are related to confounding by long-term effects of disease and 2) to what extent altered lean and fat mass (rather than BMI) account for bone deficits. Taken further, the positive effects of lean mass on cortical bone may be important for prevention of invasion of inflammatory pannus, and integral to the health of overlying cartilage. Interventions to reverse lean mass deficits in RA could therefore have a valuable impact on disease outcomes through mechanical effects on cortical bone or production of muscle- derived factors. The applicant aims to 1) quantify alterations in bone structure and body composition in RA, compared with controls, and to evaluate associations with growth factors, cytokines and structural joint damage within RA participants at baseline, 2) identify baseline disease characteristics, physical function, serologic measures, and body composition measures associated with longitudinal deteriorations in ALM, bone density and structure, joint damage and disability over 2 years, and 3) To determine if lower disease activity is associated with greater increases in BMI, independent of glucocorticoid therapy in VARA participants.

描述（由申请人提供）： 该候选人是风湿病学的初级研究员，接受过临床流行病学的高级培训，专注于以患者为导向的慢性风湿病研究。他在费城退伍军人管理局拥有悠久的临床工作历史，最近被任命为这里的临床教员。在整个培训过程中，他表现出了对退伍军人的奉献精神，并提议在退伍军人管理局发展自己的职业生涯。候选人提出了一个全面的跨学科职业发展计划，该计划将为他发展成为一名独立的临床研究者提供技能和经验。他的共同导师是 NIH K24 资助的来自 UPENN 和 VA 的高级研究人员，他们在各种慢性疾病的骨骼和关节健康方面拥有专业知识。他的多学科团队包括由 NIH 资助的生物统计学、流行病学、骨代谢、身体成分和风湿病领域的其他领导者，他们每个人都致力于协调一致的努力，以确保自己职业生涯的成功。他将利用优秀资源，包括 VA 类风湿关节炎国家登记处、CTSA 支持的临床和转化研究中心以及附近 UPENN 的临床流行病学和生物统计学中心。他还将完成与该提案相关的方法的额外正式教学培训。拟议的项目将建立在他的流行病学培训和先前的研究经验的基础上，以促进他向独立的过渡。他的长期目标是进行临床试验，以改善类风湿性关节炎 (RA) 的身体成分、骨骼健康和相关结果。这里提出的研究是为这些试验提供信息的必要的第一步。骨质疏松性骨折和关节损伤是 RA 发病率较高的原因，导致国家损失数十亿美元。1 最近的研究表明，与非退伍军人相比，美国退伍军人关节炎的患病率和严重程度更高。2 此外，退伍军人管理局还发现，关节炎、疼痛、肥胖和骨质疏松症是优先考虑的条件 女性;本申请中解决了这些问题中的每一个。低体重与 RA 的许多不良后果有关，包括骨折、关节损伤和死亡。然而，疾病本身对 BMI 的动态影响尚未得到表征，身体成分改变对 RA 结果的影响也尚未得到表征。这种慢性炎症性疾病对体重的长期影响尚未明确，可能有助于解释这些关联。同样，低体重指数与低瘦体重相关。申请人证明，健康成年人中低瘦体重和较大脂肪量与骨皮质变薄有关。鉴于 1) 类风湿性恶病质的特点是去脂体重减少，而脂肪量正常或增加，2) 去脂质量低与皮质骨变薄有关，RA 中去脂体重的减少可能会导致该人群骨折风险过高。关键的知识差距是：1）骨骼和体重指数之间的关联是否与疾病的长期影响的混杂有关；2）瘦肉量和脂肪量（而不是体重指数）的改变在多大程度上导致了骨骼缺陷。进一步来说，瘦肉块对皮质骨的积极作用可能对于预防炎性血管翳的侵袭很重要，并且对于上层软骨的健康也是不可或缺的。因此，扭转 RA 瘦体重缺陷的干预措施可能通过对皮质骨的机械作用或肌肉衍生因子的产生对疾病结果产生有价值的影响。申请人的目标是 1) 与对照组相比，量化 RA 骨结构和身体成分的变化，并评估基线时 RA 参与者与生长因子、细胞因子和结构性关节损伤的关联，2) 确定基线疾病特征、身体功能、 2 年内与 ALM 纵向恶化、骨密度和结构、关节损伤和残疾相关的血清学测量和身体成分测量，以及 3) 确定较低的疾病活动度是否与 BMI 的较大增加相关，与糖皮质激素无关VARA 参与者的治疗。