Musculoskeletal Aging in Hereditary Disorders of Connective Tissue

在结缔组织疾病队列（方案2003-086中入组了约800例受试者）中，并发症（如脊柱退行性椎间盘疾病、骨密度丢失、骨关节炎、慢性疼痛和肌肉骨骼损伤）的发生年龄远低于一般人群。确定这些异常的诊断研究包括骨密度测定（DEXA）、脊柱MRI、疼痛和生活质量问卷调查以及研究访视期间的肌肉骨骼残疾评估。我们还发现，在这一人群中，获得性结缔组织疾病如类风湿性关节炎和系统性狼疮的发病率增加。这些发现被认为与细胞外基质结构蛋白的异常组织和异常形成的基质的免疫原性增加有关。由于异常的细胞外信号而发生的继发性细胞内紊乱的确定可能导致这些疾病的治疗策略，以及受益于患有类似病症的老龄化人群。

In the connective tissue disorders cohort (approximately 800 subject enrolled in protocol 2003-086), complications such as degenerative disc disease in the spine, bone density loss, osteoarthritis, chronic pain and musculoskeletal impairment appear at a much younger age than found in the general population. The diagnostic studies to identify these abnormalities include bone densitometry (DEXA), MRI of the spine, questionnaires on pain and quality of life, and assessment of musculoskeletal disability during the study visits. We have also found an increased incidence of acquired connective tissue disorders such as rheumatoid arthritis and systemic lupus in this population. These findings are thought to be related to abnormal organization of extracellular matrix structural proteins and increased immunogenicity of the abnormally formed matrix. Determination of the secondary intracellular derangements that occur due to abnormal extracellular signals may lead to treatment strategies in these disorders, as well as benefit the aging population that suffer from similar conditions.