Musculoskeletal Aging in Hereditary Disorders of Connective Tissue

在结缔组织疾病队列中(2003-086年方案中登记了大约800名受试者)，脊柱退行性间盘疾病、骨密度丢失、骨关节炎、慢性疼痛和肌肉骨骼损伤等并发症出现的年龄比普通人群年轻得多。确定这些异常的诊断研究包括骨密度测量(DEXA)、脊柱MRI、关于疼痛和生活质量的问卷调查，以及在研究访问期间对肌肉骨骼残疾的评估。我们还发现，在这一人群中，获得性结缔组织疾病的发病率增加，如类风湿性关节炎和系统性红斑狼疮。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。确定由异常细胞外信号引起的继发性细胞内排列紊乱可能会导致这些疾病的治疗策略，并使患有类似疾病的老年人口受益。

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.