Longitudinal Study of Bone and Endocrine Disease in Children with MPS I, II, and VI: A Multi-Center Study of the Lysosomal Disease Network

大约85%的I型、II型或VI型粘多糖沉积症（MPS）患者报告每周疼痛， 50-60%的患者由于MPS相关的肌肉骨骼疾病而在日常生活活动中受到严重限制 尽管用酶替代疗法（ERT）治疗，因此，迫切需要确定 减轻肌肉骨骼疾病负担的额外疗法，以改善健康状况， MPS患者的生活质量。然而，需要量化疾病进展，以便能够 确定新疗法的疗效。这项研究是一项多机构、为期5年的纵向研究， MPS中的肌肉骨骼疾病。长期目标是确定和测试新的治疗方法， MPS中的肌肉骨骼疾病。这项研究的目的是定量描述 骨骼疾病的进展，并确定预测疾病严重程度或可用于 作为MPS I、II和VI患者的治疗靶点。我们的中心假设是骨骼疾病 随着时间的推移，炎症的生物标志物，骨和软骨的周转，将预测 随着时间的推移，骨骼疾病的严重程度。具体目标是：1）表征骨骼肌的进展 从儿童期到青年期的疾病和2）确定炎症，骨 重塑和软骨周转，可以预测骨骼疾病的进展和受损的身体 功能为了实现这些目标，每年将对参与者进行骨健康评估（双能量 X线吸收测定法、外周定量计算机断层扫描、髋关节和脊柱X线）、物理 功能（通过Biodex和握力计测量的肌肉力量、运动范围测试，以及 身体功能和疼痛的问卷调查），和骨转换生物标志物的实验室测量， 软骨损伤和炎症肌肉骨骼标准化测量数据库 MPS中的疾病将使该领域有效地推进对患有 MPS。

Approximately 85% of individuals with Mucopolysaccharidosis (MPS) type I, II, or VI report weekly pain and 50-60% have significant limitations in their activities of daily living due to MPS related musculoskeletal disease despite treatment with enzyme replacement therapy (ERT). Thus there is a critical need to identify additional therapies to alleviate the burden of musculoskeletal disease in order to improve the health and quality of life of individuals with MPS. However, disease progression needs to be quantified to be able to determine efficacy of new therpies. The proposed study is a multi-institutional, 5-year, longitudinal study of musculoskeletal disease in MPS. The long-term goal is to identify and test new therapies for musculoskeletal disease in MPS. The objective of this proposed study is to quantitatively describe the progression of skeletal disease and identify biomarkers that either predict disease severity or could be used as therapeutic targets in individuals with MPS I, II, and VI. Our central hypothesis is that skeletal disease will progress over time and that biomarkers of inflammation, and bone and cartilage turnover, will predict the severity of skeletal disease over time. Specific aims are 1) to characterize the progression of skeletal disease from childhood into young adulthood and 2) to identify prognostic biomarkers of inflammation, bone remodeling, and cartilage turnover that can predict the progression of skeletal disease and impaired physical function. To achieve these aims, participants will be evaluated annually with measures of bone health (dualenery x-ray absorptiometry, peripheral quantitative computer tomography, hip and spine x-rays), physical function (muscle strength by Biodex and hand grip dynamometer, range of motion testing, and questionnaires of physical function and pain), and laboratory measurements of biomarkers of bone turnover, cartilage breakdown, and inflammation. A database of standardized measurements of musculoskeletal disease in MPS will allow the field to efficiently move forward with therapeutic clinical trials in patients with MPS.