Risk Factors for Osteoporosis in Children & Adolescents with Myelomeningocele

描述（由申请人提供）脊柱裂或脊髓脊膜膨出（MM）是美国最常见的永久性致残疾病，也是与生命相容的最复杂的出生缺陷之一。它是由脊柱在怀孕的第一个月内无法完全闭合引起的，导致下肢不同程度的瘫痪和虚弱。骨质疏松症和骨折是这一人群中常见的问题，最有可能是由于骨骼的骨密度和机械负荷降低。脊柱裂研究的首要任务是确定骨质疏松症的危险因素，并随后减轻这些危险因素，以预防骨质疏松症和骨质疏松性骨折。由于青春期是非残疾儿童骨获得的关键时期，因此假设通过在青春期尽可能长时间保持直立活动（行走），MM儿童的骨量可能最大化。本研究将确定MM中骨质疏松症的风险因素，特别是与骨骼的骨骼和机械负荷相关的风险因素。具体目的是：（1）检查骨密度、大小和结构的纵向变化MM儿童和青少年的骨（强度）特性，并将这些变化与典型发育对照组进行比较，（2）确定骨获取缺陷和骨质疏松症发展的潜在风险因素，包括神经系统受累水平、行走状态、步态特征，和步行量（每天步数），以及（3）探索在青春期保持直立行走（直立移动）是否与骨量的显著增加相关。为了实现这些目标，将在3年随访期内对6-13岁MM儿童和青少年以及同龄对照组进行纵向评估。将使用计算机断层扫描（CT）成像测量胫骨的骨密度、尺寸和强度。步态特征将通过三维计算机步态分析进行测量，步行量将通过活动监测器进行量化。为了充分描述研究受试者的特征，还将获得其他相关信息，包括病史、体格检查、性发育的坦纳阶段、骨龄、饮食摄入和骨形成的主要决定因素。骨特性将与其他指标相关，以确定骨质疏松症的最重要风险因素，并评估直立活动（行走）在刺激MM儿童和青少年骨获得中的重要性。 骨质疏松和骨折是脊髓脊膜膨出（MM）患者的常见问题。本研究将确定MM中骨质疏松症的风险因素，并探索是否可以通过尽可能晚地保持直立活动（行走）来预防或减轻骨质疏松症的严重程度。稍微延迟向轮椅移动的过渡可能会对骨质疏松症的预防产生很大的影响。

DESCRIPTION (provided by applicant) Spina bifida or myelomeningocele (MM) is the most common permanently disabling condition in the U.S. and one of the most complex birth defects compatible with life. It is caused by failure of the spinal column to close completely during the first month of pregnancy, resulting in varying degrees of paralysis and weakness in the lower extremities. Osteoporosis and fractures are common problems in this population, most likely due to decreased ambulation and mechanical loading of the skeleton. A top priority for research in spina bifida is the identification of risk factors for osteoporosis and subsequent mitigation of these risk factors to prevent osteoporosis and osteoporotic fractures. Since adolescence is a critical period for bone acquisition in non-disabled children, it is hypothesized that bone mass may be maximized in children with MM by maintaining upright mobility (walking) as long as possible through adolescence. This study will identify risk factors for osteoporosis in MM, particularly risk factors related to ambulation and mechanical loading of the skeleton. The specific aims are (1) to examine longitudinal changes in bone density, size, and structural (strength) properties in children and adolescents with MM and to compare these changes with those in typically developing controls, (2) to identify potential risk factors for deficient bone acquisition and the development of osteoporosis, including level of neurological involvement, ambulatory status, gait characteristics, and amount of walking (steps per day), and (3) to explore whether maintaining ambulation (upright mobility) through adolescence is associated with significant gains in bone mass. To achieve these aims, children and adolescents with MM ages 6-13 years and controls of the same age will be assessed longitudinally over a 3-year follow-up period. Bone density, size, and strength will be measured in the tibia using computed tomography (CT) imaging. Gait characteristics will be measured through three-dimensional computerized gait analysis, and the amount of walking will be quantified with an activity monitor. To fully characterize the study subjects, other relevant information will also be obtained, including medical history, physical examination, Tanner stage of sexual development, skeletal age, dietary intake, and major determinants of bone formation. The bone properties will be related to the other measures to identify the most important risk factors for osteoporosis and to assess the importance of upright mobility (walking) in stimulating bone acquisition in children and adolescents with MM. PUBLIC HEALTH RELEVANCE Osteoporosis and fractures are common problems in persons with myelomeningocele (MM). This study will identify risk factors for osteoporosis in MM and explore whether osteoporosis can be prevented or lessened in severity by maintaining upright mobility (walking) as late as possible into adolescence. A slight delay in the transition to wheelchair mobility may make a large difference in osteoporosis prevention.