Bone Health in Pediatric Crohn Disease: A Low Magnitude Mechanical Stimulus Trial

描述（由申请人提供）：骨骼生长以性别、成熟度和种族特异性的皮质尺寸和小梁体积骨矿物质密度（vBMD）的增加为特征。患有克罗恩病（CD）的儿童有许多骨质增生受损的危险因素，包括生长不良、青春期延迟、营养不良、糖皮质激素治疗和骨吸收细胞因子增加。我们报道了乳糜病儿童在小梁vBMD、皮质尺寸和肌肉质量方面存在显著缺陷；骨缺损与肌肉缺损密切相关。没有合成代谢或抗骨吸收治疗在慢性儿童炎症性疾病中进行的试验。在生长过程中，增加骨量和尺寸以响应机械负荷的能力最大。最近的研究表明，每天短暂暴露于低强度机械刺激（LMMS）可提高骨量和质量。修订后的应用包括12例CD患儿的试点数据，显示出良好的依从性和无不良反应。这项为期12个月的双盲、安慰剂对照随机试验将评估160例CD患儿每日10分钟的LMMS治疗。小梁vBMD、皮质尺寸和肌肉面积将通过定量计算机断层扫描（QCT）测量。LMMS设备监测依从性；这些数据将通过调制解调器传送给心理学家，后者将与受试者密切合作，以优化依从性。所有受试者都将补充钙和维生素D。主要目的是确定与对照组相比，LMMS治疗是否会导致CD儿童小梁vBMD（胫骨和脊柱）和皮质尺寸（胫骨）增加。二级分析将检查(1)LMMS对功能性肌肉-骨单元的影响，(2)青春期阶段、体力活动（通过加速度计测量）和疾病特征（如糖皮质激素治疗）对LMMS反应的影响，(3)DXA检测治疗效果的敏感性，以及(4)随机分配到活性装置的受试者在试验完成后12个月内的骨和肌肉变化。公共卫生声明：儿童骨骼累积是终身骨骼健康的关键决定因素。美国国立卫生研究院骨质疏松共识声明呼吁进行研究，以确定促进高危儿童骨骼健康的干预措施。LMMS可能为无数慢性儿科疾病提供安全有效的治疗方法。

DESCRIPTION (provided by applicant): Skeletal growth is characterized by gender-, maturation-, and race- specific increases in cortical dimensions and trabecular volumetric bone mineral density (vBMD). Children with Crohn disease (CD) have numerous risk factors for impaired bone accrual, including poor growth, delayed puberty, malnutrition, glucocorticoid therapy and increased bone-resorptive cytokines. We reported that children with CD had significant deficits in trabecular vBMD, cortical dimensions and muscle mass; bone deficits were strongly associated with muscle deficits. No trials of anabolic or anti-resorptive bone therapies have been conducted in chronic pediatric inflammatory diseases. The capacity to increase bone mass and dimensions in response to mechanical loading is greatest during growth. Recent studies demonstrate that brief daily exposure to low magnitude mechanical stimuli (LMMS) enhances bone mass and quality. This revised application includes pilot data in 12 children with CD, demonstrating excellent adherence and no adverse effects. The proposed 12 month double blind, placebo controlled randomized trial will evaluate daily 10 minute treatments with , LMMS in 160 children with CD. Trabecular vBMD, cortical dimensions, and muscle area will be measured by quantitative computed tomography (QCT). The LMMS device monitors adherence; these data will be transmitted by modem to the psychologist who will work closely with subjects to optimize adherence. All subjects will be provided with calcium and vitamin D supplements. The primary aims are to determine if treatment with LMMS results in increased trabecular vBMD (tibia and spine) and increased cortical dimensions (tibia) in children with CD, compared with controls. Secondary analyses will examine (1) the effect of LMMS on the functional muscle-bone unit, (2) the impact of pubertal stage, physical activity (as measured by accelerometry), and disease characteristics (e.g. glucocorticoid therapy) on the response to LMMS, (3) the sensitivity of DXA to detect treatment effects, and (4) changes in bone and muscle over 12 months off therapy following completion of the trial in the subjects randomized to active devices. Public Health Statement: Childhood bone accrual is a critical determinant of life-long skeletal health. The NIH Osteoporosis Consensus Statement called for studies to identify interventions that promote bone health in children at risk. LMMS may provide a safe and effective treatment for myriad chronic pediatric diseases.