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

描述(由申请人提供)：骨骼生长的特征是皮质骨维度和骨小梁体积骨密度(VBMD)的性别、成熟度和种族特异性增加。克罗恩病(CD)儿童有许多骨积累受损的危险因素，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。我们报告了患有CD的儿童在骨小梁vBMD、皮质尺寸和肌肉质量方面有显著的缺陷；骨缺陷与肌肉缺陷密切相关。合成代谢或抗吸收骨疗法尚未在儿科慢性炎症性疾病中进行试验。在生长过程中，对机械负荷的响应增加骨量和尺寸的能力是最大的。最近的研究表明，每天短暂的低强度机械刺激(LMMS)可以提高骨量和质量。这一修订后的应用包括12名CD儿童的试验数据，显示出良好的依从性和无不良反应。这项拟议的12个月双盲安慰剂对照随机试验将评估160名CD儿童每天10分钟的LMMS治疗。骨小梁vBMD、皮质尺寸和肌肉面积将通过定量计算机断层扫描(QCT)进行测量。LMMS设备监控依从性；这些数据将通过调制解调器传输给心理学家，后者将与受试者密切合作，以优化依从性。所有受试者都将获得钙和维生素D补充剂。主要目的是确定与对照组相比，LMMS治疗是否导致CD儿童的骨小梁vBMD(胫骨和脊柱)和皮质尺寸(胫骨)增加。二次分析将检查(1)LMM对功能性肌肉-骨骼单位的影响，(2)青春期阶段、体力活动(通过加速计测量)和疾病特征(例如，糖皮质激素治疗)对LMM反应的影响，(3)DXA检测治疗效果的敏感性，以及(4)随机使用活性设备的受试者在试验结束后12个月内骨骼和肌肉的变化。公共卫生声明：儿童期骨骼累积是终生骨骼健康的关键决定因素。美国国立卫生研究院骨质疏松症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。LMM可能为多种慢性儿科疾病提供一种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.