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

儿童克罗恩病的骨骼健康：低强度机械刺激试验

• 批准号: 7266214
• 负责人: Mary Beth Leonard
• 金额: $ 60.39万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7266214
• 关键词: Adherence; Adolescence; Adolescent; Adult; Adverse effects; Animals; Architecture; Area; Bone Density; Calcium; Cerebral Palsy; Child; Childhood; Chronic; Chronic Disease; Consensus; Consensus Development Conferences; Coupled; Crohn' s disease; Daily; Data; Delayed Puberty; Devices; Diagnosis; Dimensions; Disease; Double-Blind Method; Electronics; Enrollment; Exposure to; Failure; Female Adolescents; Fracture; Gender; Glucocorticoids; Growth; Health; Incentives; Inflammatory; Intervention; Life; Malnutrition; Measures; Mechanics; Modems; Monitor; Muscle; Muscle Contraction; Osteogenesis; Osteoporosis; Osteoporosis prevention; Physical activity; Pilot Projects; Placebo Control; Placebos; Production; Psychologist; Public Health; Race; Randomized; Randomized Clinical Trials; Recording of previous events; Relative (related person); Reporting; Research; Research Personnel; Risk; Risk Factors; Sexual Maturation; Signal Transduction; Skeletal Development; Skeletal system; Skeleton; Staging; Standards of Weights and Measures; Stimulus; United States National Institutes of Health; Vertebral column; Vitamin D; Weight-Bearing state; Work; X-Ray Computed Tomography; bone; bone health; bone strength; cytokine; density; disease characteristic; monitoring device; prevent; programs; randomized placebo controlled trial; response; size; tibia; treatment effect

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.

描述（由申请方提供）：骨生长的特征是皮质尺寸和小梁体积骨矿物质密度（vBMD）的性别、成熟和种族特异性增加。克罗恩病（CD）儿童有许多骨累积受损的风险因素，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CD儿童在骨小梁vBMD、皮质尺寸和肌肉质量方面存在显著缺陷;骨缺陷与肌肉缺陷密切相关。尚未在慢性儿科炎症性疾病中进行合成代谢或抗骨吸收疗法的试验。在生长期间，响应于机械负荷而增加骨量和尺寸的能力最大。最近的研究表明，每天短暂暴露于低强度机械刺激（LMMS）可以提高骨量和质量。该修订后的应用程序包括12名CD儿童的试点数据，证明了良好的依从性，无不良反应。拟定的12个月双盲、安慰剂对照随机试验将评估160名CD儿童每日10分钟LMMS治疗。将通过定量计算机断层扫描（QCT）测量骨小梁vBMD、皮质尺寸和肌肉面积。LMMS设备监测依从性;这些数据将通过调制解调器传输给心理学家，心理学家将与受试者密切合作以优化依从性。将为所有受试者提供钙和维生素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儿童骨小梁vBMD（胫骨和脊柱）和皮质尺寸（胫骨）增加。次要分析将检查（1）LMMS对功能性肌肉-骨单位的影响，（2）青春期阶段、体力活动（通过加速度计测量）和疾病特征（3）DXA检测治疗效果的敏感性，和（4）随机分配到有源器械组的受试者在完成试验后12个月内停止治疗的骨和肌肉变化。公共卫生声明：儿童时期的骨骼累积是终生骨骼健康的关键决定因素。NIH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。LMMS可能为无数慢性儿科疾病提供安全有效的治疗。