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

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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.