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

• change in trabecular volumetric BMD for age, sex and race z-score at 6 months and 12 months, as measured by pQCT of the tibia [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• change in cortical cross sectional moment of inertia z-score at 6 months and 12 months, as measured by pQCT of the tibia [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• change in spine volumetric BMD at 12 months, as measured by QCT [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  

Skeletal growth is characterized by increases in the size of the hard outer layer of bone (cortical bone), and the density of the inner layer of bone (trabecular or "spongy" bone). Children with Crohn disease (CD) have numerous risk factors for impaired bone accumulation, including poor growth, delayed puberty, malnutrition, glucocorticoid therapy and inflammation. We reported that children with CD had significant deficits in trabecular bone mineral density (BMD), cortical dimensions, and muscle mass; bone deficits were strongly associated with muscle deficits. No trials of therapies that build bone or prevent bone breakdown 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 12-month double blind, placebo controlled randomized trial will evaluate daily 10-minute treatments with LMMS in 160 children with CD. Trabecular BMD, 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 BMD in the lower leg and spine and increased cortical dimensions in the lower leg in children with CD, compared with placebo controls. Secondary analyses will examine (1) the effect of LMMS on the functional muscle-bone unit, (2) the impact of pubertal stage, physical activity, and disease characteristics (e.g., steroid treatment) on the response to LMMS, (3) the sensitivity of dual energy x-ray absorptiometry (DXA) to detect treatment effects, and (4) changes in bone and muscle over 12 months off therapy following completion of the trial in subjects randomized to active devices.