Low Magnitude Mechanical Stimuli Effects on Bone Structure in ESRD
Condition: Renal Osteodystrophy
MeSH terms: Chronic Kidney Disease-Mineral and Bone Disorder
Study type: Interventional

Summary: 
      The proposed 6 month pilot and feasibility randomized trial will evaluate LMMS as an anabolic
      stimulus to bone in 30 adults on maintenance hemodialysis. The intervention will consist of
      20 minute daily sessions in the home standing on an active LMMS platform or a placebo device
      that emits an audible hum suggestive of an active device. Each device contains an electronic
      monitor that documents adherence. The study will examine trabecular bone volume fraction
      (bone volume/total volume, BV/TV %) and architecture using microMRI, and cortical volumetric
      BMD and dimensions using QCT at baseline and 6 months. The hypothesis is that active LMMS
      will results in greater mean changes in trabecular and cortical parameters in hemodialysis
      patients. The proposed study will test the feasibility of conducting the intervention in
      dialysis patients and will generate preliminary data on rates of change in trabecular and
      cortical parameters in the active and placebo groups.
    

Detailed description: 
      Renal osteodystrophy (ROD) is a multifactorial and pervasive disorder in chronic kidney
      disease (CKD). As renal failure progresses, ensuing abnormal parathyroid hormone (PTH)
      secretion and mineral metabolism result in sclerosis of trabecular bone, thinning of cortical
      bone, and increased cortical porosity.(1) Despite the widespread use of phosphate binders and
      vitamin D therapies, hip fracture rates and mortality risk following fractures are markedly
      greater in dialysis patients, compared with the general population.

      The vast majority of studies of bone loss in CKD relied on dual energy x-ray absorptiometry
      (DXA) measures of bone mineral density (BMD). However, DXA summarizes the total bone mass
      within the projected bone area, concealing disease effects on trabecular and cortical bone.
      For example, in high-turnover ROD, increased trabecular volume may offset cortical bone loss,
      resulting in normal or increased areal-BMD despite poor bone strength. Quantitative computed
      tomography (QCT) enables discrete assessment of trabecular and cortical volumetric BMD and
      dimensions. However, this is an incomplete solution in the setting of CKD because QCT does
      not assess trabecular architecture. Micro-magnetic resonance imaging (µMRI) provides a
      non-invasive technique to assess trabecular architecture. The µMRI data are quantified by 3D
      digital processing methods, such as topological analysis, to determine trabecular properties.
      Our pilot study of µMRI in dialysis patients revealed significant reductions in cortical
      thickness and suggested deterioration in the trabecular network. This innovative imaging
      modality may be uniquely suited to the assessment of ROD therapies.

      Mechanical forces on the skeleton arise from muscle contraction and these forces generate
      signals that modulate bone architecture. Animal studies demonstrated that daily exposure to
      low magnitude mechanical stimuli (LMMS) enhanced trabecular and cortical bone quantity and
      quality. A randomized trial of LMMS in post-menopausal women demonstrated that LMMS were
      associated with increased DXA BMD, without adverse effects. LMMS may be uniquely suited to
      restore cortical and trabecular bone structure in ROD.

      The study will enroll adults, ages 21-65 years, treated with maintenance hemodialysis at
      UPENN. The study will exclude the elderly and subjects with major co-morbid conditions in
      order to increase the likelihood that subjects will complete the 6 month intervention without
      significant interruptions due to hospitalization.
    

Intervention name(s): Low magnitude mechanical stimuli
Intervention type(s): Device
Intervention description(s): 20 minutes standing on low magnitude high frequency vibrating platform
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Renal Osteodystrophy