Renal Osteodystrophy Clinical Trial
Official title:
Low Magnitute Mechanical Stimuli Effects on Bone Structure in ESRD
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.
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.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
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