Low Magnitude Mechanical Stimuli Effects on Bone Structure in ESRD

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.