Renal osteodystrophy (ROD) is a pervasive disorder of bone metabolism in dialysis patients that results in distorted trabecular architecture and loss of cortical bone. Despite the widespread use of ROD therapies, hip fracture rates in adults on dialysis are markedly increased. The vast majority of studies of bone mass in renal disease have relied on dual energy x-ray absorptiometry (DXA) measures of bone mineral density (BMD); however, DXA does not distinguish between ROD effects on trabecular and cortical bone. Quantitative computed tomography (QCT) provides 3D measures of cortical BMD and cortical dimensions (periosteal and endosteal circumferences), and bone strength can be estimated. Micro magnetic resonance imaging (uMRI) provides measures of trabecular bone volume fraction (bone volume/total volume, BV/TV %) and micro-architecture. Our mu/MRI and QCT studies in renal disease revealed reductions in cortical thickness, cortical BMD, trabecular BV/TV, and trabecular connectivity.
The aim of treating ROD is to restore bone strength by increasing its mass and reconstructing its architecture. Mechanical forces on the skeleton arise from muscle contraction and these forces generate signals that modulate bone structure. Animal studies demonstrated that daily exposure to low magnitude mechanical stimuli (LMMS) enhanced trabecular and cortical bone quantity and quality. Randomized trials in humans suggested that brief daily exposure to LMMS enhanced trabecular and cortical bone mass, with no adverse effects. The proposed 6 month pilot and feasibility randomized trial will evaluate LMMS as an anabolic bone stimulus in 30 adults on maintenance hemodialysis. The intervention will consist of 10 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 adherence monitor. The study will examine trabecular BV/TV and architecture using uMRI, and cortical volumetric BMD and dimensions using QCT at baseline and 6 months. 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. Consistent with the Program Announcement, it is anticipated that this innovative study will lead to a full-scale clinical trial of LMMS as an anabolic bone therapy for ROD in dialysis patients.
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| Leonard, Mary B (2009) A structural approach to skeletal fragility in chronic kidney disease. Semin Nephrol 29:133-43 |
| Techawiboonwong, Aranee; Song, Hee Kwon; Leonard, Mary B et al. (2008) Cortical bone water: in vivo quantification with ultrashort echo-time MR imaging. Radiology 248:824-33 |
