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Biomarker Targets of Altered Osteoclast Activity following Rehabilitation Interventions for Post-Stroke Hemiplegia

Principal Investigator: Carolynn Patten, PhD, PT

Co-Investigators: B. Jenny Kiratli, PhD and Christopher R. Jacobs, PhD

Objective: The goal of this BAJR Center pilot project is to study effects of exercise-based therapeutic interventions on bone remodeling in persons with post-stroke hemiparesis. Stroke is the leading cause of physical disability in western industrialized nations predominantly affecting persons sixty or more years of age. It can be hypothesized that age-related compromise to bone integrity coupled with the profound disabling influence of stroke, would accelerate bone loss and lead to secondary pathologies including osteoporosis and high risk of fractures.

This pilot project seeks to determine the extent to which high-intensity exercise-based therapies intended to restore neuromuscular function in hemiparetic persons affect bone remodeling. The literature reports osteogenic effects of eccentric exercise (e.g., muscle lengthening contractions) in healthy adults. We hypothesize therefore that therapies involving eccentric resistance exercise (i.e., controlling an externally imposed load, gait) will produce physiologically significant osteogenic effects in hemiparetic adults.

Research Plan and Methods: Hemiparetic subjects (6-18 months post-stroke) who enroll in the project “Therapeutic Effects on Neuromuscular Function in Post-stroke Hemiparesis” (C. Patten, P.I.) underwent parallel studies of bone integrity and bone remodeling. Subjects received DXA scans (whole body and proximal femur) at baseline, following the two-month clinical intervention, and at follow up study one year post-intervention. These studies were conducted in conjunction with Dr. B. Jenny Kiratli in the VA Palo Alto Clinical center. Blood samples were also obtained at the same time points as DXA. Post-hoc analysis for key markers of osteoblastic and osteoclastic activity is underway.

Progress Report and Findings to Date: Eighteen subjects who participated in the “Therapeutic Effects” projects were recruited and followed. DXA scans, and blood and urine samples were being obtained to track biologic markers of bone remodeling following therapeutic intervention. DXA scans obtained at baseline and at two points following the intervention revealed a reduced rate of bone loss in the six month period following the intervention.

Research Plan for the Next Year: Analysis of biochemical markers is underway and will serve as preliminary data for additional proposals to be submitted this year. We intend to submit these data for publication in the upcoming year.

Funding Source: No outside funding



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