Activity-Dependent Rehabiliation Model to improve Bone and Muscle after SCI

The overall objective of this project is to assess the musculoskeletal gains in individuals with subacute to chronic SCI, with bone mineral density (BMD) as the primary outcome variable and volumetric measures of bone, bone markers for reabsorption and absorption, muscle volume and muscle expression of PGC-1 as secondary outcome measures. These results will address whether a novel Activity-Dependent Rehabilitation Model can ameliorate detrimental changes in muscle and bone in individuals with chronic SCI who are non-ambulatory. In addition, these results will be used for the design of a multi-site randomized controlled clinical trial o determine whether a combination of intense active stand training with bilateral electrical stimulation of the lower limbs can improve musculoskeletal outcomes more than stand training or electrical stimulation alone.The Activity-Dependent Rehabilitation Model is a combination of intense active stand training using body weight support with bilateral electrical stimulation (ES) of the lower limbs. We will determine its effects relative to stand training and supine ES alone.Specific Aims: Primary Aim: To determine effectiveness of stand training with ES to induce positive changes in bone. Hypothesis: Stand training with ES, or ES alone, will produce greater increases in bone mineral density (BMD) at the proximal tibia compared to stand training alone. Because the knee, distal femur and proximal tibia are common sites of osteoporosis and where most fractures risk occur, improved BMD at these sites would be expected to have important clinical implications. Secondary Aims: To better define the changes and the mechanisms contributing to changes in BMD with stand training and electrical stimulation. We will examine outcome variables, including BMD for hip and distal femur, markers for bone formation/resorption, 3-D volumetric for measurement of cortical/trabecular bone in lower limbs, muscle cross sectional area, and muscle expression of PGC-1 and its downstream targets in lower limbs. BMD will be examined at multiple sites of the leg to permit a comprehensive picture to be obtained of the effect of the intervention. We hypothesize that the combination of stand training with ES will lead to increased muscle contractile elements, as shown by an increase in muscle CSA and expression of PGC1-alpha. We hypothesize that this increase in muscle, combined with loading, will increase the torque produced on bone, reducing of bone loss. Our proposal addresses the mission of the Neilsen Foundation: i) as an “innovative activity based rehabilitation program” ii) to address the secondary complications that occur with “chronic spinal cord injuries”, including “osteoporosis and effects of aging with spinal cord injury”. (CHN: SCIRTS chn:wdg)