Musculoskeletal Plasticity After Spinal Cord Injury

Patients with spinal cord injury (SCI) experience metabolic syndrome, diabetes, obesity,
pressure ulcers, and cardiovascular disease at far greater rates than the general population.
A rehabilitation method to prevent or reverse the systemic metabolic consequences of SCI is a
pressing need. The purpose of this study is to determine the dose of muscle activity that can
enhance an oxidative muscle phenotype and improve clinical markers of metabolic health and
bone turnover in patients with SCI. The long-term goal of this research is to develop
exercise-based interventions to prevent secondary health conditions such as diabetes and to
ultimately protect health-related quality of life (QOL). Specific Aim 1: To compare changes
in skeletal muscle gene regulation in individuals who receive high frequency (HF)
active-resisted stance and low frequency (LF) active-resisted stance for 16 weeks. Hypothesis
1: The expression of genes regulating skeletal muscle metabolism will support that HF and LF
both instigate a shift toward an oxidative muscle phenotype. A novel finding will be that LF
is a powerful regulator of oxidative pathways in skeletal muscle. Specific Aim 2: To compare
changes in systemic markers of metabolic health and bone turnover in individuals with SCI who
receive HF or LF for 16 weeks. Hypothesis 2: HF and LF will both reduce glucose/insulin
levels and HOMA (homeostasis model assessment) score. However, only HF will demonstrate an
effect on bone turnover (higher serum levels of osteocalcin). Secondary Aim: To measure
subject-reported QOL using the EQ-5D survey metric. Hypothesis 3: HF and LF subjects will
show a trend toward improved self-reported QOL after 16 weeks. There will be an association
between metabolic improvement and improved perception of QOL. These observations will support
that this intervention has strong feasibility for future clinical translation.