Patients with spinal cord injury (SCI) undergo muscle and bone loss similar to astronauts in space. Through studies involving SCI patients, Dr. Jay R. Shapiro is evaluating the effectiveness of a potent, intravenous bisphosphonate for treating bone loss and will be determining the drug’s potential usefulness as a countermeasure to bone loss.
Overview
Defining and Preventing Bone Loss: A Microgravity Model
Principal Investigator:
Jay R. Shapiro, M.D.
Organization:
Medstar Research Institute
Technical Summary
Muscle atrophy and bone loss are major complications of spinal cord injury (SCI), chronic bed rest and exposure to microgravity. Space medicine research has amply documented the extent to which muscle and bone loss may impair strength and increase fracture risk. In our research, we theorize that the SCI patient can serve as a surrogate for studying microgravity exposure.
A primary objective of this research program is to limit the extent of bone loss in SCI patients by treatment with a potent intravenous bisphosphonate, zoledronate, for a period of one year. The zoledronate effects on bone will be measured using bone density values and femur scan structural analysis as the indicators of bone integrity. We will determine the effects of zoledronate on biomarkers of bone resorption and formation, and on serum calcitropic hormone levels.
To study the process of muscle atrophy when weightless, we will determine the relationships between changes in thigh muscle cross-sectional area measured by CT scan, muscle biopsy immunohistochemistry, muscle protein translation markers and markers for protein synthesis activation and protein degradation. To further understand mechanisms involved in bone loss, we will determine sequential changes in femur bone geometry and structural parameters obtained from DEXA scans by established 2-D curved beam analysis methods. Using femur CT images, we will measure changes in femur bone dimensions and will apply 3D, finite-element analysis to estimate fracture risk.
The new time-of-flight mass spectrometer will permit measuring the excretion of zoledronate in urine and plasma levels. We will compare these to radiologic measurements and bone biomarkers. The objectives of this research are:
- To develop a regimen for minimizing bone loss in SCI subjects that may be appropriate for astronauts during extended microgravity exposure;
- To investigate mechanisms related to muscle and bone loss during weightlessness, and;
- To explore the SCI patient as a surrogate for the investigation of microgravity-induced musculoskeletal atrophy.
This project's funding ended in 2005