Overview

The Effects of Partial Mechanical Loading and Ibandronate on Skeletal Tissues in the Adult Rat Hindquarter Suspension Model for Microgravity

Principal Investigator:
Lester W. Schultheis, M.D.

Organization:
Johns Hopkins University School of Medicine

Technical Summary

The loss of bone mass as a result of weightlessness assumes increasing importance as the duration of manned spaceflight increases. To date, efforts to maintain skeletal mass using a variety of exercise techniques or dietary modifications have proven less than effective. Our central hypothesis was that pharmacological modification of bone resorption combined with precisely designed mechanical loadbearing, may provide the best possible skeletal protection.

In earlier work, our laboratory rats were placed in a harness and counterweight system that lifted a known fraction of weight off their legs. These data constituted a preliminary dose-response relationship between weightbearing and bone. In our work with NSBRI, we focused on the 50 percent weightbearing condition to examine the effect of partial weightbearing because it provides a benchmark to estimate the effect of Martian gravity and artificial gravity on bone. Based upon evidence that osteogenesis is particularly sensitive to specific components of dynamic bone strain, we developed a unique instrument to control mechanical loadbearing on the front limbs of hindquarter suspended rats. This consisted of a platform controlled by a digital computer in negative feedback so that it would resonate with specified frequencies of impact. Our system enabled us to process aperiodic forces in the frequency domain as they are applied to bone through normal joint contact and muscle insertions during a form of ambulation. We maintained the normal spectral (Fourier component) composition of quadrupedal forces in a bipedal rat. Partial weightbearing was controlled as a simulation of reduced gravity independently from dynamic forces that simulated carefully designed exercise. We suspected that simultaneous pharmacologic inhibition of resorption and bone turn-over would be more effective with mechanical countermeasures than either regimen alone. We hoped to provide an accelerated model for the NASA JSC human bedrest studies of LeBlanc and Shackleford testing the effects of episodic resistive exercise and bisphosphonate therapy because of the more rapid bone turnover in the rat. The endpoints of the proposed treatments will include biochemical, cellular, histological, mechanical, and gross anatomical skeletal analysis in each animal and an assessment of systemic stress. No prior studies have included as completed a range of analytical procedures in the same animal.

This project's funding ended in 2000