Overview

Bone Recovery Potential after Bisphosphonate and PTH Treatment of Disuse Osteoporosis

Principal Investigator:
Mitchell B. Schaffler, Ph.D.

Organization:
Mount Sinai School of Medicine

Bone loss and bone fragility in microgravity are barriers to the success of long-term spaceflight. For countermeasures to be effective, they must prevent bone loss yet maintain mechanical integrity and allow for rapid recovery of astronauts’ normal function. Previous studies have determined that certain drugs work to prevent bone loss and as a result, are a cornerstone of current therapy. However, new advancements in the treatment of osteoporosis encourage the use of drugs that stimulate formation of new bone. Dr. Mitchell B. Schaffler is uniting the two treatments by examining whether bone that remains after loss-prevention drug treatment can recover its architecture and mechanical function when weight-bearing is restored, and if the application of bone formation-stimulating drugs will improve the recovery of bone tissue.

NASA Taskbook Entry

Technical Summary

Bone loss in microgravity and resulting bone fragility have been identified by NASA as key barriers to successful long-term spaceflight. Effective countermeasures must therefore prevent bone loss but also maintain the mechanical integrity of the tissue during prolonged spaceflight and allow rapid recovery of normal function.

Disuse osteoporosis in humans and higher mammals results from elevated bone resorption. Thus, targeting osteoclasts with anti-resorptive agents, like bisphosphonate, to prevent bone loss is a key strategy. While anti-resorptive drugs have been the cornerstones of osteoporosis therapy, anabolic agents, such as parathyroid hormone (PTH), that stimulate bone formation represent an important new advance in the treatment of osteoporosis. We hypothesize that PTH may be especially valuable in reversing disuse if the deterioration of bone architecture can be slowed such that the anabolic agent has a better initial bone scaffold on which to work.

The studies examine whether bone that remains after bisphosphonate-treatment during long-term immobilization can recover its architecture and mechanical function after restoration of mechanical usage (remobilization). We will then assess whether addition of anabolic PTH during immobilization will improve recovery of disuse bone. Recovery after long-term disuse with bisphosphonate treatment will be examined in an immobilization model. MicroCT imaging will be used to evaluate microstructure, biomechanical testing to assess function and histomorphometry to measure tissue physiological responses.

Earth Applications

The current research applies directly to prevention and treatment of osteoporosis on Earth. These studies will examine the efficacy of antiresorptive therapy in slowing the bone loss that occurs with decreased mechanical loading, and the role of the bone anabolic agent, parathyroid hormone (PTH), in accelerating bone recovery and restoring bone strength. This research uses pharmacological agents that are already approved for clinical use; thus, the findings from this research can be expected to see rapid implementation in bone loss situations occurring as a result of unloading, such as spinal cord injury and long-term immobilization.

This project's funding ended in 2008