Glucocorticoids are a class of steroids used to treat a wide array of chronic medical conditions, such as asthma, ulcerative colitis, and a number of rheumatologic disorders. Long-term use of glucocorticoids, however, causes bone loss and eventually can result in severe osteoporosis and fractures, as well as osteonecrosis (bone death). Osteonecrosis of the hip joint contributes to approximately 10% of the 500,000 hip replacements annually in the US. In addition, long-term steroid therapy significantly increases the risk of hip fractures. Currently, surgery is the only treatment option for this condition.
Now, researchers at Mount Sinai School of Medicine have found a potential new treatment for steroid-induced osteonecrosis of the hip, one that works by stimulating new blood vessel growth (angiogenesis) at the femoral head—the part of the hip joint most vulnerable to osteonecrosis from steroid therapy. The research is published in the April 27 issue of Proceedings of the National Academy of Sciences.
The Mount Sinai team, led by Mone Zaidi, M.D., Ph.D., Professor of Medicine and Physiology and Director of The Mount Sinai Bone Program, tested adrenocorticotropic hormone (ACTH) in rabbits with osteonecrosis caused by steroids. It has been observed that humans suffering from a particular type of tumor in the pituitary gland (Cushing’s disease) often have high levels of both ACTH and glucocorticoids in their bloodstream, and that they don’t typically develop osteonecrosis, although they would be expected to.
To determine whether ACTH protects against osteonecrosis caused by treatment with glucocorticoids, they injected one group of rabbits with depomedrol, a type of steroid, and another group with depomedrol plus ACTH. The rabbits treated with ACTH had dramatically reduced osteonecrosis compared with the rabbits that didn’t receive ACTH. ACTH stimulates production of a key angiogenesis-promoting protein called vascular endothelial growth factor (VEGF). Increased VEGF results in capillary formation and more blood flow to bone cells, thereby preventing cell death and bone destruction.
Presently, the medical use of ACTH is restricted to a type of infantile seizure. While these results will need to be replicated in the laboratory and validated in clinical trials, ACTH as an angiogenesis-stimulator could represent an important new treatment for osteonecrosis caused by steroid therapy