People who rely on corticosteroid medications to control the inflammation associated with conditions like rheumatoid arthritis, lupus or asthma, may eventually have to face a painful and debilitating side effect of that treatment – osteonecrosis, or death of bone tissue.
Osteonecrosis may affect any bone, but it most commonly strikes the ends of the femur, or thighbone, where it attaches to the hip.
The condition is currently incurable, and hip replacement surgery is the only option for patients looking for relief. In fact, studies show that osteonecrosis is the diagnosis behind about 10 percent of the 500,000 hip replacements performed in the U.S. each year.
But that may change.
Researchers believe they have uncovered the first agent that protects against osteonecrosis brought on by corticosteroid treatment.
Commonly prescribed corticosteroids include betamethasone (Celestone), cortisone acetate (Cortone), dexamethasone (Decadron, Hexadrol), hydrocortisone (Hydrocortone), methylprednisolone (Medrol), prednisolone (Prelone, Pediapred), and prednisone (Deltasone, Orasone, Sterapred).
“We have demonstrated in an animal model that the body’s own hormone can be injected in a way that it would, to an extent, prevent the dead bone,” says study author Mone Zaidi, MD, PhD, director of The Mount Sinai Bone Program and a professor of Medicine and Physiology at the Mount Sinai School of Medicine in New York City. “I’m very excited.”
The study was published online on April 26 in the Proceedings of the National Academy of Sciences.
Adrenocorticotropic hormone, or ACTH, is made by the body’s pituitary gland, and its main job is to stimulate the production of other hormones, such as the stress hormone cortisol.
For this study, Dr. Zaidi decided to test the hypothesis that corticosteroids suppress the body’s ACTH level, causing a chain reaction of hormone suppression that eventually leads to necrosis or death of the joint.
The research team gave rabbits 10mg/kg of corticosteroids a day for 28 days. Half the rabbits were treated with corticosteroids alone and the other half were injected with corticosteroids and ACTH.
At the end of the experiment, there was a 50 percent decrease in the level of necrosis in the rabbits treated with the steroid/ACTH combination compared with those who got corticosteroids alone.
“It’s the first time that any drug or hormone or any substance has been shown to reduce osteonecrosis of the hip in an animal model. It's never been done before. That’s why it’s so newsworthy,” Dr. Zaidi says.
He says the next step is to test this in clinical studies on humans. And, he says, the good news is these trials can be fast tracked because the ACTH compound is not only naturally produced as a hormone in the body, it’s also FDA-approved in drug form to test the sufficiency of the adrenal glands.
“The idea is to use a drug available on the marketplace for something entirely different to prevent the osteonecrosis of the hip that is induced by corticosteroids,” Dr. Zaidi says. “It could be more in humans. It could be a function of dose. It could be we aren’t using enough. it could be timing. There could be a variety of variables where you could change the percentage of necrotic bone. It’s hard to tell,” Dr. Zaidi says.
He says his findings are particularly exciting since there are currently no other medical options to the disease. “If it works in humans it would be very useful because it would save so many surgeries in the hip,” Dr. Zaidi says.
Dr. Zaidi estimates that if clinical trials in humans replicate these results, it could be just a few years before patients could take advantage of this finding. “The health-care implications could be fairly profound in a short period of time,” Dr. Zaidi says.
But Stephen Paget, MD, program director of the Multipurpose Arthritis and Musculoskeletal Diseases Center at the Hospital for Special Surgery in New York City, says caution is warranted when interpreting these results.
Dr. Paget says the fact that it is an animal study means it is too early to say if the results will translate to people.
“Until there are some better research methodology including other controls that were just treated with ACTH and there’s any kind of study done in humans, I don’t think this is ready for prime time,” Dr. Paget says.