Studies link bone disease, antiretroviral meds
NIH, California surgeon have similar findings
Recent findings by medical experts from coast to coast suggest clinicians need to be aware that HIV patients on antiretroviral medications may be at greater risk for developing osteonecrosis, also called avascular necrosis (AVN) of the hip joint area.
"In late 1996, I started noticing that I was seeing more cases of avascular necrosis of the femoral head among HIV patients," says Guy Paiement, MD, associate professor of orthopedic surgery at the University of California San Francisco and San Francisco General Hospital Medical Center. Paiement presented some of his research results at the annual meeting of the American Orthopedic Association on June 16 in Hot Springs, VA.
An increase in AVN cases among HIV patients has been confirmed by the National Institutes of Health (NIH) in Bethesda, MD.
"We had heard some anecdotal reports of cases of AVN from community physicians, and over a four-day period a couple of years ago, we had two patients in whom we diagnosed symptomatic AVN of the hip," says Joseph Kovacs, MD, senior investigator of the NIH’s critical care medicine department. The NIH study results were presented at the Infectious Diseases Society of America’s annual meeting on Sept. 8 in New Orleans. "This raised concern that this would be a potentially new problem in HIV patients," Kovacs says.
NIH investigators tested the hypothesis that HIV patients were at greater risk for AVN by using magnetic resonance imaging to evaluate 339 HIV patients. Another 118 people who were HIV negative also were scanned as a control group. Investigators found that 15, or 4.4%, of the 339 HIV patients had the disorder, although it had not yet become symptomatic. None of the 118 people in the control group had osteonecrosis.
The 15 HIV patients had lesions in one or both hips, and some of the lesions were large enough to raise concerns that they would lead to clinical symptoms.
"In our study, we tried to look at potential factors, and certainly one hypothesis is that this is related to protease inhibitors," Kovacs says. "About 90% of our HIV patients are on protease inhibitors and highly active antiretroviral therapy regimens, so that makes it difficult to identify specific drugs."
The NIH study did find that patients with osteonecrosis were more likely to have taken corticosteroids, testosterone, and lipid-lowering drugs. They also were more likely to have engaged in weight-training and body-building activities.
While it is logical to assume that the recent rise in AVN cases among HIV-infected patients is due to antiretroviral drugs, this also could be a result of the fact that HIV-infected people are living longer than they did before the drug therapies, so HIV now has time to make them susceptible to AVN, Kovacs says. However, it would take a large population of HIV patients who are not on antiretroviral therapies and who are living for a long period of time to test that possibility, he adds.
"My gut feeling is that maybe some other factor and not just HIV itself [that] is related to this disease," Kovacs says.
The NIH will continue to study AVN among HIV patients and follow the patients who showed signs of it on the MRI scans to see how many of them need hip replacement surgery.
AVN is not common in the general population. Most of the people who have it had some other risk factors, such as chronic alcoholism or a disease such as lupus that requires them to take prednisone, Paiement says. "Chronic use of prednisone has a lot of musculoskeletal complications, and the most common is osteoporosis," he adds. "But a small number develop AVN."
When Paiement first mentioned his observations of increasing numbers of AVN cases among HIV patients to other orthopedic physicians and HIV doctors, he was met with skepticism, he recalls. "So I decided to pull out these charts, and I realized that all the cases of HIV patients with AVN were people on protease inhibitors. Before 1996, I had seen one or two cases a year among HIV patients, but starting in late 1996, it was like an epidemic."
Paiement reviewed 30 cases of AVN among HIV patients. The hospital’s number of HIV cases had remained fairly steady at about 3,500 active HIV patients. The only difference in recent years has been that the demographics of the HIV patients have shifted more toward women, injection drug users, and minorities, he says.
When this sudden increase in AVN cases occurred, it seemed that something else was contributing to it. "For 18 of the patients, the only risk factor was chronic use of protease inhibitors," he says.
He since has reviewed a post-exposure prophylaxis study in which 600 people were given short-term doses of protease inhibitors, and none of those people developed AVN, he notes. "I strongly believe protease inhibitors will cause AVN only if used chronically, and just a short course of four to six weeks isn’t long enough."
While screening all HIV patients for AVN through use of an MRI scan is not cost-effective, both Kovacs and Paiement recommend clinicians watch for signs that a patient has developed osteonecrosis of the hip. "If someone is complaining of a pulled groin muscle that’s not getting better, think of AVN as a possible explanation for that," Kovacs says.
Paiement recommends clinicians order an X-ray for patients who complain of groin or hip pain or refer them to an orthopedic surgeon. "If you strongly suspect AVN, then get an MRI," he adds. "Let’s say the patient presents with groin pain that hasn’t improved over six to eight weeks, then refer the patient to an orthopedic surgeon."
It’s important to find AVN early in the disease process because if it’s identified after the femoral head collapses, it will result in arthritis and require a more costly procedure, such as hip replacement surgery, to correct it.
"If you pick up AVN before the femoral head collapses, you can do a small procedure to relive the pressure, and it could be self-limited, with the bone repairing itself," Paiement explains.
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