HIV-positive people face a 100-fold greater risk of developing bone death than the general population, according to a study completed by the National Institutes of Health. The results, released online by the University of Chicago Press, are to be published in the March 1 issue of Clinical Infectious Diseases.
Over the past decade, the widespread use of antiretroviral therapy has led to a dramatic decrease in the incidence of "classic" AIDS-related problems and has prolonged survival for HIV-positive people. During this period, however, previously unrecognized complications and side effects of antiretroviral therapy have become more prevalent. Osteonecrosis – bone death resulting from poor blood supply to an area of bone (also known as avascular necrosis) – is one such debilitating complication.
Osteonecrosis in people living with HIV was first described in 1990, with a number of case reports and small studies conducted since then. Much like reports of osteonecrosis in the general population, the most likely risk factors among HIV-positive people are believed to be corticosteroid use (e.g., prednisone), blood clotting disorders, and alcohol and tobacco use. HIV-specific risk factors include protease inhibitor use, the presence of lipodystrophy, and the use of medications like Megace (megestrol acetate) and testosterone.
The annual incidence of symptomatic osteonecrosis in the general population has been estimated to be approximately 0.003% to 0.006%. Recent retrospective studies – studies that look back on patients' medical records – have reported the annual incidence in HIV-positive people to be significantly higher, ranging from 0.03% to 0.37%. However, a true assessment of the osteonecrosis risk facing HIV-positive people requires data from prospective studies that actively follows patients over time.
The National Institutes of Health researchers, under the direction of Caryn Morse, MD, MPH, of the NIH's Critical Care Medicine Department, have completed one of the first prospective studies assessing the incidence of osteonecrosis in HIV-positive people.
The study initially included HIV-positive adults enrolled in various cohorts at the NIH campus in Bethesda. Three hundred thirty-nine volunteers underwent MRI scans of their femoral heads – the ball of the thigh bone that fits into the socket of the hip bone. Two hundred thirty-nine patients, none of whom had evidence of osteonecrosis the first time around, underwent a second MRI between 17 to 31 months later (average of 23 months).
After their second MRIs, three patients received a diagnosis of osteonecrosis of the femoral head (all three had evidence of deterioration in both femoral heads). However, none of the patients reported any symptoms indicative of osteonecrosis. This translated into an annual incidence of asymptomatic osteonecrosis of 0.65%.
Dr. Morse's group also documented 13 HIV-positive patients enrolled in other NIH studies that developed hip or groin pain and, after MRI confirmation, received a diagnosis of symptomatic hip osteonecrosis. The annual incidence of symptomatic hip osteonecrosis was calculated to be 0.26%.
The annual incidence of asymptomatic and symptomatic osteonecrosis, the Dr. Morse's group writes, "is approximately 100-fold higher than the estimated incidence in the general population."
While not reported in detail here, there was a high frequency of bone- and joint-related disease progression seen in several HIV-positive patients with osteonecrosis involved in research on the NIH campus. Approximately 59% of the patients with symptomatic osteonecrosis required total hip replacements. In turn, Dr. Morse's group writes, "interventions to prevent progression must be critically evaluated."
Source:
Morse CG, Mican JM, Jones EC, et al. The incidence and natural history of osteonecrosis in HIV-infected adults. Clin Infect Dis. Published online: January 23, 2007.
