HIV-positive individuals have a massively increased risk of osteonecrosis

People with HIV have approximately a hundred times greater risk of developing osteonecrosis (bone death) than the general population, researchers at the US National Institutes of Health have found. The findings were published in the March 1^st online edition of Clinical Infectious Diseases.

Incidence

Osteonecrosis or ‘bone death’ occurs when the blood supply to the bone is disrupted, leading to painful bone decay and loss, usually at the ends of bones such as those in the hip joint. Osteonecrosis of the hip joint usually requires hip replacement surgery.

In the general population, between 0.003 and 0.006 new cases of osteonecrosis are estimated to occur per hundred people, per year. Well-defined studies have not yet been conducted in HIV-positive people, but retrospective case studies have given estimates of 0.03 to 0.37 new cases per hundred per year. The purpose of this National Institutes of Health (NIH) study was to find the rate of new cases of osteonecrosis in a group of HIV-positive patients, and to study the natural history (progression) of the condition.

In 2002, the authors of the current paper reported that 15 (4.4%) of a group of 339 asymptomatic HIV-positive patients (at NIH clinics in Bethesda, Maryland) had osteonecrosis of the hip, confirmed by magnetic resonance imaging (MRI scan). Patients from this study were then enrolled in a prospective follow-up. Two hundred and thirty-nine participants who did not have osteonecrosis in the first study received a second MRI hip screening a median of 23 months after the first, between February 2001 and January 2002. New cases of osteonecrosis were diagnosed in three (1.3%) of these 239 patients – an incidence rate of 0.65 cases per hundred people per year.

Risk factors

The original NIH study found that osteonecrosis was two to five times more frequent in people who had ever used corticosteroids, lipid-lowering agents or testosterone, or in those who routinely did weight-training exercise. Detectable levels of anticardiolipin antibodies – an abnormality associated with blood clotting disorders – were also a risk.

Several other risk factors have been reported but not necessarily agreed upon between various studies of osteonecrosis in HIV: length of HIV infection, AIDS-defining illness or very low CD4 counts in the past, longer time on antiretroviral treatment (Mary-Krause 2006), and use of megestrol acetate (Megace) (Koller 2000). Most cases, however, have been observed after antiretroviral combination therapy came into wide use.

Natural history

A follow-up ‘natural history’ study was done on a total of 40 HIV-positive people with osteonecrosis: the fifteen diagnosed in the first study, the three diagnosed during the second MRI, thirteen from other NIH clinics, and nine from other referrals. Of these, 22 were symptomatic with hip or groin pain; 18 were asymptomatic, diagnosed only by MRI.

Of the 22 people with symptomatic hip osteonecrosis, the femoral heads (the top of the thigh bone, which forms the ‘ball’ in the ball-and-socket hip joint) of both legs were involved. In seven people, other bones were involved as well. Two (11%) of the asymptomatic and thirteen (59%) of the symptomatic patients underwent total hip replacement surgery.

Conclusions

The researchers concluded that “HIV-infected patients are at [approximately] 100-fold greater risk of developing osteonecrosis than the general population…Moreover, there is a high rate of progressive disease and a need for [total hip replacement” especially in the majority of symptomatic patients.

Comparing their own findings to existing studies, the researchers found that corticosteroid use was “consistently identified as one of the most important risk factors”. Despite some suggestions to the contrary, they believe that “it is difficult to conclude that protease inhibitors or antiretroviral combinations are independently associated” with osteonecrosis.