Osteonecrosis, literally 'bone death', is caused by poor blood supply to an area of bone. Like the other bone disorder osteoporosis, osteonecrosis has only emerged as an HIV-related condition very recently. It is not an AIDS-defining condition.

Osteonecrosis is also known as avascular necrosis and aseptic necrosis.

A recent study conducted by researchers at the United States National Institute of Health (NIH) found that osteonecrosis was very common among people with HIV. Magnetic resonance imaging (MRI) scan found that 4% of 339 HIV-infected volunteers had osteonecrosis, a surprisingly high proportion. However, many of those affected had no symptoms such as hip pain (Miller 2002).

Cause

The emergence of this serious bone condition among people with HIV so many years into the HIV / AIDS epidemic is puzzling. NIH researchers have postulated several factors which may contribute to osteonecrosis including longer survival of people with HIV, treatments and therapies, or lifestyle factors.

The NIH study did provide some clues about the cause of osteonecrosis. Those with the condition were more likely to have taken testosterone, lipid-lowering drugs and corticosteroids, which may be taken for HIV-related conditions or metabolic disorders associated with antiretroviral therapy. The individuals also were more likely to have done weight training or body building. Osteonecrosis was not associated with immunodeficiency or any pattern of antiretroviral usage. However, a recent French study has shown an association between length of exposure to highly active antiretroviral therapy (HAART) and osteonecrosis (Mary-Krause 2004).

Another study has linked aseptic bone necrosis in HIV-infected men to the use of the synthetic hormone megestrol acetate, which is used to treat AIDS wasting (Koller 2000).Further research is required to identify the risk factors for this disease in HIV-positive people.

In non-HIV-infected populations, osteonecrosis is associated with alcoholism, steroid usage, pancreatitis, radiation exposure and various hormonal diseases. It can be caused by trauma or damage to the blood vessels that supply bone with oxygen or by a blockage in the bloodstream due to fat or an air bubble, very thick blood or inflammation of the blood vessels.

Treatment

The extent of bone damage determines treatment. Core bone can be removed and new bone grafted into the area to allow a new blood supply to form. With severe bone death of the knee or hip, joint replacements may be conducted. Given the early stage of investigations into osteonecrosis among people with HIV, nothing specific is known about treatment of this condition in the context of HIV infection.

See also Osteoporosis in Symptoms and illnesses: A to Z of illnesses.

Key research

Mary-Krause (2004) analysed data from the French Hospital Database on HIV (FHDH). Osteonecrosis was diagnosed in 122 of 56,300 patients between 1996 and 2002. The incidence of osteonecrosis was found to increase with length of exposure to HAART. Patients with <1 year on HAART had an incidence ratio of 1.5 relative to untreated patients; 1-2 years: 2.9; 2-3 years: 3.2; 3-4 years 3.4; 4-5 years: 5.1; >6 years: 6.8.

Miller and colleagues (2002) at the Clinical Centre of the U.S. National Institutes of Health enrolled 339 adults with HIV infection between 1 June and 15 December 1999. Although none had hip pain, the participants were analysed for osteonecrosis risk factors by comparing data from clinic records and responses to a patient questionnaire. Those at risk underwent a blinded magnetic resonance imaging (MRI) scan of the hip bone and compared with non HIV-infected controls. Fifteen (4.4%) of the adults with HIV infection had osteonecrosis of the hip detected by MRI scan. None of the adults without HIV infection were found to have osteonecrosis. Osteonecrosis was found to be more frequent among the HIV-infected persons who had used systemic corticosteroids, lipid-lowering agents, or testosterone; those who exercised routinely by bodybuilding; and those who had detectable levels of anticardiolipin antibodies.

Gaughan (2002) reported 6 cases of avascular necrosis or Leggs-Calve-Perthes Disease (LCPD) of the hip in 2014 HIV-infected children at enrolment in the study PACTG 219. Bone disorders data were collected yearly from 1996. 2 more cases were reported during follow-up representing an incidence of 199 per 100,000 person years, significantly higher than the general population prevalence of 23 per 100,000 children. Median age of onset was 9 years. 2/3 were not taking anti-HIV drugs at time of diagnosis although all had previously taken them. 4/6 had taken antiretroviral therapy prior to diagnosis with LCPD, and 3/6 had been exposed to steroids.

Keruly (2001) reviewed all cases of avascular necrosis (AVN) from the Johns Hopkins HIV Cohort between 1995-2000. ). 15 cases occurred with an incidence rate of 1.9 per 1000 person-years compared to the population-based incidence of 0.04 per 1000 person-years Factors associated with AVN were: steroid use, CD4 below 200 and more than 5 years since HIV diagnosis. There was no association with age, race, sex, HIV transmission risk group, concurrent lipodystrophy, high lipids or particular drugs or drug classes compared to the rest of the cohort. Almost half of the people with AVN had never taken a PI or NNRTI. Authors found duration of HIV infection the factor most associated with AVN.

G鲡rd (2000) reported avascular necrosis in 5 of 1870 (0.2%) HIV-infected patients attending a single HIV/AIDS clinic since mid-1996, when this condition first appeared among HIV-infected individuals at this clinic. 3 patients underwent hip replacements, another is continuing follow-up and another improved when PI therapy was ceased.

Glesby (2000) identified 14 cases of avascular necrosis of the femoral head in an urban HIV clinic between 1992 and 2000 (12/14 after 1996). These patients were matched for initial clinic visit and baseline CD4 with controls. Cases had longer duration of ART prior to diagnosis of AVN (32 vs 14 months; p=0.06). Multivariate analysis showed that only prior PCP was independently associated with AVN. The authors concluded that prior PCP was a possible marker for corticosteroid use.

Roudiere (2000) identified 7 cases of osteonecrosis from a cohort of 508 HIV-positive individuals between 1998 and 2000. Patients had a median 66.5 months ART therapy, low CD4 cell nadirs (median 18 cells) and fat redistribution in 5 of 7 cases. All had elevated triglycerides and/or cholesterol levels and 3 developed diabetes while on PI therapy.

Low (2000) reported a single case of aseptic osteonecrosis in a patient with advanced HIV.

References

Gaughan DM et al. Osteonecrosis of the hip (Legg-Calve-Perthes disease) in human immunodeficiency virus-infected children. Pediatrics 109: E74-E84, 2002.

G鲡rd M et al. Avascular necrosis (AVN) in HIV-infected patient treated with highly active antiretroviral therapy (HAART). Fifth International Congress on Drug Therapy in HIV Infection, Glasgow, abstract P186, 2000.

Glesby MJ et al. Case control study of avascular necrosis in HIV-infected patients. Antivir Ther 5: S21, 2000.

Keruly JC et al. Increasing incidence of avascular necrosis of the hip in HIV-infected patients. J Acquir Immune Defic Syndr 28: 101-102, 2001.

Koller E et al. Aseptic necrosis in HIV seropositive patients: a possible etiologic role for megestrol acetate. AIDS Patient Care STDs 14: 405-409, 2000.

Low P et al. Bilateral osteonecrosis of femoral heads in an AIDS patient on HAART. Fifth International Congress on Drug Therapy in HIV Infection, Glasgow, abstract P187, 2000.

Mary-Krause M et al. Impact of treatment with HAART on osteonecrosis (OST) incidence in HIV infected patients. Fifteenth International AIDS Conference, Bangkok, abstract ThOrB1358, 2004.

Miller KD et al. High prevalence of osteonecrosis of the femoral head in HIV-infected adults. Ann Intern Med 137: 17-25, 2002.

Roudiere L et al. Osteonecrosis on antiretroviral therapy. Antivir Ther 5: S43, 2000.

Further information

Support site for patients with HIV-associated osteonecrosis: www.hiv-avn.com.