In high-income countries, the use of highly active antiretroviral therapy (HAART) has led to decreased rates of death due to AIDS-related infections. As a result, people with HIV/AIDS (PHAs) are living longer. Not surprisingly, some complications that were uncommon or unrecognized in the time before HAART are becoming more noticeable.
Once such complication is osteonecrosis (also known as avascular necrosis, or AVN) — the death of large numbers of bone cells, particularly in joints such as the hip. Although the hip is the most common joint affected by osteonecrosis, other parts of the body, such as the shoulder, wrist, knee and ankle, can be affected.
In general, osteonecrosis is not common. By one estimate, in HIV negative people, less than 1% (0.14%) develop this problem each year. Rates of osteonecrosis in this group have not been increasing. In contrast, among people with HIV, reports of osteonecrosis have been increasing, particularly in the last few years. A recent American study found that about 4% of 339 HIV positive people had osteonecrosis in their hip joints. This raises questions as to why some PHAs may be at increased risk for osteonecrosis.
While there are a number of conditions (more about this later) that can lead to osteonecrosis in HIV negative people, what these conditions all have in common is that large numbers of bone cells have died because their blood supply has been greatly reduced or cut off. This can happen because of blockage from blood clots and damage to blood vessels from injuries or radiation. Below are some risk factors that have been linked to osteonecrosis in HIV negative people:
Drugs:
Blood problems:
Autoimmune diseases:
Other:
Although this list is long, in both HIV positive and negative people, the most common risk factors for osteonecrosis are the use of corticosteroids and alcohol abuse.
Researchers aren't exactly sure how alcohol and corticosteroids are linked to osteonecrosis. These substances may increase the level of fat within bones. As fat levels in bone increase, they may squeeze blood vessels and reduce blood flow within the bone. The use of alcohol and corticosteroids can also increase the level of fats in the blood to higher-than-normal levels (hyperlipidemia). This may increase the deposits of fat into the bone from blood.
At least three studies have examined risk factors for osteonecrosis in HIV positive people. Importantly, all the studies included people with and without osteonecrosis. In all three studies researchers found the following:
In two of the studies, researchers found a link between alcohol abuse and osteonecrosis.
The use of bodybuilding steroids by athletes has been associated with osteonecrosis. In PHAs with less-than-normal levels of testosterone, supplements of this hormone have not been associated with osteonecrosis. However, in one study, researchers found four cases of osteonecrosis among HIV positive men who were receiving testosterone. (None of these men had testosterone deficiency.)
Rates of osteonecrosis in HIV negative people appear to be stable while clinics that treat PHAs are reporting more cases of osteonecrosis. These reports began to increase in the late 1990s. Because HAART became widely available in the latter half of the 1990s, it may appear that HAART could somehow be linked to the development of osteonecrosis. However, results from several studies so far suggest that there is no direct link between the two.
Despite this conclusion, the use of HAART by some HIV positive people could still be linked to the development of osteonecrosis. This is because some treatment regimens contain protease inhibitors, a class of drugs known to increase lipid levels in the blood. Having higher-than-normal levels of lipids is a risk factor for osteonecrosis.
The symptoms of bone disease are subtle, with "most patients complaining of mild-to-moderate pain" when they try to lift heavy weights or move a joint through its full range of motion. To find out if a person has osteonecrosis, an X-ray or magnetic scan (MRI) of the affected joint is needed. X-rays will not always detect osteonecrosis. Magnetic scans are more sensitive than X-rays in helping to detect bone disease. Another advantage of MRIs is that they can capture images of osteonecrosis in its early stages.
Depending on the severity of bone damage, different options for managing this condition may be available. Immediately decreasing exposure to risk factors, such as alcohol and corticosteroids, is an obvious first step. In the very early stages of osteonecrosis, some doctors will recommend ways to decrease weight applied to the affected joint. In the case of the hips, crutches may, for a time, be used. In some HIV positive people, these simple steps may be enough to allow necrotic spots on the bone to heal.
There are no data from studies about the use of anti-clotting agents, such as aspirin, in the prevention of further bone damage once osteonecrosis has been diagnosed.
In more established cases of osteonecrosis, a number of surgical techniques may be used. One option is called "core decompression." Here cores of affected bone are removed and the pressure inside the bone is relieved. This can stimulate the repair and growth of new blood vessels in the affected joint and may prevent further loss of bone.
A less commonly used option is to remove a small amount of healthy bone from one part of the body and graft it on to the damaged bone.
In cases of severe osteonecrosis of the hip, entire joints will have to be replaced. In young people, the lifespan of a new hip joint is between 10 and 20 years.
Corticosteroids, because of their anti-inflammatory activity can be useful in the management of several HIV/AIDS-related complications, including the following:
Corticosteroids are also used to help manage persistent asthma. Because even short-term use of these drugs may increase the risk of developing osteonecrosis, a recent editorial in the journal AIDS suggested that if these drugs must be given, the lowest dose for the shortest period of time should be used.
The editorial also suggests that all PHAs using HAART need to be regularly monitored and treated for higher-than-normal levels of lipids. As well, PHAs who abuse alcohol need to receive treatment and support.
REFERENCES
1. Allison GT, Bostrom MP and Glesby MJ. Osteonecrosis in HIV disease: epidemiology, etiologies, and clinical management. AIDS 2003 Jan 3;17(1):1-9.
2. Miller KD, Masur H, Jones EC, et al. High prevalence of osteonecrosis of the femoral head in HIV-infected adults. Ann Intern Med 2002 Jul 2;137(1):17-25.
3. Scribner AN, Troia-Cancio PV, Cox BA, et al. Osteonecrosis in HIV: a case-control study. J Acquir Immune Defic Syndr 2000 Sep 1;25(1):19-25.
4. Glesby MJ, Hoover DR and Vaamonde CM. Osteonecrosis in patients infected with human immunodeficiency virus: a case control study. J Infect Dis 2001 Aug 15;184(4):519-23.
5. Blacksin MF, Loser PC and Simon J. Avascular necrosis of bone in human immunodeficiency virus-infected patients. Clin Imaging 1999 Sep-Oct;23(5):314-8. [PubMed - indexed for MEDLINE]
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