Important note: Information in this article was accurate in June 2000. The state of the art may have changed since the publication date.
Osteonecrosis, also called avascular necrosis, occurs when blood stops flowing to the bones. This results in bone cells dying and bones becoming weak. When this happens to bone cells near a joint, that part of the joint also becomes weak and can collapse, resulting in inflammation and pain. Osteonecrosis often affects the ends of the bone linking the knee to the hip. This bone is called the femur.
In the Italian study reported previously, osteonecrosis occurred in four of 1,207 subjects, a proportion of less than one per cent. In all four cases the bone affected was the portion of the femur near the hip. Why this happened is not clear. Osteonecrosis can occur in people with the following risk factors:
The Italian team did not supply data about risk factors for osteonecrosis that the four subjects might have had. The researchers did, however, note that three of the four subjects had higher-than-normal levels of triglycerides in their blood.
Higher-than-normal levels of lipids, or fatty substances in the blood, such as triglycerides and cholesterol, have been reported in people who developed symptoms of AIDS in the early 1990s when protease inhibitors were not widely available. Since the introduction of HAART, some doctors have reported an increase in the number of their patients with high levels of triglycerides (TG) and other lipids.
How might high levels of TG and other lipids in the blood be linked to osteonecrosis? In experiments on rabbits given corticosteroids, researchers found that the animals developed high levels of lipids in their blood and deposits of fat on their bones. These abnormal deposits of fat reduced the circulation of blood to the bone. As well, fat cells in the bone marrow grew, squeezing blood vessels and reducing blood flow. It is possible that protease inhibitors, which are associated with fat redistribution and high TG levels, may have a similar, indirect impact on the bones of people who are already at risk for the development of osteonecrosis.
Finally, readers should note that use of protease inhibitors appear to affect levels of some hormones. In the large Italian study doctors reported that the drugs nelfinavir and ritonavir/saquinavir raised levels of the hormone prolactin. Other researchers have reported that protease inhibitors can affect other hormones such as estrogen, testosterone and thyroid hormones. It is possible that changes in these and other hormones may affect the health of bones.
To help stay healthy, regular exercise and a nutritional program designed to help reduce the levels of lipids in the blood are probably useful steps. In some cases the use of lipid-lowering drugs may be necessary. X-ray and magnetic scans (MRI) of the bones can be used to help doctors diagnose osteonecrosis. In cases where osteonecrosis has developed, hip replacement surgery may be needed. Further articles on bone health will appear in a future issue of TreatmentUpdate.
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