HIV-positive patients with 'dead bone' usually have other risk factors

The majority of HIV-positive patients who develop the painful bone disease osteonecrosis have pre-existing risk factors for the condition, Spanish researchers report in an article published in the July edition of the Journal of Acquired Immune Deficiency Syndromes. The investigators conducted a retrospective review of the medical records of over 10,000 HIV-positive individuals and found that among the 54 individuals developed the condition progression of the condition most commonly occurred when it involved the hip.

Osteonecrosis – literally “dead bone” – occurs when the blood supply to the bones is temporarily or permanently disrupted. Although it can happen to any bone, it usually affects the ends of bones, such as those in the hip joint. An increased risk of osteonecrosis in HIV-positive individuals was first recognised in the early 1990s, and although the risk is small (annual incidence observed in some small studies has ranged from 0.08% - 1.33%), it is still significantly higher than that seen in the general, HIV-negative, population (where the annual incidence is approximately one in 100,000).

Spanish doctors wanted to gain a better understanding of the incidence, risk factors, and outcome of osteonecrosis in HIV-positive people. They therefore conducted a retrospective analysis of the medical records of 10,000 HIV-positive patients who received treatment in 19 Spanish cities between 1990 and 2003. In patients diagnosed with the condition, the researchers looked for the presence of any factors known to increase the risk of osteonecrosis, such as local trauma, the use of corticosteroids, alcohol abuse, deep vein thrombosis, gout, hyperlipidaemia, pregnancy and the use of megestrol acetate - a treatment for wasting and weight loss in HIV-positive individuals.

A total of 54 cases of osteonecrosis were identified. The average age of the individuals at the time of osteonecrosis diagnosis was 38 years, 74% were men, and 63% had become infected with HIV due to injecting drug use. Median CD4 cell count at the time of osteonecrosis diagnosis was 343 cells/mm³. However, the investigators noted that osteonecrosis usually developed later in the course of HIV infection, as the median nadir CD4 cell count was only 90 cells/mm³, the median period since HIV diagnosis when osteonecrosis was diagnosed was over six years, and 82% of patients had a previous AIDS-defining illness.

The overwhelming majority of cases, 49 (91%), occurred after 1997, when the use of potent anti-HIV therapy became available and 96% of patients had received some form of HIV treatment. The antiretrovirals d4T (stavudine, Zerit) and ddI (Videx) which are known to cause mitochondrial toxicity, were used by 36 (76%) individuals.

Risk factors for osteonecrosis were present in 47 (87%) individuals, with 29 patients (54%) having more than one risk factor. The investigators noted that approximately 50% of patients had increased blood fats or blood sugars due to the use of antiretroviral therapy and that just under 33% had body fat changes consistent with lipodystrophy.

In most patients (29, 54%), osteonecrosis only affected one site. Overall, the hip was the most common location for the condition, and 46 patients (85%) had osteonecrosis in this site. Other sites affected included the knees and shoulders (four cases each) and the ankles (three cases). There were no significant demographic , or HIV-related differences between patients who had the condition in one or more sites. However, the investigators noted that when osteonecrosis involved the hip, it was significantly more likely to progress or cause pain (17 of 39 hip cases versus none of the eight cases involving other sites, p = 0.01).

Patients were followed for a median of 14 months, during which time four individuals died. Two new cases of osteonecrosis were observed during follow-up, providing an incidence rate of 1.5 per 100 person years.

Detailed information on the clinical course of osteonecrosis was available for 47 patients, and of these, 26 (54%) remained stable, 17 (36%) deteriorated, and four (9%) spontaneously improved.

Surgery was used as a treatment for 20 patients, 19 of whom had a hip replacement. Patients undergoing surgery were significantly more likely to be male (p = 0.03) and have a higher CD4 cell count (p = 0.03).

“This study confirms that osteonecrosis is an important complication that may lead to significant disability in adults with long-lasting HIV disease under different antiretroviral regimens”, write the investigators. However, they stress that most of the patients had conditions predisposing them to the development of the condition or had a history of severe immune suppression. “Clinicians need to be alert for early diagnosis of osteonecrosis in those patients”, conclude the investigators.