Also known as avascular necrosis of bone (AVN), this condition results from deficient blood supply to bone resulting in bone death and has been long described in HIV-infected persons.27 Subsequent studies showed that the risk of this condition is increased 100-fold in the HIV-infected population compared to the general population.26 MRI studies have shown that this condition may be found in asymptomatic HIV-infected populations.60 Established risk factors for osteonecrosis include steroids, alcohol use, smoking and coagulopathies.55 Vasculitis may have a role in causing osteonecrosis in HIV infection, possibly related to anticardiolipin antibodies.  These antibodies are associated with endothelial disruption, platelet aggregation and vascular thrombosis, representing a possible contribution to the development of osteonecrosis.56,60 HIV infection is also associated with immune activation, chronic inflammation and activation of coagulation pathways. These factors may contribute to the development of osteonecrosis. For example, elevated plasma levels of D-dimer and CRP have been associated with osteonecrosis of the hip in HIV-infected adults.57 Increased production of proinflammatory cytokines such as interleukin-6 and tumour necrosis factor have also been implicated in the pathogenesis of osteonecrosis.58  Further support of the role of inflammation in this disorder is the finding of raised levels of IgE associated with osteonecrosis.59 High levels of IgE are associated with Th2-type cytokines and high IgE levels may promote platelet activation with subsequent formation of intravascular thrombi.

In a recent large cohort-study involving 11820 participants, there were 89 cases of osteonecrosis of the femoral head giving an incidence rate per 1000 person-year follow-up of 1.0.29 In this study, there was no association between cumulative exposure to antiretroviral drugs and osteonecrosis although a small risk from these agents could not be excluded. Risk factors for osteonecrosis were a history of AIDS-defining conditions, lower CD4+ T cell counts, white race and a history of prior fracture and prior osteonecrosis.29 However, no data was collected on the use of alcohol, corticosteroids, megestrol acetate or testosterone.  Use of these agents has been related to the risk of osteonecrosis in earlier studies.31,32 An association between the use of protease inhibitors and osteonecrosis had been suggested in earlier studies.30 Progression of disease may necessitate total hip replacement and disease may subsequently develop in the other hip.43