Antiretrovirals, fractures, and osteonecrosis in a large international HIV cohort. Clinical Infectious Disease
Borges et al. on behalf of EuroSIDA aimed to study the association of exposure to antiretroviral drugs with incident fractures and osteonecrosis of the femoral head and to determine factors independently associated with these two bone outcomes.
Among 11’820 included participants during 86’118 person years of follow-up (PYFU), 496 persons had 619 incident fractures (incidence rate [IR]/1000 PYFU) and 73 persons developed 89 cases of osteonecrosis of the femoral head (IR: 1.0). After adjustment, an increased risk of incident fractures was independently associated with older age, white race, lower BMI, intravenous drug use, HCV coinfection, prior fracture, prior osteonecrosis of the femoral head, a recent non–AIDS-defining malignancy and recent cardiovascular disease. After adjustment, persons who had ever used tenofovir (TDF) (adjusted incidence rate ratio [aIRR], 1.40, P = .0008) or who were currently receiving TDF (aIRR 1.25, P = .012) had a significantly increased incidence of fractures. There was no association between cumulative exposure to TDF and fractures and no other antiretroviral was associated with fractures. Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no antiretroviral was associated with osteonecrosis.
To conclude, the risk of fractures and osteonecrosis seems to be determined by combination of host factors, HIV-specific variables and comorbidities. The study-results suggest that past and current exposure to TDF, but no other antiretroviral, was independently associated with higher incidence of fractures. The data support cautious use of TDF among HIV-positive persons at fracture risk initiating ART.