HIV Increases Bone Fracture Risk by 32% in Middle-Aged U.S. Women

HIV infection inflated the risk of a new fracture 32% in a mostly premenopausal group in the Women's Interagency HIV Study (WIHS). Older age, white race, previous fracture history, injection drug use, opiate use and smoking also independently raised the risk of any fracture in multivariate analysis.

Five years ago, WIHS investigators discerned no difference in incident fractures between mostly premenopausal women with and without HIV through 5.5 years of follow-up. The new study adds an additional 4.5 years of follow-up to compare time to new fracture at any site in 1713 women with HIV and 662 women at risk for HIV. The HIV group was older than the comparison group (median 40 versus 35 years), more likely to have hepatitis C (HCV) infection (24% versus 15%), and weighed less (74.5 kg versus 79.7 kg). Whites made up about one-quarter of each group and blacks about 60%. High proportions of both HIV-positive and negative women smoked, though smoking prevalence was significantly lower in the HIV-positive group (45% versus 51%, P = 0.01).

After a median 10-year follow-up, all-fracture incidence proved significantly higher in women with HIV (2.19 versus 1.54 per 100 person-years, P = 0.002). Fragility fracture incidence was not significantly higher in HIV-positive women (0.56 versus 0.39 per 100 person-years, P = 0.13).

In a multivariate model, HIV infection independently raised incident all-fracture risk 32% (adjusted hazard ratio [aHR] 1.32, 95% confidence interval [CI] 1.04 to 1.69). Other independent predictors were every additional 10 years of age (aHR 1.28, 95% CI 1.14 to 1.44), previous fracture (aHR 1.87, 95% CI 1.30 to 2.69), any cocaine use (aHR 1.56, 95% CI 1.22 to 1.99) and any injection drug use (aHR 1.38, 95% CI 1.09 to 1.75). Compared with black women, whites had a 25% higher risk of any fracture (aHR 1.25, 95% CI 0.99 to 1.57) and Hispanics had a 29% lower risk (aHR 0.71, 95% CI 0.53 to 0.97).

Multivariate analysis focused solely on women with HIV identified six independent predictors of incident fracture: every 10 years of age (aHR 1.25, 95% CI 1.10 to 1.43), white versus black race (aHR 1.37, 95% CI 1.06 to 1.78), Hispanic or other ethnicity versus black race (aHR 0.71, 95% CI 0.50 to 1.02), previous fracture (aHR 2.11, 95% CI 1.39 to 3.20), cigarette smoking (aHR 1.44, 95% CI 1.14 to 1.81) and an AIDS-defining illness (aHR 1.57, 95% CI 1.24 to 1.99).

The WIHS investigators believe their findings "suggest that fracture rates will increase over time in HIV-infected women as they age," particularly "among nonblack women and in women with a history of substance use."

An earlier meta-analysis of seven studies comparing fracture incidence in HIV-positive and negative people calculated a 58% higher pooled incidence of all fractures in the HIV group (incidence rate ratio [IRR] 1.58, 95% CI 1.25 to 2.00) and a 35% higher pooled incidence of fragility fractures with HIV (IRR 1.35, 95% CI 1.10 to 1.65).

Recent guidelines recommend FRAX screening for fracture risk in premenopausal HIV-positive women over 40, and in 40- to 49-year-old men with HIV. The guidelines recommend DXA scanning to determine bone mineral density in HIV-positive postmenopausal women, HIV-positive men 50 or older, and people of all ages with certain fragility fracture risk factors.

Mark Mascolini is a freelance writer focused on HIV infection.