Fracture Prediction With Modified-FRAX in Older HIV-Infected and Uninfected Men

Abstract

Background: FRAX is a validated, computer-based clinical fracture risk calculator that estimates the 10-year risk of major osteoporotic (clinical spine, forearm, hip, or shoulder) fracture, and hip fracture alone. It is widely used for decision making in fracture prevention, but it may underestimate the risk in HIV-infected individuals. Some experts recommend considering HIV as a cause of secondary osteoporosis when calculating FRAX in HIV-infected individuals.

Methods: From the Veterans Aging Cohort Study Virtual Cohort, we included 24,451 HIV-infected and uninfected men aged 50-70 years with complete data in the year 2000 to approximate all but 2 factors (ie, history of secondary osteoporosis and parental hip fracture) for modified-FRAX calculation without bone density and 10-year observational data for incident fragility fracture. The accuracy of the modified-FRAX calculation was compared by the observed/estimated (O/E) ratios of fracture by HIV status.

Results: The accuracy of modified-FRAX was less for HIV-infected [O/E = 1.62, 95% confidence interval (CI) 1.45 to 1.81] than uninfected men (O/E = 1.29, 95% CI: 1.19 to 1.40), but improved when HIV was included as a cause of secondary osteoporosis (O/E = 1.20, 95% CI: 1.08 to 1.34). However, only 3%-6% of men with incident fractures were correctly identified by the modified-FRAX using accepted FRAX thresholds for pharmacologic therapy.

Conclusions: Modified-FRAX underestimated the fracture rates more in older HIV-infected than in otherwise similar uninfected men. The accuracy improved when HIV was included as a cause of secondary osteoporosis, but it still performed poorly for case finding. Further studies are necessary to determine how to use FRAX or define an HIV-specific index to risk stratify for screening and treatment in older HIV-infected individuals.

Figure 1

Observed and modified-FRAX estimated rates of fracture by HIV status

Figure 2. Accuracy of modified-FRAX in HIV-infected men

Each panel shows a plot of the observed probability for major osteoporotic facture (error bars indicate the 95% confidence interval) versus the mean estimated fracture probability for the subgroup divided by the decile of estimated probability. The dotted line represents a perfectly calibrated model and solid line represent the best fit for HIV-uninfected men (a), HIV-infected men (b), and HIV-infected men when ‘secondary osteoporosis’ is entered into the FRAX calculation (The p values indicate the goodness of fit using the Hosmer-Lemeshow test (p<0.05 indicates a significant difference from the perfectly calibrated model).