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PIs, Proton Pump Inhibitors, Stroke Raise Fracture Risk in HIV+ Veterans
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XIX International AIDS Conference, July 22-27, 2012, Washington, DC
Mark Mascolini
Treatment with protease inhibitors (PIs) or proton pump inhibitors (PPIs) and cerebrovascular disease or stroke independently raised the risk of fragility fractures in the US Veterans Aging Cohort Study (VACS) [1]. White race, alcohol-related diagnoses, and lower body mass index also made fragility fractures more likely.
VACS investigators planned this study to see how traditional and HIV-specific fracture risk factors affected fracture rates in an analysis that controlled for HIV disease severity as estimated by the VACS Index. The VACS Index predicts 5-year mortality and intensive care unit admissions in HIV-positive people [2].
A prior study of 119,318 VACS participants found that HIV-positive veterans had a 24% higher fragility fracture risk than HIV-negative vets in an analysis that factored in demographics, non-HIV diseases, smoking, and alcohol [3] (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.11 to 1.39). But that association weakened when the analysis accounted for the HIV group's lower body mass index (HR 1.10, 95% CI 0.97 to 1.25). PI use upped the fragility fracture risk 41% in this study (HR 1.41, 95% CI 1.16 to 1.70).
During an average 6 years of follow-up in the new study [1], 40,115 HIV-positive male veterans had 588 fragility fractures of the hip, vertebrae, or upper arm. The study group averaged 46 years in age at the beginning of follow-up and 53 years at the time of fracture. Their median CD4 count stood at 278 (interquartile range [IQR] 112 to 472) and median viral load at 10,408 copies (IQR 480 to 77,987). Median VACS index score was 33 (IQR 18 to 53) and median body mass index 25 kg/m2 (IQR 22 to 28).
Cox regression analysis identified the following predictors of fragility fractures, at the noted hazard ratios (HR) (and 95% confidence intervals):
-- White race: HR 1.94 (1.64 to 2.30)
-- Cerebrovascular disease/stroke: HR 1.87 (1.09 to 3.20)
-- Alcohol-related diagnoses: HR 1.58 (1.21 to 2.08)
-- Current PPI use: HR 1.81 (1.48 to 2.20)
-- Current PI use: HR 1.28 (1.07 to 1.52)
-- Higher VACS Index score: HR 1.08 (1.06 to 1.11)
-- Higher baseline body mass index: HR 0.88 (0.78 to 0.98) (12% lower fracture risk)
Factors that did not affect fragility fracture risk in this analysis included any steroid use, tenofovir use, past or current smoking, and drug use or abuse.
The researchers noted that cerebrovascular disease strongly predicts fractures in the general population--probably because of falls. They suggested that the weak associations between fractures and steroid use or smoking (two other established risk factors) may reflect the accounting for body mass index, alcohol use, and HIV disease severity in this analysis.
References
1. Womack J, Goulet J, Gibert C, et al. Proton pump inhibitor and protease inhibitor use are associated with fragility fracture risk in HIV-positive male veterans. XIX International AIDS Conference. July 22-27, 2012. Abstract MOPE087.
2. Justice AC, McGinnis KA, Skanderson M, et al. Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers. HIV Med. 2010;11:143-151.
3. Womack JA, Goulet JL, Gibert C, et al. Increased risk of fragility fractures among HIV infected compared to uninfected male veterans. PLoS One. 2011;6(2):e17217. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017217
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