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HIV and frailty predict first fracture in middle-aged US women's cohort - doubled fracture rates
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9th International Workshop on HIV and Aging, September 13-14, 2018, New York
Mark Mascolini
HIV infection and frailty independently boosted chances of first fractures in a 10-year comparison of US women with or without HIV in the Women's Interagency HIV Study (WIHS) [1]. Women with HIV had clinically defined frailty significantly more often than women without HIV.
In the general population research links frailty to falls, fractures, disability, and death. But little is known about the impact of frailty on fracture risk in middle-aged women with HIV. A previous 10-year study of 1713 HIV-positive and 662 HIV-negative middle-aged women in the WIHS determined that HIV infection independently raised fracture risk by one third (adjusted hazard ratio [aHR] 1.32, 95% confidence interval [CI] 1.04 to 1.69, P = 0.02) [2]. An earlier study of HIV-positive men and women at least 40 years old found that frailty boosts odds of recurrent falls 17-fold [3]. Bone mineral density drops twice faster in women than men with HIV [4].
At a baseline visit WIHS researchers recorded how many HIV-positive and negative women had frailty by meeting 3 or more of the 5 Fried frailty criteria: slow gait, reduced grip strength, exhaustion, unintentional weight loss, and low physical activity. Starting in 2003 they measured time to first fracture and second fracture. For this analysis, fracture assessment continued through October 2016. The investigators counted both fragility fractures and nonfragility fractures. They used Cox proportional hazards models to identify predictors of time to first and second fracture and to assess the impact of frailty on fracture in women with and without HIV.
The analysis focused on 1332 WIHS women with HIV and 534 without HIV. HIV-negative women in WIHS are sociodemographically similar to their HIV-positive counterparts and are considered at risk for HIV infection. In this group women with HIV were significantly older than women without HIV (42 versus 39 years, P < 0.0001), and women with HIV had a significantly higher frailty rate (14% versus 8%, P = 0.0006).
Median follow-up stood at 10.6 years. Over that time frailty independently predicted time to first fracture in all women (aHR 1.71, 95% CI 1.30 to 2.26, P = 0.0001). In the subset of women with HIV, frailty predicted time to first fracture (aHR 1.91, 95% CI 1.41 to 2.58, P < 0.0001) and time from first to second fracture (aHR 1.92, 95% CI 1.18 to 3.12, P = 0.0091). HIV infection independently predicted time to first fracture (aHR 1.32, 95% CI 1.02 to 1.70, P = 0.035) but not time from first to second fracture.
Three components of the frailty index independently predicted time to first fracture in all women and in women with HIV: exhaustion (all women aHR 1.60, 95% CI 1.26 to 2.04, P = 0.0001; HIV+ women aHR 1.57, 95% CI 1.20 to 2.07, P = 0.0012), unintentional weight loss (all women aHR 1.44, 95% CI 1.06 to 1.94, P = 0.019; HIV+ women aHR 1.44, 95% CI 1.03 to 2.01, P = 0.032), and reduced grip strength (all women aHR 1.35, 95% CI 1.06 to 1.72, P = 0.017; HIV+ women aHR 1.36, 95% CI 1.03 to 1.79, P = 0.028). Exhaustion independently predicted time from first to second fracture in all women (aHR 1.98, 95% CI 1.34 to 2.93, P = 0.0007) and in women with HIV (aHR 2.16, 95% CI 1.35 to 3.46, P = 0.0013).
Among women with HIV, other factors predicting time to first fracture were current smoking (aHR 1.84, 95% CI 1.32 to 2.56, P = 0.0003) and ever using opioids (aHR 1.94, 95% CI 1.50 to 2.51, P < 0.0001). Postmenopausal status was associated with a 2-fold higher fracture risk in women with HIV (aHR 2.03, 95% CI 1.28 to 3.23, P = 0.0027).
The WIHS investigators concluded that frailty independently predicts fracture in middle-aged women with and without HIV. "As HIV-infected women continue to age," they proposed, "early frailty screening may be a useful clinical tool to identify those at greatest risk of fracture." The researchers stressed that fracture risk rises farther as women transition through the menopause, "particularly if they are already frail."
References
1. Sharma A, Shi Q, Hoover D, et al. Frailty predicts fractures among HIV-infected and uninfected women: results from the Women's Interagency HIV Study. 9th International Workshop on HIV and Aging, September 13-14, 2018, New York. Abstract 16.
2. Sharma A, Shi Q, Hoover DR, et al. Increased fracture incidence in middle-aged HIV-infected and HIV-uninfected women: updated results from the Women's Interagency HIV Study. J Acquir Immune Defic Syndr. 2015;70:54-61. www.natap.org/2015/HIV/090915_02.htm
3. Tassiopoulos K, Abdo M, Wu K, et al. Frailty is strongly associated with increased risk of recurrent falls among older HIV-infected adults. AIDS. 2017;31:2287-2294.
4. Erlandson KM, Lake JE, Sim M, et al. Bone mineral density declines twice as quickly among HIV-infected women compared with men. J Acquir Immune Defic Syndr. 2018;77:288-294.
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