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J Acquir Immune Defic Syndr. 2019 Jan 1;80(1):118-125. doi: 10.1097/QAI.0000000000001868.

Association of Fibroblast Growth Factor-23 (FGF-23) With Incident Frailty in HIV-Infected and HIV-Uninfected Individuals.

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Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
Department of Medicine, Kidney Health Research Collaborative, San Francisco VA Medical Center, University of California, San Francisco, San Francisco, CA.
Department of Medicine, University of California San Diego.
Nephrology Section, Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, CA.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Department of Medicine, University of Texas Health Science Center at Houston, Houston, TX.
Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, OH.
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.



In the Multicenter AIDS Cohort Study, we examined whether fibroblast growth factor-23 (FGF-23), a bone-derived phosphaturic hormone involved in bone metabolism, is associated with incident frailty. Furthermore, we examined whether this association differs by HIV serostatus and race.


Of 715 men assessed for frailty and selected for FGF-23 measurements using stored blood samples (2007-2011), 512 men were nonfrail at/before the baseline visit. Frailty was defined by the presence of ≥3 of the following on 2 consecutive 6-month visits within 1 year: unintentional weight loss ≥10 pounds, weakness, slowness, low energy, and low physical activity. We determined the association of FGF-23 levels with incident frailty using proportional hazards models adjusting for sociodemographics, comorbidities, and kidney function.


Sixty-five percent were HIV-infected; 29% were black. Median baseline FGF-23 levels were lower in HIV-infected vs. HIV-uninfected men (33.7 vs. 39.9 rU/mL, P = 0.006) but similar by race. During a median follow-up of 6.6 years, 32 men developed frailty; they had higher baseline FGF-23 levels vs. men who remained nonfrail (45 vs. 36 rU/mL, P = 0.02). FGF-23 (per doubling) was associated with a 1.63-fold risk of frailty [95% confidence interval (CI): 1.19 to 2.23]; results did not differ by HIV serostatus. Conversely, FGF-23 was associated with a 2.72-fold risk of frailty among blacks (95% CI: 1.51 to 4.91) but had minimal association among nonblacks (hazard ratio = 1.26, 95% CI: 0.77 to 2.05; p-interaction = 0.024).


Among men with or at-risk of HIV infection, higher FGF-23 was associated with greater risk of frailty, particularly in blacks. The mechanisms by which FGF-23 may contribute to frailty warrant further study.

[Available on 2020-01-01]

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