@article {5996, title = {Fibroblast growth factor 23, bone mineral density, and risk of hip fracture among older adults: the cardiovascular health study.}, journal = {J Clin Endocrinol Metab}, volume = {98}, year = {2013}, month = {2013 Aug}, pages = {3323-31}, abstract = {

CONTEXT: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that also inhibits calcitriol synthesis.

OBJECTIVE: Our objective was to evaluate the relationships of plasma FGF23 concentrations with bone mineral density (BMD) and hip fracture in community-dwelling older adults.

DESIGN AND SETTING: Linear regression and Cox proportional hazard models were used to examine the associations of plasma FGF23 concentrations with BMD and incident hip fracture, respectively. Analyses were also stratified by chronic kidney disease.

PARTICIPANTS: Participants included 2008 women and 1329 men >=65 years from the 1996 to 1997 Cardiovascular Health Study visit.

MAIN OUTCOME MEASURES: Dual x-ray absorptiometry measured total hip (TH) and lumbar spine (LS) BMD in 1291 participants. Hip fracture incidence was assessed prospectively through June 30, 2008 by hospitalization records in all participants.

RESULTS: Women had higher plasma FGF23 concentrations than men (75 [56-107] vs 66 [interquartile range = 52-92] relative units/mL; P < .001). After adjustment, higher FGF23 concentrations were associated with greater total hip and lumbar spine BMD in men only (β per doubling of FGF23 = 0.02, with 95\% confidence interval [CI] = 0.001-0.04 g/cm(2), and 0.03 with 95\% CI = 0.01-0.06 g/cm(2)). During 9.6 {\textpm} 5.1-11.0 years of follow-up, 328 hip fractures occurred. Higher FGF23 concentrations were not associated with hip fracture risk in women or men (adjusted hazard ratio = 0.95, with 95\% CI = 0.78-1.15, and 1.09 with 95\% CI = 0.82-1.46 per doubling of FGF23). Results did not differ by chronic kidney disease status (P > .4 for interactions).

CONCLUSIONS: In this large prospective cohort of community-dwelling older adults, higher FGF23 concentrations were weakly associated with greater lumbar spine and total hip BMD but not with hip fracture risk.

}, keywords = {Aged, Aged, 80 and over, Bone Density, Female, Fibroblast Growth Factors, Hip Fractures, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Risk, Spinal Fractures}, issn = {1945-7197}, doi = {10.1210/jc.2013-1152}, author = {Jovanovich, Anna and B{\r u}zkov{\'a}, Petra and Chonchol, Michel and Robbins, John and Fink, Howard A and de Boer, Ian H and Kestenbaum, Bryan and Katz, Ronit and Carbone, Laura and Lee, Jennifer and Laughlin, Gail A and Mukamal, Kenneth J and Fried, Linda F and Shlipak, Michael G and Ix, Joachim H} } @article {6990, title = {Fibroblast Growth Factor-23 and Frailty in Elderly Community-Dwelling Individuals: The Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {64}, year = {2016}, month = {2016 Feb}, pages = {270-6}, abstract = {

OBJECTIVES: To evaluate whether fibroblast growth factor 23 (FGF-23) is related to frailty and to characterize the nature of their joint association with mortality.

DESIGN: Cross-sectional analysis for frailty and longitudinal cohort analysis for mortality.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Community-dwelling individuals (N = 2,977; mean age 77.9 {\textpm} 4.7, 40\% male, 83\% white).

MEASUREMENTS: The predictor was serum FGF-23 concentration (C-terminal enzyme-linked immunosorbent assay), and the outcomes were frailty status (determined according to frailty phenotype criteria of weight loss, weakness, exhaustion, slowness, and low physical activity) and mortality. Multinomial logistic regression was used to assess the cross-sectional association between FGF-23 and frailty and prefrailty, adjusting for demographic characteristics, cardiovascular disease and risk factors, and kidney markers. Proportional hazards Cox proportional hazards regression was used to assess the association between FGF-23, frailty, and all-cause mortality.

RESULTS: Mean estimated glomerular filtration rate (eGFR) was 64 {\textpm} 17 mL/min per 1.73 m(2) . Median FGF-23 was 70.3 RU/mL (interquartile range 53.4-99.2); 52\% were prefrail, and 13\% were frail. After multivariate adjustment, each doubling in FGF-23 concentration was associated with 38\% (95\% confidence interval (CI) = 17-62\%) higher odds of frailty than of nonfrailty and 16\% (95\% CI = 3-30\%) higher odds of prefrailty. FGF-23 (hazard ratio (HR) = 1.16, 95\% CI = 1.10-1.23) and frailty (HR = 1.82, 95\% CI = 1.57-2.12) were independently associated with mortality, but neither association was meaningfully attenuated when adjusted for the other.

CONCLUSION: In a large cohort of older adults, higher FGF-23 was independently associated with prevalent frailty and prefrailty. FGF-23 and frailty were independent and additive risk factors for mortality. FGF-23 may be a marker for functional outcomes.

}, keywords = {Aged, Anthropometry, Biomarkers, Cardiovascular Diseases, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Fibroblast Growth Factors, Frail Elderly, Glomerular Filtration Rate, Humans, Independent Living, Longitudinal Studies, Male, Phenotype, Risk Factors, Surveys and Questionnaires}, issn = {1532-5415}, doi = {10.1111/jgs.13951}, author = {Beben, Tomasz and Ix, Joachim H and Shlipak, Michael G and Sarnak, Mark J and Fried, Linda F and Hoofnagle, Andrew N and Chonchol, Michel and Kestenbaum, Bryan R and de Boer, Ian H and Rifkin, Dena E} }