Sarah Zaheer1, Ian H de Boer2, Matthew Allison3, Jenifer M Brown1, Bruce M Psaty4,5, Cassianne Robinson-Cohen2,6, Erin D Michos7, Joachim H Ix8, Bryan Kestenbaum2,6, David Siscovick9, Anand Vaidya1. 1. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115. 2. Division of Nephrology, Department of Medicine, and. 3. Division of Preventive Medicine, University of California, San Diego, San Diego, California 92093. 4. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington 98195. 5. Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98101. 6. Kidney Research Institute, University of Washington, Seattle, Washington 98104. 7. Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205. 8. Division of Nephrology-Hypertension, University of California, San Diego, San Diego, California 92161. 9. The New York Academy of Medicine, New York, New York 10029.
Abstract
Context: Obesity is associated with poor bone mineralization and quality. Fibroblast growth factor 23 (FGF23) plays an important role in skeletal physiology. Objective: To test hypothesis that greater adiposity results in higher FGF23 levels among individuals with normal estimated glomerular filtration rate (eGFR). Design, Setting, Participants: Cross-sectional analyses among participants with eGFR ≥60 mL/min/1.73m2. We assessed the association between crude [body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR); n = 5610] and refined (abdominal adipose tissue area by computed tomography; n = 1313) measures of adiposity and FGF23 using multivariable linear regression. Main Outcome Measure: Serum FGF23. Results: FGF23 was higher across BMI categories (BMI <25: 37.7; BMI 25 to 29.99: 38.7; BMI 30 to 39.99: 39.8; BMI ≥40: 40.9 pg/mL, unadjusted P trend < 0.0001). The association between BMI and FGF23 was independent of known confounders of FGF23 (adjusted β = +7.2% higher FGF23 per 10 kg/m2; P < 0.0001). Similar results were observed using WC and WHR. Abdominal adipose tissue area was also independently associated with higher FGF23 (P < 0.01). Notably, the positive associations between FGF23 and adiposity were observed despite the fact that eGFR did not decline and serum phosphate levels did not increase with adiposity. Conclusion: In a large cohort with normal kidney function, adiposity was associated with higher FGF23 levels independent of known confounders, including eGFR and phosphate. Further studies are needed to evaluate the causes of higher FGF23 in settings of greater adiposity and the potential impact on skeletal health.
Context: Obesity is associated with poor bone mineralization and quality. Fibroblast growth factor 23 (FGF23) plays an important role in skeletal physiology. Objective: To test hypothesis that greater adiposity results in higher FGF23 levels among individuals with normal estimated glomerular filtration rate (eGFR). Design, Setting, Participants: Cross-sectional analyses among participants with eGFR ≥60 mL/min/1.73m2. We assessed the association between crude [body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR); n = 5610] and refined (abdominal adipose tissue area by computed tomography; n = 1313) measures of adiposity and FGF23 using multivariable linear regression. Main Outcome Measure: Serum FGF23. Results: FGF23 was higher across BMI categories (BMI <25: 37.7; BMI 25 to 29.99: 38.7; BMI 30 to 39.99: 39.8; BMI ≥40: 40.9 pg/mL, unadjusted P trend < 0.0001). The association between BMI and FGF23 was independent of known confounders of FGF23 (adjusted β = +7.2% higher FGF23 per 10 kg/m2; P < 0.0001). Similar results were observed using WC and WHR. Abdominal adipose tissue area was also independently associated with higher FGF23 (P < 0.01). Notably, the positive associations between FGF23 and adiposity were observed despite the fact that eGFR did not decline and serum phosphate levels did not increase with adiposity. Conclusion: In a large cohort with normal kidney function, adiposity was associated with higher FGF23 levels independent of known confounders, including eGFR and phosphate. Further studies are needed to evaluate the causes of higher FGF23 in settings of greater adiposity and the potential impact on skeletal health.
Authors: Juliet E Compston; Nelson B Watts; Roland Chapurlat; Cyrus Cooper; Steven Boonen; Susan Greenspan; Johannes Pfeilschifter; Stuart Silverman; Adolfo Díez-Pérez; Robert Lindsay; Kenneth G Saag; J Coen Netelenbos; Stephen Gehlbach; Frederick H Hooven; Julie Flahive; Jonathan D Adachi; Maurizio Rossini; Andrea Z Lacroix; Christian Roux; Philip N Sambrook; Ethel S Siris Journal: Am J Med Date: 2011-11 Impact factor: 4.965
Authors: Ravi V Shah; Venkatesh L Murthy; Siddique A Abbasi; Ron Blankstein; Raymond Y Kwong; Allison B Goldfine; Michael Jerosch-Herold; João A C Lima; Jingzhong Ding; Matthew A Allison Journal: JACC Cardiovasc Imaging Date: 2014-11-05
Authors: Bingbing Zhang; Anja T Umbach; Hong Chen; Jing Yan; Hajar Fakhri; Abul Fajol; Madhuri S Salker; Daniela Spichtig; Arezoo Daryadel; Carsten A Wagner; Michael Föller; Florian Lang Journal: Biochem Biophys Res Commun Date: 2016-01-08 Impact factor: 3.575
Authors: Melissa Orlandin Premaor; Lesley Pilbrow; Carol Tonkin; Richard A Parker; Juliet Compston Journal: J Bone Miner Res Date: 2010-02 Impact factor: 6.741
Authors: Bryan Kestenbaum; Michael C Sachs; Andy N Hoofnagle; David S Siscovick; Joachim H Ix; Cassianne Robinson-Cohen; Joao A C Lima; Joseph F Polak; Marc Blondon; John Ruzinski; Denise Rock; Ian H de Boer Journal: Circ Heart Fail Date: 2014-03-25 Impact factor: 8.790
Authors: Rupal Mehta; Xuan Cai; Alexander Hodakowski; Bharat Thyagarajan; Donglin Zeng; Phyllis C Zee; William K Wohlgemuth; Susan Redline; James P Lash; Myles Wolf; Tamara Isakova Journal: Bone Date: 2018-07-03 Impact factor: 4.398
Authors: Janet M Chiang; George A Kaysen; Anne L Schafer; Cynthia Delgado; Kirsten L Johansen Journal: J Ren Nutr Date: 2018-03-29 Impact factor: 3.655
Authors: Sofia I Karampatsou; George Paltoglou; Sofia M Genitsaridi; Penio Kassari; Evangelia Charmandari Journal: Nutrients Date: 2022-09-13 Impact factor: 6.706