FGF23-Klotho Axis and Fractures in Patients Without and With Early CKD: A Case-Cohort Analysis of CARTaGENE.
FGF23
chronic kidney disease
fracture
parathyroid hormone
α-Klotho
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
17 05 2022
17 05 2022
Historique:
received:
05
10
2021
pubmed:
10
2
2022
medline:
20
5
2022
entrez:
9
2
2022
Statut:
ppublish
Résumé
Whether fibroblast growth factor-23 (FGF23) and α-Klotho are associated with fractures, especially in chronic kidney disease (CKD), remains controversial. We evaluated how FGF23, α-Klotho, and traditional mineral parameters predict fractures in individuals with and without early CKD. We conducted a stratified case-cohort analysis using CARTaGENE, a population-based survey from Quebec, Canada. Individuals aged 40 to 69 years were selected according to outcome and CKD status (non-CKD: eGFR > 60 mL/min/1.73 m2; CKD stage 3: eGFR 30-60 mL/min/1.73 m2]). Baseline levels of c-terminal FGF23 (cFGF23), α-Klotho, parathyroid hormone (PTH), phosphate, and calcium were analyzed for associations with osteoporotic fracture incidence from recruitment (2009-2010) through March 2016. Adjusted Cox models were used, and predictors were treated linearly or flexibly using splines. A total of 312 patients (159 non-CKD; 153 CKD) were included; 98 had ≥ 1 fracture at any site during a median follow up of 70 months. Compared with non-CKD, CKD patients had increased levels of cFGF23 but similar levels of α-Klotho. cFGF23 was linearly associated with increased fracture incidence (adjusted HR = 1.81 [1.71, 1.93] per doubling for all participants). The association of α-Klotho with fracture followed a U-curve (overall P = 0.019) but was attenuated by adjustment for potential mediators (bone mineral density, phosphate, PTH). PTH and phosphate also had U-shaped associations with fracture. Associations were mostly similar between non-CKD and CKD. Adjustment for cFGF23 strongly attenuated the association between CKD status and fractures. cFGF23 is associated linearly with fracture incidence while α-Klotho, PTH, and phosphate levels have a U-shaped association.
Identifiants
pubmed: 35139204
pii: 6525346
doi: 10.1210/clinem/dgac071
pmc: PMC9113817
doi:
Substances chimiques
FGF23 protein, human
0
Parathyroid Hormone
0
Phosphates
0
Fibroblast Growth Factor-23
7Q7P4S7RRE
Glucuronidase
EC 3.2.1.31
Klotho Proteins
EC 3.2.1.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2502-e2512Subventions
Organisme : CIHR
Pays : Canada
Organisme : Fonds de Recherche du Québec - Santé
Organisme : Laval University
Organisme : FRQS
ID : 32661
Organisme : KRESCENT
ID : 150006
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Références
Osteoporos Int. 2015 Jul;26(7):1979-87
pubmed: 25690339
Osteoporos Int. 2012 Feb;23(2):483-501
pubmed: 21336492
BMC Public Health. 2010 Jun 11;10:331
pubmed: 20540727
JBMR Plus. 2021 Mar 16;5(4):e10482
pubmed: 33869997
Nephrol Dial Transplant. 2013 Sep;28(9):2283-7
pubmed: 23787542
Osteoporos Int. 2012 Jan;23(1):143-53
pubmed: 22037972
J Clin Densitom. 2015 Apr-Jun;18(2):157-64
pubmed: 25937306
Am J Epidemiol. 2009 Jun 1;169(11):1398-405
pubmed: 19357328
J Diabetes Complications. 2020 Jan;34(1):107476
pubmed: 31708378
Clin J Am Soc Nephrol. 2014 Jul;9(7):1283-303
pubmed: 24578336
J Clin Endocrinol Metab. 2013 Aug;98(8):3323-31
pubmed: 23771921
Osteoporos Int. 2004 Oct;15(10):834-41
pubmed: 15045468
Kidney Int. 2001 Dec;60(6):2079-86
pubmed: 11737582
Eur J Radiol. 2010 Feb;73(2):360-4
pubmed: 19135327
J Am Geriatr Soc. 2016 Dec;64(12):e304-e308
pubmed: 27910102
Joint Bone Spine. 2012 Dec;79(6):544-9
pubmed: 23177912
Osteoporos Int. 2021 Nov;32(11):2145-2153
pubmed: 34021765
J Bone Miner Res. 2008 Jun;23(6):939-48
pubmed: 18282132
J Bone Miner Res. 2006 Jun;21(6):809-16
pubmed: 16753011
J Bone Miner Res. 2013 Nov;28(11):2325-32
pubmed: 23677793
Kidney Int. 2016 Jul;90(1):77-89
pubmed: 27165819
Lifetime Data Anal. 2000 Mar;6(1):39-58
pubmed: 10763560
Bone. 2019 Mar;120:548-555
pubmed: 30465918
J Am Soc Nephrol. 2019 Oct;30(10):1785-1805
pubmed: 31506289
Kidney Int. 2005 Sep;68(3):1148-53
pubmed: 16105045
Osteoporos Int. 2011 Sep;22(9):2439-48
pubmed: 21161507
J Clin Endocrinol Metab. 2011 Jul;96(7):2186-93
pubmed: 21508146
Kidney Int. 2017 Sep;92(3):599-611
pubmed: 28396120
Osteoporos Int. 2019 Oct;30(10):2019-2025
pubmed: 31190122
Osteoporos Int. 2018 Oct;29(10):2345-2353
pubmed: 29959497
Int J Epidemiol. 2012 Aug;41(4):1174-86
pubmed: 22815332
J Biol Chem. 2003 Sep 26;278(39):37419-26
pubmed: 12874285
Kidney Int. 2016 Jan;89(1):135-46
pubmed: 26535997
Bone. 2017 Jul;100:36-40
pubmed: 27890549
Nephrol Dial Transplant. 2020 Oct 1;35(10):1712-1721
pubmed: 31951261
Am J Physiol Renal Physiol. 2009 Aug;297(2):F282-91
pubmed: 19515808
Proc Natl Acad Sci U S A. 2001 May 22;98(11):6500-5
pubmed: 11344269
Bone. 2007 Jun;40(6):1565-73
pubmed: 17350357
Ann Intern Med. 2009 May 5;150(9):604-12
pubmed: 19414839
J Bone Miner Res. 2007 Mar;22(3):465-75
pubmed: 17144789
Br J Radiol. 1998 Aug;71(848):861-7
pubmed: 9828799
J Clin Endocrinol Metab. 2022 May 17;107(6):e2502-e2512
pubmed: 35139204
Kidney Int Suppl. 2009 Aug;(113):S1-130
pubmed: 19644521
Int J Epidemiol. 2013 Oct;42(5):1285-99
pubmed: 23071140
Calcif Tissue Int. 1991 Aug;49(2):107-11
pubmed: 1913288
FASEB J. 2010 Sep;24(9):3438-50
pubmed: 20466874
Kidney Int. 2011 Jun;79(12):1370-8
pubmed: 21389978
Am J Epidemiol. 2011 Sep 1;174(5):613-20
pubmed: 21749976
Nature. 2006 Dec 7;444(7120):770-4
pubmed: 17086194
Stat Biosci. 2009 May 1;1(1):32
pubmed: 20174455
Am J Kidney Dis. 2020 Oct;76(4):521-532
pubmed: 32654892
JBMR Plus. 2018 Jul 05;3(1):45-55
pubmed: 30680363
J Bone Miner Res. 2017 Jun;32(6):1182-1193
pubmed: 28177140
Kidney Int. 2003 Dec;64(6):2272-9
pubmed: 14633152
J Bone Miner Res. 2012 May;27(5):1177-85
pubmed: 22228250
Nature. 1997 Nov 6;390(6655):45-51
pubmed: 9363890
J Clin Invest. 1999 Aug;104(3):229-37
pubmed: 10430604
Nephrol Dial Transplant. 2013 Feb;28(2):352-9
pubmed: 23129826
J Bone Miner Res. 2004 Mar;19(3):429-35
pubmed: 15040831
J Bone Miner Res. 2016 Apr;31(4):742-8
pubmed: 26590361
J Bone Miner Res. 2011 Apr;26(4):857-64
pubmed: 20928885