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Serum Fibroblast Growth Factor-23 (FGF-23) and Fracture Risk in Elderly Men
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2011 (English)In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 26, no 4, 857-864 p.Article in journal (Refereed) Published
Abstract [en]

A normal mineral metabolism is integral for skeletal development and preservation of bone integrity. Fibroblast growth factor-23 (FGF23) is a bone-derived, circulating factor that decreases serum concentrations of inorganic phosphorous (Pi) and 1,25-dihydroxy vitamin D3 (1,25(OH)2D3). Increased FGF23 expression is a direct or indirect culprit in several skeletal disorders, however the relation between FGF23 and fracture risk remains undetermined.  We evaluated the prospective relation between serum intact FGF23 (measured by a two-site, monoclonal antibody ELISA) and fracture risk, employing the Swedish part of the population-based, Osteoporotic Fractures in Men Study (MrOS) (n=2868; mean age 75.4 ± 3.2; median follow-up period 3.35 years). The incidence of at least one validated fracture after baseline was 20.4 per 1000-person-years. FGF23 was directly related to the over-all fracture risk (age-adjusted hazard ratio [HR] per SD increase, 1.20; 95% CI, 1.03-1.40) and vertebral fracture risk (HR, 1.33; 95% CI, 1.02-1.75). Spline models revealed a non-linear relation between FGF23 and fracture risk with the strongest relation at FGF23 levels above 55.7 pg/mL. FGF23 levels above 55.7 pg/mL were also associated with an increased risk for hip and non-vertebral fractures (HR, 2.30; 95% CI, 1.16-4.58 and HR, 1.63; 95%CI, 1.01-2.63 respectively). These relations remained essentially unaltered after adjustment for BMI, BMD, glomerular filtration rate, 25(OH)D3, PTH and other fracture risk factors. In conclusion, FGF23 is a novel predictor of fracture risk in elderly men.

Place, publisher, year, edition, pages
2011. Vol. 26, no 4, 857-864 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-130334DOI: 10.1002/jbmr.263ISI: 000288861400020PubMedID: 20928885OAI: oai:DiVA.org:uu-130334DiVA: diva2:349332
Available from: 2010-09-06 Created: 2010-09-06 Last updated: 2011-04-19Bibliographically approved
In thesis
1. The role of fibroblast growth factor-23 in chronic kidney disease-mineral and bone disorder
Open this publication in new window or tab >>The role of fibroblast growth factor-23 in chronic kidney disease-mineral and bone disorder
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fibroblast growth factor-23 (FGF23) was initially identified as the causative factor of autosomal dominant hypophosphatemic rickets. Further studies confirmed that FGF23 is predominantly expressed in the osteocytes and osteoblasts of bone and that circulating FGF23 acts on the kidney to inhibit renal phosphate reabsorption and 1,25(OH)2D3 hydroxylation.

With the progression of chronic kidney disease (CKD), the kidneys become insufficient to maintain a normal systemic mineral homeostasis, resulting in various abnormalities of bone and mineral metabolism, generally referred to as Chronic Kidney Disease – Mineral and Bone Disorders (CKD-MBD). FGF23 increases early in the course of CKD in order to maintain normal serum phosphate levels; long before a significant increase in serum phosphate can be detected. Recent studies suggest that increased FGF23 levels are associated with progression of CKD, mortality, and the development of refractory secondary hyperparathyroidism. Because FGF23 is the very earliest marker of CKD-MBD, it is of particular interest to evaluate the relation between FGF23 and CKD-MBD abnormalities, in the setting of early CKD and also in individuals with normal renal function.

In the present work, we show that FGF23 is linked to several dynamic measurements of vascular function, including endothelial dysfunction, arterial stiffness, and atherosclerosis. FGF23 is also positively associated with left ventricular mass index and an increased risk of having left ventricular hypertrophy. All associations were independent of serum phosphate and were strengthened in subjects with diminished renal function. Furthermore, we found significant evidence for an association between higher FGF23 and increased fat mass and dyslipidemia, which could represent a novel pathway linking FGF23 to cardiovascular disease. Finally, we show that FGF23 is a significant predictor of future fracture risk.

Although these associations could be reflecting the increased risk associated with hyperphosphatemia and calcitriol deficiency, current evidence points towards FGF23 being more than an innocent bystander. At the very least, FGF23 holds promise of being a bio-marker of cardiovascular status and phosphate-related toxicity both in CKD and in the general population, and might be a therapeutic target that could improve the fatal prognosis in CKD patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 83 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 594
FGF23, FGF-23, CKD, CKD-MBD, cardiovascular disease, vascular function, atherosclerosis, hypertrophy, LVMI, LVH, fractures, bone, fat mass, obesity, apolipoproteins, cholesterol, lipids
National Category
Urology and Nephrology Cardiac and Cardiovascular Systems
Research subject
Medical Science
urn:nbn:se:uu:diva-130339 (URN)978-91-554-7883-4 (ISBN)
Public defence
2010-10-16, Grönwallsalen, Akademiska sjukhuset, ingång 70, Uppsala, 09:00 (English)
Available from: 2010-09-23 Created: 2010-09-06 Last updated: 2011-01-17Bibliographically approved

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