Serum Fibroblast Growth Factor 23 (FGF23) in Patients with Rheumatoid Arthritis

Abstract

Objective Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by periarticular and systemic osteoporosis. Fibroblast growth factor 23 (FGF23), which is mainly produced by osteocytes, circulates to the kidneys and regulates bone metabolism. We herein assessed serum FGF23 and its relationship to inflammation and osteoporosis in patients with RA. Methods Sixty-one patients with RA were included. Serum concentrations of FGF23 were determined using a sandwich enzyme-linked immunosorbent assay. Results The mean (± standard deviation) serum FGF23 concentration was 34.9±9.2 (range, 21.0-61.0) pg/ mL. The serum FGF23 level was significantly and positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, disease activity score-28 based on the ESR (DAS-28 ESR) and DAS-28 CRP (r=0.261, p=0.044, r=0.280, p=0.029, r=0.409, p=0.001 and r=0.421, p=0.001, respectively). The serum matrix metalloproteinase-3 level was also significantly and positively correlated with the serum FGF23 level (r=0.331, p=0.015). Concentrations of type I collagen cross-linked N-telopeptide in the serum was significantly correlated with the serum FGF23 level (r=0.272, p=0.034). Neither the bone mineral density in the femoral neck nor lumbar was significantly correlated with the serum FGF23 level. Serum phosphate, calcium, 25-hydroxy vitamin D, and intact parathyroid hormone were not related to the serum FGF23 level. Conclusion In patients with RA, serum FGF23 is correlated with inflammation, the disease activity of RA, and bone absorption markers. Serum FGF23 may be associated with abnormal bone absorption related to RA inflammation. Further studies are necessary to clarify the mechanism underlying this association.

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

“…Inflammation is a common ground of many of the diseases associated with elevated FGF23 levels. Indeed, enhanced inflammation in CKD or in some other diseases have been independently associated with an increase in FGF23 levels. These results suggest that inflammation could be a trigger of FGF23 production.…”

Ironing out the cross talk between FGF23 and inflammation

“…Increased iFGF23 and cFGF23 levels are independently associated with higher levels of inflammatory markers in patients with CKD (52, 57). In addition, FGF23 levels correlate with (17) markers of inflammation in other inflammatory diseases (20,32,34,57,70). For example, iFGF23 was raised in the serum of patients with juvenile systemic lupus erythematosus (54) and in the cartilage of patients with rheumatoid arthritis (35).…”

Inflammation regulates fibroblast growth factor 23 production

“…Indeed, inflammation-induced alterations of known regulators of FGF23, such as systemic calcium, phosphate and vitamin-D metabolism, might contribute to FGF23 elevation during inflammation. Paracrine stimuli secreted by osteoclasts, release of matrix bound components and/or local increase in phosphate and calcium due to inflammation-induced excessive bone resorption may also stimulate FGF23 (57, •64). In this context, excess calcium released by bone resorption may stimulate Fgf23 (5) through calcineurin/NFAT pathway in osteoblasts(65).…”