The hypothesis that bone turnover influences FGF23 secretion

Abstract

To the Editor: Fibroblast growth factor 23 (FGF23) regulates serum phosphate (Pi) levels. Isakova et al. 1 commented on a blueprint for randomized trials targeting phosphorus metabolism in chronic kidney disease. In this review, Isakova et al. revealed that Pi levels were normal to high in secondary syndromes of FGF23 excess, such as kidney disease; however, the levels were low in 'primary' syndromes of FGF23 excess, such as the hereditary diseases (X-linked hypophosphatemia, autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets), and tumor-induced osteomalacia. With decrease in renal function, the serum FGF23 level is elevated; however, the phosphorus excretion decreases. Osteitis fibrosa progresses at the same time. FGF23 was secreted by osteocytes. 2 Therefore, we drew up the hypothesis that bone turnover influences FGF23 secretion. We had reported previously the response of phosphorus load to osteoprotegerin (OPG) knockout (KO) mice (Figure 1). FGF-23 expression was significantly increased by a highphosphate diet in wild-type (WT) mice, but not in OPG KO mice. NaPi2a messenger RNA expression in kidney was suppressed in WT mice receiving a high-phosphate diet, but suppression was less marked in OPG KO mice. Therefore, OPG may have a key role in mediating the response of FGF-23 to an oral phosphate load in bone cells. 3 When we evaluate the metabolism of FGF23, it is necessary to consider the structural change in the osteitis fibrosa.

Does bone structure accurately reflect serum FGF23 levels in patients with chronic kidney disease?

“…We suggest that it is necessary to consider bone structural changes in Osteitis fibrosa when evaluating FGF23 metabolism. 4 Keitaro Yokoyama 1 , Akio Nakashima 1 , Yukio Maruyama 1 , Ichiro Ohkido 1 and Takashi Yokoo 1 The Author Replies: We thank Yokoyama et al 1 for the interest in our work. Since a direct role for fibroblast growth factor 23 (FGF23) has been established in the pathogenesis of left ventricular hypertrophy, 2 FGF23 reduction by phosphate binders, as highlighted by Keitaro et al, 3 may have beneficial effects on cardiovascular outcomes.…”

“…Since a direct role for fibroblast growth factor 23 (FGF23) has been established in the pathogenesis of left ventricular hypertrophy, 2 FGF23 reduction by phosphate binders, as highlighted by Keitaro et al, 3 may have beneficial effects on cardiovascular outcomes. It is important to recognize, however, that FGF23 is regulated by factors other than mineral ions and hormones, including iron, 4 inflammation, 5 and immunosuppressive agents. 6 In addition, patients with early chronic kidney disease (CKD) have increased bone FGF23 expression, 7 suggesting that other, as yet unknown, factors associated with CKD also stimulate FGF23.…”

Estudo da contribuição molecular e celular do periósteo na craniossinostose da síndrome de Apert

“…The in vivo results we have achieved are in agreement with the in vitro results. In recent years, FGF19 has been more studied for its role as an endocrine FGF in bile acid homeos-tasis, lipolysis and gall bladder filling (Fu et al, 2004;Tomlinson, 2002;Choi et al, 2006), and, despite FGF23 (from same subfamily of endocrine FGFs) is involved in bone development through phosphate metabolism (Razzaque, 2009;Ohkido et al), this is the first time that FGF19 is related to osteogenic differentiation. FGF19 is a circulating FGF that can activate FGFR1c, 2c, 3c, and 4 in the presence of Klothoβ (Kurosu et al, 2007).…”