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 high-phosphate 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.