Fibrous dysplasia, phosphate wasting and fibroblast growth factor 23.
Fibrous dysplasia (FD) is a classic feature of McCune-Albright syndrome (MAS). Renal phosphate wasting commonly occurs in FD, contributing to the mineralization defect in FD lesions and in non-FD bones, potentially increasing bone deformity. The presence of phosphate wasting correlates with measures of FD disease activity. Hypophosphatemia and phosphate wasting in FD are accompanied by inappropriately normal or low 1,25-dihydroxyvitamin D3 concentrations, similar to X-linked hypophosphatemic rickets. Recently, fibroblast growth factor 23 (FGF23) has emerged as an important humoral factor regulating phosphate and vitamin D homeostasis. FGF23 inhibits renal tubular phosphate reabsorption and decreases 1,25-dihydroxyvitamin D3. Interestingly, FGF23 is produced by normal osteoblasts as well as the abnormal osteogenic precursors present in FD lesions. However, FD lesions likely produce FGF23 in an unregulated fashion. Elevated circulating FGF23 correlates with total body FD disease burden and the presence of phosphate wasting. MAS mutations increase immature osteoblast lineage cells causing FD, resulting in dysregulated FGF23 production and, hence, phosphate wasting.
Imel
Erik A
EA
Department of Medicine, Indiana University School of Medicine, Indanapolis, IN 46202, USA.
Econs
Michael J
MJ
D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005357:Fibrous Dysplasia of Bone / Q000209:etiology / Q000378:metabolism*; D005359:Fibrous Dysplasia, Polyostotic / Q000150:complications / Q000378:metabolism*; D006801:Humans; D010710:Phosphates / Q000378:metabolism*
C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23