Induction of FGF23-related hypophosphatemic osteomalacia by alcohol consumption

Abstract

Context Fibroblast growth factor (FGF) 23 is a hormone that regulates serum phosphate levels, the excess action of which causes chronic hypophosphatemic rickets/osteomalacia. To date, there are only two identified causes of acquired FGF23-related hypophosphatemic osteomalacia: tumor-induced osteomalacia (TIO) and osteomalacia induced by the intravenous infusion of some forms of iron preparations. In the current study, two cases of FGF23-related hypophosphatemia probably induced by chronic alcohol consumption were first introduced. Case description Case 1 and case 2 had been drinking high amounts of alcohol for more than twenty years until they were admitted to the hospital. Case 1 was a 43-year-old man with progressive worsening multiple pains and muscle weakness who exhibited chronic hypophosphatemia with increased intact FGF23 levels. A week after admission, the serum phosphate level recovered to the reference range, and the intact FGF23 level declined. Case 1 resumed drinking after discharge, and hypophosphatemia concomitant with high intact FGF23 levels recurred. The alleviation of FGF23-related hypophosphatemia was observed each time he temporarily abstained from drinking for a short period. Case 2 was a 60-year-old man with recurrent fractures and exacerbation of pain in multiple joints who also exhibited hypophosphatemia with increased intact FGF23 levels. After admission, the serum phosphate level gradually increased to the lower limit of the normal range. The intact FGF23 level decreased, but it was still higher than 30 pg/ml, and causative FGF23-producing tumors were not identified even with thorough examinations, including somatostatin receptor scintigraphy, fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) and systemic venous FGF23 sampling. He completely abstained from alcohol after discharge. Along with the serum phosphate level, intact FGF23 was subsequently decreased and had been normalized for 5 months. Both patients had no genetic mutation related to hereditary FGF23-related hypophosphatemic rickets/osteomalacia, including autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR). Conclusion Two cases of FGF23-related hypophosphatemia probably induced by alcohol were first introduced in this study. Identifying this reversible condition among acquired FGF23-related hypophosphatemic osteomalacia is critical to obtain better patient outcomes and save medical resources. This condition is similar to iron infusion-induced FGF23-related hypophosphatemia in terms of the dysregulation of FGF23 due to exogenous factors. Future research to elucidate the precise mechanism of these conditions is warranted.

Adult Presentation of X-Linked Hypophosphatemia

“…However, even among these cases, genetic diagnosis of PHEX mutation is recommended, if available, in an effort to make an accurate diagnosis [15]. In the cases of adult-onset FGF23-related hypophosphatemic osteomalacia without any of the symptoms above, the possibilities of tumor-induced osteomalacia, intravenous infusion of iron preparation-induced osteo-malacia, and alcohol-induced FGF23-related hypophosphatemic osteomalacia should be explored [16][17][18].…”

“…Endocrines 2022, 3, FOR PEER REVIEW 3 preparation-induced osteomalacia, and alcohol-induced FGF23-related hypophosphatemic osteomalacia should be explored [16][17][18].…”

Adult Presentation of X-Linked Hypophosphatemia

“…However, even among these cases, genetic diagnosis of PHEX mutation is recommended, if available, in an effort to make an accurate diagnosis [9]. In the cases of adult-onset FGF23-related hypophosphatemic osteomalacia without any of the symptoms above, the possibilities of tumor-induced osteomalacia, intravenous infusion of iron preparation-induced osteomalacia, and alcohol-induced FGF23-related hypophosphatemic osteomalacia should be explored [10,11,12].…”

ERRγ-inducible FGF23 promotes alcoholic liver injury through enhancing CYP2E1 mediated hepatic oxidative stress

“…FA-AKI, CCl 4 -ALI, autosomal dominant polycystic kidney disease and childhood biliary atresia [ 24 , 25 , [32] , [33] , [34] , [35] ]. Circulatory FGF23 levels are increased among alcoholics [ 36 , 37 ], however the source, mechanism of regulation and role of FGF23 in ALD remains to be delineated.…”