Induction of FGF23-related hypophosphatemic osteomalacia by alcohol consumption

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 (^{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.

Declaration of competing interest

All authors state they have nothing to disclose.

^{Division of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan}

^{Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan}

^{Department of Internal Medicine, Koseiren Sanjo General Hospital, Niigata, Japan}

^{Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan}

Nobuaki Ito: moc.liamg@yktotibon

^{Corresponding author at: Division of Nephrology and Endocrinology, Department of Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.}moc.liamg@yktotibon

Received 2021 Aug 26; Revised 2021 Oct 7; Accepted 2021 Oct 12.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

The patients started to abstain from alcohol on Day 0; however, case 1 resumed drinking on Day 10. N.E. = Not examined; ALP: alkaline phosphatase; BAP: bone-specific alkaline phosphatase; PTH: parathyroid hormone; TmP/GFR: tubular maximum transport of phosphate corrected for the glomerular filtration rate; AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: gamma-glutamyl transpeptidase.