Hidaka Naoko, Kato Hajime, Koga Minae, Katsura Masaki, Oyama Yuko, Kinoshita Yuka, Fukumoto Seiji, Makita Noriko, Nangaku Masaomi, Ito Nobuaki
Division of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan.
Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan.
Bone Rep. 2021 Oct 16;15:101144. doi: 10.1016/j.bonr.2021.101144. eCollection 2021 Dec.
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 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).
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.
成纤维细胞生长因子（FGF）23是一种调节血清磷酸盐水平的激素，其过度作用会导致慢性低磷血症性佝偻病/骨软化症。迄今为止，已确定的后天性FGF23相关低磷血症性骨软化症的病因仅有两种：肿瘤诱导的骨软化症（TIO）和静脉输注某些形式的铁制剂所诱导的骨软化症。在本研究中，首次介绍了两例可能由长期饮酒引起的FGF23相关低磷血症病例。
病例1和病例2长期大量饮酒超过20年，直至入院。病例1是一名43岁男性，患有进行性加重的多处疼痛和肌肉无力，表现为慢性低磷血症且完整FGF23水平升高。入院一周后，血清磷酸盐水平恢复至参考范围，完整FGF23水平下降。病例1出院后继续饮酒，低磷血症伴高完整FGF23水平复发。每次他短期戒酒时，FGF23相关低磷血症都会缓解。病例2是一名60岁男性，有反复骨折和多关节疼痛加重的症状，也表现为低磷血症且完整FGF23水平升高。入院后，血清磷酸盐水平逐渐升至正常范围下限。完整FGF23水平下降，但仍高于30 pg/ml，即使进行了全面检查，包括生长抑素受体闪烁显像、氟-18-氟脱氧葡萄糖-正电子发射断层扫描/计算机断层扫描（F-FDG-PET/CT）和全身静脉FGF23采样，也未发现产生FGF23的致病肿瘤。他出院后完全戒酒。随着血清磷酸盐水平的变化，完整FGF23随后下降，并在5个月内恢复正常。两名患者均无与遗传性FGF23相关低磷血症性佝偻病/骨软化症相关的基因突变，包括常染色体显性低磷血症性佝偻病/骨软化症（ADHR）。
本研究首次介绍了两例可能由酒精引起的FGF23相关低磷血症病例。在后天性FGF23相关低磷血症性骨软化症中识别出这种可逆情况对于获得更好的患者预后和节省医疗资源至关重要。就外源性因素导致的FGF23失调而言，这种情况与铁输注诱导的FGF23相关低磷血症相似。有必要开展进一步研究以阐明这些情况的精确机制。
