POS0575 OSTEOMALACIA INDUCED BY HYPOPHOSPHATEMIA – ROLE OF FGF 23: TWO CLINICAL CASES REPORT

Abstract

BackgroundOsteomalacia is a bone disorder characterized by decreased bone mineralization. Vitamin D deficiency and hypophosphatemia are the most frequent causes. Fibroblast growth factor 23 (FGF23) is a hormone secreted by osteocytes in response to increased calcitriol and serum phosphate levels. FGF23 main function is phosphate serum levels regulation, decreasing sodium-phosphate cotransporter expression on the proximal convoluted tubule. Thus, FGF23 reduces calcium reabsorption and increases urine phosphate excretion. FGF23 may also suppress 1α-hydroxylase, reducing vitamin D activation and calcium reabsorption.ObjectivesTo increase the awareness of hypophosphatemia-induced osteomalacia.MethodsCase reports and discussion.ResultsCase 1 –A 63-year-old man, hospitalized for total hip arthroplasty secondary to non-traumatic bilateral femoral neck fracture was evaluated by rheumatology on suspicion of osteoporosis. Medical history was relevant for a progressive paraparesis of lower limbs 6 years ago and which etiological investigation revealed a mesenchymal tumor in the body of the ninth dorsal vertebrae compressing the spinal cord. A multidisciplinary discussion concluded that the tumor was unresectable, but the patient underwent decompressive surgery to relieve neurological symptoms one year later. The patient also reported a history of multiple non-traumatic fractures in the past five years, including ribs, ankle, pelvis, femoral neck, and scapula, and denied any articular or bone pain. In laboratory evaluation, serum phosphate levels were below the laboratory detection limit, calcium and vitamin D were decreased, parathormone (PTH) was in the normal range and serum alkaline phosphatase (AF) was increased. Serum FGF23 levels were 6 times above the upper limit of normal (ULN). Thus, the diagnosis of oncogenic osteomalacia induced by an FGF23-producing mesenchymal tumor was made. The patient started intravenous phosphate repositioning in the intermediate care unit and then he continued oral phosphate, calcium, and vitamin D supplementation at home. Currently, the patient is in the oncology outpatient clinic, and he was proposed to initiate treatment with burosumab (anti-FGF23 antibody).Case 2 –A 57-year-old woman with Rendu-Osler-Weber syndrome and iron deficiency anemia, chronically supplemented with ferric carboxymaltose, was referred to the rheumatology outpatient clinic because of a right second metatarsal bone fracture associated with hypophosphatemia, vitamin D deficiency, AF and PTH elevation (above 3 times the ULN and 2 times the ULN, respectively), and normal calcium levels. Measurement of FGF23 serum levels revealed an elevation of 3 times the ULN. The diagnosis of FGF23-induced hypophosphatemia was made. The patient started oral phosphate and vitamin D supplementation and the formulation of intravenous iron was changed. Six months after the initial evaluation, the previously abnormal analytical values were within the normal range.ConclusionOsteomalacia has multiple identified causes like vitamin D deficiency, hypophosphatemia, chronic kidney disease, renal tubular acidosis, and hypophosphatasia. FGF23 is a hormone that regulates phosphate metabolism. There are several types of genetic and acquired FGF23-related hypophosphatemia, like X-linked hypophosphatemia and FGF23-producing mesenchymal tumors, respectively. In case 2, it is thought that the key mechanism responsible for the effect of iron results from the disproportionate inhibition of FGF23 degradation by the carbohydrates present in intravenous formulations with a consequent increase in its concentration and activity. The risk of hypophosphatemia and osteomalacia appears to be greater with iron carboxymaltose than with other intravenous iron formulations.