[Pathophysiology in rickets/osteomalacia].

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Abstract

[Indexed for MEDLINE] 15. Arch Endocrinol Metab. 2022 Nov 11;66(5):658-665. doi: 10.20945/2359-3997000000555. New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia. Marques JVO(1), Moreira CA(2), Borba VZC(3). Author information: (1)Residência em Endocrinologia no Serviço de Endocrinologia do Hospital de Clínicas da Universidade Federal do Paraná (SEMPR/UFPR); Certificação Board em Endocrinologia e Metabolismo pela Sociedade Brasileira de Endocrinologia e Metabologia (SBEM); Medicina Interna pela UFPR, Curitiba, PR, Brasil. (2)Departamento de Clínica Médica da Universidade Federal do Paraná (UFPR); Centro Acadêmico de Pesquisa do Instituto Pró-Renal (PRO), Curitiba, PR, Brasil. (3)Departamento de Clínica Médica da Universidade Federal do Paraná (UFPR); Unidade de Ossos do Serviço de Endocrinologia do Hospital de Clínicas da UFPR (SEMPR/UFPR), Curitiba, PR, Brasil; Unidade de Ossos da University of Arkansas for Medical Sciences (UAMS), Arkansas, EUA, vzcborba@gmail.com. Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms - overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene - can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. Conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D analogs, which may improve radiographic rickets but do not normalize growth. Complications of the conventional long-term treatment consist of hypercalcemia, hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired renal function, and potentially chronic kidney disease. Recently, burosumab, an antibody against FGF-23, was approved as a novel therapy for children and adults with X-linked hypophosphatemia and patients with tumor-induced osteomalacia. Burosumab showed good performance in different trials in children and adults. It increased and sustained the serum phosphorus levels, decreased the rickets severity and pain scores, and improved mineralization. It offers a new perspective on the treatment of chronic and disabling diseases. DOI: 10.20945/2359-3997000000555 PMCID: PMC10118827