Mitochondrial dysfunction and mitophagy blockade contribute to renal osteodystrophy in chronic kidney disease-mineral bone disorder.

Journal and index pages often block iframe embedding. This reader keeps the evidence details in Orthonotes and leaves the source page one click away.

Abstract

[Indexed for MEDLINE] 5. Metabolism. 2020 Feb;103S:154049. doi: 10.1016/j.metabol.2019.154049. Epub 2019 Dec 18. Management of X-linked hypophosphatemia in adults. Lecoq AL(1), Brandi ML(2), Linglart A(3), Kamenický P(4). Author information: (1)AP-HP, Department of Endocrinology and Reproductive Diseases, Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, filière OSCAR, and Platform of Expertise for Rare Disorders, Bicêtre Paris Saclay Hospital, Le Kremlin-Bicêtre, France. (2)Department of Surgery and Translational Medicine, University of Florence, University Hospital of Florence, Florence, Italy. (3)AP-HP, Endocrinology and Diabetes for Children, Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, filière OSCAR, and Platform of Expertise for Rare Disorders, Bicêtre Paris Saclay Hospital, Le Kremlin-Bicêtre, France; Université Paris-Saclay, INSERM, Physiologie et Physiopathologie Endocriniennes, Le Kremlin-Bicêtre, France. (4)AP-HP, Department of Endocrinology and Reproductive Diseases, Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, filière OSCAR, and Platform of Expertise for Rare Disorders, Bicêtre Paris Saclay Hospital, Le Kremlin-Bicêtre, France; Université Paris-Saclay, INSERM, Physiologie et Physiopathologie Endocriniennes, Le Kremlin-Bicêtre, France. Electronic address: peter.kamenicky@aphp.fr. X-linked hypophosphatemia (XLH) is caused by mutations in the PHEX gene which result in Fibroblast Growth Factor-23 (FG-F23) excess and phosphate wasting. Clinically, XLH children present with rickets, bone deformities and short stature. In adulthood, patients may still be symptomatic with bone and joint pain, osteomalacia-related fractures or pseudofractures, precocious osteoarthrosis, enthesopathy, muscle weakness and severe dental anomalies. Besides these musculoskeletal and dental manifestations, adult XLH patients are also prone to secondary and tertiary hyperparathyroidism, cardiovascular and metabolic disorders. Pathophysiology of hyperparathyroidism is only partially understood but FGF23 excess and deficient production of calcitriol likely contributes to its development. Similarly, the pathophysiological mechanisms of potential cardiovascular and metabolic involvements are not clear, but FGF-23 excess may play an essential role. Treatment should be considered in symptomatic patients, patients undergoing orthopedic or dental surgery and women during pregnancy and lactation. Treatment with oral phosphate salts and active vitamin D analogs has incomplete efficacy and potential risks. Burosumab, a recombinant human monoclonal antibody against FGF-23, has proven its efficacy in phase 2 and phase 3 clinical trials in adult patients with XLH, but currently its position as first line or second line treatment differ among the countries. Copyright © 2019 Elsevier Inc. All rights reserved. DOI: 10.1016/j.metabol.2019.154049