Abstract
Rickets is a group of disorders characterized by impaired mineralization of the growing skeleton. Histomorphometric basis of rickets is insufficient formation of hydroxyapatite followed by apoptosis of hypertrophic chondrocytes.
There are two types of rickets: calcipenic caused by the lack of calcium and vitamin D activity, and phosphopenic developed due to impaired phosphate resorption in proximal tubules of the kidney. X-linked hypophosphatemia (XLH) is the most common type of phosphopenic rickets.
XLH is caused by a pathogenic variant in the PHEX gene encoding the PHEX protein (phosphate-regulative endopeptidase X-linked). Lack of this endopeptidase disrupt degradation of the fibroblast growth factor 23 (FGF23), an important phosphaturic agent.
Life-long treatment with phosphate and vitamin D is required as a conventional therapy. This approach is however frequently characterized by unpleasant adverse events and is not effective in significant proportion of patients.
Significant change in treatment of XLH brought the approval of burosumab (monoclonal antibody against FGF23) by regulatory authorities in 2018. Randomized controlled trials have confirmed great potential of burosumab for rickets healing, phosphate normalization, ALP decrease and long bones deformities correction.
This publication summarizes current knowledge on pathophysiology and treatment of XLH.