X-linked hypophosphataemic rickets (XLH) is a rare congenital bone condition caused by inactivating mutations in the PHEX gene, which leads to upregulation of FGF23 and resultant hypophosphatemia. With weight-bearing lower limb deformities and impaired growth become evident. Clinical features include rachitic features, abnormal skull shape, craniosynostosis and Chiari malformation. Poor pubertal growth extenuates the short seen in adults. Dental abscesses occur in over 50% of patients.
Complications that become increasingly prevalent during adult life and impair physical function include bone pain, enthesopathy, osteoarthritis, pseudofractures, and spinal stenosis (1).
A multidisciplinary team approach to the management of children and adults with XLH should not be overlooked. Treatment of XLH has involved supplementation with calcitriol and phosphate. Burosumab, an anti-FGF23 antibody, is a recent treatment for XLH that targets the chronic upregulation of FGF23. A 24-week phase 3 randomized, double-blind, placebo-controlled Burosumab trial 134 XLH adults showed Burosumab was associated with significant improvements in serum phosphate and TmP/GFR, physical function and stiffness, with a trend towards improvement in pain (2). Healing of active fractures and pseudofractures demonstrated differences between groups, with healing occurring by 24 weeks in 43.1% of the Burosumab group and only 7.7% of placebo group with fractures. A 64-week phase 3 randomised, active-control, open-label trial of Burosumab in children aged 1-12 years was recently published (3). This study showed that Burosumab was associated with a significant improvement in rickets, lower limb bowing, serum ALP, serum phosphate and growth.
Burosumab has received FDA approval for clinical use for the treatment of XLH in adult and pediatric patients of 1 year of age and older (0.8 mg/kg every 2 weeks in children, and 1 mg/kg every 4 weeks in adults). It remains to be determined for which patients the clinical outcome would be sufficient with conventional therapy and which adults or children would benefit the most from Burosumab (1)