The goals of therapy are to correct lower limb deformities to reduce the requirement for surgery, optimise linear growth, minimise pain and improve dental health, necessitating a multidisciplinary approach. A current focus has been to improve the recognition of the XLH, as the earlier therapy is instituted the better the long-term outcomes. There are currently two medical treatment strategies, conventional therapy or anti-FGF23 monoclonal antibody.
Conventional therapy consists of multiple doses of oral phosphate (4–6 times per day) and an activated vitamin D analogue (calcitriol or alphacalcidol once a day). Higher doses are needed during phases of rapid linear growth. Medicine nonadherence and intolerance are frequent. Adverse effects include secondary hyperparathyroidism, nephrocalcinosis and cardiovascular abnormalities. Treatment monitoring is with serum alkaline phosphatase (ALP), PTH, severity of rickets assessed by X-ray (hand or knee) and intercondylar and/or intermalleolar distance, and growth. Treatment is continued until cessation of linear growth.
Conventional therapy does not fully correct the biochemical derangement nor symptoms of XLH. A limitation is that as serum phosphate levels are increased, FGF23 levels are further increased with consequent increased renal phosphate wasting, potentially reducing treatment efficacy.
Anti-FGF23 monoclonal antibody (burosumab)
Burosumab, a recombinant IgG1 monoclonal antibody, directly inhibits FGF23 activity and thus increases TmP/GFR and indirectly enhances intestinal phosphate and calcium absorption. The EMA granted marketing authorisation in 2018 for treatment for children older than 1 year with XLH and radiographical evidence of rickets; the FDA approved usage in children and adults. Burosumab is given subcutaneously every 2 weeks and is well tolerated with a reassuring safety profile. Side effects include a mild reaction at the site of injection, headache and cough. Fasting serum phosphate should be monitored regularly to achieve a phosphate in the lower end of the age-specific reference range. The monitoring required includes serum ALP, TmP/GFR and wrist X-ray, annual renal ultrasound and urine calcium: creatinine ratio3.
Compared to conventional therapy, burosumab resulted in superior improvements in radiological rickets healing, serum phosphate, growth, pain, reduction in renal phosphate wasting and functional outcomes4,5.