Burosumab as bridging therapy in autosomal dominant hypophosphatemic rickets with femoral fracture nonunion and iron deficiency

Abstract Autosomal dominant hypophosphatemic rickets (ADHR) is a rare genetic disorder, characterized by fibroblast growth factor 23 (FGF23)-mediated renal phosphate wasting and impaired bone mineralization. Iron deficiency in ADHR increases FGF23 production and can worsen hypophosphatemia. Evidence to guide optimal management in severe adult cases remains limited. We report the use of burosumab as bridging therapy in a 19-yr-old woman with genetically confirmed ADHR (FGF23 p.Arg176Trp), severe osteomalacia, iron-deficiency anemia, and a low-energy femoral diaphyseal fracture complicated by nonunion despite conventional therapy. Treatment with burosumab resulted in rapid clinical improvement, with marked reduction in musculoskeletal pain and stiffness, and restoration of independent ambulation within four months. Bone mineral density increased substantially (+11.7% at the lumbar spine and + 14.2% at the total hip at 5 mo; +63.8% and + 55.5% from baseline at approximately 11 mo, respectively), while trabecular bone score remained within the normal range, a pattern consistent with improved mineralization and preserved trabecular texture. Serum phosphate increased but did not consistently normalize at trough, prompting dose escalation. At 8 mo, the burosumab dose was increased to 50 mg (1.25 mg/kg) due to persistent hypophosphatemia; with concurrent oral iron replacement, transient hyperphosphatemia (1.61 mmol/L) occurred and was managed by delaying the next dose by 14 d and reducing the dose back to 1 mg/kg. The patient also underwent additional surgical intervention, which may have contributed to the overall outcome; radiographic callus formation was evident 5 mo post-surgery. To our knowledge, this is the first full-length report describing burosumab use in genetically confirmed ADHR with longitudinal biochemical and densitometric follow-up, and it highlights the importance of careful monitoring of phosphate and iron indices when combining therapies.