Endocrine Abstracts

JOINT153

Background: Autosomal dominant hypophosphatemic rickets (ADHR) is a rare genetic disorder characterised by FGF23-mediated phosphate wasting and impaired bone mineralisation. Mutation renders FGF23 resistant to degradation. Iron deficiency stimulates transcription levels of FGF23 and aggravates the disease. Conventional treatment with phosphate and active vitamin D analogues is challenging and commonly not optimal. Treatment with oral iron has no long-term results. Burosumab, a monoclonal antibody against FGF23, has shown efficacy in X-linked hypophosphatemia (XLH), but its use in ADHR remains unexplored. We present data for the first 12-month treatment with burosumab in ADHR patients.

Case Presentation: A 19-year-old female with ADHR, confirmed by FGF23 R176Q/W mutation, presented with severe symptoms, including bone pain and muscle weakness. Her weight was 40 kg, height 145 cm, sitting height 77 cm, arm span 142 cm, BMI 19.0 kg/m². One year prior, she had a low-energy fracture of the diaphysis right femur, which was complicated by non-union. Her bone mineral density (BMD) was low for age and sex (Z-score L1-L4 -4,4 SD, Z-score femoral neck -4,4 SD, Z-score hip -4,7 SD) and TBS was normal (1.358). Laboratory tests were as follows: 25OH vitamin D 37,7 nmol/l, P 0,39 mmol/l (0,74-1,52), corrected Ca 2,18 mmol/l (2,10-2,60), alkaline phosphatase (AP) 4,95 µkat/l (0,55-1,64), bone-specific AP (BSAP) 93,6 µg/l (4,7-27,0), iPTH 31 ng/l (16-68), TRP 80 % (>85 %), TmP/GFR 0,41 mmol/l (0,84-1,23). Treatment with calcitriol and phosphate did not resolve the symptoms. We started treatment with burosumab (40 mg every 28 days). Phosphate supplementation was discontinued seven days before initiation. Her fracture healed. Within 2 months, the patient reported significantly reduced bone and muscle pain, improved muscle strength, and regained mobility without crutches. BMD increased by 11.7% at the lumbar spine and 14.2% at the hip after 5 months, with further improvements of 46.6% and 36.2%, respectively, after 10 months. Serum phosphate levels increased but did not normalise, and AP rose to 12,96 µkat/l and BSAP to 350 µg/l in the first 3 months before starting to normalise. Transient hyperphosphatemia occurred with concurrently increased iron supplementation, necessitating dose adjustment of burosumab.

Conclusion: Burosumab is potentially an effective treatment for ADHR, demonstrating rapid symptom relief, improved BMD, and enhanced fracture healing. While burosumab was well-tolerated, careful management of concurrent iron therapy is essential to avoid hyperphosphatemia. Further studies with larger cohorts are needed.