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Anti-FGF23 Monoclonal Antibody (X-Linked Hypophosphataemia) Pregnancy: Avoid — no human data; FGF23 affects placental phosphate transport. Use only if clearly necessary in pregnancy with specialist oversight.

Burosumab

Brand names: Crysvita

Adult dose

Dose: 1 mg/kg every 4 weeks, rounded to nearest 10 mg (minimum 10 mg, maximum 90 mg)
Route: Subcutaneous injection
Frequency: Every 4 weeks
Max: 90 mg per injection
X-linked hypophosphataemia (XLH) in adults. Dose based on weight — round to nearest 10 mg vial. Inject into abdomen, upper arm, or thigh. Do not use with oral phosphate supplements — hyperphosphataemia risk when FGF23 is neutralised. Serum phosphate and ALP used to assess response. Source: BNF 90; MHRA SPC Crysvita.

Paediatric dose

Dose: Children ≥1 year: 0.8 mg/kg every 2 weeks (minimum 10 mg); round to nearest 10 mg. Adolescents with open epiphyses: 0.8 mg/kg every 2 weeks mg/kg
Route: Subcutaneous
Frequency: Every 2 weeks (children); every 4 weeks (adults)
Max: 90 mg per injection
Children: every 2 weeks. Monitor serum phosphate (target: 1.0–1.5 mmol/L lower end of normal range). Stop oral phosphate supplements before starting. Licensed from 1 year. Source: BNF for Children 2024; MHRA SPC.

Dose adjustments

Renal

eGFR <30 mL/min: not recommended — increased risk of hyperphosphataemia. Burosumab significantly increases phosphate reabsorption; use with caution in impaired renal phosphate excretion.

Hepatic

No dose adjustment required — not hepatically metabolised via CYP enzymes.

Paediatric weight-based calculator

Children: every 2 weeks. Monitor serum phosphate (target: 1.0–1.5 mmol/L lower end of normal range). Stop oral phosphate supplements before starting. Licensed from 1 year. Source: BNF for Children 2024; MHRA SPC.

Clinical pearls

  • FGF23 — the pathophysiology key: XLH is caused by PHEX gene mutations → excess FGF23 production → FGF23 inhibits renal phosphate reabsorption + suppresses 1-alpha-hydroxylase (1,25-dihydroxyvitamin D) → phosphaturia + low active vitamin D → hypophosphataemia + rickets/osteomalacia. Burosumab neutralises FGF23, restoring phosphate reabsorption.
  • Paradigm shift from oral phosphate: conventional treatment (oral phosphate + calcitriol) requires 4–6 daily doses, causes GI side effects, risks secondary hyperparathyroidism, and does not address the underlying FGF23 excess. Burosumab monthly injection normalises phosphate without constant oral supplementation.
  • ATLAS trial (adults): burosumab significantly improved serum phosphate, fracture healing on MRI, osteomalacia on bone biopsy (50% reduction in osteoid volume), and pain vs conventional therapy (active comparator). NEJM 2018 paediatric trial: 94% of children achieved rickets healing at week 40 vs 0% placebo.
  • Stop oral phosphate BEFORE starting: if patient is on conventional therapy (oral phosphate + calcitriol), must stop oral phosphate ≥1 week before first injection. Continuing oral phosphate with burosumab — where FGF23 is neutralised — causes severe hyperphosphataemia.
  • NICE TA745: recommended for XLH in adults and children ≥1 year who have severe disease manifestations (rickets, painful fractures, pseudofractures, skeletal deformities, or profound growth failure) uncontrolled with conventional therapy. Source: BNF 90; Carpenter et al. NEJM 2018; NICE TA745; MHRA SPC Crysvita.

Contraindications

  • Concurrent oral phosphate supplements (hyperphosphataemia risk — must stop ≥1 week before starting burosumab)
  • Concurrent active vitamin D analogues (calcitriol, alfacalcidol) unless specifically directed by specialist — hyperphosphataemia risk
  • eGFR <30 mL/min (insufficient renal phosphate clearance)
  • Serum phosphate above normal range at initiation

Side effects

  • Injection site reactions (pain, erythema, bruising — most common)
  • Headache, fever, rash
  • Hyperphosphataemia (if concurrent phosphate supplements — stop them before starting)
  • Nephrocalcinosis (long-term if serum phosphate chronically supranormal — avoid overtreatment)
  • Tooth abscess, dental abnormalities (XLH-related — burosumab improves but does not eliminate dental manifestations)
  • Vitamin D supplementation may need adjustment — FGF23 affects vitamin D metabolism

Interactions

  • Oral phosphate supplements: must be stopped at least 1 week before starting burosumab. Concurrent use risks hyperphosphataemia
  • Active vitamin D analogues (calcitriol, alfacalcidol): combined use risks hypercalciuria and hyperphosphataemia — stop vitamin D supplements before starting unless specialist advises
  • No CYP interactions — monoclonal antibody metabolism

Monitoring

  • Serum phosphate (at 2 and 4 weeks after first dose, then monthly — target: lower half of normal range or slightly below)
  • Serum calcium and urinary calcium-to-creatinine ratio (hypercalciuria monitoring)
  • Serum 25-OH vitamin D (supplementation may be needed)
  • eGFR (renal phosphate handling)
  • Renal ultrasound for nephrocalcinosis at baseline and annually
  • Rickets severity score (RSS) in children (radiological); MRI for fracture/pseudofracture healing in adults

Reference: BNFc; BNF 90; BNF for Children 2024; Carpenter et al. NEJM 2018 (paediatric XLH); NICE TA745 (burosumab); MHRA SPC Crysvita. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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