Clinical Scenario:
A 5-year-old boy has progressive genu varum and poor linear growth. He was initially treated for nutritional rickets with adequate vitamin D, and his 25-OH vitamin D level subsequently normalized, but the skeletal abnormalities persisted. Examination shows short stature, genu varum and widened wrists. He has recurrent dental abscesses. Investigations reveal low serum phosphate, normal calcium, markedly elevated ALP and normal PTH. Urinary phosphate excretion is inappropriately high for his degree of hypophosphatemia.
What is the most appropriate disease-specific treatment?
A. Calcium supplementation
B. High-dose cholecalciferol
C. Oral phosphate plus calcitriol
D. Burosumab
E. Ergocalciferol plus calcium
Correct answer explanation:
Correct answer: D. Burosumab
The child has hypophosphatemic rickets with renal phosphate wasting, normal calcium/PTH and persistent rickets despite correction of vitamin D deficiency. This pattern is characteristic of X-linked hypophosphatemia (XLH), usually caused by pathogenic variants in PHEX, resulting in excessive FGF23 activity. FGF23 decreases renal phosphate reabsorption and suppresses calcitriol production.
Burosumab is a monoclonal antibody against FGF23. By inhibiting excessive FGF23 activity, it increases renal phosphate reabsorption and improves phosphate homeostasis and rickets. In children ≥12 months with XLH, the 2025 International Working Group guideline strongly recommends burosumab over conventional therapy, when available.
Why the other options are incorrect
A. Calcium supplementation — Incorrect
Calcium is not the primary abnormality in XLH. Serum calcium is usually normal, while the fundamental problem is renal phosphate wasting. Calcium supplementation therefore does not correct the underlying pathophysiology.
B. High-dose cholecalciferol — Incorrect
Cholecalciferol is appropriate for nutritional vitamin D deficiency, but this child has persistent rickets despite correction of vitamin D status. XLH is primarily an FGF23-mediated phosphate-wasting disorder, so simply giving more nutritional vitamin D does not correct the renal phosphate loss.
C. Oral phosphate plus calcitriol — Not the best answer when burosumab is available
This is the conventional treatment for XLH and remains an appropriate alternative when burosumab is unavailable. However, current pediatric guidelines recommend burosumab over conventional phosphate + active vitamin D therapy in children ≥12 months. Conventional therapy also requires multiple daily doses and carries risks including hypercalciuria, nephrocalcinosis and hyperparathyroidism.
E. Ergocalciferol plus calcium — Incorrect
This combination treats nutritional deficiencies rather than the underlying renal phosphate-wasting mechanism of XLH. The patient’s normal vitamin D status and persistent hypophosphatemic rickets make nutritional rickets unlikely.
Important exam point
If burosumab is unavailable, the recommended conventional approach is active vitamin D (usually calcitriol or alfacalcidol), generally combined with oral phosphate. The 2025 guideline specifically states that phosphate should not be used as monotherapy.
Reference:
Linglart A, et al. X-Linked Hypophosphatemia Management in Children: An International Working Group Clinical Practice Guideline. Journal of Clinical Endocrinology & Metabolism. 2025;110(7):2055–2084. Full guideline – Oxford Academic
