Abstract
PURPOSE: X-linked hypophosphatemia is characterized by skeletal abnormalities, particularly lower limb angular deformities. Although burosumab has demonstrated short-term clinical improvements, its mid- to long-term effects on skeletal alignment remain underexplored. This study evaluated skeletal outcomes of burosumab therapy over 2 years, focusing on lower limb deformities. METHODS: We retrospectively analyzed 20 pediatric X-linked hypophosphatemia patients (10 boys and 10 girls) who initiated burosumab at a mean age of 7.5 ± 2.4 years. Rickets severity score, mechanical axis deviation, mechanical lateral distal femoral angle, medial proximal tibial angle, lateral distal tibial angle, and standing height were assessed at baseline, 12 months, and 24 months. Outcomes were analyzed using age-standardized z-scores. RESULTS: Rickets severity improved from the first year, with Rickets Severity Score decreasing from 3.5 ± 1.2 to 0.6 ± 0.5 at 24 months (mean change 2.9; 95% confidence interval 2.4-3.4). Lower limb alignment also improved: |z|-mechanical axis deviation decreased from 2.3 ± 1.6 to 1.0 ± 1.0 (change 1.3; 95% confidence interval 0.9-1.7), showing progressive correction from the first year. |z|-mechanical lateral distal femoral angle improved mainly at 24 months, decreasing from 2.7 ± 2.1 to 1.3 ± 1.2 (change 1.4; 95% confidence interval 0.8-2.0). |z|-medial proximal tibial angle and |z|-lateral distal tibial angle showed smaller overall changes (0.8 and 0.9, respectively), indicating modest tibial correction. Standing-height z-scores remained stable (-1.5 ± 0.8 to -1.3 ± 0.7), with no measurable change in growth over 2 years. CONCLUSIONS: Burosumab therapy may improve skeletal deformities in pediatric X-linked hypophosphatemia. Early improvements in rickets severity were followed by gains in alignment, particularly mechanical axis deviation and mechanical lateral distal femoral angle, though standing height remained unaffected. Longer-term follow-up is required to confirm sustained skeletal benefits. LEVEL OF EVIDENCE: Level IV.