ENOrphanet Journal of Rare Diseases | Clinical Observation of Burosumab Initiation in Infants with X-Linked Hypophosphatemia
Date: February 07, 2026
Classification: Frontiers
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This study reports three cases of XLH infants treated with burosumab before six months of age, demonstrating the potential benefits of early intervention in promoting linear growth and improving skeletal deformities, with favorable drug tolerability.
Literature Overview
The article titled 'Burosumab in infants with X-linked hypophosphatemic rickets: a case series,' published in the Orphanet Journal of Rare Diseases, retrospectively summarizes the clinical characteristics, treatment courses, and follow-up results of at least one year for three infants with X-linked hypophosphatemic rickets (XLH) who initiated burosumab treatment before the age of one. Using real-world data, the study demonstrates the impact of early intervention on growth, skeletal development, and biochemical markers, providing preliminary evidence for optimizing treatment in pediatric XLH patients. Employing a case series design, the research evaluated linear growth, Rickets Severity Score (RSS), mechanical axis deviation (MAD), neck-shaft angle (NSA), and laboratory parameters. Results showed that although serum phosphate levels did not fully normalize, overall growth trajectories remained stable or improved, skeletal deformities were effectively controlled, and no severe adverse reactions occurred. The study emphasizes the importance of individualized treatment and close monitoring, suggesting that early use of burosumab may improve long-term outcomes in infants with XLH.Background Knowledge
X-linked hypophosphatemia (XLH) is a rare inherited metabolic bone disorder caused by mutations in the PHEX gene, leading to elevated levels of fibroblast growth factor 23 (FGF23), which in turn causes renal phosphate wasting and impaired bone mineralization. Affected children often present with rachitic bone deformities, short stature, bone pain, and dental complications. Conventional therapy involves oral phosphate supplements combined with active vitamin D analogs, but has limited efficacy, numerous side effects, and requires frequent dosing. Burosumab is a humanized monoclonal antibody targeting FGF23 that restores renal phosphate reabsorption by neutralizing excess FGF23, thereby improving mineralization. It was approved for the treatment of XLH in 2018, and in 2022 the FDA expanded its indication to include children aged six months and older. However, data on the efficacy and safety of initiating treatment in infancy remain scarce. This study focuses on this knowledge gap, exploring the clinical effects of starting burosumab within the first months of life, aiming to evaluate its impact on growth trajectories and skeletal development, and to provide real-world evidence for optimizing dosing strategies in infants. Current research challenges include balancing biochemical improvements with functional outcomes and ensuring long-term safety monitoring, especially during critical developmental periods. The study's contribution lies in filling the data gap on early intervention, offering significant clinical guidance.
Research Methods and Experiments
The study employed a prospective case series design, enrolling three XLH infants followed at the Metabolic Bone Clinic of Tel Aviv Sourasky Medical Center and Meir Medical Center, all of whom initiated burosumab treatment before one year of age. Shortly after diagnosis, patients began conventional therapy (oral phosphate and calcitriol), which was discontinued seven days prior to starting burosumab. The initial dose of burosumab was 0.8 mg/kg (rounded to the nearest 10 mg), with subsequent dose adjustments based on clinical, biochemical (serum phosphate, alkaline phosphatase), and radiological findings. Patients were monitored every 2–4 weeks during the first six months of treatment, then every 3–6 months once stabilized. Growth parameters (weight, length, weight/length ratio, BMI) were calculated as Z-scores using WHO or CDC growth standards. Skeletal X-rays were evaluated every 6–12 months by two independent orthopedic specialists using the Thacher Rickets Severity Score (RSS) system. Mechanical axis deviation (MAD) was assessed via the Mikulicz line, and neck-shaft angle (NSA) was measured by pediatric orthopedic surgeons. Laboratory tests included serum phosphorus, calcium, creatinine, alkaline phosphatase, FGF23, PTH, and urinary phosphorus and calcium, with calculations of tubular reabsorption of phosphate (TRP) and TmP/GFR.Key Conclusions and Insights
Research Significance and Outlook
This study provides important real-world evidence for the early use of burosumab in infants with XLH, indicating that initiating treatment early in life may help maintain normal growth trajectories and effectively prevent skeletal deformities. Achieving a neutral mechanical axis serves as key radiological evidence supporting the structural benefits of the drug in improving lower limb alignment. The study highlights the importance of individualized dose adjustment, suggesting that current guideline-recommended doses may be insufficient to achieve optimal outcomes in infants, necessitating flexible adjustments based on clinical response.
Despite the small sample size and lack of a control group, the findings lay the groundwork for future larger, prospective studies. Long-term follow-up will be essential to assess final adult height, bone density, dental complications, and drug safety. Additionally, the study suggests that non-phosphate factors (such as sleep-disordered breathing) may influence growth, underscoring the need for multidisciplinary management. Future research should explore optimal initiation timing, dose titration strategies, and biomarkers to refine treatment protocols for infants with XLH.
Conclusion
This case series study systematically evaluated the clinical outcomes of three infants with X-linked hypophosphatemic rickets (XLH) who initiated burosumab treatment between 6 and 7 months of age, with follow-up lasting at least one year. The results indicate that early initiation of burosumab is feasible and well tolerated in real-world clinical practice. Although serum phosphate levels did not fully normalize in any patient, overall linear growth was maintained or improved, and skeletal health showed significant benefits, including neutral mechanical axis deviation, low rickets severity scores, and absence of new long bone deformities. These findings suggest that early use of burosumab in infancy may effectively prevent or mitigate skeletal complications associated with XLH. The study also found that patients generally required higher-than-recommended doses to achieve therapeutic goals, highlighting the need for individualized treatment strategies. One patient experienced growth delay, which improved following adenoidectomy, suggesting that comorbidity management is crucial for overall growth. Overall, this study provides positive evidence for early intervention in children with XLH, supporting the use of burosumab in infants to improve long-term skeletal and growth outcomes. However, due to limitations in sample size and follow-up duration, larger and longer-term studies are still needed to confirm these findings and further clarify optimal dosing regimens and long-term safety.
