Bone Abstracts

Burosumab, a monoclonal antibody targeting fibroblast growth factor 23, is now available for clinical use in children with X-linked hypophosphatemia (XLH). We aimed to explore the effects of burosumab in children with XLH in a clinical setting, considering:

a) Biochemistry

b) Growth

c) Lower limb deformity (LLD)

d) Radiology

e) Motor function

Methods: Clinical/biochemical data were reviewed at 6 (N=8) and 9 (N=9) months for a cohort of children with XLH started on burosumab. Motor function was assessed with 6-minute walk test (6MWT). Radiographs were scored by a consultant radiologist. Paired t-tests were performed (significance=P<0.05).

Results: Mean age at commencement was 7.0 years (range=1.6–16.7). Mean starting dose was 0.6 mg/kg, increasing to 1.1 mg/kg and 1.3 mmol/kg at 6 and 9 months.

Biochemistry: All patients initially had low/low-normal serum phosphate levels that improved and normalised with burosumab. Mean±S.D. levels were 0.7±0.1 at baseline, 1.0±0.2 at 6 months, and 1.1±0.1mmol/l at 9 months (P<0.001). ALP levels were initially raised (Mean±S.D. 412±69IU/l) with reduction into normal range by 9 months (Mean±S.D. 310±89 IU/l, N=8, P<0.01). All patients had low calculated renal tubular reabsorption of phosphate (TmP/GFR), which increased from Mean±S.D. 0.57±0.11 (RR=1.15–2.44) to 1.07±0.15 at 6 months (N=9, P<0.001) and 0.96±0.12 at 9 months (N=8, P<0.001). PTH and urinary calcium:creatine ratios remained normal.

Growth parameters: Height Z-scores significantly increased, with Mean±S.D. −2.60±0.87 at baseline and −2.38±0.87 at 9 months P<0.01.

Lower limb deformity: LLD was recorded in 7 children; varus (N=4), valgus (N=2), and windswept (N=1). The most severely affected patient, with initial intermalleolar distance of 10 cm, noted progression of deformity on treatment. All others noted an improvement at 9 months (N=5), with straightening evident in photographs and reduction of intercondylar or intermalleolar distances.

Radiology: Thatcher score (maximum score 10) improved in 6 patients at 6 months and was unchanged in three patients (Mean±S.D. decreased from 2±1.9 to 0.5±0.4, P=0.02).

Motor function: 6MWT (N=4) distances improved but were all still below normal reference range by at least 130 m. Mean±S.D. was 258±87m at baseline and 402±82m at 6 months.

Conclusion: In a single UK centre, burosumab treatment of children with XLH improves biochemical markers, growth, LLD, radiological scores and 6MWT.

Disclosure: Moira S Cheung is on Advisory Board for Kyowa Kirin.