ESPE Abstracts

Background/aim: Hyperparathyroidism (HPHT) is a common feature in patients with X-linked hypophosphatemia (XLH) especially when treated with vitamin D analogues and phosphate supplements. Although the exact mechanism is not clear, it is assumed that phosphate supplements taken chronically stimulate parathyroid hormone (PTH) secretion. We prospectively assessed the effect of a novel pathogenetic treatment anti-FGF23 (burosumab) on PTH levels in children with XLH.

Patients and methods: 37 XLH-children (23 girls / 14 boys; 8.8±3.2 years) were switched from conventional therapy to burosumab and completed at least three years of burosumab therapy. Subjects with secondary HPTH at baseline were excluded from analysis. The biochemical parameters of calcium-phosphate metabolism were measured at baseline (M0) and then every 6 months under burosumab (M6 up to M36). According to our national guidelines, the target serum phosphate upon burosumab was >1.2 mmol/l (>3.7 mg/dl).

Results: After three years of treatment with burosumab, there was a global increase of PTH levels from 39.1±18.2 (M0) to 54.8±27.6 ng/l (M36) (18.5-88 ng/l) (P=0.001). Four subjects of 37 (10.8 %) developed secondary HPTH with mean±SD PTH levels equal to 110±17.9 ng/l. The subjects who developed HPTH tended to be older (10.0±1.2 vs 8.7±3.4 yrs, P=0.43, respectively) and had significantly higher PTH levels at baseline (62.8±22.5 vs 36.3±15.7 ng/l, P=0.004, respectively), in comparison to those without HPTH. Subjects with HPTH tended to have higher levels of serum phosphate at M36 (1.33 vs 1.19 mmol/l, P=0.11, respectively) and higher delta of phosphate increase from M0 to M36 (94% vs 63%, P=0.051, respectively), in comparison to those without HPTH. None of the children developed tertiary hyperparathyroidism.

Conclusion: This is the first study describing the effect of anti-FGF23 treatment on PTH secretion in children with XLH. Although the benefit on phosphate homeostasis and bone mineralization has been fully demonstrated, we suggest that prolonged anti-FGF23 treatment may stimulate PTH secretion thus leading to development of hyperparathyroidism after three years of treatment. Nonetheless, longer follow-up study is needed to better understand and describe this phenomenon.