Hyperparathyroidism after 3 years of burosumab in children affected with X-linked hypophosphatemia

Hyperparathyroidism (HPTH) is a common feature in patients with X-linked hypophosphatemia (XLH), especially when treated with vitamin D analogs and phosphate supplements. Although the exact mechanism is not clear, it is assumed that prolonged intake of phosphate supplements stimulates parathyroid hormone (PTH) secretion. We prospectively assessed the effect of burosumab on PTH levels in children with XLH.

Thirty-seven children (8.8 ± 3.2 years) were switched from phosphate supplements and vitamin D analogs to burosumab and completed at least 3 years of therapy. Biochemical parameters of calcium-phosphate homeostasis were measured at baseline and prospectively every 6 months. Target serum phosphate under burosumab was >1.2 mmol/L (>3.7 mg/dL).

After 3 years of treatment, there was a global increase of PTH levels from 39.1 ± 18.2 to 54.8 ± 27.6 ng/L (P = .001) (normal range 18.5-88 ng/L). Four of 37 subjects (10.8%) developed secondary HPTH after 3 years. None developed tertiary HPTH. Subjects who developed HPTH had higher serum phosphate at M36 (1.33 vs 1.19 mmol/L, P = .11, respectively), in comparison with those without HPTH. A significant increase in PTH was correlated with the increase in serum phosphate >1.3 mmol/L (P = .012); serum phosphate positively and independently correlated with PTH in logistic regression analysis (odds ratio = 2.1, 95% CI = 1.1-3.8, P = .021).

We suggest that higher serum phosphate levels in the context of prolonged treatment with burosumab may stimulate PTH secretion in some patients with XLH, leading to HPTH. Careful follow-up and preventive measures to limit the development of secondary HPTH should be applied in treated children.