The Effect of Recombinant Human Growth Hormone in Children With X-Linked Hypophosphatemia

Background. X-linked hypophosphatemia (XLH) is characterized clinically by rickets and growth retardation. Conventional treatment of XLH with oral phosphate and vitamin D fails to normalize linear growth. Objective. To determine the benefit and the potential side effects of recombinant human growth hormone (rhGH) therapy in patients with XLH. Design and Methods. A randomized, double-blind, crossover study was performed throughout a 24-month period in five children with XLH, each patient serving as his own control. The effect of 12 months of rhGH therapy on height, mineral metabolism, glucose and lipid metabolism, hemoglobin, thyroid and parathyroid function, serum 1,25-(OH)2 vitamin D, osteocalcin, growth hormone, urinary calcium, phosphate, nephrocalcinosis, renal function, and bone density was compared with the effects of 12 months of placebo administration on the same parameters. Results. The average age (mean ± SEM) of the patients at the start of the study was 5.6 ± 1.4 years. Growth hormone therapy improved the height standard deviation score (z-score) from a baseline of −2.66 ± 0.21 to −2.02 ± 0.25 and to −1.46 ± 0.28, after 3 and 12 months, respectively. At the start of the control period the heightz-score was −2.27 ± 0.30 compared with −2.22 ± 0.16 after 12 months of placebo administration. The growth velocity standard deviation score was −1.90 ± 0.40 during the 12 months of placebo administration and +4.04 ± 1.50 during the 12 months of rhGH therapy. An increase in serum phosphate from 0.88 ± 0.07 mmol/L to 1.17 ± 0.14 mmol/L and tubular maximum for phosphate reabsorption (TmP/GFR) from 2.12 ± 0.15 to 3.41 ± 0.25 mg/dL, was observed after 3 months of rhGH therapy. However, both serum phosphate and TmP/GFR were unchanged from baseline after 6, 9, and 12 months of rhGH therapy. Neither serum phosphate nor TmP/GFR changed from baseline during the placebo administration. Insulin-like growth factor 1 (IGF-1) increased from 114 ± 25 to 354 ± 51 ng/mL after 12 months of rhGH therapy. Despite the increase in IGF-1 after rhGH therapy, the value did not exceed normal serum concentration. IGF-1 did not change from baseline after 12 months of placebo administration. Neither therapy with rhGH nor with placebo had an effect on glucose and lipid metabolism, hemoglobin, thyroid and parathyroid function, serum 1,25-(OH)2 vitamin D, alkaline phosphatase, osteocalcin, urinary calcium excretion, the grade of nephrocalcinosis, glomerular filtration rate, or urinary albumin excretion. Twelve months of rhGH therapy increased bone mass and width but not density. Twelve months of placebo administration had no effect on bone mass, width, or density. Conclusion. Patients with XLH have an improvement in linear growth and a transient increase in serum phosphate attributable to a transient decrease in urinary phosphate excretion when treated with rhGH.