Recombinant Human Growth Hormone in X-linked Hypophosphatemia Is Questioned

A ribbons model of Human Growth Hormone, also known as Somatotropin, with a translucent surface model.
X-linked hypophosphatemia treatments vary, and some studies suggest combining human growth hormone with conventional therapies may help. This study investigated if adding recombinant human growth hormone therapy increased good outcomes.

A systematic review failed to find sufficient evidence to support giving recombinant human growth hormone (rhGH) therapy to children with X-linked hypophosphatemia (XLH). These findings were published in the Cochrane Database of Systematic Reviews.

Researchers from the University of Nottingham and University of Liverpool in the United Kingdom searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and other medical databases from January 2011- 2021 for studies of rhGH therapy used in children with XLH.

Two studies, published in 1997 and 2011, met the researchers’ inclusion criteria and comprised a total patient population of 20 children. The 1997 study was a randomized, double-blind, cross-over study of 5 children (aged mean 5.6±1.4 years and 40% were boys) with XLH and lasted 24 months. The 2011 study was a randomized, controlled, parallel group study of 15 children (aged mean 7.3±1.7 years and 47% were boys) with XLH and lasted 3 years.

The rhGH doses in the 1997 study were 0.08 mg/kg/day and 0.4 mg/kg/week in the 2011 study.

The 1997 study found that height standard deviation score (SDS) score increased from -2.66±0.21 at baseline to -1.46±0.28 after 3 and 12 months, respectively, with rhGH therapy. Scores increased from -2.27±0.30 compared with 2.22±0.16 after 12 months of placebo. Over the course of the year, growth velocity was 4.04±1.50 among the rhGH recipients and -1.90±0.40 among the control group participants. The 2011 study reported an increase in height SDS of +1.1 from baseline in the rhGH-treated group, showing no significant change in the control group.

The studies also assessed height, serum phosphate, serum alkaline phosphatase activity, serum insulin-like growth factor, renal function, bone mineral density, sitting height, arm length, and leg length. Significant differences compared with placebo were observed for serum phosphate at 3 years (mean difference [MD], 0.18 mmol/L; 95% CI, 0.08-0.28); serum alkaline phosphatase acidity at 1 year (MD, 91.00 IU/L; 25.21-156.79); and serum insulin-like growth factor at 6 months (MD, 1.38 SDS; 95% CI, 0.19-2.57), 1 year (MD, 1.95 SDS, 95% CI, 0.97-2.93 SDS), 2 years (MD, 1.95 SDS; 95% CI, 0.79-3.11), and 3 years (MD, 2.70 SDS; 95% CI, 1.29-4.11).

This analysis was limited by the small number of participants and the authors’ acknowledgment that the certainty of the evidence in the 2 studies were determined to be “low or very low.”

“We were unable to find any conclusive evidence to show whether the use of rhGH therapy in children with XLH is associated with changes in longitudinal growth, mineral metabolism, endocrine, renal function, bone mineral density, body proportions, and also with any adverse effects,” the study authors concluded. “We need more multicenter, adequately-powered and well-designed randomized controlled studies to address these important issues.”

Disclosure: This research was supported in part by the Cochrane Cystic Fibrosis and Genetic Disorders Group. Please see the original reference for a full list of disclosures.


Smith_S, Remmington_T. Recombinant growth hormone therapy for X-linked hypophosphatemia in children. Cochrane Database Syst Rev. Published online October 7th, 2021. doi:10.1002/14651858.CD004447.pub3