Effects of Growth Hormone Treatment on Body Proportions and Final Height Among Small Children With X-Linked Hypophosphatemic Rickets

Abstract

ABSTRACT. Background. X-linked hypophosphatemic rickets (XLH) is characterized by rickets, disproportionate short stature, and impaired renal phosphate reabsorption and vitamin D metabolism. Despite oral phosphate and vitamin D treatment, most children with XLH demonstrate reduced adult height.Objective. To determine the beneficial effects of recombinant human growth hormone (rhGH) therapy on body proportions and adult height among patients with XLH.Methods. Three initially prepubertal short children (age, 9.4 -12.9 years) with XLH were treated with rhGH for 3.1 to 6.3 years until adult height was attained.Results. rhGH treatment led to sustained increases in standardized height for all children. The median adult height was 0.9 SD (range: 0.5-1.3 SD) greater than that at the initiation of rhGH treatment and exceeded the predicted adult height by 6.2 cm (range: 5.3-9.8 cm). However, longitudinal growth of the trunk was stimulated more than leg growth. During rhGH treatment, the standardized sitting height increased by 1.6 SD (range: 1.1-2.7 SD), compared with baseline values. In contrast, the median subischial leg length did not change consistently (median change: 0.3 SD; range: ؊0.1 to 0.6 SD).Conclusion. The increase in final height after rhGH treatment is of potential benefit for children with XLH. However, the exaggeration of disproportionate truncal growth observed for our prepubertal patients is a potential negative effect of treatment and should be confirmed with additional studies. Pediatrics 2004;113:e593-e596. URL: http://www.pediatrics.org/cgi/content/full/113/ 6/e593; growth hormone treatment, hypophosphatemic rickets, growth failure, disproportionate growth, final height.ABBREVIATIONS. XLH, X-linked hypophosphatemic rickets; GH, growth hormone; rhGH, recombinant human growth hormone. X -linked hypophosphatemic rickets (XLH) is an inherited disorder of phosphate homeostasis characterized by disproportionate short stature, rickets and osteomalacia, hypophosphatemia, aberrant phosphate reabsorption, and disturbance of vitamin D metabolism. 1 XLH is caused by mutations in the PHEX gene, encoding a membrane-bound endopeptidase. PHEX is expressed in bones and teeth but not in kidney, and efforts are underway to elucidate how PHEX function relates to the mutant phenotype. 2

Growth in X-linked hypophosphatemic rickets

“…Further, rhGH in XLHR has been associated with disproportionate growth in favor of the trunk [17], viewed as a negative outcome [5], although most reports did not demonstrate such disproportionate growth [1,2,10,22,23]. Our experience with rhGH in short children with XLHR ( Fig.…”

“…Some authors reported a slight and sustained increase in serum phosphate level [4,5,10,17,18,31], while others observed that effect to be transient [23] or absent [3]. Thus, most authors did not change the prescription of phosphate salts.…”

“…Further, treatment with recombinant human growth hormone (rhGH) in short patients with XLHR is controversial, due to the lack of controlled clinical trials [7]. Results in small cohorts have demonstrated improvement in mean height and growth velocity Z-scores in XLHR patients treated with rhGH [7,17,18], and thus some short children might benefit from this therapy [3,5,10].…”

Growth hormone treatment in a child with X-linked hypophosphataemic rickets

“…[9][10][11][12] Growth hormone acts as a phosphate sparing agent and thus lower the dosage of phosphate required during treatment. This is more effective in improving biochemical defects, ensuring compliance and minimising adverse effects such as nephrocalcinosis.…”

Hypophosphatemic rickets and osteomalacia

“…The results have varied in terms of reestablishment of phosphorus homeostasis and the achievement of a better growth performance (62)(63)(64)(65). In two studies improvement in growth was noticed but with increased disproportion between upper and lower segments, predominating the trunk growth (66,67). Systematic review on the use of rhGH in patients with XHR does not show conclusive evidence in favor of rhGH changing the statural growth, mineral metabolism, mineral density nor body proportions (68).…”