These data show that children with CD treated with GH sustain increased height velocity and improved bone mineral density. In contrast, Calenda et al suggested that treatment with GH for 1 year (0.05 mg/kg/d) did not improve growth or nutritional status compared with placebo in CD.13
The investigators suggested that this lack of effect may be due to an insufficient dose of GH and that responses were only seen in patients receiving concomitant nutritional support, or in patients with well-controlled disease. Our study was not placebo-controlled, but comparison with a retrospective group of patients matched for height, sex, and age revealed a significant response in growth rate despite varying disease activity (PCDAI), a slightly lower but standard dose of GH, and without specific nutritional support. As in other studies, corticosteroid therapy did not appear to impact GH treatment, although the number of patients in our study is too small to make any conclusion about this observation.12,16
Nevertheless, none of our patients required increased use of corticosteroids, and the one patient (#6) taking prednisone was weaned during the course of GH treatment.
A total of 10 other pediatric IBD patients in uncontrolled GH treatment trials have been reported, in two published (3 patients each) and one abstract (4 patients) reports.10,14,15
Results vary, with one study showing no growth effect and two showing increased height velocity. None had reported on bone density studies in the course of therapy.
An equally important finding was the enhanced bone density observed in our patients. Bone mineral content is recognized as a significant issue in children with chronic disease. Calcium and vitamin D supplementation has not made any significant impact in this problem, and various protocols are underway to determine whether bisphosphonates will improve the bone mineral content of patients with CD.19, 21–25
The observation that GH helps improve bone mineral density suggests GH may be a viable alternative to these other therapies.
Despite persistent growth, our group of patients did not appear to achieve any consistent clinical improvement in their CD activity. Further study is necessary to determine the role of GH as a primary treatment strategy or as an adjunct for growing children and adolescents undergoing treatment with other modalities.
Ideally, advancement in bone age should not exceed the change in chronological age. Although the mean increase in bone age was less than 1 year, 5 of 9 subjects showed an increase in bone age greater than 1 year. Rapid advancement of bone age could potentially lead to compromised adult final height. Due to the heterogeneity of the chronological ages and pubertal stages of the patients in our study, our data cannot be used to determine the significance of the changes in bone age. Thus, well-controlled, prospective, longitudinal trials are required prior to recommending widespread use of GH to treat growth impairment in pediatric patients with CD.
This report has several limitations. Although we were able to utilize a large and robust database to find three matched comparisons for each of the eight subjects in the final analysis, the comparison group is retrospective. The extent and location of disease may influence the response to treatment (i.e. colitis compared with more diffuse or small intestinal involvement). The number of subjects enrolled is too small to control for concomitant medications, including corticosteroids, and nutritional and other supplements. A recent report documents sustained growth among patients with CD treated with infliximab alone, although a role for GH to aid those patients who are growth delayed needs to be systematically investigated in this group of patients.26
Comparison patients were matched for age and sex but not for pubertal stage. The optimal dose and dosing regimen for GH may be different than that employed in this protocol. Additionally, the effects of nutritional factors (e.g., amount of calcium and vitamin D) and activity levels on growth and bone mineralization were not evaluated and need to be considered in future studies.
Despite these limitations, our report suggests that GH can improve height growth in children and adolescents with CD. Furthermore, GH appears to improve bone mineralization and body composition in these patients. Controlled and systematic investigations are warranted to determine the efficacy of GH in treating growth delay as a complication of CD.