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Growth Hormone Treatment in Children with Rheumatic Disease, Corticosteroid Induced Growth Retardation, and Osteopenia« Back to Volume 22, Issue 2, June 2006 - Table of Contents It is well known that children who receive chronic steroids and/or methotrexate are at risk for linear growth failure. Whether or not exogenous human growth hormone (hGH) can reverse these effects remains unknown. There are very few trials of growth hormone therapy in children receiving corticosteroids that are controlled and address both growth retardation and bone mineral density (BMD). The current study addresses both and uses a randomized controlled group. Seventeen pre-pubertal children with rheumatic disease including juvenile idiopathic arthritis (JIA), systemic lupus erythmatosus (SLE), mixed connective tissue disease (MCTD), and dermatomyositis were enrolled. Patients were randomized to a group receiving treatment with hGH or a control group receiving no treatment. The dose of hGH administered was 4 IU/m2/day (~0.045 mg/kg/week) for 2 years. Patients were stratified for age and height standard deviation scores (SDS). Height was measured at 3 month intervals and height, target height, and body mass index (BMI) were expressed as SDS. Bone age was calculated every 6 months and BMD studies of the lumbar spine and total body composition were measured every 6 months using DEXA. Body composition and BMD parameters were corrected to bone age. Results were compared with age- and sex-matched references. Prior to the start of the study, all children underwent GH stimulation testing with arginine. In addition PTH, 1,25 dihydroxyvitamin D, 25 hydroxyvitamin D, carboxy terminal telopeptide of type I collagen (ICTP), procollagen type I C-terminal propeptide (PICP), calcium, alkaline phosphatase, inorganic phosphate, creatinine, IGF-I, and IGFBP-3 were measured every 6 months. An oral glucose tolerance test was performed at the start and the end of the study. Ten children were randomized to receive hGH and 7 to be in the control group. A total 16 patients completed the study; one child in the control group discontinued because of bone marrow transplantation. The 2 groups were comparable at baseline with regard to all parameters. Three of the children had decreased GH secretion to the stimulation test. A significant mean increase in height SDS (0.42 ± 0.16 SDS; p=0.03) was seen in the growth hormone treated group and a non-significant decrease in the controls (—0.18 ± 0.11 SD) resulting in a difference of 0.6 ± 0.19 SDS between the 2 groups (p=0.02). The ratio of change in bone age to change in chronologic age was not different in either group. Lumbar spine BMD in the hGH treated group increased by 0.52 ± 0.22 SDS during the 2 years. This significance was no longer seen after correction for bone size. Bone mineral density for total body did not increase significantly and the changes in bone mineral density between the 2 groups were not significantly different. Lean body mass increased significantly in the hGH treated group. Neither the decrease in fat nor the change in BMI SDS was significantly different between the groups. There was no difference in methotrexate or prednisone dose between the 2 groups throughout the study and differences in the other biochemical markers of growth and metabolism were not different. There was a significant negative correlation (r = —0.61; p=0.012) between the dose of prednisone and the change in baseline height SDS after 2 years in the combined groups, but not between the groups. Nine children had impaired glucose tolerance at the start of the study while only 3 had impaired glucose tolerance after 2 years. The authors pointed out that this was the first trial with a control group to evaluate the effect of hGH on both height and BMD and body composition. They discussed previous studies in similar children that have shown more dramatic increases in height SDS, but state that those have included pubertal as well as prepubertal children or failed to include a control group. Grote and colleagues concluded that hGH does have a significant effect on growth irrespective of the disease activity or the dose of steroids and methotrexate used, and that perhaps a longer duration of treatment may be necessary to evaluate the effect on BMD. Editor’s CommentThis is a very interesting and potentially important study. The authors are to be congratulated on including a control group. Pediatric endocrinologists are frequently faced with short children who have been receiving chronic corticosteroids for years. At the current time there is no effective treatment for their growth failure nor for the observed osteopenia. Thus the results of this study are promising. It is hoped that similar studies will be undertaken in other large centers and that perhaps a higher dose of hGH might be safely considered since there was no ratio change in bone age to chronological age nor any increase in glucose intolerance at the hGH dose used in this study. William L. Clarke, MD
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
