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The growth hormone and somatomedin axis in short children with osteogenesis imperfecta
J C Marini1, S Bordenick, G Heavner
1Human Genetics Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Insights
Children with osteogenesis imperfecta (OI) show growth deficiency. Studies revealed abnormalities in the growth hormone-somatomedin axis, with some OI children exhibiting blunted responses to growth hormone stimulation. Growth hormone or clonidine treatment may improve growth rates in these children.
Area of Science:
- Pediatric Endocrinology
- Skeletal Dysplasias
- Growth Hormone Axis
Background:
- Growth deficiency is common in osteogenesis imperfecta (OI), affecting various disease severity types.
- The role of the growth hormone (GH) and somatomedin axis in OI-related growth failure requires further elucidation.
- Previous studies have not comprehensively assessed GH secretion and responsiveness in prepubertal children with OI.
Purpose of the Study:
- To investigate the status of growth-related hormones and GH responsiveness in short prepubertal children with OI.
- To evaluate the potential of GH and clonidine in augmenting growth rates in children with OI.
- To identify potential correlations between GH axis abnormalities and growth response to treatment.
Main Methods:
- Assessed 22 prepubertal children with OI (types I, III, and IV) using GRH stimulation, provocative GH tests, 24-h GH secretion monitoring, and somatomedin-C generation tests.
- Administered exogenous GH or clonidine to six OI children with below-average GH secretion for at least six months.
- Measured growth rate increases and analyzed baseline study correlations with treatment response.
Main Results:
- No children met standard criteria for GH deficiency; however, nine OI children showed decreased GRH responsiveness.
- Mean 24-h GH and peak GH responses to provocative agents were within normal ranges for the OI group.
- A blunted somatomedin-C response to GH was observed in 13 of 22 OI children, suggesting GH resistance.
- Treatment with GH or clonidine resulted in significant growth rate increases (≥4.7 cm/yr) in some participants.
- Growth response to treatment could not be predicted from baseline endocrine evaluations.
Conclusions:
- Abnormalities within the GH-somatomedin axis are present in some children with OI, independent of standard GH deficiency criteria.
- GH resistance may contribute to growth deficiency in certain OI patients.
- Exogenous GH and clonidine show potential for enhancing growth rates in OI children, though long-term effects on final stature remain undetermined.
Abstract:
Growth deficiency is a cardinal feature of severe osteogenesis imperfecta (OI) and a frequent feature of mild to moderate forms of this disease. We have investigated the status of hormones related to growth in 22 short prepubertal children, 13 males and 9 females, with various types of OI. Ten children had Sillence type III OI, 10 had type IV, and 2 had type I. Evaluation included GRH stimulation, three standard GH provocative tests (arginine-insulin tolerance test, L-dopa), 24-h sampling for measurement of unstimulated GH secretion and a somatomedin-C generation test. None of these children had GH deficiency by standard criteria. We found that 9 OI children had decreased responsiveness to GRH, similar to the GRH response of GH-deficient children. Overall, however, mean 24-h GH values and mean peak GH response to provocative agents of OI children were within the normal range. In the somatomedin generation test, the OI children as a group showed a blunted response, with 13 of 22 having less than a 2-fold stimulation of somatomedin-C by GH. This suggested resistance of the liver and other somatomedin-C secreting tissues to GH. The group with blunted insulin-like growth factor-I response did not correlate significantly with the group with decreased GRH response. To investigate the responsiveness of OI bone to growth stimulation, six OI children with less than average integrated GH secretion were enrolled in a pilot study in which one child received exogenous GH and six received clonidine for at least 6 months. The child treated with exogenous GH and three of six treated with clonidine experienced at least a 4.7 cm/yr increase over their pretreatment growth rates. Growth response could not be predicted from baseline studies. We conclude that abnormalities of the GH-somatomedin axis exist in some children with OI. Administration of GH or clonidine may augment growth rates in OI children; however, the effect of these agents on final stature is unknown.