Craniofacial growth in growth hormone-deficient rats after growth hormone supplementation

Growth hormone (GH) supplementation is an established therapy to increase stature in GH-deficient or short-for-age children, but comparatively little is known of its effects on the craniofacial skeleton.

Using a mutant strain of Lewis rats (dw/dw) in which GH levels were 6% to 10% of normal, but other trophic hormones were unaffected, we investigated the differential susceptibility of craniofacial measures to GH supplementation, characterized their potential for partial or complete catch-up growth, and compared their growth changes with those in long bones. At 24 days of age and for 3 subsequent weeks, radiographs of the lateral head, upper limb, and lower limb were obtained from 3 groups of growing rats (n = 8-9 in each group): dwarf (experimental) with GH injection, dwarf (sham) with vehicle injection, and wild type (control) with vehicle injection. The x-ray images were scanned, standardized points digitized, and linear distances measured. Absolute growth curves were generated for each group by using multilevel modeling procedures and iterative generalized least-squares curve fitting.

For every measure, growth differences were evident between the experimental and the sham groups, but the treatment effect varied inversely with relative maturity of the measure. Although all craniofacial measures showed some catch-up growth, only 31% of craniofacial measures had complete catch-up compared with all limb measures. The percentage of catch-up varied inversely with relative maturity of the measure. Our results suggest that the effects of GH supplementation vary considerably, so that measures with the lowest relative maturity (greatest baseline potential) show the greatest treatment effect and catch-up, whereas more mature measures show less growth response to GH replacement.

These results suggest that, depending on the timing of GH supplementation, there is potential for change in proportions or shape of the craniofacial complex.