Comparative Study of the Changes in Insulin-Like Growth Factor-I, Procollagen-III N-Terminal Extension Peptide, Bone Gla-Protein, and Bone Mineral Content in Children with Turner's Syndrome Treated with Recombinant Growth Hormone*

Abstract

Six girls (7-13 yr old) with Turner''s syndrome and short stature were treated for 1 yr with recombinant human GH (0.15 U/kg .cntdot. day, sc) and had sequential determinations of serum insulin-like growth factor-I (IGF-I), osteocalcin, and procollagen-III. Bone mineral content and density of the spine and radius were measured before treatment and at 90 and 360 days. Two girls received small doses of ethinyl estradiol (0.025 .mu.g/kg) in addition to GH. Height velocity increased by 144% after 3 months of treatment. IGF-I was normal (0.75 .+-. 0.20 kU/L) before treatment and increased by 90% on day 1 and by 290% on day 360. Procollagen-III was low before treatment; it peaked at 53.0 .+-. 14.7 .mu.g/L (260% above baseline) on day 30, then decreased to the normal range. Serum osteocalcin increased more slowly to reach a plateau on day 90 of 23.7 .+-. 1.2 .mu.g/L (46% above baseline). Before treatment, bone mineral content of the spine was 25% lower than that of children matched for bone age. Bone mineral contents of the the peripheral and axial skeleton were increased by 10% and 17%, respectively, after 1 yr of treatment, an increase commensurate with that of bone age in the four patients who did not receive estrogen. On day 90, however, although radius mineral density was already increased by 3%, the mineral density of the lumbar spine was significantly decreased by 4%. We conclude that treatment with GH increases IGF-I, collagen turnover, osteoblastic function, and height velocity in Turner''s syndrome. However, the is no catch-up of bone mineral content after 1 yr of treatment, and an early effect of GH is to decrease spine mineral density.