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.

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.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 micrograms/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 micrograms/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 micrograms/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 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, there 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.