URINARY PYRIDINIUM COLLAGEN CROSS-LINKS PREDICT GROWTH-PERFORMANCE INCHILDREN WITH IDIOPATHIC SHORT STATURE AND WITH GROWTH-HORMONE (GH) DEFICIENCY TREATED WITH GH - SKELETAL METABOLISM DURING GH TREATMENT

GH is able to promote longitudinal growth in children with GH-deficien cy (GHD) and in some children with idiopathic short stature (ISS). The objectives of this study were to evaluate the predictive value of bon e and collagen markers on the growth response to GH therapy in childre n with ISS and with GHD, and to characterize the effects of GH treatme nt on bone and collagen turnover in children with ISS and with GHD. Tw enty prepubertal short, slowly growing, children treated with GH, 15 I U/m(2) per week, were studied; of them 13 (10 males) had ISS and 7 (5 males) had GHD. An overnight 12-h urinary collection and a fasting mor ning blood sample were obtained at baseline, 1, 3, 6, and 12 months of treatment. Urinary levels of collagen cross-links, pyr idinoline (Pyd ) and deoxypyridinoline (Dpd), and circulating levels of osteocalcin, intact PTH, calcitonin, procollagen type III aminoterminal propeptide (PIIINP), insulin-like growth factor-I, and alkaline phosphatase were determined. Urinary collection was also obtained from 127 healthy chil dren (51 males) aged 6-13 yr. In children with ISS, the changes in Dpd over 1 month of GH therapy were related to the changes in height velo city (HV) over 1 yr of therapy (r = 0.67; P < 0.05); the changes in Py d after 1 month of GH treatment were related to the changes in HV at 6 months of OH treatment (r = 0.57; P < 0.05). All the other markers ev aluated were not related to the HV changes in children with ISS. In ch ildren with GHD, the changes in Pyd and in Dpd after 1 month of GH tre atment were positively related to the changes in HV after 12 months of therapy (r = 0.82; P < 0.05, and r = 0.82; P < 0.05, respectively). T he changes in Pyd after 1 month were also related to the HV changes af ter 6 months of GH (r = 0.77; P < 0.05). Positive relationships betwee n the HV after 6 months of GH and the increases of PIIINP (r = 0.80; P < 0.05) and osteocalcin (r = 0.77; P < 0.05) after 3 months of GH the rapy were observed. All patients showed urinary Dpd and Pyd excretions in the normal range. In patients with ISS, Pyd (P < 0.05), Dpd (P < 0 .05), osteocalcin (P < 0.01), PIIINP (P < 0.01), and alkaline phosphat ase (P < 0.01) increased longitudinally during the GH treatment and th e increments reached a maximum after 3-6 months of therapy. Patients w ith GHD showed an increase of the same markers but the increases occur red earlier, after 1 month of GH therapy. The collagen cross-links, Py d and Dpd, could be helpful early markers in predicting the responsive ness to GH therapy in children with ISS and with GHD. GH treatment sti mulates bone and collagen metabolism.