Effects of 12 months rhGH treatment on bone and collagen turnover in children with constitutional growth delay

Serum bone Gla protein (BGP), marker of osteoblast function, serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and urinary free deoxypyridinoline (DPD), markers of bone resorption, and the aminoterminal propeptide of type III procollagen (PIIINP), marker of type III collagen turnover, were determined in eight prepubertal children (8 males, age range 7-9.6 yr, Tanner stage I) with constitutional growth delay (CGD), before and after 6-12 months of treatment with rhGH (Saizen, Serono, 0.6 IU/kg/week, s.c.). Serum BGP (mean+/-SD: 15.4+/-1.7 ng/ml), ICTP (9.4+/-1.6 ng/ml) and urinary DPD/creatinine (11.3+/-1.7 nmol/mmol) levels were significantly lower (p<0.02, p<0.0001 and p<0.02, respectively) in children with CGD than in healthy age-matched controls (BGP: 18.9+/-3.6 ng/ml, ICTP: 14.3+/-2.6 ng/ml, DPD: 20.7+/-10.0 nmol/mmol), while PIIINP levels of patients were similar to those recorded in controls (6.3+/-0.7 vs 6.7+/-2.3 ng/ml, respectively). Serum BGP, urinary free DPD/creatinine and PIIINP levels significantly increased after 6 (BGP: 20.9+/-2.1 ng/ml, p<0.0001; DPD/creatinine: 16.3+/-3.6 nmol/mmol, p<0.001; PIIINP: 8.1+/-1.6 ng/ml, p<0.005) and 12 months (BGP: 19.2+/-2.0 ng/ml, p<0.0001; DPD/creatinine: 19.7+/-5.1 nmol/mmol, p<0.001; PIIINP: 8.8+/-1.9 ng/ml, p<0.002) of GH treatment. Serum ICTP levels did not significantly change after 6 months (10.6+/-2.1 ng/ml), while a significant increase (p<0.002) was evident after 12 months of therapy (13.6+/-1.3 ng/ml). Our study shows that BGP, ICTP and DPD/creatinine levels are significantly reduced in children with CGD, thus indicating the presence of low bone turnover in this form of short stature. Since GH treatment is able to reactivate bone remodeling and increase collagen synthesis, it is tempting to speculate that a partial GH-IGF-I defect (i.e. locally at bone level) might be one of the factors involved in determining the biochemical alterations of bone metabolism found in this clinical condition.