Effects of 12 months rhGH treatment on bone and collagen turnover in children with constitutional growth delay
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Published on: June 11, 2017
A Sartorio1, A Conti, S Ferrero
1Research Center for Growth Disorders (LSRE), Italian Institute for Auxology, IRCCS, Milan, Italy.
Insights
Children with constitutional growth delay (CGD) exhibit low bone turnover, indicated by reduced bone Gla protein (BGP), carboxyterminal cross-linked telopeptide of type I collagen (ICTP), and deoxypyridinoline (DPD) levels. Growth hormone treatment effectively increases these bone markers, suggesting improved bone remodeling.
Area of Science:
- Pediatric Endocrinology
- Bone Metabolism Research
- Biochemical Markers of Bone Health
Background:
- Constitutional growth delay (CGD) is a common cause of short stature in children.
- Bone metabolism markers, including osteoblast and resorption markers, may be altered in CGD.
- The role of growth hormone (GH) in bone development and remodeling is well-established.
Purpose of the Study:
- To investigate serum and urinary bone metabolism markers in prepubertal children with CGD.
- To evaluate the effect of recombinant human GH (rhGH) treatment on these bone markers.
- To explore potential underlying mechanisms of altered bone metabolism in CGD.
Main Methods:
- Measurement of serum bone Gla protein (BGP), ICTP, and urinary free deoxypyridinoline (DPD)/creatinine in 8 prepubertal children with CGD.
- Comparison of marker levels with age-matched healthy controls.
- Assessment of marker levels before and after 6-12 months of rhGH treatment.
Main Results:
- Children with CGD showed significantly lower serum BGP, ICTP, and urinary DPD/creatinine levels compared to controls.
- Serum PIIINP levels were similar between CGD patients and controls.
- rhGH treatment led to significant increases in BGP, DPD/creatinine, and PIIINP levels after 6 and 12 months.
- Serum ICTP levels increased significantly only after 12 months of rhGH treatment.
Conclusions:
- Children with CGD exhibit low bone turnover, evidenced by reduced BGP, ICTP, and DPD levels.
- rhGH treatment stimulates bone remodeling and collagen synthesis in children with CGD.
- A potential partial GH-IGF-I defect may contribute to the observed bone metabolism alterations in CGD.
Abstract:
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.
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