Collagen metabolites in the prediction of response to GH therapy in short children
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Published on: July 9, 2021
P Tapanainen1, M Knip, L Risteli
1Department of Pediatrics, University of Oulu, Finland.
Insights
Serum collagen metabolites, C-terminal propeptide of type I procollagen (PICP) and N-terminal propeptide of type III procollagen (PIIINP), can predict growth hormone (GH) treatment response in short children. Higher PICP and PIIINP levels correlate with better long-term height increases.
Area of Science:
- Biochemistry
- Pediatric Endocrinology
- Metabolic Research
Background:
- Growth hormone (GH) therapy is crucial for treating short stature.
- Predicting treatment response is essential for optimizing therapeutic outcomes.
- Collagen metabolites offer potential biomarkers for assessing bone growth and GH efficacy.
Purpose of the Study:
- To investigate the predictive role of serum collagen metabolites, specifically PICP and PIIINP, in response to GH treatment.
- To determine the correlation between baseline and early-stage metabolite levels and long-term height velocity.
- To assess the impact of GH therapy on circulating PICP and PIIINP concentrations.
Main Methods:
- Serum PICP and PIIINP levels were measured using radioimmunoassay (RIA) in 35 short children before and at various time points during GH therapy.
- Children included those with GH deficiency (GHD) and undefined short stature (USS).
- Height SDS and relative height increase (RHI) over 6 and 12 months were used as response measures.
Main Results:
- GH therapy significantly increased serum PICP and PIIINP levels from 5 days onwards, with sustained increases up to 3 months.
- PICP concentrations at 3 months showed a strong correlation with 6-month RHI in the whole group and GHD group.
- PIIINP concentrations at 3 months demonstrated the strongest correlation with 1-year RHI in the whole group and USS group.
Conclusions:
- GH therapy unequivocally elevates circulating PICP and PIIINP concentrations.
- Serum PICP and PIIINP levels serve as valuable predictors of long-term response to GH therapy in short children.
- These collagen metabolites can aid in personalized treatment strategies for pediatric growth disorders.
Abstract:
To evaluate the role of collagen metabolites in the prediction of the response to GH treatment we measured the serum concentrations of the C-terminal propeptide of type I procollagen (PICP) and the N-terminal propeptide of type III procollagen (PIIINP) with specific RIAs in 35 short children (16 boys) before and after 5 days, 5 weeks and 3 months of GH therapy. The mean age of the children was 10.3 years (range 1.9-16.4 years) and the bone age ranged from 1.2 to 12.5 years (mean 7.6 years). The initial mean relative height (RH) was -3.6 SDS (range -6.6 to -2.4 S.D.). Nineteen children were found to have GH deficiency (GHD; peak GH responses in two pharmacological tests < 10 micrograms/l), while the remaining 16 were considered to have undefined short stature (USS). The children were treated with recombinant human GH (0.1 U/kg given subcutaneously at bedtime 6-7 times/week). The increases in RHI over the first 6 and 12 months of therapy were used as response measures. There was already a significant increase (P < 0.001) in both the serum PICP and PIIINP levels at 5 days, and the concentrations continued to rise up to 3 months, PICP levels rising less than the PIIINP levels. In the whole group the RHI over 6 months correlated most strongly with the absolute PICP concentrations at 3 months (rS = 0.59; P < 0.05), while the absolute PIIINP concentrations at 3 months showed the strongest relation to the one year RHI (rS = 0.69; P < 0.001). In the GHD group the 6 month RHI was most strongly related to the absolute PICP concentration at 3 months (rS = 0.59; P < 0.05). In the USS group the absolute PICP concentrations at 3 months correlated most strongly with the one year RHI (rS = 0.82; P < 0.01). Significant correlations were also observed between the absolute PIIINP levels at 3 months and the 6 month RHI (rS = 0.60; P < 0.05) and 12 month RHI (rS = 0.76; P < 0.01) in this group. These results show that GH therapy results in an unequivocal increase in circulating concentrations of PICP and PIIINP. The serum PICP and PIIINP concentrations may be of value in the prediction of the long-term response to GH therapy.
