Background: GH promotes longitudinal growth and bone modeling/remodeling. The bone formation markers intact amino-terminal propeptide of type 1 procollagen (PINP), bone-specific alkaline phosphatase (BALP), and osteocalcin reflect different stages in bone formation, i.e. proliferation with collagen synthesis, matrix maturation, and mineralization.
Objective: The purpose was to study the time course of different bone formation markers during GH treatment in prepubertal children with a broad range of GH secretion, and to study the bone markers relation to the first year growth response during GH treatment.
Methods: The study group, out of clinical trials TRN 89-071, 88-080 and 88-171, comprised 115 short prepubertal children (boys=99) mean±S.D., 9.38±2.16 years, on GH treatment (33±0.06 μg/kg per day) for 1 year. Samples were taken at baseline, after 1 and 2 weeks, 1 and 3 months, and at 1 year following GH treatment. PINP, BALP, and osteocalcin were measured using the automated IDS-iSYS immunoassay system.
Results: PINP, BALP, and osteocalcin, increased significantly during GH treatment (Fig). PINP increased after 1 week (P=0.00082), whereas BALP and osteocalcin after 1 month (P<0.0001 and P=0.0032 respectively). PINP levels at 1 and 3 months correlated positively, whereas the osteocalcin levels at 1 week and the percentage change after 1 month correlated negatively with the first year growth response. Using multiple regression analyses, the variance of first year GH growth response was explained to 16% using bone markers and auxological variables, to 30% after 2 weeks and to 26% after 3 months. Adding IGF1SDS and IGFBP3SDS, only IGFBP3SDS improved the explained variance at start to 40% and at 3 months to 47%.
Conclusion: The demonstrated short-term increase of the bone formation markers PINP, BALP, and osteocalcin showed different time patterns, reflecting different stages of bone formation, and correlated with the first year increase of growth response during GH treatment.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology