Serum levels of intact molecular osteocalcin in children with growth hormone (GH) deficiency during GH therapy: an early predictor of GH therapy

Abstract

Recently we developed a sandwich enzyme immunoassay (EIA) specific for intact molecular osteocalcin (I-OC), produced only by osteoblast cell and partially released into blood circulation, to establish a specific biochemical marker of bone formation. In order to confirm whether serum I-OC levels constitute a specific marker for bone formation and to assess the relationship between serum I-OC levels and growth response to growth hormone (GH) therapy, we measured the serum I-OC in serial serum samples using this EIA from 61 children with GH deficiency who showed significant bone growth during GH therapy. The serum I-OC levels in children with GH deficiency before GH therapy were slightly lower than those in normal children (Kanzaki S. et al., J. Clin Endocrinol Metab. 1992;75:1104-9), and had a wide distribution overlapped with the normal range. These levels were apparently increased during GH treatment; that is, in contrast to the levels of 22.9 +/- 1.5 ng/ml (mean +/- SE) before GH treatment, the levels after 1 and 2 months of GH treatment were 29.1 +/- 1.6 ng/ml and 32.5 +/- 1.8 ng/ml, respectively. However, they decreased slightly at 3 months and then they gradually rose to 37.5 +/- 2.8 ng/ml after 12 months, I-OC ratios, represented by the I-OC level at each month of GH therapy in relation to pretreatment level, correlated well with the growth response (growth velocity, growth velocity SD score and delta growth velocity SD score) after 12 months of GH treatment. Correlation coefficients of the growth velocity versus I-OC ratio at 1 and 6 months of GH treatment were 0.677 (p < 0.001, N = 58) and 0.752 (p < 0.001, N = 55), respectively. However, both IGF-I and ALP ratios represented in the same way as the I-OC ratio, correlated poorly as compared with the I-OC ratio. These results demonstrate that the change of serum I-OC levels indicates a direct and sensitive reflection of bone formation, because serum I-OC levels significantly increased with the growth response to GH therapy. The measurement of serum I-OC levels after 1 month of GH treatment may be a useful tool in predicting improved growth velocity during long-term GH therapy.