SERUM PROPEPTIDE AND INTACT MOLECULAR OSTEOCALCIN IN NORMAL-CHILDREN AND CHILDREN WITH GROWTH-HORMONE (GH) DEFICIENCY - A POTENTIAL MARKER OF BONE-GROWTH AND RESPONSE TO GH THERAPY

To establish a sensitive marker for bone formation we have developed a sandwich enzyme-linked immunosorbent assay for intact osteocalcin (OC) and its propeptide. Serum levels of these peptides were studied in 185 normal children, aged 4-15 yr, and in 23 GH-deficient children treated with GH. The serum levels of the propeptide in normal prepubescent children were 1.43 +/- 0.23 (mean +/- SE) mug/L in boys and 1.53 +/- 0.23 mug/L in girls. The peak value occurred at the age of 13 yr in boys (2.91 +/- 0.42 mug/L) and 11 yr in girls (2.34 +/- 0.34 mug/L). The serum intact OC levels in prepubescent boys and girls were 18.8 +/- 2.1 and 20.7 +/- 2.1 mug/L, respectively, and these levels increased to 41.0 +/- 3.7 mug/L in boys aged 13 yr and to 27.0 +/- 2.5 mug/L in girls aged 11 yr. In the GH-deficient patients, a 2.3-fold increase in the propeptide level and a 1.7-fold increase in the intact OC level was observed after 1 month of GH therapy. Serum propeptide and intact OC levels after 1 month of GH therapy correlated with the growth response after 12 months of GH therapy (r = 0.660 and P < 0.01, for propeptide; r = 0.537 and P < 0.01 for intact OC). These results show that since both propeptide and intact OC in serum were increased when the growth rate was elevated, these peptides are sensitive markers of bone formation. Serum levels of these peptides, particularly propeptide, after 1 month of GH therapy might be a helpful predictor of the growth response to long term GH therapy.