Serum osteocalcin and urinary deoxypyridinoline: response prediction in children on recombinant human growth hormone replacement therapy

ABSTRACT

In children and adolescents, markers of bone and collagen metabolism reflect the dynamics of skeletal growth and development. Treatment with recombinant human growth hormone [rhGH] has a marked effect on bone formation and resorption. This bone remodeling is well reflected on specific markers that can be measured in blood and urine. The aim of this study was to assess the potential role of bone remodeling markers in the assessment of the response to rhGH in GHD children. The study included 35 children and adolescents, 20 of which had GHD [14 boys and 6 girls], with a mean age of 14.46 +/- 2.47 years and 15 controls [8 boys and 7 girls], 11.3 +/- 2.01 years old, Anthropometric measurements were performed, and blood and morning urine samples were collected for estimation of total serum calcium, inorganic phosphorus, total ALP, OC and urinary DPD. DPD values were corrected to urinary creatinine concentrations and expressed as deoxypyridinoline/creatinine [DPD/cr] ratio. Patients started rhGH therapy, laboratory assays were repeated after 3 months, and anthropometric measurements were repeated at 3-monthly intervals for one full year. Bone turnover markers [calcium, phosphate, ALP, OC, and urinary DPD] were measured before and after 3 months of onset of rhGH. The results showed that in all patients, rhGH evoked continuous improvements in height standard deviation scores [SDS], with no significant effect on weight SDS. Height velocity SDS [HVSDS] was high during the first 3 months of rhGH, decreased thereafter, supporting the waning of rhGH, Pre-treatment Level of the ALP and OC were lower in patients than controls. Differences in serum OC levels between patients and controls were high enough to discriminate between the two groups [p<0.0001]. Both increased substantially after rhGH, Basal and after 3 months value of ALP, OC and DPDlcr ratio was 106.95 +/- 32.76 and 144.75 +/- 38.20 IUIL; 6.80 +/- /- 3.74 and 31.78 +/- 26.12 nglml; 23.69 +/- 22.49 and 37.75 +/- 29.28; with p=0.008, p=0.0001 and p>0.05, respectively. There was a significant positive correlation between the both serum ALP basal and after 3 months and overall 1st year HVSDS [r=0.69, p=0.019, p=0.86, p=0.001, respectively]. There was a significant positive correlation between serum levels of OC and urinary DPDlcr ratio in both, patients before rhGH [r=0.538, p=0.014] and controls [r=0.654, p=0.008]. Basal values of DPD/cr were positively correlated with HVSDS after 3 months [r=0.48, p0.034] and after 3 months of rhGH DPD/cr were positively correlated with height SDS [r=0.46, p=0.04]