J. Paediafr. Child Health (1992) 28,432-435
Serum osteocalcin in normal and short Chinese children L. C. K. LOW and Y. L. LAU Department of Paediatrics, University of Hong Kong, Hong Kong
Abstract Serum osteocalcin was measured by radioimmunoassay in 200 normal children and adolescents, and seven growth hormone (GH) deficient and seven non-growth hormone deficient (NGHD) short children. There was a sex- and age-dependent change in the serum osteocalcin concentrations in normal children and adolescents with a pattern similar to the childhood height velocity curves. The serum osteocalcin concentration was in the low normal range in most patients with GH deficiency and NGHD short stature. GH therapy significantly increased the growth velocity in both groups of short children. GH treatment resulted in a significant rise in serum osteocalcin concentrations after 6 and 12 months in NGHD children but a more variable change was observed in GH-deficient children. Although osteocalcin levels may give some biochemical indication of growth, these measurements should be used together with auxological and other biochemical measurements to assess growth reliably.
Key words: growth hormone deficiency; osteocalcin; short stature.
Osteocalcin or bone GLA-protein is the most abundant noncollagenous protein of the bone matrix.’ Human osteocalcin has a molecular weight of 5.8 kDa and is composed of 49 amino acids with y-carboxyglutamic acid at positions 17, 21 and 24.’ Although the precise function of osteocalcin in bone mineral metabolism is still unknown, its serum value represents newly synthesized osteocalcin. which is primarily an index of bone f ~ r m a t i o nMeasurement .~ of serum osteocalcin has been shown to be useful in the study of metabolic bone diseases and in children with growth In the present study findings of serum osteocalcin concentrations as a marker of bone growth in normal children and in short Chinese children before and after recombinant growth hormone (GH)treatment are presented.
METHOD Two hundred normal healthy school children and adolescents (93 girls and 107 boys) between the ages of 2 and 20 years, seven prepubertal non-growth hormone deficient short children (NGHD) and seven prepubertal children with GH deficiency, were included in the study. Blood was drawn between 09.00 and 12.00 h from the normal children after having obtained written informed consent from their parents. The seven prepubertal short children were all below the third percentile in height, had a GH response of more than 20 miu/L to provocative stimuli, growth velocity less than 5.5 cm/year and a delay in bone age greater than 2 years (Table 1). The children with GH deficiency all had a G H response of less than 10 miu/L to two provocative
Correspondence L C K Low, Department of Paediatrics, Oueen Mary Hospital. Pokfulam, Hong Kong L C K Low BSC MB. ChB. FRCP. Reader Y L Lau, MD. MRCP. Lecturer Accepted for
publication 9 December 1991
stimuli (Table 1). The children with an organic cause for their GH deficiency received GH treatment 2-5 years after adequate treatment of the underlying disease. Three patients received thyroxine replacement, three patients were on DDAVP and only one patient was on hydrocortisone replacement (10 rng/m‘ per day). Blood samples were drawn from the short and GH deficient patients between 09.00 and 10.00 h before recombinant GH treatment and at 3, 6 and 12 months after treatment. The NGHD children received 0.1 unit/kg of GH subcutaneously per day whereas the GH deficient children received 0.07 unit/kg subcutaneously per day. Serum from the blood samples was stored at -70°C until analysis. Serum osteocalcin concentrations were measured by radioimmunoassay using the standard protocol of the Osteocalcin RIA kit (Incstar Corporation Stillwater, Minnesota, USA). The values were expressed as the mean and s.d. and the results were analysed by ANOVA followed by the Student’s t-test. As there is a variation in serum osteocalcin levels with age, the serum osteocalcin concentrations in the short children before GH treatment were expressed as the s.d. score for age.
RESULTS
The changes in the mean serum osteocalcin concentrations with age in normal male and female children and adolescents are shown in Fig. 1. The serum osteocalcin concentrations increased with age in both sexes, rising to a peak earlier in girls and then falling to adult levels by 14-16 years old in girls and after 16 years old in boys. With GH treatment, there was a significant increase in growth velocity from the pretreatment value of 4.6k0.32 cm/year to 8.37k0.87 cm/year after 1 year (P
Serum osteocalcin in normal and short Chinese children L. C. K. LOW and Y. L. LAU Department of Paediatrics, University of Hong Kong, Hong Kong
Abstract Serum osteocalcin was measured by radioimmunoassay in 200 normal children and adolescents, and seven growth hormone (GH) deficient and seven non-growth hormone deficient (NGHD) short children. There was a sex- and age-dependent change in the serum osteocalcin concentrations in normal children and adolescents with a pattern similar to the childhood height velocity curves. The serum osteocalcin concentration was in the low normal range in most patients with GH deficiency and NGHD short stature. GH therapy significantly increased the growth velocity in both groups of short children. GH treatment resulted in a significant rise in serum osteocalcin concentrations after 6 and 12 months in NGHD children but a more variable change was observed in GH-deficient children. Although osteocalcin levels may give some biochemical indication of growth, these measurements should be used together with auxological and other biochemical measurements to assess growth reliably.
Key words: growth hormone deficiency; osteocalcin; short stature.
Osteocalcin or bone GLA-protein is the most abundant noncollagenous protein of the bone matrix.’ Human osteocalcin has a molecular weight of 5.8 kDa and is composed of 49 amino acids with y-carboxyglutamic acid at positions 17, 21 and 24.’ Although the precise function of osteocalcin in bone mineral metabolism is still unknown, its serum value represents newly synthesized osteocalcin. which is primarily an index of bone f ~ r m a t i o nMeasurement .~ of serum osteocalcin has been shown to be useful in the study of metabolic bone diseases and in children with growth In the present study findings of serum osteocalcin concentrations as a marker of bone growth in normal children and in short Chinese children before and after recombinant growth hormone (GH)treatment are presented.
METHOD Two hundred normal healthy school children and adolescents (93 girls and 107 boys) between the ages of 2 and 20 years, seven prepubertal non-growth hormone deficient short children (NGHD) and seven prepubertal children with GH deficiency, were included in the study. Blood was drawn between 09.00 and 12.00 h from the normal children after having obtained written informed consent from their parents. The seven prepubertal short children were all below the third percentile in height, had a GH response of more than 20 miu/L to provocative stimuli, growth velocity less than 5.5 cm/year and a delay in bone age greater than 2 years (Table 1). The children with GH deficiency all had a G H response of less than 10 miu/L to two provocative
Correspondence L C K Low, Department of Paediatrics, Oueen Mary Hospital. Pokfulam, Hong Kong L C K Low BSC MB. ChB. FRCP. Reader Y L Lau, MD. MRCP. Lecturer Accepted for
publication 9 December 1991
stimuli (Table 1). The children with an organic cause for their GH deficiency received GH treatment 2-5 years after adequate treatment of the underlying disease. Three patients received thyroxine replacement, three patients were on DDAVP and only one patient was on hydrocortisone replacement (10 rng/m‘ per day). Blood samples were drawn from the short and GH deficient patients between 09.00 and 10.00 h before recombinant GH treatment and at 3, 6 and 12 months after treatment. The NGHD children received 0.1 unit/kg of GH subcutaneously per day whereas the GH deficient children received 0.07 unit/kg subcutaneously per day. Serum from the blood samples was stored at -70°C until analysis. Serum osteocalcin concentrations were measured by radioimmunoassay using the standard protocol of the Osteocalcin RIA kit (Incstar Corporation Stillwater, Minnesota, USA). The values were expressed as the mean and s.d. and the results were analysed by ANOVA followed by the Student’s t-test. As there is a variation in serum osteocalcin levels with age, the serum osteocalcin concentrations in the short children before GH treatment were expressed as the s.d. score for age.
RESULTS
The changes in the mean serum osteocalcin concentrations with age in normal male and female children and adolescents are shown in Fig. 1. The serum osteocalcin concentrations increased with age in both sexes, rising to a peak earlier in girls and then falling to adult levels by 14-16 years old in girls and after 16 years old in boys. With GH treatment, there was a significant increase in growth velocity from the pretreatment value of 4.6k0.32 cm/year to 8.37k0.87 cm/year after 1 year (P
