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Serum biochemical markers of bone turnover in healthy infants and children
M Tommasi1, L Bacciottini, A Benucci
1Department of Pathophysiology, University of Florence, Italy.
Insights
This study establishes reference values for key bone metabolism markers in children. These findings are crucial for diagnosing and monitoring metabolic bone diseases in pediatric populations.
Area of Science:
- Pediatric Endocrinology
- Biochemistry
- Bone Metabolism
Background:
- Accurate reference ranges for bone metabolism markers are essential for diagnosing and monitoring pediatric bone diseases.
- Previous studies may lack comprehensive data across a wide pediatric age range.
- Understanding age- and sex-specific variations in bone markers is critical for clinical interpretation.
Purpose of the Study:
- To establish age- and sex-specific reference values for serum osteocalcin (OC), bone alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP), parathyroid hormone (PTH), and 1,25 dihydroxyvitamin D [1,25(OH)2D] in normal children.
- To analyze the correlation of these markers with age and growth spurts.
- To provide a basis for the clinical application of these biochemical assays in pediatric metabolic bone disease management.
Main Methods:
- Cross-sectional study involving 241 healthy infants and children (1.9 months to 14 years).
- Measurement of serum OC, BAP, PICP, ICTP, PTH, and 1,25(OH)2D.
- Data normalization for children over 2 years using body surface area to account for biological variations.
- Statistical analysis to determine correlations with age and establish reference ranges (mean +/- 2SD).
Main Results:
- Serum osteocalcin (OC) showed increases during growth spurts, with peak values in puberty and significant positive correlations with age in both sexes (p < 0.00001 for males 2-14 yrs, p < 0.001 for females 2-12 yrs).
- Elevated bone alkaline phosphatase (BAP) was observed in the first two years of life, with a positive correlation with age in females older than 2 years (p < 0.01).
- Highest levels of PICP and ICTP were found in infants under one year, with PICP decreasing significantly by age 2; no significant age-correlated changes were observed for PICP and ICTP in children over 2 years.
Conclusions:
- Established reference values for OC, BAP, PICP, ICTP, PTH, and 1,25(OH)2D in normal children across different age groups.
- Demonstrated age- and sex-specific patterns for key bone metabolism markers, particularly during infancy and puberty.
- These reference values are vital for the accurate diagnosis and monitoring of metabolic bone diseases in pediatric patients.
Abstract:
Serum osteocalcin (OC), bone alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP), parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D [1,25(OH)2D] were measured in 241 normal infants and children (134 males and 107 females aged 1.9 months-14 years, 1.8 months-12 years, respectively). Regarding the analysis of data for children above 2 yrs, we chose data with the following normalization: data/body surface x standard body surface, to eliminate biological variations not exclusively related to chronological age. The increase in serum OC occurred at the expected age of growth spurts in both sexes: in the first year of life OC values (mean +/- SD) were 82.6 +/- 34.3 and 60.2 +/- 32.9 OC ng/ml in males and females, respectively; during puberty, peak values occurred at the age of 10-12 yrs in girls (76.6 +/- 25.8) and at the age of 12-14 yrs in boys (113 +/- 48.3). Furthermore, significant positive correlations with age were found for males from 2 to 14 yrs (p < 0.00001) and for females from 2 to 12 yrs (p < 0.001). Elevated levels of BAP occurred in the first year, 70.4 +/- 28.2 and 71.8 +/- 28.5, and in the second year, 69.4 +/- 26.7 and 67.4 +/- 33.8 ng/ml, for males and females, respectively. For children older than 2 yrs, a positive correlation with age (p < 0.01) was found for females only, with a peak value of 67.2 +/- 13.9 at the age of 10-12 yrs. For ages 2-14 yrs the reference values (mean +/- 2SD) were 15.5 - 90.3 and 17.2 - 95.2 ng/ml for males and females, respectively. The highest PICP levels (1354 +/- 680 ng/ml in males and 1041 +/- 766 in females) were observed in infants less than 1 year of age, decreasing by about 60% at the age of 2. There was no significant change in serum PICP for children older than 2 yrs with values covering a range (mean +/- 2SD) of 52 - 544 and 18 - 546 ng/ml in males and females, respectively. Similarly, the highest ICTP values were seen in infants younger than 1 year (29.7 +/- 11.7 and 29.5 +/- 20.1 ng/ml in males and females, respectively). In the ages from 2 to 14 yrs there did not seem to be any systematic age-correlated changes, with values covering a range (mean +/- 2SD) of 6.06 - 24.5 in boys and 6.84 - 22.9 ng/ml in girls. Serum PTH concentrations (mean +/- SD) in infancy were 27.2 +/- 19.3 pg/ml for males and 25.8 +/- 10.8 for females. Normal ranges (mean +/- 2SD) in the older group were 5.77 - 53.1 and 6.71 - 57.3 pg/ml for males and females, respectively. Serum 1,25(OH)2D presented values of 47.3 +/- 28.1 and 38.7 +/- 18.2 pg/ml under 2 yrs for males and females, respectively. The ranges (mean +/- 2SD) in children above 2 yrs were 9.5 - 101 pg/ml in boys and 10.9 - 88.4 in girls. The results of this study contribute to the establishment of reference values in normal children for these biochemical assays; these reference values are needed when the above biological markers will be applied in the monitoring of metabolic bone diseases.