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Bone alkaline phosphatase isoenzyme and carboxy-terminal propeptide of type-I procollagen in healthy Chinese girls and boys.

The bones of children grow at a faster rate during the first few years of childhood and puberty. Recently, advances in assays for biochemical markers of bone formation have provided noninvasive means to study bone growth and metabolism in children (1-14). Because of the variations in the rate of bone growth in different age groups and possible ethnic differences, age-specific reference ranges for bone formation markers must be established in a particular pediatric population.

Conventional bone formation markers such as osteocalcin (1) have been shown to correlate with serum concentrations of insulin-like growth factor-I and testosterone in children and adolescents. In pathological conditions, osteocalcin (2-4) is lower in growth hormone-deficient children and increases with replacement therapy. Osteocalcin, however, is labile and possesses problems in sample processing and storage (15). Recently, two other bone formation markers in serum, bone alkaline phosphatase isoenzyme (BAP) (16) and the carboxy-terminal propeptide of type-I procollagen (PICP) (17), were shown to be sensitive and specific markers of bone formation. BAP has been shown to be lower in children with growth hormone deficiency (5). When these children were treated with growth hormone, BAP showed a substantial increase (5). Both PICP and BAP were also used to monitor the response to growth-promoting agents in short apparently healthy children (6). On the other hand, in children with precocious puberty treated with gonadotropin-releasing hormone agonists, PICP decreased, suggesting a favorable retarding effect on skeletal growth (7). PICP was reported to be lower in children treated with glucocorticoid for asthma (8) or inflammatory bowel disease (9). The serum concentration correlated with the growth velocities in children and adolescents having inflammatory bowel disease with or without corticosteroid therapy (9). These two markers are chemically much more stable than osteocalcin; therefore, their measured concentrations should be less sensitive to processing and storage conditions. The aim of this study was to investigate the age-related changes in serum concentrations of BAP and PICP in healthy Taiwanese girls and boys <18 years of age.

We collected fasting morning serum samples from 110 girls and 120 boys from the urban Taipei area in 1997. All of them gave blood for the purpose of hepatitis screening and were found to have normal liver, kidney, and thyroid function. None of them was receiving any medication or had diseases that could affect bone metabolism. After venipuncture, serum samples were aliquoted and stored at -70[degrees]C until analysis. The procedures were in accordance with the revised Helsinki declaration in 1983. Serum BAP was measured with immunocatalytic kits (Metra Biosystem). The interassay imprecision (CV) was 8% and the interassay CV was 11% at 25 U/L in our laboratory. Serum PICP was measured with radioimmunoassay kits (Orion Diagnostic). The interassay CV was 7% and the interassay CV was 9% at 285 [micro]g/L. All of the samples showed concentrations well above the detection limits of these assays.

The values of BAP and PICP of the different age groups are shown in Table 1. Both BAP and PICP showed sigmoid regression curves with increasing age (Fig. 1). Both markers showed mean values approximately fourfold higher than the upper reference limit for adults in the first 3 years of life in both genders. The PICP then was substantially lower after 3 years of age in both girls and boys until puberty. Prepubertal PICP was one- to twofold higher than the upper reference limit for adults. During puberty, PICP increased again to a mean of 250 [micro]g/L, approximately twofold higher than the upper limit of adults in each gender. After puberty, both girls (ages, 13-18 years) and boys (ages, 15-18 years) showed mean PICP concentrations at approximately the upper reference limit for adults. In contrast to the substantial decrease in PICP, BAP showed sustained high values in prepubertal girls and boys, a phenomenon similar to that of osteocalcin (13, 14). However, unlike the lack of higher osteocalcin in the first few years of life (13, 14), BAP was higher during the first 3 years of life than the prepubertal values during the next 5 years. After puberty, BAP showed a gradual decrease in girls and boys. In general, girls showed decreased postpubertal values of both markers 2 years earlier than boys, reflecting the earlier completion of puberty in girls. The correlation between PICP and BAP was significant in boys (n = 120; r = 0.261; P = 0.004), in girls (n = 110; r = 0.426; P = 0.0001), and in boys and girls together (n = 230; x = 0.306; P = 0.0001).


Although various bone markers have been used extensively in physiologic and clinical research in adults, much less information is available in children. Metabolic bone disorders in childhood are caused mainly by defects in osteoblastic functions, which emphasizes the important role of bone formation markers in pediatrics. The two markers examined in this study are stable, suitable for long-term storage, and showed little overlap between the adult values and the childhood/adolescent values. Unlike osteocalcin, they clearly showed higher concentrations in infancy, when the rate of growth was fastest. Both appear to be good tools for clinical and physiologic research.


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Keh-Sung Tsai, [1] Men-Hwang Jang, [3] Sandy Huey-Jen Hsu, [1] Wern-Cherng Cheng, [1] and Mei-Hwei Chang [2] (Departments of [1] Laboratory Medicine and [2] Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China; [3] Department of Laboratory Medicine, Taipei City Psychiatric Center, Taipei, Taiwan, Republic of China; * address correspondence to this author at: Department of Laboratory Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan, Republic of China; fax 8862-23224263, e-mail
Table 1. Mean values ([+ or -] SD) of PICP and BAP in
different age groups of both genders.

 Early childhood Prepubertal

 Girls Boys Girls

Age, years 0-2 0-2 3-8
n 20 20 43
PICP, 557 [+ or -] 260 784 [+ or -] 329 216 [+ or -] 93
 Range 230-1104 211-1310 155-558
BAP, U/L 122 [+ or -] 19 104 [+ or -] 21 106 [+ or -] 16
 Range 81-142 62-132 70-139

 Prepubertal Pubertal

 Boys Girls Boys

Age, years 3-9 9-12 10-14
n 50 37 41
PICP, 223 [+ or -] 118 243 [+ or -] 65 268 [+ or -] 113
 Range 147-930 122-373 123-618
BAP, U/L 94 [+ or -] 17 112.4 [+ or -] 16 114 [+ or -] 21
 Range 63-135 66-137 58-140


 Girls Boys

Age, years 13-17 15-18
n 10 9
PICP, 129 [+ or -] 29 155 [+ or -] 20
 Range 74-167 127-189
BAP, U/L 39 [+ or -] 23 59 [+ or -] 19
 Range 8-82 30-89

 Young adult (a)

 Women Men

Age, years 20-50 20-50
n 118 68
PICP, 82 [+ or -] 22 116 [+ or -] 11
 Range 37-133 77-163
BAP, U/L 17 [+ or -] 6 20 [+ or -] 8
 Range 6-34 10-45

(a) Values for young adults were from Tsai et al. (18).
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Title Annotation:Technical Briefs
Author:Tsai, Keh-Sung; Jang, Men-Hwang; Hsu, Sandy Huey-Jen; Cheng, Wern-Cherng; Chang, Mei-Hwei
Publication:Clinical Chemistry
Date:Jan 1, 1999
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