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 pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children.
Of or relating to pediatrics. 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 labile /la·bile/ (la´bil)
1. gliding; moving from point to point over the surface; unstable; fluctuating.
2. chemically unstable.
1. and possesses problems in sample processing and storage (15). Recently, two other bone formation markers in serum, bone alkaline phosphatase isoenzyme alkaline phosphatase isoenzyme Clinical chemistry Any of the organ-specific alkaline phosphatase isoenzymes: liver, bone, intestine and placenta; intestinal AP occurs almost exclusively in individuals with blood group B or O and is ↑ 8 hrs after a fatty meal; (BAP BAP - 1.
[Listed in CACM 2(5):16 (May 1959)].
PICP Pacific Initial Communications Package (USAF)
PICP Potential Irrigated Crop Production
PICP Physical Inventory Control Program (US DoD) ) (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 growth hormone deficiency Hypopituitarism Endocrinology A condition which affects 1:4000 children; ♂:♀, 3-4:1 Etiology 70% of GHD is idiopathic and attributed to a prenatal insult, possibly due to hypothalamic dysfunction, given that GHD children (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 glucocorticoid /glu·co·cor·ti·coid/ (-kor´ti-koid)
1. any of the group of corticosteroids predominantly involved in carbohydrate metabolism, and also in fat and protein metabolism and many other activities (e.g. for asthma (8) or inflammatory bowel disease inflammatory bowel disease
n. Abbr. IBD
Any of several incurable and debilitating diseases of the gastrointestinal tract characterized by inflammation and obstruction of parts of the intestine. (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 venipuncture /veni·punc·ture/ (ven?i-pungk´chur) surgical puncture of a vein.
ve·ni·punc·ture or ve·ne·punc·ture
n. , 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 sigmoid /sig·moid/ (sig´moid)
1. shaped like the letter C or S.
2. sigmoid colon.
sig·moid or sig·moi·dal
1. Having the shape of the letter S. 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 prepubertal /pre·pu·ber·tal/ (-pu´ber-tal) before puberty; pertaining to the period of accelerated growth preceding gonadal maturity. 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 boys and girls
mercurialisannua. together (n = 230; x = 0.306; P = 0.0001).
[FIGURE 1 OMITTED]
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 osteoblastic
emanating from or pertaining to an osteoblast. 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.
(1.) Johansen JS, Giwerman A, Hartwell D. Thoger Nielsen C, Price PA, Christiansen C, et al. Serum bone Gla-protein as a marker of bone growth in children and adolescents: correlation with age, height, serum insulin-like growth factor 1, and serum testosterone. J Clin Endocrinol Metab 1988;67: 273-8.
(2.) Delmas PD, Chatelain P, Malaval L, Bonne n. 1. A female servant charged with the care of a young child. G. Serum bone Gla-protein in growth hormone deficient children. J Bone Miner Res 1986;4:333-8.
(3.) Nielsen HK, Jorgensen JOL, Brixen K, Christiansen JS. Serum osteocalcin and bone isoenryme alkaline phosphatase in growth hormone-deficient patients: dose-response studies with biosynthetic human GH. Calcif Tissue Int 1991;48:82-7.
(4.) Stamoyannou L, Karachaliou F, Giourelie E, Voskaki E, Mengreli C, Barsocas CS. Effect of growth hormone therapy on bone metabolism of growth hormone deficient children. Eur J Pediatr 1997;156:592-6.
(5.) Tobiume H, Kanazaki S, Hida S, Ono T, Moriwake T, Yamanochi S, et al. Serum bone alkaline phosphatase isoenryme levels in normal children and children with growth hormone deficiency: potential marker for bone formation and response to GH therapy. J Clin Endocrinol Metab 1997;82: 2056-61.
(6.) Crofton PM, Stirling HF, Schonau E, Kelnar CJ. Bone alkaline phosphatase and collagen markers as early predictors of height velocity response to growth-promoting treatment in short normal children. Clin Endocrinol 1996; 44:385-94.
(7.) Boot AM, De Muinck Keizer-Schrama S, Pols HA, Krenning EP, Drop SL. Bone mineral density bone mineral density
See bone density.
bone mineral density A measurement of bone mass, expressed as the amount of mineral–in grams divided by the area scanned in cm2. See Bone densitometry. and body composition before and during treatment with gonadotropin-releasing hormone agonist A gonadotropin-releasing hormone agonist (GnRH agonist) is a synthetic peptide modeled after the hypothalamic neurohormone GnRH that interacts with the gonadotropin-releasing hormone receptor to elicit its biologic response, the release of the pituitary hormones FSH and LH. in children with central precocious and early puberty. J Clin Endocrinol Metab 1998;41:1560-6.
(8.) Birkebaek NH, Esberg G, Andersen K, Wolthers 0, Hassager C. Bone and collagen turnover during treatment with inhaled dry powder budesonide and beclomethasone dipropionate. Arch Dis Child 1995;73:524-7.
(9.) Hyamas JS, Treem WR, Carey DE, Wyzga N, Eddy E, Goldberg D, Moore RE. Comparison of collagen propeptide as growth markers in children with inflammatory bowel disease. Gastroenterology 1991;100:971-5.
(10.) Tommasi M, Baccitottini L, Benucci A, Brocchi A, Passeri A, Saracini A, et al. Serum biochemical markers of bone turnover in healthy infants. Int J Biol Markers 1996;11:159-64.
(11). Crofton PM, Wade JC, Taylor MRH MRH Memory Repeater Hub
MRH Main Rotor Head (helicopters)
MRH Multi-Resolution Homogenization
MRH Mastic Roller Hybrid
MRH Mataillos Rejuntaos de Hafen (MMO gaming guild) , Holland CV. Serum concentrations of carboxy-terminal propeptide of type I procollagen, amino-terminal propeptide of type III procollagen, cross-linked carboxy-terminal telopeptide of type I collagen, and their interrelationships in schoolchildren. Clin Chem 1997; 43:1577-81.
(12.) Weaver CM, Peacock M, Martin BR, Plawecki KL, McCabe GP. Calcium retention estimated from indicators of skeletal status in adolescent girls and young women. Am J Clin Nutr 1996;64:67-70.
(13.) Cioffi M, Molinari AM, Gazzerro P. Di Finizio B, Frata M, Deufemia A, Puca GA. Serum osteocalcin in 1634 healthy children. Clin Chem 1997;43: 543-5.
(14.) Lo S-F, Huang J-L, Chem L-C, Yeh K-W, Yang D-C, Hsieh K-H. Serum osteocalcin levels of normal children in Taiwan. Acta Paediatr Sin 1997;38: 443-7.
(15.) Banfi G, Daverio R. In vitro stability of osteocalcin. Clin Chem 1994;40: 883-4.
(16.) Gomez B Jr, Ardakani S, Ja T, Jenkins D, Cereli MJ, Daniloff GY, Gung VT. Monoclonal antibody assay for measuring bone-specific alkaline phosphatase activity in serum. Clin Chem 1995;41:1560-6.
(17.) Parfitt AM, Simon LS, Villaneuva AR, Krane SM. Procollagen type I carboxyterminal extension peptide in serum as a marker of collagen biosynthesis Biosynthesis
The synthesis of more complex molecules from simpler ones in cells by a series of reactions mediated by enzymes. The overall economy and survival of the cell is governed by the interplay between the energy gained from the breakdown of compounds in bone. Correlation with iliac bone formation rates and comparison with total alkaline phosphatase. J Bone Miner Res 1987;2:427-36.
(18.) Tsai K-S, Pan W-H, Hsu SH-J, Cheng W-C, Chen C-K, Chieng P-U, et al. Sexual difference in bone markers and bone mineral density of normal Chinese. Calcif Tissue Int 1996;59:454-60.
Keh-Sung Tsai,  Men-Hwang Jang,  Sandy Huey-Jen Hsu,  Wern-Cherng Cheng,  and Mei-Hwei Chang  (Departments of  Laboratory Medicine and  Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China;  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 firstname.lastname@example.org)
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 [micro]g/L 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 [micro]g/L 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 Postpubertal Girls Boys Age, years 13-17 15-18 n 10 9 PICP, 129 [+ or -] 29 155 [+ or -] 20 [micro]g/L 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 [micro]g/L 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).