Differential effect of age, gender and puberty on bone formation rate assessed by measurement of bone-specific alkaline phosphatase in healthy Italian children and adolescents

  • Stefano Mora
  • Laura Cafarelli
  • Paola Erba
  • Maria Puzzovio
  • Ilaria Zamproni
  • Vania Giacomet
  • Alessandra Viganò
Original Article


Bones undergo intensive modeling during growth, a process involving both formation and resorption processes. Bone formation can be accurately monitored by measurements of bone-specific alkaline phosphatase (BAP) in serum. The lack of appropriate reference values has hampered the use of BAP in pediatric subjects. The purposes of the present study were to verify the effect of age, gender, and puberty on BAP concentration in healthy children, and to generate reference curves. Morning blood samples were collected from 239 healthy children and adolescents (113 boys), aged 4.5–20.9 years. Anthropometric measurements and pubertal stage were recorded. Blood samples were also obtained from 37 healthy young adults (13 men), aged 21.5–30.2 years. BAP concentration varied significantly with age, showing a peak at age 10–12 years in girls and 12–14 years in boys. Prepubertal concentration of BAP was six- to sevenfold higher than in healthy adults. We observed significantly higher BAP values at the beginning of puberty (stage II) compared to prepubertal stage in both sexes. The effect of puberty was independent from age and gender. We demonstrated that BAP serum concentration varies with age in children and adolescents, and we provided equations to calculate reference values. Because BAP concentrations vary markedly according to the pubertal stage, the values of BAP obtained in single patients should be compared to reference considering not only age and sex, but also the stage of pubertal development.


Bone alkaline phosphatase Bone formation Children Puberty Bone metabolism 



This work was supported in part by grant no 30G.31 from Istituto Superiore di Sanità, VI Programma Nazionale di Ricerca sull’AIDS, 2006.


  1. 1.
    Mora S, Gilsanz V (2003) Establishment of peak bone mass. Endocrinol Metab Clin N Am 32:39–63CrossRefGoogle Scholar
  2. 2.
    Rauch F (2005) Bone growth in length and width: the Yin and Yang of bone stability. J Muskoloskelet Neuronal Interact 5:194–201Google Scholar
  3. 3.
    Karsentry G, Kronenberg HM (2003) Postnatal bone growth: growth plate biology, modeling, and remodeling. In: Glorieux FH, Pettifor JM, Jüppner H (eds) Pediatric bone. Biology and disease. Academic Press, San Diego, pp 119–133Google Scholar
  4. 4.
    Rauch F (2006) Geometric strength: bone size during skeletal development. Curr Opin Endocrionol Diabetes 13:10–14CrossRefGoogle Scholar
  5. 5.
    Shönau E, Rauch F (2003) Biochemical markers of bone metabolism. In: Glorieux FH, Pettifor JM, Jüppner H (eds) Pediatric bone. Biology and disease. Academic Press, San Diego, pp 339–357Google Scholar
  6. 6.
    Baroncelli I, Bertelloni S, Ceccarelli C, Cupelli D, Saggese G (2000) Dynamics of bone turnover in children with GH deficiency treated with GH until final height. Eur J Endocrinol 142:549–556CrossRefPubMedGoogle Scholar
  7. 7.
    Mora S, Barera G (2004) Bone mass and bone metabolism in pediatric gastrointestinal disorders. J Pediatr Gastroenterol Nutr 39:129–140CrossRefPubMedGoogle Scholar
  8. 8.
    Leonard MB (2007) Glucocorticoid-induced osteoporosis in children: impact of the underlying disease. Pediatrics 119:S166–S174CrossRefPubMedGoogle Scholar
  9. 9.
    Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, Cerutti F, Gargantini L, Greggio N, Tonini G, Cicognani A (2006) Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest 29:581–593PubMedGoogle Scholar
  10. 10.
    Tanner JM, Whitehouse RH (1976) Clinical longitudinal standards for height, weight, height velocity and weight velocity and stages of puberty. Arch Dis Child 51:170–179CrossRefPubMedGoogle Scholar
  11. 11.
    Camozzi V, Tossi A, Simoni E, Pagani F, Francucci CM, Moro L (2007) Role of biochemical markers of bone remodeling in clinical practice. J Endocrinol Invest 30:13–17PubMedGoogle Scholar
  12. 12.
    Banfi G, Daverio R (1994) In vitro stability of osteocalcin. Clin Chem 40:883–884Google Scholar
  13. 13.
    Posen S, Grunstein HS (1982) Turnover rate of skeletal alkaline phosphatase in humans. Clin Chem 28:153–154PubMedGoogle Scholar
  14. 14.
    Tobiume H, Kanzaki S, Hida S, Ono T, Moriwake T, Yamauchi S, Tanaka H, Seino Y (1997) Serum bone alkaline phosphatase isoenzyme levels in normal children and children with growth hormone (GH) deficiency: a potential marker for bone formation and response to GH therapy. J Clin Endocrinol Meta 82:2056–2061CrossRefGoogle Scholar
  15. 15.
    Kanbur NÖ, Derman O, Kmik E (2005) The relationships between pubertal development, IGF-1 axis, and bone formation in healthy adolescents. J Bone Miner Metab 23:76–83CrossRefPubMedGoogle Scholar
  16. 16.
    Mora S, Prinster C, Proverbio MC, Bellini A, de Poli SC, Weber G, Abbiati G, Chiumello G (1998) Urinary markers of bone turnover in healthy children and adolescents: age-related changes and effect of puberty. Calcif Tissue Int 63:369–374CrossRefPubMedGoogle Scholar
  17. 17.
    Tsai K-S, Jang M-H, Hsu SH-J, Cheng W-C, Chang M-H (1999) Bone alkaline phosphatase isoenzyme and carboxy-terminal propeptide of type-I procollagen in healthy Chinese girls and boys. Clin Chem 45:136–138PubMedGoogle Scholar
  18. 18.
    Rauchenzauner M, Schmid A, Heinz-Erian P, Kapelari K, Falkensammer G, Griesmacher A, Finkenstedt G, Högler W (2007) Sex- and age-specific reference curves for serum markers of bone turnover in healthy children from 2 months to 18 years. J Clin Endocrinol Metab 92:443–449CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2009

Authors and Affiliations

  • Stefano Mora
    • 1
  • Laura Cafarelli
    • 2
  • Paola Erba
    • 2
  • Maria Puzzovio
    • 1
  • Ilaria Zamproni
    • 1
  • Vania Giacomet
    • 2
  • Alessandra Viganò
    • 2
  1. 1.Laboratory of Pediatric EndocrinologyBoNetwork, San Raffaele Scientific InstituteMilan (MI)Italy
  2. 2.Department of PediatricsL. Sacco HospitalMilanItaly

Personalised recommendations