Skip to main content

Advertisement

Log in

A biochemical approach for assessing cutoffs at the age thresholds of 14 and 18 years: a pilot study on the applicability of bone specific alkaline phosphatase on an Italian sample

  • Original Article
  • Published:
International Journal of Legal Medicine Aims and scope Submit manuscript

Abstract

Background

The majority of age estimation methods analyze morphological changes of specific skeletal (or dental) structures reflecting global bone development (biological parameter) in order to estimate a chronological value. This morphological and structural development is the consequence of a very active tissue metabolism and intensive modeling process which involve both bone formation and bone resorption. Several biochemical markers of bone formation and bone resorption are available, and specific biochemical tests can be performed on blood or urine samples, but such markers of bone turnover have never been employed for age estimation in living individuals for forensic purposes. The aim of this study was to ascertain the applicability of serum bone alkaline phosphatase (BALP) concentration in the age estimation for forensic purposes. We focused on the legal age thresholds of 14 and 18 years (LAT) because, in Italy, the former is considered the minimum age for criminal responsibility and the latter defines adult age and the possibility of applying general criminal laws.

Materials and methods

This study analyzed, from a forensic point of view, BALP and Tanner stages of 202 healthy white individuals (116 females and 86 males) between the ages of 10 and 30 years.

We derived a linear logistic model to estimate the probability that an individual was older or younger than LAT using two variables: BALP concentration and Tanner stages. The predictive accuracy of the test was assessed by the determination of the receiver-operating characteristic curve (ROC curve). The test was performed to identify a threshold (cutoff) that could be used to assign an individual to the population of those younger or older than LAT.

Results

ROC curve showed that the use of both serum BALP concentration and Tanner stages has a very good level of reliability in age assessment (the area under the ROC curve, AUC, ranged from 0.918 to 0.962). Best results were obtained in the assessment of male over 18 years of age (sensibility and specificity respectively of 0.90 and 0.93 with an accuracy of 0.92). Worst results were obtained in the assessment of female over 18 years of age (sensibility and specificity respectively of 0.87 and 0.82 with an accuracy of 0.84). We also calculated the probability of the correctness in the age estimation.

Conclusion

The results showed that the use of serum BALP concentration in the age assessment could be a promising and integrative method to established ones, but more research has to be done to validate the value of the proposed method in the forensic practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Cipriani D (2009) Children’s rights and the minimum age of criminal responsibility: a global perspective. Ashgate Publishing, Farnham

    Google Scholar 

  2. Greulich WW, Pyle SI (1959) Radiographic atlas of skeletal development of the hand and wrist, Sdth edn. Stanford University Press, Stanford

    Google Scholar 

  3. Tanner JM, Whitehouse RH, Cameron N (1990) Valutazione della maturazione scheletrica e predizione dell’altezza adulta (Metodo TW2). Prima edizione italiana. Martinucci Pubblicazioni Mediche, Napoli

    Google Scholar 

  4. Demirjian A, Goldstein H, Tanner JM (1973) A new system of dental age assessment. Hum Biol 45(2):211–227

    CAS  PubMed  Google Scholar 

  5. Schmeling A, Schulz R, Reisinger W, Mühler M, Wernecke KD, Geserick G (2004) Studies on the time frame for ossification of the medial clavicular epiphyseal cartilage in conventional radiography. Int J Legal Med 118(1):5–8

    Article  PubMed  Google Scholar 

  6. Schulz R, Mühler M, Reisinger W, Schmidt S, Schmeling A (2008) Radiographic staging of ossification of the medial clavicular epiphysis. Int J Legal Med 122(1):55–58

    Article  PubMed  Google Scholar 

  7. Schmeling A, Reisinger W, Geserick G, Olze A (2005) The current state of forensic age estimation of live subjects for the purpose of criminal prosecution. Forensic Sci Med Pathol 1(4):239–246

    Article  PubMed  Google Scholar 

  8. Schmeling A, Grundmann C, Fuhrmann A, Kaatsch HJ, Knell B, Ramsthaler F, Reisinger W, Riepert T, Ritz-Timme S, Rösing FW, Rötzscher K, Geserick G (2008) Criteria for age estimation in living individuals. Int J Leg Med 122:457–460

    Article  CAS  Google Scholar 

  9. Wittschieber D, Ottow C, Vieth V, Küppers M, Schulz R, Hassu J, Bajanowski T, Püschel K, Ramsthaler F, Pfeiffer H, Schmidt S, Schmeling A (2015) Projection radiography of the clavicle: still recommendable for forensic age diagnostics in living individuals? Int J Legal Med 129(1):187–193

    Article  PubMed  Google Scholar 

  10. Magnusson P, Larsson L, Magnusson M, Davie MW, Sharp CA (1999) Isoforms of bone alkaline phosphatase: characterization and origin in human trabecular and cortical bone. J Bone Miner Res 14(11):1926–1933

    Article  PubMed  CAS  Google Scholar 

  11. Mora S, Cafarelli L, Erba P, Puzzovio M, Zamproni I, Giacomet V, Viganò A (2009) 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. J Bone Miner Metab 27(6):721–726

    Article  PubMed  CAS  Google Scholar 

  12. Posen S, Grunstein HS (1982) Turnover rate of skeletal alkaline phosphatase in humans. Clin Chem 28(1):153–154

    Article  PubMed  CAS  Google Scholar 

  13. 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 Metab 82(7):2056–2061

    PubMed  CAS  Google Scholar 

  14. 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 29:581–593

    Article  PubMed  CAS  Google Scholar 

  15. Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Arch Dis Child 44(235):291–303

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Marshall WA, Tanner JM (1970) Variations in the pattern of pubertal changes in boys. Arch Dis Child 45(239):13–23

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Core Team Development R (2013) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, http://www.R-project.org

    Google Scholar 

  18. Mincer HH, Harris EF, Berryman HE (1993) The A.B.F.O. study of third molar development and its use as an estimator of chronological age. J Forensic Sci 38(2):379–390

    Article  PubMed  CAS  Google Scholar 

  19. Hackman L, Black S (2013) Age estimation from radiographic images of the knee. J Forensic Sci 58(3):732–737

    Article  PubMed  Google Scholar 

  20. Schmidt S, Koch B, Schulz R, Reisinger W, Schmeling A (2007) Comparative analysis of the applicability of the skeletal age determination methods of Greulich-Pyle and Thiemann-Nitz for forensic age estimation in living subjects. Int J Legal Med 121(4):293–296

    Article  PubMed  Google Scholar 

  21. Davies C, Hackman L, Black S (2014) The persistence of epiphyseal scars in the adult tibia. Int J Legal Med 128(2):335–343

    Article  PubMed  Google Scholar 

  22. Cameriere R, Ferrante L, De Angelis D, Scarpino F, Galli F (2008) The comparison between measurement of open apices of third molars and Demirjian stages to test chronological age of over 18 year olds in living subjects. Int J Legal Med 122(6):493–497

    Article  PubMed  CAS  Google Scholar 

  23. Thevissen PW, Pittayapat P, Fieuws S, Willems G (2009) Estimating age of majority on third molars developmental stages in young adults from Thailand using a modified scoring technique. J Forensic Sci 54(2):428–432

    Article  PubMed  Google Scholar 

  24. Loder RT, Estle DT, Morrison K, Eggleston D, Fish DN, Greenfield ML, Guire KE (1993) Applicability of the Greulich and Pyle skeletal age standards to black and white children of today. Am J Dis Child 147(12):1329–1333

    CAS  PubMed  Google Scholar 

  25. Ontell FK, Ivanovic M, Ablin DS, Barlow TW (1996) Bone age in children of diverse ethnicity. AJR Am J Roentgenol 167(6):1395–1398

    Article  PubMed  CAS  Google Scholar 

  26. Mora S, Boechat MI, Pietka E, Huang HK, Gilsanz V (2001) Skeletal age determinations in children of European and African descent: applicability of the Greulich and Pyle standards. Pediatr Res 50(5):624–628

    Article  PubMed  CAS  Google Scholar 

  27. Rikhasor RM, Qureshi AM, Rathi SL, Channa NA (1999) Skeletal maturity in Pakistani children. J Anat 195(Pt 2):305–308

    Article  PubMed  PubMed Central  Google Scholar 

  28. Koc A, Karaoglanoglu M, Erdogan M, Kosecik M, Cesur Y (2001) Assessment of bone ages: is the Greulich-Pyle method sufficient for Turkish boys? Pediatr Int 43(6):662–665

    Article  PubMed  CAS  Google Scholar 

  29. Chiang K-H, Shau-Bin CA, Yen P-S (2005) The reliability of using Greulich-Pyle method to determine children’s bone age in Taiwan. Tzu Chi Med J 17:417–420

    Google Scholar 

  30. Lewis CP, Lavy CB, Harrison WJ (2002) Delay in skeletal maturity in Malawian children. J Bone Joint Surg Br 84(5):732–734

    Article  PubMed  CAS  Google Scholar 

  31. Olze A, Schmeling A, Taniguchi M, Maeda H, van Niekerk P, Wernecke KD, Geserick G (2004) Forensic age estimation in living subjects: the ethnic factor in wisdom tooth mineralization. Int J Legal Med 118(3):170–173, Epub 2004 Feb 6

    Article  PubMed  Google Scholar 

  32. Cole TJ, Cole AJ (1992) Bone age, social deprivation, and single parent families. Arch Dis Child 67(10):1281–1285

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Schmeling A, Schulz R, Danner B, Rösing FW (2006) The impact of economic progress and modernization in medicine on the ossification of hand and wrist. Int J Leg Med 120(2):121–126

    Article  Google Scholar 

  34. Schmeling A, Reisinger W, Loreck D, Vendura K, Markus W, Geserick G (2000) Effects of ethnicity on skeletal maturation: consequences for forensic age estimations. Int J Leg Med 113(5):253–258

    Article  CAS  Google Scholar 

  35. Kimura K (1977) Skeletal maturity of the hand and wrist in Japanese children in Sapporo by the TW2 method. Ann Hum Biol 4(5):449–453

    Article  PubMed  CAS  Google Scholar 

  36. Kimura K (1977) Skeletal maturity of the hand and wrist in Japanese children by the TW2 method. Ann Hum Biol 4(4):353–356

    Article  PubMed  CAS  Google Scholar 

  37. Greulich WW (1957) A comparison of the physical growth and development of American-born and native Japanese children. Am J Phys Anthropol 15(4):489–515

    Article  PubMed  CAS  Google Scholar 

  38. Meijerman L, Maat GJ, Schulz R, Schmeling A (2007) Variables affecting the probability of complete fusion of the medial clavicular epiphysis. Int J Legal Med 121(6):463–8

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kreitner KF, Schweden FJ, Riepert T, Nafe B, Thelen M (1998) Bone age determination based on the study of the medial extremity of the clavicle. Eur Radiol 8(7):1116–1122

    Article  PubMed  CAS  Google Scholar 

  40. Ferrante L, Cameriere R (2009) Statistical methods to assess the reliability of measurements in the procedures for forensic age estimation. Int J Leg Med 123(4):277–283

    Article  CAS  Google Scholar 

  41. Christenson RH (1997) Biochemical markers of bone metabolism: an overview. Clin Biochem 30(8):573–593

    Article  PubMed  CAS  Google Scholar 

  42. Seibel MJ (2005) Biochemical markers of bone turnover part I: biochemistry and variability. Clin Biochem Rev 26(4):97–122

    PubMed  PubMed Central  Google Scholar 

  43. Szulc P, Seeman E, Delmas PD (2000) Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int 11(4):281–294

    Article  PubMed  CAS  Google Scholar 

  44. Huang Y, Eapen E, Steele S, Grey V (2011) Establishment of reference intervals for bone markers in children and adolescents. Clin Biochem 44(10–11):771–778

    Article  PubMed  CAS  Google Scholar 

  45. Watts N (1999) Clinical utility of biochemical markers of bone remodelling. Clin Chem 45:1359–1368

    Article  PubMed  CAS  Google Scholar 

  46. Christenson RH (1997) Biochemical markers of bone metabolism: an overview. Clin Biochem 30:573–593

    Article  PubMed  CAS  Google Scholar 

  47. Baroncelli GI, Bertelloni S, Ceccarelli C, Amato V, Saggese G (2000) Bone turnover in children with vitamin D deficiency rickets before and during treatment. Acta Paediatr 89(5):513–518

    Article  PubMed  CAS  Google Scholar 

  48. Seibel MJ (2006) Biochemical markers of bone turnover part II: clinical applications in the management of osteoporosis. Clin Biochem Rev 27(3):123–138

    PubMed  PubMed Central  Google Scholar 

  49. Brown JP, Albert C, Nassar BA, Adachi JD, Cole D, Davison KS, Dooley KC, Don-Wauchope A, Douville P, Hanley DA, Jamal SA, Josse R, Kaiser S, Krahn J, Krause R, Kremer R, Lepage R, Letendre E, Morin S, Ooi DS, Papaioaonnou A, Ste-Marie L-G (2009) Bone turnover markers in the management of postmenopausal osteoporosis. Clin Biochem 42:929–942

    Article  PubMed  CAS  Google Scholar 

  50. Magnusson P, Häger A, Larsson L (1995) Serum osteocalcin and bone and liver alkaline phosphatase isoforms in healthy children and adolescents. Pediatr Res 38(6):955–961

    Article  PubMed  CAS  Google Scholar 

  51. 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(2):443–449

    Article  PubMed  CAS  Google Scholar 

  52. Gundberg CM, Looker AC, Nieman SD, Calvo MS (2002) Patterns of osteocalcin and bone specific alkaline phosphatase by age, gender, and race or ethnicity. Bone 31(6):703–708

    Article  PubMed  CAS  Google Scholar 

  53. Garamendi PM, Landa MI, Ballesteros J, Solano MA (2005) Reliability of the methods applied to assess age minority in living subjects around 18 years old. A survey on a Moroccan origin population. Forensic Sci Int 10 154(1):3–12

    Article  CAS  Google Scholar 

  54. Pinchi V, Norelli GA, Pradella F, Vitale G, Rugo D, Nieri M (2012) Comparison of the applicability of four odontological methods for age estimation of the 14 years legal threshold in a sample of Italian adolescents. J Forensic Odontostomatol 30(2):17–25

    PubMed  PubMed Central  Google Scholar 

  55. Galić I, Lauc T, Brkić H, Vodanović M, Galić E, Biazevic MG, Brakus I, Badrov J, Cameriere R (2015) Forensic Sci Int 252:191, e1-5

    Article  PubMed  Google Scholar 

  56. Cameriere R, De Luca S, De Angelis D, Merelli V, Giuliodori A, Cingolani M, Cattaneo C, Ferrante L (2012) Reliability of Schmeling’s stages of ossification of medial clavicular epiphyses and its validity to assess 18 years of age in living subjects. Int J Legal Med 126(6):923–932

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Adriano Tagliabracci.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tisè, M., Ferrante, L., Mora, S. et al. A biochemical approach for assessing cutoffs at the age thresholds of 14 and 18 years: a pilot study on the applicability of bone specific alkaline phosphatase on an Italian sample. Int J Legal Med 130, 1149–1158 (2016). https://doi.org/10.1007/s00414-016-1382-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-016-1382-8

Keyword

Navigation