Advertisement

International Journal of Legal Medicine

, Volume 125, Issue 2, pp 181–198 | Cite as

State-of-the-art of bone marrow analysis in forensic toxicology: a review

  • Nathalie Cartiser
  • Fabien Bévalot
  • Laurent Fanton
  • Yvan Gaillard
  • Jérôme Guitton
Review Article

Abstract

Although blood is the reference medium in the field of forensic toxicology, alternative matrices are required in case of limited, unavailable or unusable blood samples. The present review investigated the suitability of bone marrow (BM) as an alternative matrix to characterize xenobiotic consumption and its influence on the occurrence of death. Basic data on BM physiology are reported in order to highlight the specificities of this matrix and their analytical and toxicokinetic consequences. A review of case reports, animal and human studies involving BM sample analysis focuses on the various parameters of interpretation of toxicological results: analytic limits, sampling location, pharmacokinetics, blood/BM concentration correlation, stability and postmortem redistribution. Tables summarizing the analytical conditions and quantification of 45 compounds from BM samples provide a useful tool for toxicologists. A specific section devoted to ethanol shows that, despite successful quantification, interpretation is highly dependent on postmortem interval. In conclusion, BM is an interesting alternative matrix, and further experimental data and validated assays are required to confirm its great potential relevance in forensic toxicology.

Keywords

Bone marrow Forensic toxicology BM physiology 

Notes

Acknowledgements

The authors would like to express their gratitude to Dr. Martine French for providing the pictures of histologic sections of bone marrow (Fig. 1).

Figure 2 was reprinted from Seminars in Nuclear Medicine, 37(3), Judy S. Blebea, Mohamed Houseni, Drew A. Torigian, Chengzhong Fan, Ayse Mavi, Ying Zhuge, Tad Iwanaga, Shipra Mishra, Jay Udupa, Jiyuan Zhuang, Rohit Gopal, and Abass Alavi, Structural and Functional Imaging of Normal Bone Marrow and Evaluation of its Age-Related Changes, pages 186, Copyright (2010), with permission from Elsevier.

Nathalie Cartiser is grateful to ‘Association Nationale de la Recherche et de la Technologie, Service CIFRE’ for the PhD grant.

References

  1. 1.
    Cengiz S, Ulukan O, Ates I, Tugcu H (2006) Determination of morphine in postmortem rabbit bone marrow and comparison with blood morphine concentrations. Forensic Sci Int 156:91–94PubMedCrossRefGoogle Scholar
  2. 2.
    McIntyre LM, King CV, Boratto M, Drummer OH (2000) Post-mortem drug analyses in bone and bone marrow. Ther Drug Monit 22:79–83PubMedCrossRefGoogle Scholar
  3. 3.
    Winek CL, Morris EM, Wahba WW (1993) The use of bone marrow in the study of postmortem redistribution of nortriptyline. J Anal Toxicol 17:93–98PubMedGoogle Scholar
  4. 4.
    Frank WE, Llewellyn BE (1999) A time course study on STR profiles derived from human bone, muscle, and bone marrow. J Forensic Sci 44:778–782PubMedGoogle Scholar
  5. 5.
    Dmitrienko Iu A, Kononenko VI, Lakiza BS (1983) Postmortem changes in bone marrow tissue as a criterion of time of death. Sud Med Ekspert 26:19–21PubMedGoogle Scholar
  6. 6.
    Findlay AB (1976) Bone marrow changes in the post mortem interval. J Forensic Sci Soc 16:213–218PubMedCrossRefGoogle Scholar
  7. 7.
    Hao LG, Deng SX, Zhao XC (2007) Recent advancement in relationship between DNA degradation and postmortem interval. Fa Yi Xue Za Zhi 23:145–147PubMedGoogle Scholar
  8. 8.
    Luo GH, Chen YC, Cheng JD, Wang JF, Gao CL (2006) Relationship between DNA degradation and postmortem interval of corrupt corpse. Fa Yi Xue Za Zhi 22:7–9PubMedGoogle Scholar
  9. 9.
    Gruspier KL, Pollanen MS (2000) Limbs found in water: investigation using anthropological analysis and the diatom test. Forensic Sci Int 112:1–9PubMedCrossRefGoogle Scholar
  10. 10.
    Pollanen MS (1997) The diagnostic value of the diatom test for drowning: II. J Forensic Sci 42:286–290PubMedGoogle Scholar
  11. 11.
    Roll P, Beham A, Beham-Schmid C (2009) Post-mortem histopathological investigations of the bone marrow in forensic medicine: an important issue for both the forensic and clinical pathologist. Forensic Sci Int 186:e17–e20PubMedCrossRefGoogle Scholar
  12. 12.
    Sakai K, Takatsu A, Shigeta A, Abe S, Ikegami M, Takagi K (2007) Sudden death due to undiagnosed acute promyelocytic leukemia: a case report. Int J Leg Med 121:311–314CrossRefGoogle Scholar
  13. 13.
    Umezawa A, Yamada T, Ogawa Y, Kuramochi S, Watanabe Y (1990) Postmortem diagnosis of acute megakaryocytic leukemia. Usefulness of immunohistochemistry and tissue hemogram. Acta Pathol Jpn 40:693–698PubMedGoogle Scholar
  14. 14.
    Casier H, Thomas F, Delaunois AL (1943) La répartition de l'alcool chez l'homme et les animaux au cours de l'intoxication éthylique. Arch Int Pharmacodyn 69:186–204Google Scholar
  15. 15.
    Winek CL, Cibulas W Jr, Wahba WW (1981) A comparative study of ethchlorvynol levels in blood versus bone marrow. Forensic Sci Int 17:197–202PubMedCrossRefGoogle Scholar
  16. 16.
    Winek CL, Costantino AG, Wahba WW, Collom WD (1985) Blood versus bone marrow pentobarbital concentrations. Forensic Sci Int 27:15–24PubMedCrossRefGoogle Scholar
  17. 17.
    Winek CL, Esposito FM (1981) Comparative study of ethanol levels in blood versus bone marrow, vitreous humor, bile and urine. Forensic Sci Int 17:27–36PubMedCrossRefGoogle Scholar
  18. 18.
    Winek CL, Janssen JK (1982) Blood versus bone marrow isopropanol concentrations in rabbits. Forensic Sci Int 20:11–20PubMedCrossRefGoogle Scholar
  19. 19.
    Winek CL, Jones T (1980) Blood versus bone marrow ethanol concentrations in rabbits and humans. Forensic Sci Int 16:101–109PubMedCrossRefGoogle Scholar
  20. 20.
    Winek CL, Luhanik JM (1981) A storage study of ethanol in rabbit and human bone marrow. Forensic Sci Int 17:191–196PubMedCrossRefGoogle Scholar
  21. 21.
    Winek CL, Matejczyk RJ, Buddie EG (1983) Blood, bone marrow and eye fluid ethanol concentrations in putrefied rabbits. Forensic Sci Int 22:151–159PubMedCrossRefGoogle Scholar
  22. 22.
    Winek CL, Pluskota M, Wahba WW (1982) Plasma versus bone marrow flurazepam concentration in rabbits. Forensic Sci Int 19:155–163PubMedCrossRefGoogle Scholar
  23. 23.
    Winek CL, Susa D (1982) Blood versus bone marrow methanol concentrations in rabbits. Forensic Sci Int 19:165–175PubMedCrossRefGoogle Scholar
  24. 24.
    Winek CL, Westwood SE, Wahba WW (1990) Plasma versus bone marrow desipramine: a comparative study. Forensic Sci Int 48:49–57PubMedCrossRefGoogle Scholar
  25. 25.
    Lafreniere NM, Watterson JH (2009) Detection of acute fentanyl exposure in fresh and decomposed skeletal tissues. Forensic Sci Int 185:100–106PubMedCrossRefGoogle Scholar
  26. 26.
    Lafreniere NM, Watterson JH (2010) Detection of acute fentanyl exposure in fresh and decomposed skeletal tissues: Part II. The effect of dose-death interval. Forensic Sci Int 194:60–66PubMedCrossRefGoogle Scholar
  27. 27.
    Vandenboer TC, Grummett SA, Watterson JH (2008) Utility of immunoassay in drug screening in skeletal tissues: sampling considerations in detection of ketamine exposure in femoral bone and bone marrow following acute administration using ELISA. J Forensic Sci 53:1474–1482PubMedGoogle Scholar
  28. 28.
    Watterson J (2006) Challenges in forensic toxicology of skeletonized human remains. Analyst 131:961–965PubMedCrossRefGoogle Scholar
  29. 29.
    Watterson JH, Botman JE (2009) Detection of acute diazepam exposure in bone and marrow: influence of tissue type and the dose-death interval on sensitivity of detection by ELISA with liquid chromatography tandem mass spectrometry confirmation. J Forensic Sci 54:708–714PubMedCrossRefGoogle Scholar
  30. 30.
    Watterson JH, Vandenboer TC (2008) Effects of tissue type and the dose-death interval on the detection of acute ketamine exposure in bone and marrow with solid-phase extraction and ELISA with liquid chromatography-tandem mass spectrometry confirmation. J Anal Toxicol 32:631–638PubMedGoogle Scholar
  31. 31.
    Blebea JS, Houseni M, Torigian DA, Fan C, Mavi A, Zhuge Y et al (2007) Structural and functional imaging of normal bone marrow and evaluation of its age-related changes. Semin Nucl Med 37:185–194PubMedCrossRefGoogle Scholar
  32. 32.
    Hwang S, Panicek DM (2007) Magnetic resonance imaging of bone marrow in oncology, Part 1. Skeletal Radiol 36:913–920PubMedCrossRefGoogle Scholar
  33. 33.
    Vande Berg BC, Malghem J, Lecouvet FE, Maldague B (2001) Normal bone marrow: dynamic aspects in magnetic resonance imaging. J Radiol 82:127–135PubMedGoogle Scholar
  34. 34.
    Derrickson B, Tortora GJ (2007) Principes d'anatomie et de physiologie. De Boeck, BruxellesGoogle Scholar
  35. 35.
    Kierszenbaum AL (2006) Histologie et Biologie Cellulaire: Une introduction à l'anatomie pathologique. De Boeck, BruxellesGoogle Scholar
  36. 36.
    Griffith JF, Yeung DK, Antonio GE, Lee FK, Hong AW, Wong SY et al (2005) Vertebral bone mineral density, marrow perfusion, and fat content in healthy men and men with osteoporosis: dynamic contrast-enhanced MR imaging and MR spectroscopy. Radiology 236:945–951PubMedCrossRefGoogle Scholar
  37. 37.
    Fan C, Hernandez-Pampaloni M, Houseni M, Chamroonrat W, Basu S, Kumar R et al (2007) Age-related changes in the metabolic activity and distribution of the red marrow as demonstrated by 2-deoxy-2-[F-18]fluoro-d-glucose-positron emission tomography. Mol Imaging Biol 9:300–307PubMedCrossRefGoogle Scholar
  38. 38.
    Liney GP, Bernard CP, Manton DJ, Turnbull LW, Langton CM (2007) Age, gender, and skeletal variation in bone marrow composition: a preliminary study at 3.0 Tesla. J Magn Reson Imaging 26:787–793PubMedCrossRefGoogle Scholar
  39. 39.
    Maniatis A, Tavassoli M, Crosby WH (1971) Factors affecting the conversion of yellow to red marrow. Blood 37:581–586PubMedGoogle Scholar
  40. 40.
    Gurevitch O, Slavin S, Feldman AG (2007) Conversion of red bone marrow into yellow—cause and mechanisms. Med Hypotheses 69:531–536PubMedCrossRefGoogle Scholar
  41. 41.
    Bigelow CL, Tavassoli M (1984) Fatty involution of bone marrow in rabbits. Acta Anat Basel 118:60–64PubMedCrossRefGoogle Scholar
  42. 42.
    Chen WT, Shih TT, Chen RC, Lo SY, Chou CT, Lee JM et al (2001) Vertebral bone marrow perfusion evaluated with dynamic contrast-enhanced MR imaging: significance of aging and sex. Radiology 220:213–218PubMedGoogle Scholar
  43. 43.
    Hwang S, Panicek DM (2007) Magnetic resonance imaging of bone marrow in oncology, Part 2. Skeletal Radiol 36:1017–1027PubMedCrossRefGoogle Scholar
  44. 44.
    Rosen BR, Fleming DM, Kushner DC, Zaner KS, Buxton RB, Bennet WP et al (1988) Hematologic bone marrow disorders: quantitative chemical shift MR imaging. Radiology 169:799–804PubMedGoogle Scholar
  45. 45.
    Daldrup-Link HE, Henning T, Link TM (2007) MR imaging of therapy-induced changes of bone marrow. Eur Radiol 17:743–761PubMedCrossRefGoogle Scholar
  46. 46.
    Aguayo A, Giles F, Albitar M (2003) Vascularity, angiogenesis and angiogenic factors in leukemias and myelodysplastic syndromes. Leuk Lymphoma 44:213–222PubMedCrossRefGoogle Scholar
  47. 47.
    Panteli K, Zagorianakou N, Agnantis NJ, Bourantas KL, Bai M (2005) Clinical correlation of bone marrow microvessel density in essential thrombocythemia. Acta Haematol 114:99–103PubMedCrossRefGoogle Scholar
  48. 48.
    Zetterberg E, Lundberg LG, Palmblad J (2004) Characterization of blood vessels in bone marrow from patients with chronic myeloid leukemia and polycythemia vera. Scand J Clin Lab Invest 64:641–647PubMedCrossRefGoogle Scholar
  49. 49.
    Schloegl H, Rost T, Schmidt W, Wurst FM, Weinmann W (2006) Distribution of ethyl glucuronide in rib bone marrow, other tissues and body liquids as proof of alcohol consumption before death. Forensic Sci Int 156:213–218PubMedCrossRefGoogle Scholar
  50. 50.
    Raikos N, Tsoukali H, Njau SN (2001) Determination of opiates in postmortem bone and bone marrow. Forensic Sci Int 123:140–141PubMedCrossRefGoogle Scholar
  51. 51.
    Grellner W, Glenewinkel F (1997) Exhumations: synopsis of morphological and toxicological findings in relation to the postmortem interval. Survey on a 20-year period and review of the literature. Forensic Sci Int 90:139–591PubMedCrossRefGoogle Scholar
  52. 52.
    Rothschild MA, Schmidt V, Schneider V (1996) Adipocere—problems in estimating the length of time since death. Med Law 15:329–335PubMedGoogle Scholar
  53. 53.
    William D, Haglund MHS (eds) (1997) Forensic taphonomy: the postmortem fate of human remains. CRC PressGoogle Scholar
  54. 54.
    Guillot E, de Mazancourt P, Durigon M, Alvarez JC (2007) Morphine and 6-acetylmorphine concentrations in blood, brain, spinal cord, bone marrow and bone after lethal acute or chronic diacetylmorphine administration to mice. Forensic Sci Int 166:139–144PubMedCrossRefGoogle Scholar
  55. 55.
    Maeda H, Oritani S, Nagai K, Tanaka T, Tanaka N (1997) Detection of bromisovalum from the bone marrow of skeletonized human remains: a case report with a comparison between gas chromatography/mass spectrometry (GC/MS) and high-performance liquid chromatography/mass spectrometry (LC/MS). Med Sci Law 37:248–253PubMedGoogle Scholar
  56. 56.
    Ito S, Kudo K, Imamura T, Jitsufuchi N, Kimura K (1997) Detection of drugs and poisons in postmortem tissues—determination of paraquat in tissues of rabbits buried underground. Nihon Hoigaku Zasshi 51:83–88PubMedGoogle Scholar
  57. 57.
    Kojima T, Okamoto I, Miyazaki T, Chikasue F, Yashiki M, Nakamura K (1986) Detection of methamphetamine and amphetamine in a skeletonized body buried for 5 years. Forensic Sci Int 31:93–102PubMedCrossRefGoogle Scholar
  58. 58.
    Maeda H, Zhu BL, Ishikawa T, Oritani S, Michiue T, Li DR et al (2006) Evaluation of post-mortem ethanol concentrations in pericardial fluid and bone marrow aspirate. Forensic Sci Int 161:141–143PubMedCrossRefGoogle Scholar
  59. 59.
    Bévalot F, Dujourdy L, Fanton L, Cartiser N, Magné L, Besacier F et al (2008) Statistic interpretation of meprobamate concentrations in bone marrow, vitreous and bile. Proceedings of International Meeting of The International Association of Forensic Toxicologists, February 18–23, Washington, United States of America. Abstract K59, p 431Google Scholar
  60. 60.
    Bévalot F, Fanton L, Le Meur C, Malicier D (2005) Analysis of bone marrow in post mortem toxicology. Proceedings of XVII International Congress of the International Association of Forensic Sciences, August 21–26, Hong Kong, China. Abstract A0847, p 246Google Scholar
  61. 61.
    Akcan R, Hilal A, Daglioglu N, Cekin N, Gulmen MK (2009) Determination of pesticides in postmortem blood and bone marrow of pesticide treated rabbits. Forensic Sci Int 189:82–87PubMedCrossRefGoogle Scholar
  62. 62.
    Gorczynski LY, Melbye FJ (2001) Detection of benzodiazepines in different tissues, including bone, using a quantitative ELISA assay. J Forensic Sci 46:916–918PubMedGoogle Scholar
  63. 63.
    Rochdi M, Sabouraud A, Baud FJ, Bismuth C, Scherrmann JM (1992) Toxicokinetics of colchicine in humans: analysis of tissue, plasma and urine data in ten cases. Hum Exp Toxicol 11:510–516PubMedCrossRefGoogle Scholar
  64. 64.
    Takatori T, Tomii S, Terazawa K, Nagao M, Kanamori M, Tomaru Y (1991) A comparative study of diazepam levels in bone marrow versus serum, saliva and brain tissue. Int J Leg Med 104:185–188CrossRefGoogle Scholar
  65. 65.
    Bal TS, Hewitt RW, Hiscutt AA, Johnson B (1989) Analysis of bone marrow and decomposed body tissue for the presence of paracetamol and dextropropoxyphene. J Forensic Sci Soc 29:219–223PubMedCrossRefGoogle Scholar
  66. 66.
    Noguchi TT, Nakamura GR, Griesemer EC (1978) Drug analyses of skeletonizing remains. J Forensic Sci 23:490–492PubMedGoogle Scholar
  67. 67.
    Kudo K, Sugie H, Syoui N, Kurihara K, Jitsufuchi N, Imamura T et al (1997) Detection of triazolam in skeletal remains buried for 4 years. Int J Leg Med 110:281–283CrossRefGoogle Scholar
  68. 68.
    Higuchi T, Kogawa H, Satoh M, Tatsuno M, Tsuchihashi H (1996) Application of high-performance liquid chromatography/mass spectrometry to drug screening. Am J Forensic Med Pathol 17:21–23PubMedCrossRefGoogle Scholar
  69. 69.
    Nagata T, Kimura K, Hara K, Kudo K (1990) Methamphetamine and amphetamine concentrations in postmortem rabbit tissues. Forensic Sci Int 48:39–47PubMedCrossRefGoogle Scholar
  70. 70.
    Casier HT, Delaunois AL (1943) La répartition de l'alcool chez l'homme et les animaux au cours de l'intoxication éthylique. Arch Int Pharmacodyn 69:186Google Scholar
  71. 71.
    Isokoski M, Alha A, Laiho K (1968) Bone marrow alcohol content in cadavers. J Forensic Med 15:9–11PubMedGoogle Scholar
  72. 72.
    Hoiseth G, Karinen R, Johnsen L, Normann PT, Christophersen AS, Morland J (2008) Disappearance of ethyl glucuronide during heavy putrefaction. Forensic Sci Int 176:147–151PubMedCrossRefGoogle Scholar
  73. 73.
    Helander A, Dahl H (2005) Urinary tract infection: a risk factor for false-negative urinary ethyl glucuronide but not ethyl sulfate in the detection of recent alcohol consumption. Clin Chem 51:1728–1730PubMedCrossRefGoogle Scholar
  74. 74.
    Schloegl H, Dresen S, Spaczynski K, Stoertzel M, Wurst FM, Weinmann W (2006) Stability of ethyl glucuronide in urine, post-mortem tissue and blood samples. Int J Leg Med 120:83–88CrossRefGoogle Scholar
  75. 75.
    Helander A, Hagelberg CA, Beck O, Petrini B (2009) Unreliable alcohol testing in a shipping safety programme. Forensic Sci Int 189:e45–e47PubMedCrossRefGoogle Scholar
  76. 76.
    Helander A, Olsson I, Dahl H (2007) Postcollection synthesis of ethyl glucuronide by bacteria in urine may cause false identification of alcohol consumption. Clin Chem 53:1855–1857PubMedCrossRefGoogle Scholar
  77. 77.
    Baranowski S, Serr A, Thierauf A, Weinmann W, Grosse Perdekamp M, Wurst FM et al (2008) In vitro study of bacterial degradation of ethyl glucuronide and ethyl sulphate. Int J Leg Med 122:389–893CrossRefGoogle Scholar
  78. 78.
    Halter CC, Laengin A, Al-Ahmad A, Wurst FM, Weinmann W, Kuemmerer K (2009) Assessment of the stability of the ethanol metabolite ethyl sulfate in standardised degradation tests. Forensic Sci Int 186:52–55PubMedCrossRefGoogle Scholar
  79. 79.
    Hoiseth G, Karinen R, Christophersen A, Morland J Practical use of ethyl glucuronide and ethyl sulfate in postmortem cases as markers of antemortem alcohol ingestion. Int J Legal Med 124:143–148Google Scholar
  80. 80.
    Fanton L, Bevalot F, Gustin MP, Paultre CZ, Le Meur C, Malicier D (2009) Interpretation of drug concentrations in an alternative matrix: the case of meprobamate in bile. Int J Leg Med 123:97–102CrossRefGoogle Scholar
  81. 81.
    Sato Y, Kondo T, Takayasu T, Ohshima T (2000) Detection of methamphetamine in a severely burned cadaver—a case report. Nihon Hoigaku Zasshi 54:420–424PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Nathalie Cartiser
    • 1
    • 2
  • Fabien Bévalot
    • 2
    • 3
  • Laurent Fanton
    • 3
  • Yvan Gaillard
    • 2
  • Jérôme Guitton
    • 1
    • 4
  1. 1.Université de Lyon, Université Claude Bernard Lyon 1, ISPB-Faculté de pharmacie, Laboratoire de ToxicologieLyon cedex 08France
  2. 2.Laboratoire LAT LUMTOXLyonFrance
  3. 3.Université de Lyon, Université Claude Bernard Lyon 1, Institut de Médecine LégaleLyon cedex 08France
  4. 4.Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Laboratoire de pharmacologie-toxicologiePierre BéniteFrance

Personalised recommendations