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Study of thorium-induced micro-structural changes in mice femoral bone using SR-µCT

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Abstract

Objective

The present study aims to investigate early morphological and mineral density changes in bone tissues of Swiss albino mice, one month after the intravenous treatment of thorium [thorium nitrate (1 mg/100 µl); 40 mg/Kg)].

Methods

Synchrotron X-ray micro-tomographic imaging along with detailed quantitative analysis was applied to visualize and quantify morphological and mineral density changes in proximal and distal epiphysis regions of mice femur bone. Serum ALP analysis was done to assess the mechanisms of thorium-induced bone parameter changes.

Results

2D and 3D SR-µCT images are shown to depict morphological changes due to Th. Analysis of calibrated SR-µCT images shows the changes in trabecular bone thickness, volume fractions and connectivity and bone mineral density. The measured level of serum ALP showed a decrease in ALP level in thorium-treated mice.

Conclusions

Our study provides novel insights about the effect of thorium on mice bone tissues morphology and mineral density which may have significant implications in the study of mechanism of thorium interaction with bone tissues. The study also suggests the usefulness of SR-µCT technique for the characterization of heavy metal toxicity-induced structure and mineral density changes in bone samples.

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Data availability

The data that support the findings of this study are available from the corresponding author, [AKA] upon reasonable request.

References

  1. Weiner S, Wagner HD (1998) The material bone: structure-mechanical function relations. Annu Rev Mater Sci 28:271–298. https://doi.org/10.1146/annurev.matsci.28.1.271

    Article  CAS  Google Scholar 

  2. Koester KJ, Barth HD, Ritchie RO (2011) Effect of aging on the transverse toughness of human cortical bone: evaluation by R-curves. J Mech Behav Biomed Mater 4:1504–1513. https://doi.org/10.1016/j.jmbbm.2011.05.020

    Article  CAS  PubMed  Google Scholar 

  3. Patra JK, Das G, Fraceto LF et al (2018) Nano based drug delivery systems: Recent developments and future prospects 10 technology 1007 nanotechnology 03 chemical sciences 0306 physical chemistry (incl. structural) 03 chemical sciences 0303 macromolecular and materials chemistry 11 medical and he. J Nanobiotechnology 16:1–33. https://doi.org/10.1186/s12951-018-0392-8

    Article  CAS  Google Scholar 

  4. Wu CT, Lu TY, Chan DC et al (2014) Effects of arsenic on osteoblast differentiation in vitro and on bone mineral density and microstructure in rats. Environ Health Perspect 122:559–565. https://doi.org/10.1289/ehp.1307832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Duranova H, Martiniakova M, Omelka R et al (2014) Changes in compact bone microstructure of rats subchronically exposed to cadmium. Acta Vet Scand 56:64. https://doi.org/10.1186/s13028-014-0064-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rodríguez J, Mandalunis PM (2018) A review of metal exposure and its effects on bone health. J Toxicol. https://doi.org/10.1155/2018/4854152

  7. Lim H-S, Lee H-H, Kim T-H, Lee B-R (2016) Relationship between Heavy Metal Exposure and Bone Mineral Density in Korean Adult. J Bone Metab 23:223. https://doi.org/10.11005/jbm.2016.23.4.223

    Article  PubMed  PubMed Central  Google Scholar 

  8. Anantharaman K, Shivakumar V, Saha D (2008) Utilisation of thorium in reactors. J Nucl Mater 383:119–121. https://doi.org/10.1016/j.jnucmat.2008.08.042

    Article  CAS  Google Scholar 

  9. Schaffer MB (2013) Abundant thorium as an alternative nuclear fuel Important waste disposal and weapon proliferation advantages. Energy Policy 60:4–12. https://doi.org/10.1016/j.enpol.2013.04.062

    Article  CAS  Google Scholar 

  10. Kumar A, Ali M, Mishra P et al (2009) Thorium-induced neurobehavioural and neurochemical alterations in Swiss mice. Int J Radiat Biol 85:338–347. https://doi.org/10.1080/09553000902781071

    Article  CAS  PubMed  Google Scholar 

  11. Kumar A, Mishra P, Ghosh S et al (2008) Thorium-induced oxidative stress mediated toxicity in mice and its abrogation by diethylenetriamine pentaacetate. Int J Radiat Biol 84:337–349. https://doi.org/10.1080/09553000801983133

    Article  CAS  PubMed  Google Scholar 

  12. Stehney AF, Lucas HF (2000) Thorium isotopes in autopsy samples from thorium workers. Health Phys 78:8–14. https://doi.org/10.1097/00004032-200001000-00003

    Article  CAS  PubMed  Google Scholar 

  13. Harrist TJ, Schiller AL, Trelstad RL et al (1979) Thorotrast-associated sarcoma of bone. A case report and review of the literature. Cancer 44:2049–2058. https://doi.org/10.1002/1097-0142(197912)44:6

    Article  CAS  PubMed  Google Scholar 

  14. Muramatsu Y, Ishikawa Y, Yoshida S, Mori T (1999) Determination of thorium in organs from Thorotrast patients by inductively coupled plasma mass spectroscopy and X-ray fluorescence. Radiat Res 152:S97. https://doi.org/10.2307/3580123

    Article  CAS  PubMed  Google Scholar 

  15. Warnakulasuriya T, Williams S, Dabarera M et al (2017) Frequency of micronuclei among persons resident in the vicinity of a mineral sand processing factory in Pulmoddai, Sri Lanka. Mutagenesis 32:511–516. https://doi.org/10.1093/MUTAGE/GEX019

    Article  CAS  PubMed  Google Scholar 

  16. Conibear SA (1983) Long term health effects of thorium compounds on exposed workers: the complete blood count. Health Phys 44(Suppl 1):231–237. https://doi.org/10.1097/00004032-198306001-00020

    Article  CAS  PubMed  Google Scholar 

  17. Chen XA, Cheng YE, Rong Z (2005) Recent results from a study of thorium lung burdens and health effects among miners in China. J Radiol Prot 25:451–460. https://doi.org/10.1088/0952-4746/25/4/007

    Article  CAS  PubMed  Google Scholar 

  18. Farid I, Conibear SA (1983) Hepatic function in previously exposed thorium refinery workers as compared to normal controls from the health and nutrition survey. Health Phys 44(Suppl 1):221–230. https://doi.org/10.1097/00004032-198306001-00019

    Article  CAS  PubMed  Google Scholar 

  19. Creff G, Safi S, Roques J et al (2016) Actinide(IV) deposits on bone: potential role of the osteopontin-thorium complex. Inorg Chem 55:29–36. https://doi.org/10.1021/acs.inorgchem.5b02349

    Article  CAS  PubMed  Google Scholar 

  20. Frantellizzi V, Cosma L, Brunotti G et al (2020) Targeted alpha therapy with thorium-227. Cancer Biother Radiopharm 35:437–445. https://doi.org/10.1089/CBR.2019.3105

    Article  CAS  PubMed  Google Scholar 

  21. Ogawa K, Washiyama K (2012) Bone target radiotracers for palliative therapy of bone metastases. Curr Med Chem 19:3290–3300. https://doi.org/10.2174/092986712801215865

    Article  CAS  PubMed  Google Scholar 

  22. Taylor GN, Jee WSS, Christensen WR et al (1966) Thorium-228 induced fractures in beagles. Health Phys 12:889–893. https://doi.org/10.1097/00004032-196607000-00002

    Article  CAS  PubMed  Google Scholar 

  23. Babosova R, Duranova H, Omelka R et al (2016) Structural changes in femoral bone microstructure of female rabbits after intramuscular administration of quercetin. Acta Vet Scand 58:1–6. https://doi.org/10.1186/s13028-016-0225-4

    Article  CAS  Google Scholar 

  24. Freese M, Rizzo LY, Pohlmann JD et al (2019) Bone resorption and body reorganization during maturation induce maternal transfer of toxic metals in anguillid eels. Proc Natl Acad Sci USA 166:11339–11344. https://doi.org/10.1073/pnas.1817738116

    Article  CAS  Google Scholar 

  25. Larrue A, Rattner A, Peter ZA et al (2011) Synchrotron radiation micro-CT at the micrometer scale for the analysis of the three-dimensional morphology of microcracks in human trabecular bone. PLoS ONE 6:e21297. https://doi.org/10.1371/journal.pone.0021297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ma S, Boughton O, Karunaratne A et al (2016) Synchrotron imaging assessment of bone quality. Clin Rev Bone Miner Metab 14:150–160. https://doi.org/10.1007/s12018-016-9223-3

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bayat S, Apostol L, Boller E et al (2005) In vivo imaging of bone micro-architecture in mice with 3D synchrotron radiation micro-tomography. Nucl Instrum Methods Phys Res Sect A Accel Spectrom, Detect Assoc Equip 548:247–252. https://doi.org/10.1016/j.nima.2005.03.097

    Article  CAS  Google Scholar 

  28. Tang L, Chen X, Bao Y et al (2016) CT imaging biomarkers of bone damage induced by environmental level of cadmium exposure in male rats. Biol Trace Elem Res 170:146–151. https://doi.org/10.1007/s12011-015-0447-8

    Article  CAS  PubMed  Google Scholar 

  29. Sankaramanivel S, Jeyapriya R, Hemalatha D et al (2006) Effect of chromium on vertebrae, femur and calvaria of adult male rats. Hum Exp Toxicol 25:311–318. https://doi.org/10.1191/0960327105ht627oa

    Article  CAS  PubMed  Google Scholar 

  30. Ha C, M Y, G H, et al (2013) Differential development of the distal and proximal femoral epiphysis and physis in mice. Bone 52:337–346. https://doi.org/10.1016/J.BONE.2012.10.011

    Article  Google Scholar 

  31. Lavado-García JM, Puerto-Parejo LM, Roncero-Martín R, et al (2017) Dietary intake of cadmium, lead and mercury and its association with bone health in healthy premenopausal women. Int J Environ Res Public Health. https://doi.org/10.3390/ijerph14121437

  32. Belyaeva EA, Dymkowska D, Wieckowski MR, Wojtczak L (2008) Mitochondria as an important target in heavy metal toxicity in rat hepatoma AS-30D cells. Toxicol Appl Pharmacol 231:34–42. https://doi.org/10.1016/j.taap.2008.03.017

    Article  CAS  PubMed  Google Scholar 

  33. Lavery TJ, Kemper CM, Sanderson K et al (2009) Heavy metal toxicity of kidney and bone tissues in South Australian adult bottlenose dolphins (Tursiops aduncus). Mar Environ Res 67:1–7. https://doi.org/10.1016/j.marenvres.2008.09.005

    Article  CAS  PubMed  Google Scholar 

  34. Rodríguez J, Mandalunis PM (2016) Effect of cadmium on bone tissue in growing animals. Exp Toxicol Pathol Off J Ges Toxikol Pathol 68:391–397. https://doi.org/10.1016/j.etp.2016.06.001

    Article  CAS  Google Scholar 

  35. Monir AU, Gundberg CM, Yagerman SE et al (2010) The effect of lead on bone mineral properties from female adult C57/BL6 mice. Bone 47:888–894. https://doi.org/10.1016/j.bone.2010.07.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ishikawa Y, Humphreys JAH, Collier CG et al (1999) Revised organ partition of thorium-232 in thorotrast patients. Radiat Res 152:S102. https://doi.org/10.2307/3580124

    Article  CAS  PubMed  Google Scholar 

  37. Lucas LK, de Oliveira MS, de Alencar MAV (2019) Evaluation of the effect of three constituent metals of monazita on the radiosensibility of human osteoblasts. J Environ Radioact. https://doi.org/10.1016/j.jenvrad.2019.106011

  38. Agrawal AK, Singh B, Kashyap YS et al (2015) Design, development and first experiments on the X-ray imaging beamline at Indus-2 synchrotron source RRCAT, India. J Synchrotron Radiat 22:1531–1539. https://doi.org/10.1107/S1600577515016276

    Article  CAS  PubMed  Google Scholar 

  39. Agrawal A, Singh B, Kashyap Y et al (2017) Synchrotron-based X-ray microimaging facility for biomedical research. J Radiat Cancer Res 8:153. https://doi.org/10.4103/jrcr.jrcr_29_17

    Article  Google Scholar 

  40. Herman GT (2009) Filtered backprojection for parallel beams. In: Fundamentals of computerized tomography. Advances in pattern recognition. Springer, London. https://doi.org/10.1007/978-1-84628-723-7_8

  41. Limaye A (2012) Drishti: a volume exploration and presentation tool. In: Stock SR (ed) Developments in X-ray tomography, vol VIII. SPIE, p 85060X

  42. Ketcham RA, Ryan TM (2004) Quantification and visualization of anisotropy in trabecular bone. J Microsc 213:158–171. https://doi.org/10.1111/j.1365-2818.2004.01277.x

    Article  CAS  PubMed  Google Scholar 

  43. Chiba K, Nango N, Kubota S et al (2012) Relationship between microstructure and degree of mineralization in subchondral bone of osteoarthritis: a synchrotron radiation μCT study. J Bone Miner Res 27:1511–1517. https://doi.org/10.1002/jbmr.1609

    Article  PubMed  Google Scholar 

  44. Yang X, Shen X, Long J, Chen H (2012) An improved median-based Otsu image thresholding algorithm. AASRI Procedia 3:468–473. https://doi.org/10.1016/j.aasri.2012.11.074

    Article  Google Scholar 

  45. Doube M, Klosowski MM, Arganda-Carreras I et al (2010) BoneJ: free and extensible bone image analysis in ImageJ. Bone 47:1076–1079. https://doi.org/10.1016/j.bone.2010.08.023

    Article  PubMed  PubMed Central  Google Scholar 

  46. Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671–675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. da Silva AMH, Alves JM, da Silva OL, da Silva Junior NF (2014) Two and three-dimensional morphometric analysis of trabecular bone using X-ray microtomography (μCT). Rev Bras Eng Biomed 30:93–101. https://doi.org/10.1590/rbeb.2014.011

    Article  Google Scholar 

  48. Odgaard A (1997) Three-dimensional methods for quantification of cancellous bone architecture. Bone 20:315–328. https://doi.org/10.1016/S8756-3282(97)00007-0

    Article  CAS  PubMed  Google Scholar 

  49. Doube M (2015) The ellipsoid factor for quantification of rods, plates, and intermediate forms in 3D geometries. Front Endocrinol (Lausanne) 6:15. https://doi.org/10.3389/fendo.2015.00015

    Article  PubMed  Google Scholar 

  50. Costantini M, Colosi C, Mozetic P et al (2016) Correlation between porous texture and cell seeding efficiency of gas foaming and microfluidic foaming scaffolds. Mater Sci Eng C 62:668–677. https://doi.org/10.1016/j.msec.2016.02.010

    Article  CAS  Google Scholar 

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Acknowledgements

The authors acknowledge Dr. S.M. Yusuf, Director Physics Group, & Dr. L. M. Pant Head, Technical Physics Division, for his support and encouragement in beamline development and utilization activities of imaging beamline. AKA acknowledges the support of Dr. Mayank Shukla for development activities of imaging beamline. Authors also acknowledge the RRCAT, Indore, particularly Indus synchrotron operation division for providing the beam time for the experiments. This project did not receive any specific grant from funding agencies

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Authors and Affiliations

  1. Technical Physics Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India

    Ashish K. Agrawal, Balwant Singh & Yogesh Kashyap

  2. Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India

    Rakhee Yadav, Manjoor Ali, Amit Kumar & Badri N. Pandey

  3. Homi Bhabha National Institute, Mumbai, 400 094, India

    Ashish K. Agrawal, Rakhee Yadav, Balwant Singh, Amit Kumar, Yogesh Kashyap & Badri N. Pandey

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  1. Ashish K. Agrawal
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Correspondence to Ashish K. Agrawal or Badri N. Pandey.

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Conflict of interest

Ashish K. Agrawal, Rakhee Yadav, Balwant Singh, Manjoor Ali, Amit Kumar, Yogesh Kashyap, and Badri N. Pandey declare that we have no conflict of interest.

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All the experiments were adhered to the guidelines of the Institutional Animal Ethics Committee of BARC regarding the experimental use of animals.

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Agrawal, A.K., Yadav, R., Singh, B. et al. Study of thorium-induced micro-structural changes in mice femoral bone using SR-µCT. Toxicol. Environ. Health Sci. 15, 399–410 (2023). https://doi.org/10.1007/s13530-023-00191-8

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