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Hepatocyte growth factor administration increases bone soluble phosphate and alters bone chemical structure in diabetic hypertensive rats

A Correction to this article was published on 20 August 2021

This article has been updated

Abstract

Hepatocyte growth factor (HGF) is a novel potential therapy for improving bone health in patients with type II diabetes and hypertension, but its effect on the bone molecular structure is not revealed yet. Here, X-ray absorption near edge structure (XANES) spectroscopy was used to explore the effects elicited by HGF on the bone chemical structure. This study assessed local calcium (Ca) and phosphorus (P) coordination of diabetic hypertensive rat bones, each with and without HGF treatment. Results revealed that HGF has significant effects on Ca and P coordination chemistry as confirmed by presence of more soluble phosphates in the HGT-treated groups. Data indicated that treated bones have a poorly developed phosphate structure as evidenced by drastic drop in post-edge shoulder in P L2, 3-edge compared to diabetic hypertensive and diabetic control bone. Presence of soluble Ca and P, products of bone resorption, with HGF treatment suggests unbalanced bone resorption and formation.

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References

  1. American Diabetes Association, Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2018. Diabetes Care 41(Suppl 1), S13 (2018)

    Google Scholar 

  2. A. D. Association, Economic costs of diabetes in the U.S. in 2017. Diabetes Care 41(5), 917 LP (2018)

  3. N. Napoli, R. Strollo, A. Paladini, S.I. Briganti, P. Pozzilli, S. Epstein, The alliance of mesenchymal stem cells, bone, and diabetes. Int. J. Endocrinol. 2014, 690783 (2014)

    Google Scholar 

  4. C. Conte, S. Epstein, N. Napoli, Insulin resistance and bone: a biological partnership. Acta Diabetol. 55(4), 305 (2018)

    CAS  Google Scholar 

  5. E.S. Strotmeyer, J.A. Cauley, A.V. Schwartz, M.C. Nevitt, H.E. Resnick, J.M. Zmuda, D.C. Bauer, F.A. Tylavsky, N. De Rekeneire, T.B. Harris, A.B. Newman, Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: the health, aging, and body composition study. J. Bone Miner. Res. 19(7), 1084 (2004)

    Google Scholar 

  6. L. Ma, L. Oei, L. Jiang, K. Estrada, H. Chen, Z. Wang, Q. Yu, M.C. Zillikens, X. Gao, F. Rivadeneira, Association between bone mineral density and type 2 diabetes mellitus: a meta-Analysis of observational studies. Eur. J. Epidemiol. 27(5), 319 (2012)

    CAS  Google Scholar 

  7. K.T. Tonks, C.P. White, J.R. Center, D. Samocha-Bonet, J.R. Greenfield, Bone turnover is suppressed in insulin resistance, independent of adiposity. J. Clin. Endocrinol. Metab. 102(4), 1112 (2017)

    Google Scholar 

  8. A.J. Burghardt, A.S. Issever, A.V. Schwartz, K.A. Davis, U. Masharani, S. Majumdar, T.M. Link, High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 95(11), 5045 (2010)

    CAS  Google Scholar 

  9. J.M. Patsch, A.J. Burghardt, S.P. Yap, T. Baum, A.V. Schwartz, G.B. Joseph, T.M. Link, Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J. Bone Miner. Res. 28(2), 313 (2013)

    Google Scholar 

  10. E.W. Yu, M.S. Putman, N. Derrico, G. Abrishamanian-Garcia, J.S. Finkelstein, M.L. Bouxsein, Defects in cortical microarchitecture among African-American women with type 2 diabetes. Osteoporos. Int. 26(2), 673 (2015)

    CAS  Google Scholar 

  11. E.A.C. de Waard, J.J.A. de Jong, A. Koster, H.H.C.M. Savelberg, T.A. van Geel, A.J.H.M. Houben, M.T. Schram, P.C. Dagnelie, C.J. van der Kallen, S.J.S. Sep, C.D.A. Stehouwer, N.C. Schaper, T.T.J.M. Berendschot, J.S.A.G. Schouten, P.P.M.M. Geusens, J.P.W. van den Bergh, The association between diabetes status, HbA1c, diabetes duration, microvascular disease, and bone quality of the distal radius and tibia as measured with high-resolution peripheral quantitative computed tomography—the Maastricht Study. Osteoporos. Int. 29(12), 2725 (2018)

    Google Scholar 

  12. C. Poiana, C. Capatina, Fracture risk assessment in patients with diabetes mellitus. J. Clin. Densitom. 20(3), 432 (2017)

    Google Scholar 

  13. P. Vestergaard, Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes - A meta-analysis. Osteoporos. Int. 18(4), 427 (2007)

    CAS  Google Scholar 

  14. E.S. Strotmeyer, J.A. Cauley, A.V. Schwartz, M.C. Nevitt, H.E. Resnick, D.C. Bauer, F.A. Tylavsky, N. De Rekeneire, T.B. Harris, A.B. Newman, Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging, and body composition study. Arch. Intern. Med. 165(14), 1612 (2005)

    Google Scholar 

  15. S. Pscherer, K. Kostev, F.W. Dippel, W. Rathmann, Fracture risk in patients with type 2 diabetes under different antidiabetic treatment regimens: a retrospective database analysis in primary care. Diabetes Metab. Syndr. Obes. Targets Ther. 9, 17 (2016)

    CAS  Google Scholar 

  16. M. Monami, B. Cresci, A. Colombini, L. Pala, D. Balzi, F. Gori, V. Chiasserini, N. Marchionni, C.M. Rotella, E. Mannucci, Bone fractures and hypoglycemic treatment in type 2 diabetic patients: a case-control study. Diabetes Care 31(2), 199 (2008)

    Google Scholar 

  17. J.R. Petrie, T.J. Guzik, R.M. Touyz, Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms. Can. J. Cardiol. 34(5), 575 (2018)

    Google Scholar 

  18. R. Libianto, D. Batu, R.J. MacIsaac, M.E. Cooper, E.I. Ekinci, Pathophysiological links between diabetes and blood pressure. Can. J. Cardiol. 34(5), 585 (2018)

    Google Scholar 

  19. E. Ferrannini, W.C. Cushman, Diabetes and hypertension: the bad companions. Lancet 380(9841), 601 (2012)

    Google Scholar 

  20. K.T. Mills, J.D. Bundy, T.N. Kelly, J.E. Reed, P.M. Kearney, K. Reynolds, J. Chen, J. He, Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation 134(6), 441 (2016)

    Google Scholar 

  21. B.D. Mitchell, M.P. Stern, S.M. Haffner, H.P. Hazuda, J.K. Patterson, Risk factors for cardiovascular mortality in Mexican Americans and non-Hispanic whites. Am. J. Epidemiol. 131(3), 423 (1990)

    CAS  Google Scholar 

  22. G. Lastra, S. Syed, L.R. Kurukulasuriya, C. Manrique, J.R. Sowers, Type 2 diabetes mellitus and hypertension: an update. Endocrinol. Metab. Clin. N. Am. 43(1), 103 (2014)

    Google Scholar 

  23. N.K.C. Lima, F. Abbasi, C. Lamendola, G.M. Reaven, Prevalence of insulin resistance and related risk factors for cardiovascular disease in patients with essential hypertension. Am. J. Hypertens. 22(1), 106 (2009)

    CAS  Google Scholar 

  24. K. Tsuda, I. Nishio, Y. Masuyama, Bone mineral density in women with essential hypertension. Am. J. Hypertens. 14, 704 (2001)

    CAS  Google Scholar 

  25. F.P. Cappuccio, E. Meilahn, J.M. Zmuda, J.A. Cauley, High blood pressure and bone-mineral loss in elderly white women: A prospective study. Lancet 354(9183), 971 (1999)

    CAS  Google Scholar 

  26. P. Vestergaard, L. Rejnmark, L. Mosekilde, Hypertension is a risk factor for fractures. Calcif. Tissue Int. 84(2), 103 (2009)

    CAS  Google Scholar 

  27. S. Yang, N.D. Nguyen, J.R. Center, J.A. Eisman, T.V. Nguyen, Association between hypertension and fragility fracture: a longitudinal study. Osteoporos. Int. 25(1), 97 (2014)

    CAS  Google Scholar 

  28. G.A. MacGregor, F.P. Cappuccio, The kidney and essential hypertension: a link to osteoporosis? J. Hypertens. 11, 781 (1993)

    CAS  Google Scholar 

  29. J.I. Barzilay, B.R. Davis, S.L. Pressel, A. Ghosh, R. Puttnam, K.L. Margolis, P.K. Whelton, The impact of antihypertensive medications on bone mineral density and fracture risk. Curr. Cardiol. Rep. 19(9), 76 (2017)

    Google Scholar 

  30. R.N. Frisch, K.M. Curtis, K.K. Aenlle, G.A. Howard, Hepatocyte growth factor and alternative splice variants—expression, regulation and implications in osteogenesis and bone health and repair. Expert Opin. Ther. Targets 20(9), 1087 (2016)

    CAS  Google Scholar 

  31. Y.M. Whang, S.P. Jung, M.K. Kim, I.H. Chang, S.I. Park, Targeting the hepatocyte growth factor and c-met signaling axis in bone metastases. Int. J. Mol. Sci. 20(2), 384 (2019)

    Google Scholar 

  32. Y. Matsuda, K. Matsumoto, T. Nakamura, T. Ichida, Hepatocyte growth factor suppresses the onset of liver cirrhosis and abrogates lethal hepatic dysfunction in rats1. J. Biochem. 118(3), 643 (1995)

    CAS  Google Scholar 

  33. R. Sherriff-Tadano, A. Ohta, F. Morito, M. Mitamura, Y. Haruta, S. Koarada, Y. Tada, K. Nagasawa, I. Ozaki, Antifibrotic effects of hepatocyte growth factor on scleroderma fibroblasts and analysis of its mechanism. Mod. Rheumatol. 16(6), 364 (2006)

    CAS  Google Scholar 

  34. M. Jinnin, H. Ihn, Y. Mimura, Y. Asano, K. Yamane, K. Tamaki, Effects of hepatocyte growth factor on the expression of Type I collagen and matrix metalloproteinase-1 in normal and scleroderma dermal fibroblasts. J. Invest. Dermatol. 124(2), 324 (2005)

    CAS  Google Scholar 

  35. S.R. Van Doren, Matrix metalloproteinase interactions with collagen and elastin. Matrix Biol. 44–46, 224 (2015)

    Google Scholar 

  36. H. Lodish, A. Berk, S.L. Zipursky, P. Matsudaira, D. Baltimore, J. Darnell, The dynamic Plant Cell Wall, Molecular Cell Biology. 4th edn. (W. H. Freeman and Company, New York, 2000)

  37. K. Fuller, J. Owens, T.J.  Chambers, The effect of hepatocyte growth factor on the behaviour of osteoclast. Biochem. Biophys. Res. Commun. 212(2), 334 (1995)

    CAS  Google Scholar 

  38. M. Grano, F. Galimi, G. Zambonin, S. Colucci, E. Cottone, A.Z. Zallone, P.M. Comoglio, Hepatocyte growth factor is a coupling factor for osteoclasts and osteoblasts in vitro. Proc. Natl. Acad. Sci. U.S.A. 93(15), 7644 (1996)

    CAS  Google Scholar 

  39. I.E. Adamopoulos, Z. Xia, Y.S. Lau, N.A. Athanasou, Hepatocyte growth factor can substitute for M-CSF to support osteoclastogenesis. Biochem. Biophys. Res. Commun. 350(2), 478 (2006)

    CAS  Google Scholar 

  40. K.K. Aenlle, K.M. Curtis, B.A. Roos, G.A. Howard, Hepatocyte growth factor and p38 promote osteogenic differentiation of human mesenchymal stem cells. Mol. Endocrinol. 28(5), 722 (2014)

    Google Scholar 

  41. Q. Wen, L. Zhou, C. Zhou, M. Zhou, W. Luo, L. Ma, Change in hepatocyte growth factor concentration promote mesenchymal stem cell-mediated osteogenic regeneration. J. Cell. Mol. Med. 16(6), 1260 (2012)

    CAS  Google Scholar 

  42. M. Hossain, R. Irwin, M.J. Baumann, L.R. McCabe, Hepatocyte growth factor (HGF) adsorption kinetics and enhancement of osteoblast differentiation on hydroxyapatite surfaces. Biomaterials 26(15), 2595 (2005)

    CAS  Google Scholar 

  43. K. Goshima, J. Nakase, Q. Xu, K. Matsumoto, H. Tsuchiya, Repair of segmental bone defects in rabbit tibia promoted by a complex of β-tricalcium phosphate and hepatocyte growth factor. J. Orthop. Sci. 17(5), 639 (2012)

    CAS  Google Scholar 

  44. T. Ohno, S. Hirano, S.-I. Kanemaru, M. Yamashita, H. Umeda, A. Suehiro, Y. Tamura, T. Nakamura, J. Ito, Y. Tabata, Drug delivery system of hepatocyte growth factor for the treatment of vocal fold scarring in a Canine model. Ann. Otol. Rhinol. Laryngol. 116(10), 762 (2007)

    Google Scholar 

  45. E.D. Ingall, J.A. Brandes, J.M. Diaz, M.D. de Jonge, D. Paterson, I. McNulty, W.C. Elliott, P. Northrup, Phosphorus K-edge XANES spectroscopy of mineral standards. J. Synchrotron Radiat. 18(2), 189 (2011)

    CAS  Google Scholar 

  46. H. Demirkiran, Y. Hu, L. Zuin, N. Appathurai, P.B. Aswath, XANES analysis of calcium and sodium phosphates and silicates and hydroxyapatite–Bioglass®45S5 co-sintered bioceramics. Mater. Sci. Eng. C 31(2), 134 (2011)

    CAS  Google Scholar 

  47. O.O. Aruwajoye, H.K.W. Kim, P.B. Aswath, Bone apatite composition of necrotic trabecular bone in the femoral head of immature piglets. Calcif. Tissue Int. 96(4), 324 (2015)

    CAS  Google Scholar 

  48. B. Sindhupakorn, S. Thienpratharn, P. Kidkhunthod, A structural study of bone changes in knee osteoarthritis by synchrotron-based X-ray fluorescence and X-ray absorption spectroscopy techniques. J. Mol. Struct. 1146, 254 (2017)

    CAS  Google Scholar 

  49. J. Rajendran, S. Gialanella, P.B. Aswath, XANES analysis of dried and calcined bones. Mater. Sci. Eng. C 33(7), 3968 (2013)

    CAS  Google Scholar 

  50. J. Kruse, P. Leinweber, K.-U. Eckhardt, F. Godlinski, Y. Hu, L. Zuin, Phosphorus L2,3-edge XANES: overview of reference compounds. J. Synchrotron Radiat. 16(2), 247 (2009)

    CAS  Google Scholar 

  51. S. Sato, E.G. Neves, D. Solomon, B. Liang, J. Lehmann, Biogenic calcium phosphate transformation in soils over millennial time scales. J. Soils Sediments 9(3), 194 (2009)

    CAS  Google Scholar 

  52. J. Liu, Y. Hu, J. Yang, D. Abdi, B.J. Cade-Menun, Investigation of soil legacy phosphorus transformation in long-term agricultural fields using sequential fractionation, P K-edge XANES and solution P NMR spectroscopy. Environ. Sci. Technol. 49(1), 168 (2015)

    CAS  Google Scholar 

  53. K. Güngör, A. Jürgensen, K.G. Karthikeyan, Determination of phosphorus speciation in dairy manure using XRD and XANES spectroscopy. J. Environ. Qual. 36(6), 1856 (2007)

    Google Scholar 

  54. M.E. Fleet, X. Liu, Calcium L2,3-edge XANES of carbonates, carbonate apatite, and oldhamite (CaS). Am. Miner. 94(8–9), 1235 (2009)

    CAS  Google Scholar 

  55. S.J. Naftel, T.K. Sham, Y.M. Yiu, B.W. Yates, Calcium L-edge XANES study of some calcium compounds. J. Synchrotron Radiat. 8(2), 255 (2001)

    CAS  Google Scholar 

  56. M.P. Seah, S.J. Spencer, AES of bulk insulators—control and characterisation of the surface charge. J. Electron Spectrosc. Relat. Phenom. 109(3), 291 (2000)

    CAS  Google Scholar 

  57. A. Cros, Charging effects in X-ray photoelectron spectroscopy. J. Electron. Spectrosc. Relat. Phenomena 59(1), 1 (1992)

    CAS  Google Scholar 

  58. B. Gilbert, R. Andres, P. Perfetti, G. Margaritondo, G. Rempfer, G. De Stasio, Charging phenomena in PEEM imaging and spectroscopy. Ultramicroscopy 83(1), 129 (2000)

    CAS  Google Scholar 

  59. M.E. Fleet, X. Liu, Coupled substitution of type A and B carbonate in sodium-bearing apatite. Biomaterials 28(6), 916 (2007)

    CAS  Google Scholar 

  60. M.E. Fleet, X. Liu, Location of type B carbonate ion in type A-B carbonate apatite synthesized at high pressure. J. Solid State Chem. 177(9), 3174 (2004)

    CAS  Google Scholar 

  61. M.E. Fleet, X. Liu, P.L. King, Accommodation of the carbonate ion in apatite: an FTIR and X-ray structure study of crystals synthesized at 2–4 GPa. Am. Minera. 89(10), 1422 (2004)

    CAS  Google Scholar 

  62. W. Li, X.-M. Liu, Y. Hu, Potassium and calcium K-edge XANES in chemical compounds and minerals: implications for geological phase identification. Geostand. Geoanal. Res. 44(4), 805 (2020)

    CAS  Google Scholar 

  63. M.L. Baker, M.W. Mara, J.J. Yan, K.O. Hodgson, B. Hedman, E.I. Solomon, K- and L-edge X-ray absorption spectroscopy (XAS) and resonant inelastic X-ray scattering (RIXS) determination of differential orbital covalency (DOC) of transition metal sites. Coord. Chem. Rev. 345, 182 (2017)

    CAS  Google Scholar 

  64. M. Salarian, W.Z. Xu, Z. Wang, T.-K. Sham, P.A. Charpentier, Hydroxyapatite–TiO2-based nanocomposites synthesized in supercritical CO2 for bone tissue engineering: physical and mechanical properties. ACS Appl. Mater. Interfaces 6(19), 16918 (2014)

    CAS  Google Scholar 

  65. J. Cosmidis, K. Benzerara, N. Nassif, T. Tyliszczak, F. Bourdelle, Characterization of Ca-phosphate biological materials by scanning transmission X-ray microscopy (STXM) at the Ca L2,3-, P L2,3- and C K-edges. Acta Biomater. 12, 260 (2015)

    CAS  Google Scholar 

  66. K. Väänänen, Mechanism of osteoclast mediated bone resorption–rationale for the design of new therapeutics. Adv. Drug Deliv. Rev. 57(7), 959 (2005)

    Google Scholar 

  67. W.J. Boyle, W.S. Simonet, D.L. Lacey, Osteoclast differentiation and activation. Nature 423(6937), 337 (2003)

    CAS  Google Scholar 

  68. M. Kitada, Y. Ogura, D. Koya, Rodent models of diabetic nephropathy: their utility and limitations. Int. J. Nephrol. Renovasc. Dis. 9, 279 (2016)

    CAS  Google Scholar 

  69. U. Janssen, S.G. Riley, A. Vassiliadou, J. Floege, A.O. Phillips, Hypertension superimposed on type II diabetes in Goto Kakizaki rats induces progressive nephropathy. Kidney Int. 63(6), 2162 (2003)

    Google Scholar 

  70. X. Ren, Z. Meng, H. Yang, H. Li, K. Xu, W. Zheng, P. Feng, J. Wang, Synergistic effects of combining anti-midkine and hepatocyte growth factor therapies against diabetic nephropathy in rats. Am. J. Med. Sci. 350(1), 47 (2015)

    Google Scholar 

  71. G.L. Bovenkamp, U. Zanzen, K.S. Krishna, J. Hormes, A. Prange, X-ray absorption near-edge structure (XANES) spectroscopy study of the interaction of silver ions with Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli. Appl. Environ. Microbiol. 79(20), 6385 (2013)

    CAS  Google Scholar 

  72. S. L. Hulbert, G. P. Williams, 1. Synchrotron Radiation Sources. Experimental Methods in the Physical Sciences31, 1–25 (1998)

  73. C. Bonnelle, Chapter 7. X-Ray spectroscopy. Annu. Reports Sect. “C” (Phys. Chem. 84(0), 201 (1987).

  74. N. Berrah, L. Fang, B. Murphy, T. Osipov, K. Ueda, E. Kukk, R. Feifel, P. van der Meulen, P. Salen, H.T. Schmidt, R.D. Thomas, M. Larsson, R. Richter, K.C. Prince, J.D. Bozek, C. Bostedt, S. Wada, M.N. Piancastelli, M. Tashiro, M. Ehara, Double-core-hole spectroscopy for chemical analysis with an intense X-ray femtosecond laser. Proc. Natl. Acad. Sci. U.S.A. 108(41), 16912 (2011)

    CAS  Google Scholar 

  75. S. J. Gurman, in ed. by K. H. J. Buschow, R. W. Cahn, M. C. Flemings, B. Ilschner, E. J. Kramer, S. Mahajan, T. Veyssière, Encyclopedia of Materials: Science and Technology. (Elsevier, Oxford, 2001), pp. 256–259

  76. A.J. Achkar, T.Z. Regier, E.J. Monkman, K.M. Shen, D.G. Hawthorn, Determination of total x-ray absorption coefficient using non-resonant x-ray emission. Sci. Rep. 1, 182 (2011)

    CAS  Google Scholar 

  77. Y.F. Hu, L. Zuin, G. Wright, R. Igarashi, M. McKibben, T. Wilson, S.Y. Chen, T. Johnson, D. Maxwell, B.W. Yates, T.K. Sham, R. Reininger, Commissioning and performance of the variable line spacing plane grating monochromator beamline at the Canadian Light Source. Rev. Sci. Instrum. 78(8), 83109 (2007)

    CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Kimaya Vyavhare for her help and support during the sample’s analysis. Also, the authors would like to thank the Canadian Light Source team (Drs. Tom Regier, Zachary Arthur, Lucia Zuin, David Wang, and Mohsen Shakouri) for their great support and assistance during collection and interpretation of this data. All XANES experiments were conducted at the Canadian Light Source, Saskatoon, Saskatchewan, Canada that is supported by NSERC, NRC, CIHR, and the University of Saskatchewan.

Funding

The authors want to thank the National Institutes of Health (NIH), the University of Texas at Arlington (UTA), and the UTA College of Nursing & Health Innovation Bone-Muscle Research Center (UTA-CONHI-BMRC) for their generous support for this study. The following NIH Grants supported KA and VV: (Grant Number 1R03DE023872-01, 1R56DE027964-01A1-01, NIH S10OD025230). Also, we thank the UTA-CONHI for their generous support for the first author KA via the CRS Pilot Grant.

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Correspondence to Venu Varanasi.

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This article was updated to correct corresponding author, equal author contribution note, and the graphical abstract.

Venu Veranasi was an editor of this journal during the review and decision stage. For the JMR policy on review and publication of manuscripts authored by editors, please refer to http://www.mrs.org/editor-manuscripts/.

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Awad, K., Boyes, N.G., Iqbal, R. et al. Hepatocyte growth factor administration increases bone soluble phosphate and alters bone chemical structure in diabetic hypertensive rats. Journal of Materials Research 36, 3936–3951 (2021). https://doi.org/10.1557/s43578-021-00300-8

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Keywords

  • Bone
  • Fracture
  • Chemical composition
  • Tissue
  • Biomedical
  • XANES
  • HGF