Abstract
Radiation therapy (RT) is an established treatment modality for malignant neoplasms. RT induces tissue damage that may lead to osteoradionecrosis in more severe cases. Suitable animal models to study RT-induced changes in membranous craniofacial bone are currently not available. The aim of this study was therefore to quantify RT-induced changes in cranial microcirculation using a newly developed calvaria chamber model and to relate these changes to RT-induced histological damage. New Zealand white rabbits received a total radiation dose of 18.75 Gy through the calvaria chamber, and the number of vessels, the vessel length density (VLD), and angiogenic sprouting were quantified on a weekly basis during a 12-week period. At the end of 12 weeks, the RT-treated (n = 5) or control (n = 5) calvarias were biopsied for histopathological analysis. RT resulted in a steep reduction in the number of vessels and the VLD during the first 3 weeks, particularly in larger-diameter vessels, followed by a flat stabilization/remodeling phase in the subsequent 9 weeks that never restored to baseline values. Histomorphometric analysis revealed a high degree of osteocytic depletion, prominent hypocellularity in the lacunae and intraosseous vasculature, enlarged and nonconcentric Haversian systems, and a severely disorganized bone matrix in the RT-treated calvarias. Despite the prevalence of some angiogenic potential, the RT-induced effects in the early phase persisted in the intermediate to late phase, which may have contributed to the poor recovery of the RT-treated bone.
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Mendes RL, Nutting CM, Harrington KJ (2002) Managing side effects of radiotherapy in head and neck cancer. Hosp Med 63:712–717
Bond WR Jr, Matthews JL, Finney JW (1967) The influence of regional oxygenation on osteoradionecrosis. Oral Surg Oral Med Oral Pathol 23:99–113
Marx RE (1983) Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg 41:283–288
Pappas GC (1969) Bone changes in osteoradionecrosis. A review. Oral Surg Oral Med Oral Pathol 27:622–630
Carano RA, Filvaroff EH (2003) Angiogenesis and bone repair. Drug Discov Today 8:980–989
Hom DB, Adams GL, Monyak D (1995) Irradiated soft tissue and its management. Otolaryngol Clin North Am 28:1003–1019
Urken ML, Buchbinder D, Costantino PD, Sinha U, Okay D, Lawson W, Biller HF (1998) Oromandibular reconstruction using microvascular composite flaps: report of 210 cases. Arch Otolaryngol Head Neck Surg 124:46–55
Kroll SS, Schusterman MA, Reece GP, Miller MJ, Evans GR, Robb GL, Baldwin BJ (1996) Choice of flap and incidence of free flap success. Plast Reconstr Surg 98:459–463
Winet H (1996) The role of microvasculature in normal and perturbed bone healing as revealed by intravital microscopy. Bone 19:39S–57S
Penel G, Delfosse C, Descamps M, Leroy G (2005) Composition of bone and apatitic biomaterials as revealed by intravital Raman microspectroscopy. Bone 36:893–901
Takahashi S, Sugimoto M, Kotoura Y, Sasai K, Oka M, Yamamuro T (1994) Long-term changes in the haversian systems following high-dose irradiation. An ultrastructural and quantitative histomorphological study. J Bone Joint Surg Am 76:722–738
Lopes CB, Pinheiro AL, Sathaiah S, Duarte J, Cristinamartins M (2005) Infrared laser light reduces loading time of dental implants: a Raman spectroscopic study. Photomed Laser Surg 23:27–31
International Atomic Energy Agency (2005) Radiation oncology physics: a handbook for teachers and students. E.B. Podgorsak, sponsored by IAEA, Vienna
Arnold M, Stas P, Kummermehr J, Schultz-Hector S, Trott KR (1998) Radiation-induced impairment of bone healing in the rat femur: effects of radiation dose, sequence and interval between surgery and irradiation. Radiother Oncol 48:259–265
Wolf E, Roser K, Hahn M, Welkerling H, Delling G (1992) Enzyme and immunohistochemistry on undecalcified bone and bone marrow biopsies after embedding in plastic: a new embedding method for routine application. Virchows Arch A Pathol Anat Histopathol 420:17–24
Wood B, McNaughton D (2002) Raman excitation wavelength investigation of single red blood cells in vitro. J Raman Spectrosc 33:517–523
Wood B, Caspers P, Puppels GJ, Pandiancherri S, McNaughton D (2007) Resonance Raman spectroscopy of red blood cells using near-infrared laser excitation. Anal Bioanal Chem 387:1691–1703
Lakshmi RJ, Alexander M, Kurien J, Mahato KK, Kartha VB (2003) Osteoradionecrosis (ORN) of the mandible: a laser Raman spectroscopic study. Appl Spectrosc 57:1100–1116
Penel G, Leroy G, Rey C, Bres E (1998) MicroRaman spectral study of the PO4 and CO3 vibrational modes in synthetic and biological apatites. Calcif Tissue Int 63:475–481
Penel G, Leroy G, Rey C, Sombret B, Huvenne JP, Bres E (1997) Infrared and Raman microspectrometry study of fluor-fluor-hydroxy and hydroxy-apatite powders. J Mater Sci Mater Med 8:271–276
Legeros RZ (1994) Biological and synthetic apatites. In: Brown P, Constantz BE (eds) Hydroxyapatites and related compounds. CRC Press, Boca Raton, FL, pp 3–28
Rey C, Collins B, Goehl T, Dickson IR, Glimcher MJ (1989) The carbonate environment in bone mineral: a resolution-enhanced Fourier transform infrared spectroscopy study. Calcif Tissue Int 45:157–164
Malizos KN, Papatheodorou LK (2005) The healing potential of the periosteum molecular aspects. Injury 36(Suppl 3):S13–S19
Aitasalo K (1986) Bone tissue response to irradiation and treatment model of mandibular irradiation injury. An experimental and clinical study. Acta Otolaryngol Suppl 428:1–54
Okunieff P, Wang X, Rubin P, Finkelstein JN, Constine LS, Ding I (1998) Radiation-induced changes in bone perfusion and angiogenesis. Int J Radiat Oncol Biol Phys 42:885–889
Neuman WF (1969) The milieu interieur of bone: Claude Bernard revisited. Fed Proc 28:1846–1850
McCarthy I (2006) The physiology of bone blood flow: a review. J Bone Joint Surg Am 88(Suppl 3):4–9
Briggs PJ, Moran CG, Wood MB (1998) Actions of endothelin-1, 2, and 3 in the microvasculature of bone. J Orthop Res 16:340–347
Brinker MR, Lippton HL, Cook SD, Hyman AL (1990) Pharmacological regulation of the circulation of bone. J Bone Joint Surg Am 72:964–975
Dimitrievich GS, Fischer-Dzoga K, Griem ML (1984) Radiosensitivity of vascular tissue. I. Differential radiosensitivity of capillaries: a quantitative in vivo study. Radiat Res 99:511–535
O’Connor MM, Mayberg MR (2000) Effects of radiation on cerebral vasculature: a review. Neurosurgery 46:138–149; discussion 150–151
Fischer-Dzoga K, Dimitrievich GS, Griem ML (1984) Radiosensitivity of vascular tissue. II. Differential radiosensitivity of aortic cells in vitro. Radiat Res 99:536–546
Jacobsson M, Albrektsson T, Turesson I (1985) Dynamics of irradiation injury to bone tissue. A vital microscopic investigation. Acta Radiol Oncol 24:343–350
Jee W, Arnold JS (1960) Effect of internally deposited radioisotopes upon blood vessels of cortical bones. Proc Soc Exp Biol Med 105:351–356
Kenzora JE, Steele RE, Yosipovitch ZH, Glimcher MJ (1978) Experimental osteonecrosis of the femoral head in adult rabbits. Clin Orthop Relat Res:8–46
King MA, Casarett GW, Weber DA (1979) A study of irradiated bone: I. histopathologic and physiologic changes. J Nucl Med 20:1142–1149
LaRue S, Wrigley RH, Powers BE (1987) A review of the effects of radiation-therapy on bone. Vet Radiol 28:17–22
Fajardo LF (1982) Pathology of radiation injury. Masson, New York
Narayan K, Cliff WJ (1982) Morphology of irradiated microvasculature: a combined in vivo and electron-microscopic study. Am J Pathol 106:47–62
Chen T, Burke KA, Zhan Y, Wang X, Shibata D, Zhao Y (2007) IL-12 facilitates both the recovery of endogenous hematopoiesis and the engraftment of stem cells after ionizing radiation. Exp Hematol 35:203–213
Desmons SO, Delfosse CJ, Rochon P, Buys B, Penel G, Mordon S (2008) Laser preconditioning of calvarial bone prior to an X-ray radiation injury: a preliminary in vivo study of the vascular response. Lasers Surg Med 40:28–37
Acknowledgments
We are grateful to Prof. Vincent Everts (Academic Center for Dentistry Amsterdam, Vrije Universiteit) for assistance with histological analysis and Dr. Jan van Marle (Department of Cell Biology and Histology, Academic Medical Center) for assistance with the microscopic techniques.
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Desmons, S., Heger, M., Delfosse, C. et al. A Preliminary Investigation into the Effects of X-Ray Radiation on Superficial Cranial Vascularization. Calcif Tissue Int 84, 379–387 (2009). https://doi.org/10.1007/s00223-009-9217-y
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DOI: https://doi.org/10.1007/s00223-009-9217-y