Zoledronate가 토끼장골에서 채취한 상악동 골이식부위 치유에 미치는 영향

EFFECT OF ZOLEDRONATE TO BONE HEALING PROCESS AFTER ILIAC BONE GRAFT INTO MAXILLARY SINUS IN RABBIT

  • 송준호 (인제대학교 의과대학 부산백병원 구강악안면외과) ;
  • 이수운 (인제대학교 의과대학 부산백병원 구강악안면외과) ;
  • 박상준 (인제대학교 의과대학 부산백병원 구강악안면외과)
  • Song, Jun-Ho (Department of Oral and Maxillofacial Surgery, Pusan Paik hospital,, Inje University) ;
  • Lee, Soo-Woon (Department of Oral and Maxillofacial Surgery, Pusan Paik hospital,, Inje University) ;
  • Park, Sang-Jun (Department of Oral and Maxillofacial Surgery, Pusan Paik hospital,, Inje University)
  • 발행 : 2009.06.30

초록

Objective : Recently, we are interested in bisphosphonate related osteonecrosis of the jaw (BRONJ). Most of patients with osteonecrosis have taken medicine bisphosphonate for a long time. But the mechanism of osteonecrosis in BRONJ was not clarified yet. The aim of this study is to evaluate the difference of bone healing effect after bone graft from ilium to maxillary sinus in rabbits between zoledronate-treated and zoledronate-not treated groups. Method : The subjects was divided into two groups. The experimental group was 9 rabbits, treated with intraperitoneal administration of zoledronate(0.06mg/kg) once per week for 3 weeks. In control group, same procedure was applied but administerd saline instead of zoledronate. After 4 weeks, surgical operation under local anesthesia (ketamine 3.0cc, xylazine 1.0cc) was done. At postoperative 1, 2, 4, 8 weeks later, each rabbits were sacrificed and removed the bone grafted area. Gross, radiologic and histopathologic exminations of bone grafted area were performed. Result : There were no conspicuous differences of radiological findings between experimental and control groups in any experimental weeks. In experimental group, new bone formation appeared earlier than control group at 1 week after operation, and maturation of bony tissue were more conspicuous at 2 and 4 weeks after operation, compared with control group. In 8 weeks after operation, similar microscopic findings were noted in both groups. Conclusion : In the bisphosphonate-treated rabbits, new bone formation in the bone grafted area appeared earlier and bony maturation was more concpicuous, even though there were no significant differences of gross and radiological findings. These findings suggest that bisphosphonate might be promotive effect in the healing process in early stage after administration.

키워드

참고문헌

  1. Grynpas MD, Acito A, Dimitriu M, Mertz BP, Very JM.Changes in bone mineralization, architecture and mechanicalproperties due to long-term (1 year) administration ofpamidronate (APD) to adult dogs. Osteoporos 1992; Int 2:74-81 https://doi.org/10.1007/BF01623840
  2. Alakangas A, Selander K, Mulari M, Halleen J. Aledronate disturbsvesicular trafficking in osteoclasts. Calcif Tissue Int 2002;70:40-7 https://doi.org/10.1007/s002230010047
  3. Luckman SP, Hughes DE, Coxon FP. Nitrogen-containing bisphosphonatesinhibit the mevalonate pathway and prevent posttranslationalprenylation of GTP-bonding proteins, including Ras.J Bone Miner Res 1998;13:581-9 https://doi.org/10.1359/jbmr.1998.13.4.581
  4. Zhang FL, Casey PJ. Protein prenylation : molecular mechanismand functional sequences. Annu Rev Biochem 1996;65:241-69 https://doi.org/10.1146/annurev.bi.65.070196.001325
  5. Vitte C. Fleisch. Bisphosphonates induce osteoblasts to secrete an inhibitor of osteoclast-mediated resorption. Endocrinology1996;137:2324-33 https://doi.org/10.1210/en.137.6.2324
  6. Sahni M, Guenther HL, Fleisch. Bisphosphonates act on rat boneresorption though the medication of osteoblasts. J Clin Inves1993;91:2004-11 https://doi.org/10.1172/JCI116422
  7. Fleisch H, Russel RGG, Bisaz S et al. The influence of pyrophosphate analogues (diphosphonates) on the precipitation and dissolution of calcium phosphate in vitro and in vivo. Calcif TissueRes, Supple 1968;2:10-10A https://doi.org/10.1007/BF02065192
  8. Audran M, Clochon P. Treatment of Paget's disease of bone with(4-chlorophenyl) thiomethylene bisphosphonate. Clin Rheumatol1989;8:71-9 https://doi.org/10.1007/BF02031073
  9. Adami S, Bolzicco GP. The use dichloromethylene bisphosphonateand aminobutane bisphosphoate in hypercalcemia of malignancy. Bone Miner 1987;2:395-404
  10. Schmidli RS, Wilson I. Aminopropylidene bisphosphonate(APD) in mild primary hyperparathyroidism : effect on clinical status. Clin Endocrinol 1990;32:293-300 https://doi.org/10.1111/j.1365-2265.1990.tb00869.x
  11. Passeri M, Baroni MC. Intermittent treatment with intravenous 4-amino-1-hydroxybutylidene-1, 1-bisphosphonate (AHBuBP) inthe therapy of postmenopausal osteoporosis. Bone Miner 1991;15:237-48 https://doi.org/10.1016/0169-6009(91)90129-N
  12. Shoji K, Horiuch H. Inhibitory effects of a bisphosphonate(residronate) on experimental periodontitis in rats. J periodontolRes 1995;30:277-84 https://doi.org/10.1111/j.1600-0765.1995.tb02134.x
  13. Adachi H, Igarashi K. Effects of topical administration of a bisphosphonate(risedronate) on orthodontic tooth movements in rat. J Dent Res 1994;73:1478-84 https://doi.org/10.1177/00220345940730081301
  14. Igarashi K, Mitani H. Anchorage and retensive effects of a bisphosphonate(AHBuBP) on tooth movements in rat. Am J OrthodDentofac Orthop 1994;106:279-89 https://doi.org/10.1016/S0889-5406(94)70048-6
  15. Hughes DW. Inhibition of osteoclast-like cell formation by bisphosphonatein long-term cultures of human bone marrow. J ClinInvest 1989; 83:1930-5 https://doi.org/10.1172/JCI114100
  16. Cocchini MG, Fleisch H. Bisphosphonate in vitro specifically inhibit,among the hematopoietic series, the development of themouse mononuclear phagocyte lineage. J Bone Miner Res 1990;5:1019-27 https://doi.org/10.1002/jbmr.5650051005
  17. Hughes DE, Wright KR. Bisphosphonate promote apoptosis inmurine osteoclasts in vitro and in vivo. J Bone Miner Res 1995;10:1478-87 https://doi.org/10.1002/jbmr.5650101008
  18. Yu X, Scholler J. Pretreatment of an osteoblastic like cell linewith bisphosphonates inhibits its PTH-stimulated induction of osteoclasticbone resorption. J Bone Miner Res [Suppl 1] 1994;9:S232(abstract)
  19. Nakagawa N, Yasuda H. Basic fibroblast growth factor inducesosteoclast formation by reciprocally regulating the production ofosteoclast differentiation factor and osteoclastogenesis inhibitoryfactor in mouse osteoblastic cells. Biochem Biophys ResCommun 1999;265:158-63 https://doi.org/10.1006/bbrc.1999.1601
  20. Sahni M, Grunther HL. Bisphosphonates act on Rat bone resorptionthrough the medication of osteoblast. J Clin Invest 1993;91:2004-11 https://doi.org/10.1172/JCI116422
  21. Schenk R, Merz WA. Effect of EHDP and Cl2MDP on the calcificationand resorption of cartilage and bone in the tibial epiphysisand metaphysics of rat. Calcif Tissue Res 1973;11:196-214 https://doi.org/10.1007/BF02547219
  22. Tenenbaum HC, Torontail M. Effect of Bisphosphonates and Inorganic Pyrophosphate on osteogenesis in vitro. Bone 1992;13:249-55 https://doi.org/10.1016/8756-3282(92)90205-B
  23. Brunsvold MA. Effect of a bisphosphonate on experimental periodontitisin monkeys. J Periodontol 1992;63:825-30 https://doi.org/10.1902/jop.1992.63.10.825
  24. O'uchi N, Nishikawa H. Inhibitory effects of YM175, a bisphosphonate,on the progression of experimental periodontitis in beagle dogs. J Periodontal Res 1998;33:196-204 https://doi.org/10.1111/j.1600-0765.1998.tb02191.x
  25. Burcu OC, Gonca CK. Effect of risedronate on alveolar bone loss and angiogenesis: a stereologic study in rat. J. Periodontol 2008;79:1955-9 https://doi.org/10.1902/jop.2008.080041
  26. American Association of Oral and Maxillofacial surgeon.Position Paper on Bisphosphonate-Related Osteonecrosis of the jaw-2009 Update 4 page
  27. Regina Landesberg. Inhibition of oral mucosa cell wound healingby bisphosphonates, J. oral and maxillofacial surgery 2008;66:839-7 https://doi.org/10.1016/j.joms.2008.01.026
  28. A. Alper. Experimental evaluation of the effects of zoledronicacid on regenerate bone formation and osteoporosis in mandibularDO, J. oral and maxillofacial surgery 2006;64:1232-6 https://doi.org/10.1016/j.joms.2006.04.038
  29. L.E. Bilston. Zoledronic acid improves the mechanical propertiesof normal and healing bone. Clin Biomech 2002;17:716 https://doi.org/10.1016/S0268-0033(02)00108-0