The Journal of Contemporary Dental Practice

Register      Login



Volume / Issue

Online First

Related articles

VOLUME 23 , ISSUE 6 ( June, 2022 ) > List of Articles


Comparison between Effect of Bisphosphonates, Concentrated Growth Factors or Combination on Rabbits’ Tibial Bone Defects Healing: An Experimental Study

Mohammed Ahmed Naji, Hamdy Abd El Mageed Marzook, Rana Mohamed Nagah El Qashty, Fakhreldin Hassan Abdel–Rahman

Keywords : Histochemical, Histological, Masson trichrome

Citation Information : Naji MA, Marzook HA, El Qashty RM, Abdel–Rahman FH. Comparison between Effect of Bisphosphonates, Concentrated Growth Factors or Combination on Rabbits’ Tibial Bone Defects Healing: An Experimental Study. J Contemp Dent Pract 2022; 23 (6):572-581.

DOI: 10.5005/jp-journals-10024-3348

License: CC BY-NC 4.0

Published Online: 23-09-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Aim: This study was designed to evaluate the effect of bisphosphonates (BIS) or concentrated growth factors (CGF) or a combination of them on bone defect healing. Materials and methods: Bone defects of 3-mm width and 6-mm depth were prepared in 24 rabbit tibias unilaterally, then randomly divided into the following four equal groups: 1. Group I: No treatment 2. Group II: Treated by BIS 3. Group III: Treated by CGF 4. Group IV: Treated by BIS + CGF Animals were equally sacrificed at 4 weeks, and at 6 weeks then tibias were processed for hematoxylin and eosin (H&E) and Masson's trichrome (MTC) staining. The data were subjected to one-way analysis of variance (ANOVA) followed by post hoc Tukey test and unpaired Student's t-test. Results: In group IV, the quality of newly formed bone was better than any other group with increased mineralization and decreased collagen, followed by group III, then group I, while group II showed the least favorable results. The statistical analysis showed a significant difference between groups. Conclusion: Mixing BIS with CGF showed the best healing, and bone quality results, followed by CGF-treated group, then control, and finally, BIS-treated group. Clinical significance: Using CGF as a scaffold and mixing it with BIS could help accelerate the healing of bone defects, reduce healing time, and minimize the risk of infection.

PDF Share
  1. Ghiasi MS, Chen J, Vaziri A, et al. Bone fracture healing in mechanobiological modeling: A review of principles and methods. Bone reports 2017;6:87–100. DOI: 10.1016/j.bonr.2017.03.002.
  2. Bayani M, Torabi S, Shahnaz A, et al. Main properties of nanocrystalline hydroxyapatite as a bone graft material in treatment of periodontal defects. A review of literature. Biotechnol Biotechnol Equip 2017;31(2):215–220. DOI: 10.1080/13102818.2017.1281760.
  3. Kim SY, Kim YK, Park YH, et al. Evaluation of the healing potential of demineralized dentin matrix fixed with recombinant human bone morphogenetic protein-2 in bone grafts. Materials (Basel) 2017;10(9):1049. DOI: 10.3390/ma10091049.
  4. Singh A, Gill G, Kaur H, et al. Role of osteopontin in bone remodeling and orthodontic tooth movement: A review. Prog Orthod 2018;19(1):18. DOI: 10.1186/s40510-018-0216-2.
  5. Kökdere NN, Baykul T, Findik Y. The use of platelet-rich fibrin (PRF) and PRF-mixed particulated autogenous bone graft in the treatment of bone defects: An experimental and histomorphometrical study. Dent Res J 2015;12(5):418–424. DOI: 10.4103/1735-3327.166188.
  6. Pirpir C, Yilmaz O, Candirli C, et al. Evaluation of effectiveness of concentrated growth factor on osseointegration. Int J Implant Dent 2017;3(1):7. DOI: 10.1186/s40729-017-0069-3.
  7. Kim SY, Ok HG, Birkenmaier C, et al. Can denosumab be a substitute, competitor, or complement to bisphosphonates? Korean J Pain 2017;30(2):86–92. DOI: 10.3344/kjp.2017.30.2.86.
  8. Pazianas M, van der Geest S, Miller P. Bisphosphonates and bone quality. Bonekey Rep 2014;3:529. DOI: 10.1038/bonekey.2014.24.
  9. Giannasi C, Niada S, Farronato D, et al. Nitrogen containing bisphosphonates impair the release of bone homeostasis mediators and matrix production by human primary pre-osteoblasts. Int J Med Sci 2019;16(1):23. DOI: 10.7150/ijms.27470.
  10. Whitman DH, Berry RL, Green DM. Platelet gel: An autologous alternative to fibrin glue with applications in oral and maxillofacial surgery. J Oral Maxillofac Surg 1997;55(11):1294–1299. DOI: 10.1016/s0278-2391(97)90187-7.
  11. Etulain J. Platelets in wound healing and regenerative medicine. Platelets 2018;29(6):556–568. DOI: 10.1080/09537104.2018.1430357.
  12. Choukroun J, Diss A, Simonpieri A, et al. Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part V: histologic evaluations of PRF effects on bone allograft maturation in sinus lift. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101(3):299–303. DOI: 10.1016/j.tripleo.2005.07.012.
  13. Nityasri AS, Pradeep KJJDHODT. Role of CGF (Concentrated Growth Factor) in periodontal regeneration. J Dent Health Oral Disord Ther 2018;9(2):350–352. DOI: 10.15406/jdhodt.2018.09.00407.
  14. John PK, Valliaveettil TG, George AK, et al. Platelet concentrates for periodontal regeneration. Ann Dent UM 2020;27:55–65. DOI: 10.22452/adum.vol27no9.
  15. Herath TDK, Saigo L, Schaller B, et al. In vivo efficacy of neutrophil-mediated bone regeneration using a rabbit calvarial defect model. Int J Mol Sci 2021; 22(23):13016. DOI: 10.3390/ijms222313016.
  16. Shiu S, Lee W, Chen S, et al. Effect of different bone grafting materials and mesenchymal stem cells on bone regeneration: A micro-computed tomography and histomorphometric study in a rabbit calvarial defect model. Int J Mol Sci 2021;22(15):8101. DOI: 10.3390/ijms22158101.
  17. Srisubut S, Teerakapong A, Vattraphodes T, et al. Effect of local delivery of alendronate on bone formation in bioactive glass grafting in rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104(4):e11–e6. DOI: 10.3390/ijms22158101.
  18. Mourão CFdAB, Gheno E, Lourenço ES, et al. Characterization of a new membrane from concentrated growth factors associated with denaturized Albumin (Alb-CGF) for clinical applications: A preliminary study. Int J Growth Factors Stem Cells Dent 2018;1(2):64–69. DOI: 10.4103/GFSC.GFSC_21_18. DOI: 10.1016/j.bone.2010.04.592.
  19. Holstein J, Herrmann M, Schmalenbach J, et al. Deficiencies of folate and vitamin B12 do not affect fracture healing in mice. Bone 2010;47(1):151–155. DOI: 10.1016/j.bone.2010.04.592.
  20. Meraw SJ, Reeve CM. Qualitative analysis of peripheral peri-implant bone and influence of alendronate sodium on early bone regeneration. J Periodontol 1999;70(10):1228–1233. DOI: 10.1902/jop.1999.70.10.1228.
  21. Chen H, Sun J, Hoemann CD, et al. Drilling and microfracture lead to different bone structure and necrosis during bone-marrow stimulation for cartilage repair. J Orthop Res 2009;27(11):1432–1438. DOI: 10.1002/jor.20905.
  22. Kim HC, Song JM, Kim CJ, et al. Combined effect of bisphosphonate and recombinant human bone morphogenetic protein 2 on bone healing of rat calvarial defects. Maxillofac Plast Reconstr Surg 2015;37(1):16. DOI: 10.1186/s40902-015-0015-3.
  23. Cruz MdA, Gabbai–Armelin PR, Santana AdF, et al. In vivo biological effects of marine biosilica on a tibial bone defect in rats. Brazilian Arch Biol Technol 2020;63:e20190084. DOI: 10.1590/1678-4324-2020190084.
  24. Fernandez de Grado G, Keller L, Idoux–Gillet Y, et al. Bone substitutes: A review of their characteristics, clinical use, and perspectives for large bone defects management. J Tissue Eng 2018;9:2041731418776819. DOI: 10.1177/2041731418776819.
  25. Yoon JR, Seo IW, Shin YS. Use of autogenous onlay bone graft for uncontained tibial bone defects in primary total knee arthroplasty. BMC Musculoskelet Disord 2017;18(1):502. DOI: 10.1186/s12891-017-1826-4.
  26. Naylor K, McCloskey E, Jacques R, et al. Clinical utility of bone turnover markers in monitoring the withdrawal of treatment with oral bisphosphonates in postmenopausal osteoporosis. Osteoporos Int 2019;30(4):917–922. DOI: 10.1007/s00198-018-04823-5.
  27. Arıcan G, Özmeriç A, Fırat A, et al. Micro-ct findings of concentrated growth factors (cgf) on bone healing in masquelet's technique: An experimental study in rabbits. Arch Orthop Trauma Surg 2022;142(1):83–90. DOI: 10.1007/s00402-020-03596-z.
  28. Yuan X, Pei X, Zhao Y, et al. A Wnt-responsive PDL population effectuates extraction socket healing. J Dent Res 2018;97(7):803–809. DOI: 10.1177/0022034518755719.
  29. Stübinger S, Dard M. The rabbit as experimental model for research in implant dentistry and related tissue regeneration. J Invest Surg 2013;26(5):266–282. DOI: 10.3109/08941939.2013.778922.
  30. Khalil NM, Noureldin MG. Comparison of single versus multiple low-level laser applications on bone formation in extraction socket healing in rabbits (histologic and histomorphometric study). J Oral Maxillofac Surg 2019;77(9):1760–1768. DOI: 10.1016/j.joms.2019.03.037.
  31. Salih SI, Al-Falahi NH, Saliem AH, et al. Effectiveness of platelet-rich fibrin matrix treated with silver nanoparticles in fracture healing in rabbit model. Vet World 2018;11(7):944. DOI: 10.14202/vetworld.2018.944-952.
  32. Tebyanian H, Norahan MH, Eyni H, et al. Effects of collagen/β-tricalcium phosphate bone graft to regenerate bone in critically sized rabbit calvarial defects. J Appl Biomater Funct Mater 2019;17(1):2280800018820490. DOI: 10.1177/2280800018820490.
  33. Gao SY, Zheng GS, Wang L, et al. Zoledronate suppressed angiogenesis and osteogenesis by inhibiting osteoclasts formation and secretion of PDGF-BB. PloS One. 2017;12(6):e0179248. DOI: 10.1371/journal.pone.0179248.
  34. Alidadi S, Oryan A. Biotechnology. Effects of bisphosphonates on bone fracture healing: An overview on new preclinical animal and clinical studies. Indian J Vet Sci Biotechnol 2022;18(1):2. DOI: 10.21887/ijvsbt.18.1.1.
  35. Barton DW, Smith CT, Piple AS, et al. Timing of bisphosphonate initiation after fracture: What does the data really say? Geriatr Orthop Surg Rehabil 2020;11:2151459320980369. DOI: 10.1177/2151459320980369.
  36. Lechner J, von Baehr V, Zimmermann B. Osteonecrosis of the jaw beyond bisphosphonates: Are there any unknown local risk factors? Clin Cosmet Investig Dent 2021;13:21–37. DOI: 10.2147/CCIDE.S288603.
  37. Kwak EJ, Cha IH, Nam W, et al. Effects of locally administered rh BMP-2 and bisphosphonate on bone regeneration in the rat fibula. Oral Dis 2018;24(6):1042–1056. DOI: 10.1111/odi.12864.
  38. Kim TH, Kim SH, Sándor GK, et al Comparison of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF) in rabbit-skull defect healing. Arch Oral Biol 2014;59(5):550–558. DOI: 10.1016/j.archoralbio.2014.02.004.
  39. Borsani E, Bonazza V, Buffoli B, et al. Beneficial effects of concentrated growth factors and resveratrol on human osteoblasts in vitro treated with bisphosphonates. Biomed Res Int 2018;2018:4597321. DOI: 10.1155/2018/4597321.
  40. Wang X, Tong S, Huang S, et al. Application of a new type of natural calcined bone repair material combined with concentrated growth factors in bone regeneration in rabbit critical-sized calvarial defect. Biomed Res Int 2020;2020:8810747. DOI: 10.1155/2020/8810747.
  41. Lei L, Yu Y, Han J, et al. Quantification of growth factors in advanced platelet-rich fibrin and concentrated growth factors and their clinical efficacy as adjunctive to the GTR procedure in periodontal intrabony defects. J Periodontol 2020;91(4):462–472. DOI: 10.1002/JPER.19-0290.
  42. Masuki H, Okudera T, Watanebe T, et al. Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF). Int J Implant Dent 2016;2(1):19. DOI: 10.1186/s40729-016-0052-4.
  43. Li F, Jiang P, Pan J, et al. Synergistic application of platelet-rich fibrin and 1% alendronate in periodontal bone regeneration: A meta-analysis. Biomed Res Int 2019;2019:9148183. DOI: 10.1155/2019/9148183.
  44. Abdik H, Avşar Abdik E, Demirci S, et al. The effects of bisphosphonates on osteonecrosis of jaw bone: A stem cell perspective. Mol Biol Rep 2019;46(1):763–776. DOI: 10.1007/s11033-018-4532-x.
  45. Koyama C, Hirota M, Okamoto Y, et al. A nitrogen-containing bisphosphonate inhibits osteoblast attachment and impairs bone healing in bone-compatible scaffold. J Mech Behav Biomed Mater 2020;104:103635.
  46. Chavarry NGM, Perrone D, Farias MLF, et al. Alendronate improves bone density and type I collagen accumulation but increases the amount of pentosidine in the healing dental alveolus of ovariectomized rabbits. Bone 2019;120:9–19. DOI: 10.1016/j.bone.2018.09.022.
  47. Mijiritsky E, Assaf HD, Peleg O, et al. Use of PRP, PRF and CGF in periodontal regeneration and facial rejuvenation: A narrative review. Biology (Basel) 2021;10(4):317. DOI: 10.3390/biology10040317.
  48. Fang D, Long Z, Hou J. Clinical application of concentrated growth factor fibrin combined with bone repair materials in jaw defects. J Oral Maxillofac Surg 2020;78(6):882–892. DOI: 10.1016/j.joms.2020.01.037.
  49. Kanoriya D, Pradeep AR, Garg V, et al. Mandibular degree II furcation defects treatment with platelet-rich fibrin and 1% alendronate gel combination: A randomized controlled clinical trial. J Periodontol 2017;88(3):250–258. DOI: 10.1902/jop.2016.160269.
  50. Wanikar I, Rathod S, Kolte AP. Clinico–radiographic evaluation of 1% alendronate gel as an adjunct and smart blood derivative platelet rich fibrin in grade II furcation defects. J Periodontol 2019;90(1):52–60. DOI: 10.1002/JPER.18-0146.
  51. Tiwari UO, Chandra R, Tripathi S, et al. Comparative analysis of platelet-rich fibrin, platelet-rich fibrin with hydroxyapatite and platelet-rich fibrin with alendronate in bone regeneration: A cone-beam computed tomography analysis. J Conserv Dent JCD. 2020;23(4):348–353. DOI: 10.4103/JCD.JCD_228_20.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.