Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model

OZER, TAHA; Aktaş, Alper; Firat, Aysegul; KAYMAZ, Fevziye Figen; Çelik, Hakan Hamdi; ocak, mert; Avağ, Canseda

doi:10.3906/sag-2011-109

Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model

Taha ÖZER, (Hacettepe Üniversitesi, Diş Hekimliği Fakültesi, Ağız, Diş ve Çene Cerrahisi Anabilim Dalı, Ankara, Türkiye)

Alper AKTAŞ, (Hacettepe Üniversitesi, Diş Hekimliği Fakültesi, Ağız, Diş ve Çene Cerrahisi Anabilim Dalı, Ankara, Türkiye)

Canseda AVAĞ, (Hacettepe Üniversitesi, Diş Hekimliği Fakültesi, Ağız, Diş ve Çene Cerrahisi Anabilim Dalı, Ankara, Türkiye)

Ayşegül FIRAT, (Hacettepe Üniversitesi, Tıp Fakültesi, Anatomi Anabilim Dalı, Ankara, Türkiye)

Mert OCAK, (Sağlık Meslek Yüksekokulu, Ankara Üniversitesi, Ankara, Türkiye)

Fevziye Figen KAYMAZ, (Hacettepe Üniversitesi, Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Ankara, Türkiye)

H. Hamdi ÇELİK (Hacettepe Üniversitesi, Tıp Fakültesi, Anatomi Anabilim Dalı, Ankara, Türkiye)

Turkish Journal of Medical Sciences

2 0

Yıl: 2021 Cilt: 51 Sayı: 6 Sayfa Aralığı: 3115 - 3125 Metin Dili: İngilizce DOI: 10.3906/sag-2011-109 İndeks Tarihi: 05-01-2022

Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model

Öz:

Background/aim: Guided bone regeneration (GBR) is commonly performed to repair bone defects, and rigid occlusive titanium barriers play a vital role in bone formation in regions with no prior bone tissue. The statin, rosuvastatin (RSV), strongly affects bone apposition when applied locally. Here, we aimed to evaluate the anabolic effects of locally applied RSV with a xenograft placed on rabbit calvaria. Materials and methods: Two rigid occlusive titanium caps were used in 16 rabbits after decorticating the calvarial bone. In the control group, the area under the cap was filled with a xenograft, while in the RSV group, a xenograft in combination with RSV (1 mg) was used. In both groups, at 6 and 12 weeks, new bone, residual graft, soft tissue areas, and histological and radiological bone volume were evaluated. Results: At 12 weeks, histologically, the RSV group exhibited superior new bone proportion values, and radiologically, new bone and total bone volume in the RSV group were significantly higher than in the control group (p < 0.05); there were no significant differences at 6 weeks (p > 0.05). Conclusion: According to our results, RSV applied locally under a titanium barrier on an area to be repaired with bone grafts increases new bone and total bone volume.Key words: Rosuvastatin, xenografting, bone transplantation, osteogenesis, HMG-CoA reductase inhibitors

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Nguyen TT, Mui B, Mehrabzadeh M, Chea Y, Chaudhry Z et al. Regeneration of tissues of the oral complex: current clinical trends and research advances. Journal of the Canadian Dental Association 2013; 79: d1.
2. Rakhmatia YD, Ayukawa Y, Furuhashi A, Koyano K. Current barrier membranes: titanium mesh and other membranes for guided bone regeneration in dental applications. Journal of Prosthodontic Research 2013; 57 (1): 3-14. Doi: 10.1016/j. jpor.2012.12.001
3. Schmid J, Hammerle CHF, Olah AJ, Lang NP. MembranePermeability Is Unnecessary for Guided Generation of New Bone - an Experimental-Study in the Rabbit. Clinical Oral Implants Research 1994; 5 (3): 125-130. Doi: 10.1034/j.1600- 0501.1994.050302.x
4. Min S, Sato S, Saito M, Ebihara H, Arai Y et al. Microcomputerized tomography analysis: dynamics of bone augmentation within a titanium cap in rabbit calvarium. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 2008; 106 (6): 892-895. Doi: 10.1016/j. tripleo.2008.04.012
5. Murai M, Sato S, Koshi R, Yokoyama K, Ikeda K et al. Effects of the enamel matrix derivative and beta-tricalcium phosphate on bone augmentation within a titanium cap in rabbit calvarium. Journal of Oral Science 2005; 47 (4): 209-217. Doi: 10.2334/ josnusd.47.209
6. Mundy G, Garrett R, Harris S, Chan J, Chen D et al. Stimulation of bone formation in vitro and in rodents by statins. Science 1999; 286 (5446): 1946-1949. Doi: 10.1126/ science.286.5446.1946
7. Maeda T, Kawane T, Horiuchi N. Statins augment vascular endothelial growth factor expression in osteoblastic cells via inhibition of protein prenylation. Endocrinology 2003; 144 (2): 681-692. Doi: 10.1210/en.2002-220682
8. Tan J, Yang N, Fu X, Cui YY, Guo Q et al. Single-Dose Local Simvastatin Injection Improves Implant Fixation via Increased Angiogenesis and Bone Formation in an Ovariectomized Rat Model. Medical Science Monitor 2015; 21: 1428-1439. Doi: 10.12659/MSM.892247
9. Karlson BW, Palmer MK, Nicholls SJ, Lundman P, Barter PJ. Doses of rosuvastatin, atorvastatin and simvastatin that induce equal reductions in LDL-C and non-HDL-C: Results from the VOYAGER meta-analysis. European Journal of Preventive Cardiology 2016; 23 (7): 744-747. Doi: 10.1177/2047487315598710
10. Monjo M, Rubert M, Wohlfahrt JC, Ronold HJ, Ellingsen JE et al. In vivo performance of absorbable collagen sponges with rosuvastatin in critical-size cortical bone defects. Acta Biomaterialia 2010; 6 (4): 1405-1412. Doi: 10.1016/j. actbio.2009.09.027
11. Ayukawa Y, Okamura A, Koyano K. Simvastatin promotes osteogenesis around titanium implants. Clinical Oral Implants Research 2004; 15 (3): 346-350. Doi: 10.1046/j.1600- 0501.2003.01015.x
12. Oxlund H, Andreassen TT. Simvastatin treatment partially prevents ovariectomy-induced bone loss while increasing cortical bone formation. Bone 2004; 34 (4): 609-618. Doi: 10.1016/j.bone.2003.12.014
13. Santic V, Cvek SZ, Sestan B, Bobinac D, Tudor A et al. Treatment of tibial bone defect with rotational vascular periosteal graft in rabbits. Collegium Antropologicum 2009; 33 (1): 43-50.
14. Cucchi A, Sartori M, Parrilli A, Aldini NN, Vignudelli E et al. Histological and histomorphometric analysis of bone tissue after guided bone regeneration with non-resorbable membranes vs resorbable membranes and titanium mesh. Clinical Implant Dentistry and Related Research 2019; 21 (4): 693-701. Doi: 10.1111/cid.12814
15. Clementini M, Morlupi A, Canullo L, Agrestini C, Barlattani A. Success rate of dental implants inserted in horizontal and vertical guided bone regenerated areas: a systematic review. International Journal of Oral and Maxillofacial Surgery 2012; 41 (7): 847-852. Doi: 10.1016/j.ijom.2012.03.016
16. Jensen T, Schou S, Svendsen PA, Forman JL, Gundersen HJ et al. Volumetric changes of the graft after maxillary sinus floor augmentation with Bio-Oss and autogenous bone in different ratios: a radiographic study in minipigs. Clinical Oral Implants Research 2012; 23 (8): 902-910. Doi: 10.1111/j.1600- 0501.2011.02245.x
17. Block MS. The Processing of Xenografts Will Result in Different Clinical Responses. Journal of Oral and Maxillofacial Surgery 2019; 77 (4): 690-697. Doi: 10.1016/j.joms.2018.10.004
18. Bottino MC, Thomas V, Schmidt G, Vohra YK, Chu TM et al. Recent advances in the development of GTR/GBR membranes for periodontal regeneration--a materials perspective. Dental Materials Journal 2012; 28 (7): 703-721. Doi: 10.1016/j. dental.2012.04.022
19. Zellin G, Linde A. Effects of different osteopromotive membrane porosities on experimental bone neogenesis in rats. Biomaterials 1996; 17 (7): 695-702. Doi: 10.1016/0142- 9612(96)86739-1
20. Linde A, Thoren C, Dahlin C, Sandberg E. Creation of new bone by an osteopromotive membrane technique: an experimental study in rats. Journal of Oral and Maxillofacial Surgery 1993; 51 (8): 892-897. Doi: 10.1016/s0278-2391(10)80111-9
21. Ezirganli S, Polat S, Baris E, Tatar I, Celik HH. Comparative investigation of the effects of different materials used with a titanium barrier on new bone formation. Clinical Oral Implants Research 2013; 24 (3): 312-319. Doi: 10.1111/j.1600- 0501.2011.02323.x
22. Ozdemir H, Ezirganli S, Isa Kara M, Mihmanli A, Baris E. Effects of platelet rich fibrin alone used with rigid titanium barrier. Archives of Oral Biology 2013; 58 (5): 537-544. Doi: 10.1016/j.archoralbio.2012.09.018
23. Zhang Y, Bradley AD, Wang D, Reinhardt RA. Statins, bone metabolism and treatment of bone catabolic diseases. Pharmacological Research 2014; 88: 53-61. Doi: 10.1016/j. phrs.2013.12.009
24. Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundamental & Clinical Pharmacology 2005; 19 (1): 117-125. Doi: 10.1111/j.1472-8206.2004.00299.x
25. Gutierrez GE, Lalka D, Garrett IR, Rossini G, Mundy GR. Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations. Osteoporosis International 2006; 17 (7): 1033-1042. Doi: 10.1007/s00198-006-0079-0
26. Wu Z, Liu C, Zang G, Sun H. The effect of simvastatin on remodelling of the alveolar bone following tooth extraction. International Journal of Oral and Maxillofacial Surgery 2008; 37 (2): 170-176. Doi: 10.1016/j.ijom.2007.06.018
27. Ibrahim HK, Fahmy RH. Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration. Drug Delivery 2016; 23 (9): 3181- 3192. Doi: 10.3109/10717544.2016.1160458
28. Mukozawa A, Ueki K, Marukawa K, Okabe K, Moroi A et al. Bone healing of critical-sized nasal defects in rabbits by statins in two different carriers. Clinical Oral Implants Research 2011; 22 (11): 1327-1335. Doi: 10.1111/j.1600-0501.2010.02135.x
29. Liu C, Zhu J, Hai B, Zhang W, Wang H et al. Single intraosseous injection of simvastatin promotes endothelial progenitor cell mobilization, neovascularization, and wound healing in diabetic rats. Plastic and Reconstructive Surgery 2020; 145 (2): 433-443. Doi: 10.1097/PRS.0000000000006502
30. Toth PP. An update on the benefits and risks of rosuvastatin therapy. Postgraduate Medical Journal 2014; 126 (2): 7-17. Doi: 10.3810/pgm.2014.03.2736
31. Pradeep AR, Garg V, Kanoriya D, Singhal S. 1.2% Rosuvastatin Versus 1.2% Atorvastatin Gel Local Drug Delivery and Redelivery in Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Placebo-Controlled Clinical Trial. Journal of Periodontology 2016; 87 (7): 756-762. Doi: 10.1902/jop.2016.150706
32. Garg S, Pradeep AR. 1.2% Rosuvastatin and 1.2% Atorvastatin Gel Local Drug Delivery and Redelivery in the Treatment of Class II Furcation Defects: A Randomized Controlled Clinical Trial. Journal of Periodontology 2017; 88 (3): 259-265. Doi: 10.1902/jop.2016.160399
33. Turer A, Turer CC, Balli U, Durmuslar MC, Onger ME et al. Effect of Local Rosuvastatin Administration on Calvarial Bone Defects. Journal of Craniofacial Surgery 2016; 27 (8): 2036- 2040. Doi: 10.1097/SCS.0000000000002763
34. Turer A, Durmuslar MC, Sener I, Misir AF, Onger ME. The Effect of Local Rosuvastatin on Mandibular Fracture Healing. Journal of Craniofacial Surgery 2016; 27 (8): e758-e761. Doi: 10.1097/SCS.0000000000003120
35. Ito K, Minegishi T, Takayama T, Tamura T, Yamada Y et al. Effects of ipriflavone on augmented bone using a guided bone regeneration procedure. Clinical Oral Implants Research 2007; 18 (1): 60-68. Doi: 10.1111/j.1600-0501.2006.01284.x
36. Marechal M, Eyckmans J, Schrooten J, Schepers E, Luyten FP et al. Bone augmentation with autologous periosteal cells and two different calcium phosphate scaffolds under an occlusive titanium barrier: an experimental study in rabbits. Journal of Periodontology 2008; 79 (5): 896-904. Doi: 10.1902/ jop.2008.070043
37. Yamada Y, Tamura T, Hariu K, Asano Y, Sato S et al. Angiogenesis in newly augmented bone observed in rabbit calvarium using a titanium cap. Clinical Oral Implants Research 2008; 19 (10): 1003-1009. Doi: 10.1111/j.1600-0501.2008.01554.x
38. Min S, Sato S, Murai M, Okuno K, Fujisaki Y et al. Effects of marrow penetration on bone augmentation within a titanium cap in rabbit calvarium. Journal of Periodontology 2007; 78 (10): 1978-1984. Doi: 10.1902/jop.2007.070086
39. Tamimi FM, Torres J, Tresguerres I, Clemente C, LopezCabarcos E et al. Bone augmentation in rabbit calvariae: comparative study between Bio-Oss and a novel beta-TCP/ DCPD granulate. Journal of Clinical Periodontology 2006; 33 (12): 922-928. Doi: 10.1111/j.1600-051X.2006.01004.x
40. Deluiz D, Oliveira LS, Pires FR, Tinoco EM. Time-dependent changes in fresh-frozen bone block grafts: tomographic, histologic, and histomorphometric findings. Clinical Implant Dentistry and Related Research 2015; 17 (2): 296-306. Doi: 10.1111/cid.12108

APA	OZER T, Aktaş A, Avağ C, Firat A, ocak m, KAYMAZ F, Çelik H (2021). Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model. , 3115 - 3125. 10.3906/sag-2011-109
Chicago	OZER TAHA,Aktaş Alper,Avağ Canseda,Firat Aysegul,ocak mert,KAYMAZ Fevziye Figen,Çelik Hakan Hamdi Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model. (2021): 3115 - 3125. 10.3906/sag-2011-109
MLA	OZER TAHA,Aktaş Alper,Avağ Canseda,Firat Aysegul,ocak mert,KAYMAZ Fevziye Figen,Çelik Hakan Hamdi Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model. , 2021, ss.3115 - 3125. 10.3906/sag-2011-109
AMA	OZER T,Aktaş A,Avağ C,Firat A,ocak m,KAYMAZ F,Çelik H Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model. . 2021; 3115 - 3125. 10.3906/sag-2011-109
Vancouver	OZER T,Aktaş A,Avağ C,Firat A,ocak m,KAYMAZ F,Çelik H Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model. . 2021; 3115 - 3125. 10.3906/sag-2011-109
IEEE	OZER T,Aktaş A,Avağ C,Firat A,ocak m,KAYMAZ F,Çelik H "Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model." , ss.3115 - 3125, 2021. 10.3906/sag-2011-109
ISNAD	OZER, TAHA vd. "Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model". (2021), 3115-3125. https://doi.org/10.3906/sag-2011-109

APA	OZER T, Aktaş A, Avağ C, Firat A, ocak m, KAYMAZ F, Çelik H (2021). Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model. Turkish Journal of Medical Sciences, 51(6), 3115 - 3125. 10.3906/sag-2011-109
Chicago	OZER TAHA,Aktaş Alper,Avağ Canseda,Firat Aysegul,ocak mert,KAYMAZ Fevziye Figen,Çelik Hakan Hamdi Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model. Turkish Journal of Medical Sciences 51, no.6 (2021): 3115 - 3125. 10.3906/sag-2011-109
MLA	OZER TAHA,Aktaş Alper,Avağ Canseda,Firat Aysegul,ocak mert,KAYMAZ Fevziye Figen,Çelik Hakan Hamdi Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model. Turkish Journal of Medical Sciences, vol.51, no.6, 2021, ss.3115 - 3125. 10.3906/sag-2011-109
AMA	OZER T,Aktaş A,Avağ C,Firat A,ocak m,KAYMAZ F,Çelik H Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model. Turkish Journal of Medical Sciences. 2021; 51(6): 3115 - 3125. 10.3906/sag-2011-109
Vancouver	OZER T,Aktaş A,Avağ C,Firat A,ocak m,KAYMAZ F,Çelik H Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model. Turkish Journal of Medical Sciences. 2021; 51(6): 3115 - 3125. 10.3906/sag-2011-109
IEEE	OZER T,Aktaş A,Avağ C,Firat A,ocak m,KAYMAZ F,Çelik H "Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model." Turkish Journal of Medical Sciences, 51, ss.3115 - 3125, 2021. 10.3906/sag-2011-109
ISNAD	OZER, TAHA vd. "Evaluation of the effects of locally applied rosuvastatin on bone formation in a threedimensional reconstruction rabbit xenograft model". Turkish Journal of Medical Sciences 51/6 (2021), 3115-3125. https://doi.org/10.3906/sag-2011-109