Research Progress of Simvastatin in Promoting Osseointegration and Improving Poor Osteogenic Conditions

doi:10.13701/j.cnki.kqyxyj.2019.08.003

Abstract

Abstract: With the rapid development of medical technology and the continuous improvement of people's living condition, implant restoration is more likely to become the first choice for patients with dentition defects. For a along time, poor bone condition and poor osseointegration are important causes of implant failure. How to promote the integration of implants with surrounding bone tissue and further improve the initial stability of implants in patients with poor bone condition has become a hot issue for many scholars. A large number of studies have confirmed that simvastatin has the effect of promoting osteogenesis. Simvastatin has great potential for osteogenesis under adverse conditions, such as osteoporosis, periodontitis, and diabetes. This article reviews the mechanism of simvastatin in promoting osseointegration of implants, the mode and dosage of administration, and the improvement of poor osteogenesis conditions.

Key words: simvastatin, osteointegration, osteoporosis, periodontitis, diabetes

XIN Xirui, ZHOU Yanmin. Research Progress of Simvastatin in Promoting Osseointegration and Improving Poor Osteogenic Conditions[J]. Journal of Oral Science Research, 2019, 35(8): 734-737.

References

[1] Sahid MNA, Liu S, Kiyoi T, et al. Inhibition of the mevalonate pathway by simvastatin interferes with mast cell degranulation by disrupting the interaction between Rab27a and double C2 alpha proteins [J]. Eur J Pharmacol,2017,814:255-263.
[2] Dai L, Xu M, Wu H, et al. The functional mechanism of simvastatin in experimental osteoporosis [J]. J Bone Miner Metab, 2016, 34(1): 23-32.
[3] Nyan M, Hao J, Miyahara T, et al. Accelerated and enhanced bone formation on novel simvastatin-loaded porous titanium oxide surfaces [J]. Clin Implant Dent Relat Res, 2014,16(5):675-683.
[4] Yamashita M, Otsuka F, Mukai T, et al. Simvastatin antagonizes tumor necrosis factor-alpha inhibitionof bone morphogenetic proteins-2-induced osteoblast differentiation by regulating Smad signaling and Ras/Rho-mitogenactivated protein kinase pathway [J]. J Endocrinol, 2008, 196(3):601-613.
[5] Lv J, Xiu P, Tan J, et al. Enhanced angiogenesis and osteogenesis in critical bone defects by the controlled release of BMP-2 and VEGF: implantation of electron beam melting-fabricated porous Ti6Al4V scaffolds incorporating growth factor-doped fibrin glue [J]. Biomed Mater,2015,10(3):035013.
[6] Maeda T, Kawane T, Horiuchi N, et al. Statins augment vascular endothelial growth factor expression in osteoblastic cells via inhibition of protein prenylation [J]. Endocrinology, 2003, 144(2): 681-692.
[7] Sato T, Morita I, Murota S, et al. Involvement of cholesterol in osteoclastlike cell formation via cellular fusion [J]. Bone,1998,3(2):135-140.
[8] Liu S, Bertl K, Sun H, et al. Effect of simvastatin on the osteogenetic behavior of alveolar osteoblasts and periodontal ligament cells [J]. Hum Cell, 2012,25(2):29-35.
[9] Ayukawa Y, Ogino Y, Moriyama Y, et al. Simvastatin enhances bone formation around titanium implants in rat tibiae [J]. J Oral Rehabil, 2010, 37(2):123-130.
[10] López-Álvarez M, López-Puente V, Rodríguez-Valencia C, et al. Osteogenic effects of simvastatin-loaded mesoporous titania thin films [J]. Biomed Mater, 2018, 13(2): 025017.
[11] 侯丽娟,赵彬,贾丽红.辛伐他汀与Bio-Oss骨粉复合物修复种植体周骨缺损的实验研究[J].中国现代医生, 2012, 50(11): 13-14.
[12] Du Z, Chen J, Yan F, et al. Serum bone formation marker correlation with improved osseointegration in osteoporotic rats treated with simvastatin [J]. Clin Oral Implants Res,2013,24(4):422-427.
[13] 顾勤益,梁国强,徐荣耀,等.辛伐他汀促进种植体骨整合的实验研究[J].口腔生物医学, 2016, 7(3): 134-139.
[14] Tan J, Yang N, Fu X, et al. Single-dose local simvastatin injection improves implant fixation via increased angiogenesis and bone formation in an ovariectomized rat model [J]. Med Sci Monit, 2015, 21:1428-1439.
[15] Mansour G, Al Ashwah A, Koura A. Evaluation of Simvastatin grafting around immediate dental implants in dogs [J]. Implant Dent, 2014, 23(2): 195-199.
[16] Faraco-Schwed FN, Mangueira LM, Ribeiro JV, et al. Removal torque analysis of implants in rabbit tibia after topical application of simvastatin gel [J]. J Oral Implantol, 2014, 40(1):53-59.
[17] Xu R, Shi G, Xu L, et al. Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity [J]. J Tissue Eng Regen Med, 2018, 12(5):1209-1219.
[18] Yang G, Song L, Guo C, et al. Bone responses to simvastatin-loaded porous implant surfaces in an ovariectomized model [J]. Int J Oral Maxillofac Implants, 2012, 27(2): 369-374.
[19] Nyan M, Hao J, Miyahara T, et al. Accelerated and enhanced bone formation on novel simvastatin-loaded porous titanium oxide surfaces [J]. Clin Implant Dent Relat Res, 2014, 16(5):675-683.
[20] Fang W, Zhao S, He F, et al. Influence of simvastatin-loaded implants on osseointegration in an ovariectomized animal model [J]. Biomed Res Int, 2015, 2015:831504.
[21] Zhao S, Wen F, He F, et al. In vitro and in vivo evaluation of the osteogenic abilityof implant surfaces with a local delivery of simvastatin [J]. Int J Oral Maxillofac Implants, 2014, 29(1): 211-220.
[22] Liu Y, Zhang X, Liu Y, et al. Bi-functionalization of a calcium phosphate-coated titanium surface with slow-release simvastatin and metronidazole to provide antibacterial activities and pro-osteodifferentiation capabilities [J]. PLoS One, 2014, 9(5):e97741.
[23] Tanigo T, Takaoka R, Tabata Y. Sustained release of water-insoluble simvastatin from biodegradable hydrogel augments bone regeneration[J]. J Control Release, 2010, 143(2): 201-206.
[24] Liu H, Li W, Liu C, et al. Incorporating simvastatin/poloxamer 407 hydrogel into 3D-printed porous Ti6Al4V scaffolds for the promotion of angiogenesis, osseointegration and bone ingrowth [J]. Biofabrication, 2016, 8(4): 045012.
[25] Li Y, Zhang Z, Zhang Z. Porous chitosan/nano-hydroxyapatite composite scaffolds incorporating simvastatin-loaded PLGA microspheres for bone repai [J]. Cells Tissues Organs, 2018, 205(1):20-31.
[26] Liu X, Zhang Y, Li S, et al. Study of a new bone-targeting titanium implant-bone interface [J]. Int J Nanomedicine, 2016, 11:6307-6324.
[27] Fu X, Tan J, Sun CG,et al. Intraosseous injection of simvastatin in poloxamer 407 hydrogel improves pedicle-screw fixation in ovariectomized minipigs [J]. J Bone Joint Surg Am, 2016, 98(22): 1924-1932.
[28] Shahrezaee M, Oryan A, Bastami F, et al. Comparative impact of systemic delivery of atorvastatin, Simvastatin, and lovastatin on bone mineral density of the ovariectomized rats [J]. Endocrine, 2018, 60(1):138-150.
[29] 郭涛,杨川,吾斯曼江·艾尔肯,等.辛伐他汀促进骨质疏松症大鼠种植体骨结合的实验研究[J].新疆医科大学学报, 2017, 40(9): 1187-1190.
[30] Dai L, Xu M, Wu H, et al. The functional mechanism of simvastatin in experimental osteoporosis [J]. J Bone Miner Metab, 2016, 34(1): 23-32.
[31] Jin J, Zhang X, Lu Z, et al. Simvastatin inhibits lipopolysaccharide-induced osteoclastogenesis and reduces alveolar boneloss in experimental periodontal disease [J]. J Periodontal Res, 2014, 49(4): 518-526.
[32] Machado WM, Prestes AP, Costa TP, et al. The effect of simvastatin on systemic inflammation and endothelial dysfunction induced by periodontitis [J]. J Periodontal Res, 2014, 49(5): 634-641.
[33] Gunjiganur Vemanaradhya G, Emani S, Mehta DS, et al. Effect of 1.2% of simvastatin gel as a local drug delivery system on gingival crevicular fluid interleukin-6 & interleukin-8 levels in non surgical treatment of chronic periodontitis patients [J]. Arch Oral Biol, 2017, 82: 55-61.
[34] Hu XF, Wang L, Xiang G, et al. Angiogenesis impairment by the NADPH oxidase-triggered oxidative stress at the bone-implantinterface: critical mechanisms and therapeutic targets for implant failure under hyperglycemic conditions in diabetes [J]. Acta Biomater,2018, 73: 470-487.
[35] Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase [J]. Science, 2001, 292(5519):1160-1164.
[36] Ezirganli S, kazancioglu HO, Mihmanli, et al. The effect of local simvastatin application on critical size defects in the diabetic rats [J]. Clin Oral Implants Res, 2014, 25(8): 969-976.