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01.01.2024 | Review

Effect of simvastatin topical use on alveolar bone after tooth extraction: a scoping review

verfasst von: Jiordanne Araújo Diniz, Ana Cláudia Amorim Gomes Dourado, Davi da Silva Barbirato, Karoline Gomes da Silveira, Ricardo José de Holanda Vasconcellos, José Rodrigues Laureano Filho

Erschienen in: Clinical Oral Investigations | Ausgabe 1/2024

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Abstract

Objectives

Conducting a scoping review (SR) to assess scientific evidence for topical simvastatin’s impact on alveolar bone regeneration and determine its level of support for clinical applications.

Materials and methods

This SR followed the PRISMA-ScR and OSF registries protocol; systematic searching was conducted on MEDLINE/PubMed, Cochrane, Embase, Scopus, Web of Science, and LILACS, to identify relevant articles until June 2023. Inclusion criteria covered clinical trials, case series, prospective and retrospective studies, along with in vivo investigations, involving participants of any sex and age.

Results

Out of 1312 identified studies, 20 (9 in vivo, 11 RCTs) met inclusion criteria. RCTs focused on third molar extraction, in vivo on mandibular incisor surgery. The majority of RCTs employed a collagen sponge and a simvastatin concentration of 10mg; conversely, most in vivo studies favored polylactide-co-glycolide and a 2 mg simvastatin concentration. RCTs had 3-month follow-ups; in vivo, studies extended to 8 weeks. Seven RCTs assessed pain outcomes, simvastatin did not significantly affect pain in six studies. Among four RCTs on postoperative swelling, only two observed a significant increase in the simvastatin group. In general, positive bone formation and the absence of adverse effects directly linked to topical simvastatin were observed across the study models.

Conclusions

Intra-alveolar simvastatin post-tooth extraction has been to be shown to be effective and safe for preserving alveolar bone, with varied concentrations and carriers, with no significant adverse effects.

Clinical relevance

This review provides critical insights into the effects of simvastatin on alveolar bone regeneration, informing potential benefits and possible challenges associated with its post-extraction application.

OSF Registry protocol

osf.io/q3bnf

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Li X, Liu X, Ni S, Liu Y, Sun H, Lin Q (2019) Enhanced osteogenic healing process of rat tooth sockets using a novel simvastatin-loaded injectable microsphere-hydrogel system. J Craniomaxillofac Surg 47:1147–1154. https://doi.org/10.1016/j.jcms.2019.04.011CrossRefPubMed

Diniz JA, Barbirato DS, Nascimento EHL, Pontual AA, Dourado ACAG, Laureano Filho JR (2022) Tomographic evaluation of the effect of simvastatin topical use on alveolar bone microarchitecture, pain and swelling after mandibular third molar extraction: a randomized controlled trial. Clin Oral Investig 26:3533–3545. https://doi.org/10.1007/s00784-021-04322-8CrossRefPubMed

Oliveira MN, Rau LH, Marodin A, Corrêa M, Corrêa LR, Aragones A, Magini RS (2017) Ridge preservation after maxillary third molar extraction using 30% porosity PLGA/HA/β-TCP scaffolds with and without simvastatin: a pilot randomized controlled clinical trial. Implant Dent 26:832–840. https://doi.org/10.1097/ID.0000000000000655CrossRef

Deepanjali M, Prasad TS, Manodh P (2022) Efficacy of simvastatin in bone regeneration after surgical removal of mandibular third molars. Oral Maxillofac Surg. https://doi.org/10.1007/s10006-022-01081-y

Srinivas B, Das P, Rana MM, Qureshi AQ, Vaidya KC, Raziuddin SJA (2018) Wound healing and bone regeneration in postextraction sockets with and without platelet-rich fibrin. Ann Maxillofac Surg 8:28–34. https://doi.org/10.4103/ams.ams_153_17CrossRefPubMedPubMedCentral

Gupta S, Del Fabbro M, Chang J (2019) The impact of simvastatin intervention on the healing of bone, soft tissue, and TMJ cartilage in dentistry: a systematic review and meta-analysis. Int J Implant Dent 5:17–27. https://doi.org/10.1186/s40729-019-0168-4CrossRefPubMedPubMedCentral

Degala S, Bathija NA (2018) Evaluation of the efficacy of simvastatin in bone regeneration after surgical removal of bilaterally impacted third molars-a split-mouth randomized clinical trial. J Oral Maxillofac Surg 76:1847–1858. https://doi.org/10.1016/j.joms.2018.04.035CrossRefPubMed

Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G (1999) Stimulation of bone formation in vitro and in rodents by statins. Science 286:1946–1949. https://doi.org/10.1126/science.286.5446.1946CrossRefPubMed

Wang Z, Li Y, Zhou F, Piao Z, Hao J (2016) Effects of statins on bone mineral density and fracture risk. Medicine 95:1–8. https://doi.org/10.1097/MD.0000000000003042CrossRef

10.

Griffiths SL, Cartmell SH (2012) Use of statins for enhancing bone-tissue-engineered grafts. Eur J Plast Surg 35:151–157. https://doi.org/10.1007/s00238-007-0190-2CrossRef

11.

Tan J, Yang N, Fu X, Cui Y, Guo Q, Ma T, Yin X, Leng H, Song C (2015) Single-dose local simvastatin injection improves implant fixation via increased angiogenesis and bone formation in an ovariectomized rat model. Med Sci Monit 21:1428–1439. https://doi.org/10.12659/MSM.892247CrossRefPubMedPubMedCentral

12.

Yin H, Li J, Yu X, Fu Z (2011) Effects of simvastatin on osseointegration in a canine total hip arthroplasty model: an experimental study. J Arthroplast 26:1534–1539. https://doi.org/10.1016/j.arth.2010.10.008CrossRef

13.

Gutierrez GE, Lalka D, Garrett IR, Rossini G, Mundy GR (2006) Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations. Osteoporos Int 17:1033–1042. https://doi.org/10.1007/s00198-006-0079-0CrossRefPubMed

14.

Pradeep AR, Priyanka N, Kalra N, Naik SB, Singh SP, Martande S (2012) Clinical efficacy of subgingivally delivered 1.2-mg simvastatin in the treatment of individuals with class II furcation defects: a randomized controlled clinical trial. J Periodontol 83:1472–1479. https://doi.org/10.11607/prd.2936CrossRefPubMed

15.

Barootchi S, Tavelli L, Majzoub J, Stefanini M, Wang HL (2000) Avila-Ortiz G (2023) Alveolar ridge preservation: complications and cost-effectiveness. Periodontology 92:235–262. https://doi.org/10.1111/prd.12469CrossRef

16.

Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D, Moher D, Peters MDJ, Horsley T, Weeks L, Hempel S, Akl EA, Chang C, McGowan J, Stewart L, Hartling L, Aldcroft A, Wilson MG, Garritty C et al (2018) PRISMA Extension for Scoping Reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med 169:467–473. https://doi.org/10.7326/M18-0850CrossRefPubMed

17.

Arksey H, O’Malley L (2005) Scoping studies: towards a methodological framework. Int J Soc Res Methodol 1:19–32. https://doi.org/10.1080/1364557032000119616CrossRef

18.

Levac D, Colquhoun H, O'Brien KK (2010) Scoping studies: advancing the methodology. Implement Sci 5:69. https://doi.org/10.1186/1748-5908-5-69CrossRefPubMedPubMedCentral

19.

Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33:159–174. https://doi.org/10.2307/2529310CrossRefPubMed

20.

Howick J, Chalmers I, Glasziou P, Greenhalgh T, Heneghan C, Liberati A, Moschetti I, Phillips B, Thornton H (2011) Explanation of the 2011 oxford centre for evidence-based medicine (OCEBM) levels of evidence (background document). Oxford centre for evidence-based medicine. https://www.cebm.ox.ac.uk/resources/levels-of-evidence/explanation-of-the-2011-ocebm-levels-of-evidence/. Accessed 26 Jun 2023

21.

Campbell M, McKenzie JE, Sowden A, Katikireddi SV, Brennan SE, Ellis S, Hartmann-Boyce J, Ryan R, Shepperd S, Thomas J, Welch V, Thomson H (2020) Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ 368:l6890. https://doi.org/10.1136/bmj.l6890CrossRefPubMedPubMedCentral

22.

Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW (2014) SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 14:43. https://doi.org/10.1186/1471-2288-14-43CrossRefPubMedPubMedCentral

23.

Sterne J, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, Emberson JR, Hernán MA, Hopewell S, Hróbjartsson A, Junqueira DR, Jüni P, Kirkham JJ, Lasserson T, Li T et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ (Clin Res Eed) 366:l4898. https://doi.org/10.1136/bmj.l4898CrossRef

24.

Sato D, Nishimura K, Ishioka T, Kondo H, Kuroda S, Kasugai S (2005) Local application of simvastatin to rat iincisor socket: carrier-dependent effect on bone augmentation. J Oral Tissue Engin 2:81–85. https://doi.org/10.11223/jarde.2.81CrossRef

25.

Nishimura K (2008) Local application of simvastatin to rat incisor sockets augments bone. Kokubyo Gakkai Zasshi 75:49–54. https://doi.org/10.5357/koubyou.75.49CrossRefPubMed

26.

Tanigo T, Takaoka R, Tabata Y (2010) Sustained release of water-insoluble simvastatin from biodegradable hydrogel augments bone regeneration. J Control Release 143:201–206. https://doi.org/10.1016/j.jconrel.2009.12.027CrossRefPubMed

27.

Maruo K, Sato D, Machida T, Kasugai S (2010) Effects of alpha-tricalcium phosphate containing simvastatin on alveolar ridge augmentation. J Oral Tissue Engin 7:143–152. https://doi.org/10.11223/jarde.7.143CrossRef

28.

Wu Z, Liu C, Zang G, Sun H (2008) The effect of simvastatin on remodelling of the alveolar bone following tooth extraction. Int J Oral Maxillofac Surg 37:170–176. https://doi.org/10.1016/j.ijom.2007.06.018CrossRefPubMed

29.

Liu C, Wu Z, Sun HC (2009) The effect of simvastatin on mRNA expression of transforming growth factor-beta1, bone morphogenetic protein-2 and vascular endothelial growth factor in tooth extraction socket. Int J Oral Sci 1:90–98. https://doi.org/10.4248/ijos.08011CrossRefPubMedPubMedCentral

30.

Abdi Z, Azizian M, Abbasi N, Darabi A, Abdal K (2021) Socket preservation using freeze-dried bone allograft with and without simvastatin in rats. J Mazandaran Univ Med Sci 31:1–10

31.

Sherif Y, El Masry N, Karam S, Nasra M (2016) Evaluation of local administration of simvastatin on height and width of the healing extraction socket in rat mandible. Alex Dent J 41:283–286. https://doi.org/10.21608/adjalexu.2016.58040CrossRef

32.

Saifi AM, Giraddi GB, Ahmed N (2017) Healing of extraction socket following local application of simvastatin: a split mouth prospective study. J Oral Biol Craniofacial Res 7:106–112. https://doi.org/10.1016/j.jobcr.2017.04.001CrossRef

33.

Sezavar M, Bohlouli B, Farhadi S, Tabatabaee S, Latifi R (2018) Simvastatin effects on dental socket quality: a comparative study. Contemp Clin Dent 9:55–59. https://doi.org/10.4103/ccd.ccd_719_17CrossRefPubMedPubMedCentral

34.

Cruz R, Moraschini V, Calasans-Maia MD, de Almeida DCF, Sartoretto SC, Granjeiro JM (2021) Clinical efficacy of simvastatin gel combined with polypropylene membrane on the healing of extraction sockets: a triple-blind, randomized clinical trial. Clin Oral Implants Res 32:711–720. https://doi.org/10.1111/clr.13740CrossRefPubMed

35.

Mahdi HS, Sahar SH, Al-Adili (2021) Efficacy of simvastatin and gel foam combination local application on bone density, after surgical removal of mandibular third molars. J Res Med Dent Sci 9:472–477

36.

Abu sheehah H, Hosny A, El Mohandes W (2022) Evaluation of simvastatin efficacy on bone regeneration for socket preservation. Al-Azhar J Dent Sci 25:43–48. https://doi.org/10.21608/ajdsm.2020.44274.1119CrossRef

37.

Chauhan AS, Maria A, Managutti A (2015) Efficacy of simvastatin in bone regeneration after surgical removal of mandibular third molars: a clinical pilot study. J Maxillofac Oral Surg 14:578–585. https://doi.org/10.1007/s12663-014-0697-6CrossRefPubMed

38.

Soliman O, Hussein A, Gobran H (2020) Evaluation and comparison of histologic changes in extraction sites grafted with simvastatin mixed with nanobone. Egypt J Oral and Maxillofac Surg 11:111–117. https://doi.org/10.21608/omx.2020.39319.1081CrossRef

39.

Maritz FJ, Conradie MM, Hulley PA, Gopal R, Hough S (2001) Effect of statins on bone mineral density and bone histomorphometry in rodents. Arterioscler Thromb Vasc Biol 10:1636–1641. https://doi.org/10.1161/hq1001.097781CrossRef

40.

Oryan A, Alidadi S, Moshiri A, Maffulli N (2014) Bone regenerative medicine: classic options, novel strategies, and future directions. J Orthop Surg Res 9:18. https://doi.org/10.1186/1749-799X-9-18CrossRefPubMedPubMedCentral

41.

Shuid AN, Ibrahim N, Mohd Amin MC, Mohamed IN (2013) Drug delivery systems for prevention and treatment of osteoporotic fracture. Curr Drug Targets 14:1558–1564. https://doi.org/10.2174/1389450114666131108153905CrossRefPubMed

42.

Liu X, Holzwarth JM, Ma PX (2012) Functionalized synthetic biodegradable polymer scaffolds for tissue engineering. Macromol Biosci 12:911–919. https://doi.org/10.1002/mabi.201100466CrossRefPubMed

43.

Lima CAA, Favarini VT, Torres AM, da Silva RA, Sato RFL (2017) Oral dexamethasone decreases postoperative pain, swelling, and trismus more than diclofenac following third molar removal : a randomized controlled clinical trial. Oral Maxillofac Surg 21:321–326. https://doi.org/10.1007/s10006-017-0635-0CrossRefPubMed

44.

Oryan A, Kamali A, Moshiri A (2015) Potential mechanisms and applications of statins on osteogenesis: current modalities, conflicts and future directions. J Control Release 215:12–24. https://doi.org/10.1016/j.jconrel.2015.07.022CrossRefPubMed

45.

Leung BP, Sattar N, Crilly A, Prach M, Carey M, Payne DW, Madhok R, Campbell C, Gracie AJ, Liew FY, McInnes IB (2003) A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol 170:1524–1530. https://doi.org/10.4049/jimmunol.170.3.1524CrossRefPubMed

46.

Ritto FG, Pimentel T, Canellas JVS, Junger B, Cruz M, Medeiros PJ (2019) Randomized double-blind clinical trial evaluation of bone healing after third molar surgery with the use of leukocyte and platelet-rich fibrin. Int J Oral Maxillofac Surg 48:1088–1093. https://doi.org/10.1016/j.ijom.2019.01.020CrossRefPubMed

47.

Sordi MB, Curtarelli RB, Mantovani IF, Moreira AC, Fernandes CP, Cruz ACC, Magini RS (2021) Enhanced osteoinductive capacity of poly(lactic-co-glycolic) acid and biphasic ceramic scaffolds by embedding simvastatin. Clin Oral Investig 26:2693–2701. https://doi.org/10.1007/s00784-021-04240-9CrossRefPubMed

48.

Sendyk DI, Deboni MC, Pannuti CM, Naclério-Homem MG, Wennerberg A (2016) The influence of statins on osseointegration: a systematic review of animal model studies. J Oral Rehabil 43:873–882. https://doi.org/10.1111/joor.12438CrossRefPubMed

49.

Esmaeili V, Boostani H, Ahmadpour F (2023) Efficacy of spongy xenogeneic scaffold loaded with simvastatin in the treatment of severe alveolar horizontal defect: a clinical and histological study. Niger J Clin Pract 26:369–375. https://doi.org/10.4103/njcp.njcp_86_22CrossRefPubMed

Titel: Effect of simvastatin topical use on alveolar bone after tooth extraction: a scoping review
verfasst von: Jiordanne Araújo Diniz
Ana Cláudia Amorim Gomes Dourado
Davi da Silva Barbirato
Karoline Gomes da Silveira
Ricardo José de Holanda Vasconcellos
José Rodrigues Laureano Filho
Publikationsdatum: 01.01.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Clinical Oral Investigations / Ausgabe 1/2024
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-023-05482-5

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Effect of simvastatin topical use on alveolar bone after tooth extraction: a scoping review