Simvastatin's Application in dentistry. A narrative review.
DOI:
https://doi.org/10.32828/mdj.v21i2.1218Keywords:
Simvastatin, Dentistry, Orthodontics, Endodontics, PeriodonticsAbstract
Simvastatin a pharmaceutical drug, belongs to the statin’s family, that shares the same properties of their mechanism of action which is summarized by the lowering of hypercholesteremia, by averting the production of mevalonate from HMG-CoA which is a compulsory product in the cholesterol synthesis pathway. Th proved effect of oral administration of Simvastatin on increasing of bone formation and reduction of bone resorption by over expression of BMP-2 and lowering the bone resorption markers abetted by its safe use and feasibility made it an interest point of many researchers. Various dental studies have shown a positive response to both oral and local administration of statins concerning periodontal health, including a notable decrease in tooth mobility, improved clinical attachment levels, and enhanced bone fill in cases of type II diabetes having chronic periodontitis. Researchers propose that simvastatin may partially mitigate the frequency and severity of relapse, while others indicate that exosome-based drug delivery holds considerable promise for therapeutic applications in orthodontics. Furthermore, simvastatin exhibits diverse effects and applications across various fields of dentistry. The aim of this review is to entails the benefits and applications of statins in many domains of dentistry including original manuscripts for the last five years.
References
1- AGARWAL, A. & MATHUR, R. 2010. Maxillary Expansion. Int J Clin Pediatr Dent, 3, 139-46.
2- AL-ASKAR, M., AL-KHERAIF, A. A., AHMED, H. B., KELLESARIAN, S. V., MALMSTROM, H. & JAVED, F. 2017. Effectiveness of mechanical debridement with and without adjunct antimicrobial photodynamic therapy in the treatment of periodontal inflammation among patients with prediabetes. Photodiagnosis and Photodynamic Therapy, 20, 91-94.
3- ALMARJI, W., LAFLOUF, M. & TOLIBAH, Y. A. 2024. Evaluation of the modified 3Mix-Simvastatin combination in non-instrumental endodontic therapy of necrotic primary molars: A two-arm randomized controlled trial. Clin Exp Dent Res, 10, e860.
4- ALSAEED, M. A. & AL-GHABAN, N. M. H. 2023. Chitosan Nanoparticle/Simvastatin for Experimental Maxillary Bony Defect Healing: A Histological and Histomorphometrical Study. Biomimetics (Basel), 8.
5- ALSAEED, M. A., AL-GHABAN, N. M. H. & KARAIBRAHIMOĞLU, A. 2023. The influence of Simvastatin carried by Chitosan nanoparticle on bone regeneration using Masson’s Trichrome histochemical stain. Journal of Baghdad College of Dentistry, 35, 65-74.
6- ALSWAFEERI, H., ELKENANY, W., MOWAFY, M. & KARAM, S. 2018. Effect of local administration of simvastatin on postorthodontic relapse in a rabbit model. Am J Orthod Dentofacial Orthop, 153, 861-871.
7- ARIPIRALA, M., BANSAL, K., MATHUR, V. P., TEWARI, N., GUPTA, P. & LOGANI, A. 2021. Comparative evaluation of diode laser and simvastatin gel in pulpotomy of primary molars: A randomized clinical trial. J Indian Soc Pedod Prev Dent, 39, 303-309.
8- ARMITAGE, G. C. 2003. Diagnosis of periodontal diseases. J Periodontol, 74, 1237-47.
9- BARCA, E., CIFCIBASI, E. & CINTAN, S. 2015. Adjunctive use of antibiotics in periodontal therapy. J Istanb Univ Fac Dent, 49, 55-62.
10- BILVINAITE, G., DRUKTEINIS, S., SIMOLIUNAS, E., WIDBILLER, M. & SAKIRZANOVAS, S. 2024. Effect of Calcium Silicate-Based Intracanal Medicament and Calcium Hydroxide on Growth Factor TGF-β1 Release from Root Canal Dentine. J Funct Biomater, 15.
11- BORTON, A. J., FREDERICK, J. P., DATTO, M. B., WANG, X. F. & WEINSTEIN, R. S. 2001. The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis. J Bone Miner Res, 16, 1754-64.
12- BRAYER, W. K., MELLONIG, J. T., DUNLAP, R. M., MARINAK, K. W. & CARSON, R. E. 1989. Scaling and root planing effectiveness: the effect of root surface access and operator experience. J Periodontol, 60, 67-72.
13- BRONZE-UHLE, E. S., MELO, C., DA SILVA, I. S. P., STUANI, V. T., BUENO, V. H., RINALDO, D., DE SOUZA COSTA, C. A., LISBOA FILHO, P. N. & SOARES, D. G. 2025. Simvastatin-Loaded Chitosan Microspheres as a Biomaterial for Dentin Tissue Engineering. J Biomed Mater Res B Appl Biomater, 113, e35536.
14- CALIXTO, J. C., VILLABOIM DE CASTRO LIMA, C. E., FREDERICO, L., PIO DOS SANTOS DE CASTRO LIMA, R. & ANBINDER, A. L. 2011. The influence of local administration of simvastatin in calvarial bone healing in rats. Journal of Cranio-Maxillofacial Surgery, 39, 215-220.
15- CERRITELLI, L., HATZOPOULOS, S., CATALANO, A., BIANCHINI, C., CAMMAROTO, G., MECCARIELLO, G., IANNELLA, G., VICINI, C., PELUCCHI, S., SKARZYNSKI, P. H. & CIORBA, A. 2022. Rapid Maxillary Expansion (RME): An Otolaryngologic Perspective. J Clin Med, 11.
16- CHAK, R. K., SINGH, R. K., MUTYALA, J. & KILLI, N. K. 2022. Clinical Radiographic Evaluation of 3Mixtatin and MTA in Primary Teeth Pulpotomies: A Randomized Controlled. Int J Clin Pediatr Dent, 15, S80-s86.
17- CHANG, C. H., LIN, C. P., CHEN, Y. K., HSIAO, Y. F. & WANG, Y. H. 2023. Simvastatin Attenuates Areca Nut Extract-Induced Subdermal Fibrosis in Mice by Targeting TGF-β Signaling Pathways. Curr Issues Mol Biol, 45, 8622-8632.
18- COBB, C. M. J. J. O. C. P. 2002. Clinical significance of non‐surgical periodontal therapy: an evidence‐based perspective of scaling and root planing. 29, 22-32.
19- CVEK, M. J. D. T. 1992. Prognosis of luxated non‐vital maxillary incisors treated with calcium hydroxide and filled with gutta‐percha. A retrospective clinical study. 8, 45-55.
20- DEEPANJALI, M., PRASAD, T. S. & MANODH, P. 2023. Efficacy of simvastatin in bone regeneration after surgical removal of mandibular third molars. Oral Maxillofac Surg, 27, 427-432.
21- EL SHAFEI, S. F., RAAFAT, S. N., AMIN, A. H. & RIZK, F. N. 2022. Effect of local application of platelet-rich fibrin scaffold loaded with simvastatin on peri-implant bone changes. J Indian Prosthodont Soc, 22, 152-160.
22- ESTRELA, C., BUENO, M. R., AZEVEDO, B. C., AZEVEDO, J. R. & PÉCORA, J. D. 2008. A New Periapical Index Based on Cone Beam Computed Tomography. Journal of Endodontics, 34, 1325-1331.
23- FARZAN, A., MOSHIRI, A., ANDALIB, S., SHAMSI, M. & MOTAMED, N. 2022. Effect of Simvastatin and Low-Level Laser Therapy on Sutural Bone Formation After Expansion in Rats: Biomechanical, Computed Tomography and Immunohistochemical Assessment. J Lasers Med Sci, 13, e21.
24- FERREIRA, L. N., PUPPIN-RONTANI, R. M. & PASCON, F. M. 2020. Effect of Intracanal Medicaments and Irrigants on the Release of Transforming Growth Factor Beta 1 and Vascular Endothelial Growth Factor from Cervical Root Dentin. J Endod, 46, 1616-1622.
25- FERRER-LUQUE, C. M., HERNÁNDEZ, M., SOLANA, C. & RUIZ-LINARES, M. 2024. Simvastatin Efficacy on Endodontic Biofilms: An In Vitro Study. Materials (Basel), 17.
26- GRANAT, M. M., EIFLER-ZYDEL, J. & KOLMAS, J. 2024. Statins-Their Role in Bone Tissue Metabolism and Local Applications with Different Carriers. Int J Mol Sci, 25.
27- GUPTA, S., VERMA, P., TIKKU, A. P., CHANDRA, A., YADAV, R. K., BHARTI, R. & BAINS, R. 2020. "Effect of local application of simvastatin in bone regeneration of peri-apical defects-a clinico-radiographic study. J Oral Biol Craniofac Res, 10, 583-591.
28- GUTHRIE, R. M. 2006. How safe is aggressive statin therapy? Prog Cardiovasc Nurs, 21, 140-5.
29- HAN, G., CHEN, Y., HOU, J., LIU, C., CHEN, C., ZHUANG, J. & MENG, W. 2010. Effects of simvastatin on relapse and remodeling of periodontal tissues after tooth movement in rats. American Journal of Orthodontics and Dentofacial Orthopedics, 138, 550.e1-550.e7.
30- HARSHA, G., MADHAVI, S., ARTHI, S. & HARITHA, S. 2023. Evaluation of efficacy of simvastatin in bone regeneration following local application in third molar extraction socket: A randomized control trial. Natl J Maxillofac Surg, 14, 286-293.
31- HASSAN, A. M. & AL KAYAT, A. 2015. Effect of systemic administration of Simvastatin on dental implant stability: A random clinical study. Journal of Baghdad College of Dentistry, 27, 133-137.
32- HEGDE, V. & ARORA, S. 2015. Effect of intracanal medicaments on push-out bond strength of Smart-Seal system. J Conserv Dent, 18, 414-8.
33- ISHIHARA, T., MIYAZAKI, M., NOTANI, N., KANEZAKI, S., KAWANO, M. & TSUMURA, H. 2017. Locally Applied Simvastatin Promotes Bone Formation in a Rat Model of Spinal Fusion. J Orthop Res, 35, 1942-1948.
34- JIA, W., ZHAO, Y., YANG, J., WANG, W., WANG, X., LING, L. & GE, L. 2016. Simvastatin Promotes Dental Pulp Stem Cell–induced Coronal Pulp Regeneration in Pulpotomized Teeth. Journal of Endodontics, 42, 1049-1054.
35- JOHNSON, G. K., REINHARDT, R. A., TUSSING, G. J. & KREJCI, R. F. 1989. Fiber optic probe augmented sonic scaling versus conventional sonic scaling. J Periodontol, 60, 131-6.
36- JUN, J. H., OH, K. C., PARK, K. H., JUNG, N., LI, J. & MOON, H. S. 2021. Improvement of Osseointegration by Ultraviolet and/or Simvastatin Treatment on Titanium Implants with or without Bone Graft Materials. Materials (Basel), 14.
37- KAJI, H., KANATANI, M., SUGIMOTO, T. & CHIHARA, K. 2005. Statins modulate the levels of osteoprotegerin/receptor activator of NFkappaB ligand mRNA in mouse bone-cell cultures. Horm Metab Res, 37, 589-92.
38- KILLEEN, A. C., KRELL, L. E., BERTELS, M., CHRISTIANSEN, M. M., ANDERSON, L., HATTERVIG, R. L., SAMSON, K. K., WANG, D. & REINHARDT, R. A. 2022. Effect of locally applied simvastatin on clinical attachment level and alveolar bone in periodontal maintenance patients: A randomized clinical trial. J Periodontol, 93, 1682-1690.
39- KOHLI, S. S. & KOHLI, V. S. 2011. Role of RANKL-RANK/osteoprotegerin molecular complex in bone remodeling and its immunopathologic implications. Indian J Endocrinol Metab, 15, 175-81.
40- LIU, X., MUHAMMED, F. K. & LIU, Y. 2022. Simvastatin encapsulated in exosomes can enhance its inhibition of relapse after orthodontic tooth movement. Am J Orthod Dentofacial Orthop, 162, 881-889.
41- MOAZAMI, F., SAHEBI, S., JAMSHIDI, D. & ALAVI, A. 2014. The long-term effect of calcium hydroxide, calcium-enriched mixture cement and mineral trioxide aggregate on dentin strength. Iran Endod J, 9, 185-9.
42- MOREIRA, C. P., SIEGL, R. M. C., TEDESCO, T. K., GIMENEZ, T., FLORIANO, I. & IMPARATO, J. C. J. B. D. S. 2022. Lesion sterilization and tissue repair of primary molar to the eruption of its permanent successor: a case report. 25.
43- MUMCU, E. & BEKLEN, A. 2019. The effect of smoking on the marginal bone loss around implant-supported prostheses. Tob Induc Dis, 17, 43.
44- 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, 1946-9.
45- OKAMOTO, Y., SONOYAMA, W., ONO, M., AKIYAMA, K., FUJISAWA, T., OSHIMA, M., TSUCHIMOTO, Y., MATSUKA, Y., YASUDA, T., SHI, S. & KUBOKI, T. 2009. Simvastatin Induces the Odontogenic Differentiation of Human Dental Pulp Stem Cells In Vitro and In Vivo. Journal of Endodontics, 35, 367-372.
46- PENG, B., WANG, L., HAN, G. & CHENG, Y. 2024. Mesenchymal stem cell-derived exosomes: a potential cell-free therapy for orthodontic tooth stability management. Stem Cell Research & Therapy, 15, 342.
47- PIVA, E., TARLÉ, S. A., NÖR, J. E., ZOU, D., HATFIELD, E., GUINN, T., EUBANKS, E. J. & KAIGLER, D. 2017. Dental Pulp Tissue Regeneration Using Dental Pulp Stem Cells Isolated and Expanded in Human Serum. Journal of Endodontics, 43, 568-574.
48- PRADEEP, A. R. & THORAT, M. S. 2010. Clinical effect of subgingivally delivered simvastatin in the treatment of patients with chronic periodontitis: a randomized clinical trial. J Periodontol, 81, 214-22.
49- RAHMAN, S., GV, G. & MEHTA, D. S. 2020. A clinico-microbiological and biochemical study evaluating the adjunctive use of antimicrobial photodynamic therapy and local drug delivery of 1.2 % simvastatin gel compared to scaling and root planing alone. Photodiagnosis Photodyn Ther, 32, 102017.
50- REDDY, K. H., PRASANTHI, G., DEVIPRIYA, B., MALINI, D. L., MOHAN, T. M. & AGARWAL, V. 2025. Comparative evaluation of transforming growth factor-beta 1 release from dentin matrix with double antibiotic paste, probiotics, and simvastatin as intracanal medicaments: An in vitro study. J Conserv Dent Endod, 28, 456-461.
51- ROSYIDA, N. F., ANA, I. D., PUDYANI, P. S. & NUGROHO, A. K. 2025. Inhibition of Orthodontic Relapse by Local Application of Simvastatin-Loaded Gelatin Hydrogel in a Rabbit Model. Orthod Craniofac Res, 28, 289-295.
52- RUAN, F., ZHENG, Q. & WANG, J. 2012. Mechanisms of bone anabolism regulated by statins. Biosci Rep, 32, 511-9.
53- SAIFI, A. M., GIRADDI, G. B. & AHMED, N. 2017. Healing of extraction socket following local application of simvastatin: A split mouth prospective study. Journal of Oral Biology and Craniofacial Research, 7, 106-112.
54- SERINO, G., ROSLING, B., RAMBERG, P., SOCRANSKY, S. & LINDHE, J. J. J. O. C. P. 2001. Initial outcome and long‐term effect of surgical and non‐surgical treatment of advanced periodontal disease. 28, 910-916.
55- SHARAF ELDEEN, A., EL-SHALL, O. & ATTIA, M. J. A.-A. J. O. D. 2022. Effect of Systemic Administration of Simvastatin on Dental Implant Stability. 9, 12.
56- SURESH, S., NARAYANA, S., JAYAKUMAR, P., SUDHAKAR, U. & PRAMOD, V. 2013. Evaluation of anti-inflammatory effect of statins in chronic periodontitis. Indian J Pharmacol, 45, 391-4.
57- THANGAMANI, S., MOHAMMAD, H., ABUSHAHBA, M. F., HAMED, M. I., SOBREIRA, T. J., HEDRICK, V. E., PAUL, L. N. & SELEEM, M. N. 2015. Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent. Sci Rep, 5, 16407.
58- TSAI, C.-Y., TANG, C. Y., TAN, T.-S., CHEN, K.-H., LIAO, K.-H. & LIOU, M.-L. 2018. Subgingival microbiota in individuals with severe chronic periodontitis. Journal of Microbiology, Immunology and Infection, 51, 226-234.
59- VON ARX, T. 2005. Failed root canals: the case for apicoectomy (periradicular surgery). J Oral Maxillofac Surg, 63, 832-7.
60- WONG, R. W. K. & RABIE, A. B. M. 2005. Histologic and Ultrastructural Study on Statin Graft in Rabbit Skulls. Journal of Oral and Maxillofacial Surgery, 63, 1515-1521.
61- YUAN, X., YUAN, Z., WANG, Y., WAN, Z., WANG, X., YU, S., HAN, J., HUANG, J., XIONG, C., GE, L., CAI, Q. & ZHAO, Y. 2022. Vascularized pulp regeneration via injecting simvastatin functionalized GelMA cryogel microspheres loaded with stem cells from human exfoliated deciduous teeth. Mater Today Bio, 13, 100209.
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