Barrios-Garay K, Toledano-Serrabona J, Gay-Escoda C, Sánchez-Garcés MÁ. Clinical effect of vitamin C supplementation on bone healing: A systematic review. Med Oral Patol Oral Cir Bucal. 2022 May 1;27 (3):e205-15.



doi:10.4317/medoral.24944

https://dx.doi.org/doi:10.4317/medoral.24944


1. Aghajanian P, Hall S, Wongworawat M, Mohan S. The roles and mechanisms of actions of vitamin C in bone: New developments. J Bone Miner Res. 2015;30:1945-55.

https://doi.org/10.1002/jbmr.2709

PMid:26358868 PMCid:PMC4833003

2. Duygulu F, Yakan B, Karaoglu S, Kutlubay R, Karahan OI, Ozturk A. The effect of zymosan and the protective effect of various antioxidants on fracture healing in rats. Arch Orthop Trauma Surg. 2007;127:493-501.

https://doi.org/10.1007/s00402-007-0395-7

PMid:17639432 

3. Kim SH, Kim JS, Shin HS, Keen CL. Influence of smoking on markers of oxidative stress and serum mineral concentrations in teenage girls in Korea. Nutrition. 2003;19:240-3.

https://doi.org/10.1016/S0899-9007(02)01002-X

PMid:12620526

4. Buettner GR. The pecking order of free radicals and antioxidants: Lipid peroxidation, α-yocopherol, and ascorbate. Arch Biochem Biophys. 1993;300:535-43.

https://doi.org/10.1006/abbi.1993.1074

PMid:8434935 

5. Schwarz RI. Procollagen secretion meets the minimum requirements for the rate-controlling step in the ascorbate induction of procollagen synthesis. J Biol Chem. 1985;260:3045-9.

https://doi.org/10.1016/S0021-9258(18)89470-4

PMid:3972816

6. Vuorela A, Myllyharju J, Nissi R, Pihlajaniemi T, Kivirikko KI. Assembly of human prolyl 4-hydroxylase and type III collagen in the yeast Pichia pastoris: Formation of a stable enzyme tetramer requires coexpression with collagen and assembly of a stable collagen requires coexpression with prolyl 4-hydroxylase. EMBO J. 1997;16:6702-12.

https://doi.org/10.1093/emboj/16.22.6702

PMid:9362485 PMCid:PMC1170275

7. Marini JC, Cabral WA, Barnes AM, Chang W. Components of the collagen prolyl 3-hydroxylation complex are crucial for normal bone development. Cell Cycle. 2007;6:1675-81.

https://doi.org/10.4161/cc.6.14.4474

PMid:17630507 

8. Franceschi RT, Iyer BS. Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cells. J Bone Miner Res. 1992;7:235-46.

https://doi.org/10.1002/jbmr.5650070216

PMid:1373931 

9. Urban K, Höhling HJ, Lüttenberg B, Szuwart T, Plate U. An in vitro study of osteoblast vitality influenced by the vitamins C and E. Head Face Med. 2012;8:1-10.

https://doi.org/10.1186/1746-160X-8-25

PMid:23021517 PMCid:PMC3489720

10. Carr AC, Maggini S. Vitamin C and immune function. Nutrients. 2017;9:1-25.

https://doi.org/10.3390/nu9111211

PMid:29099763 PMCid:PMC5707683

11. Ekrol I, Duckworth AD, Ralston SH, Court-Brown CM, McQueen MM. The influence of vitamin C on the outcome of distal radial fractures. J Bone Joint Surg Am. 2014;96:1451-9.

https://doi.org/10.2106/JBJS.M.00268

PMid:25187584 

12. Moores J. Vitamin C: A wound healing perspective. Br J Community Nurs. 2013;S6:S8-11.

https://doi.org/10.12968/bjcn.2013.18.Sup12.S6

PMid:24796079 

13. Benic GI, Hämmerle CHF. Horizontal bone augmentation by means of guided bone regeneration. Periodontol 2000. 2014;66:13-40.

https://doi.org/10.1111/prd.12039

PMid:25123759 

14. Donos N, Dereka X, Mardas N. Experimental models for guided bone regeneration in healthy and medically compromised conditions. Periodontol 2000. 2015;68:99-121.

https://doi.org/10.1111/prd.12077

PMid:25867982 

15. Thrivikraman G, Athirasala A, Twohig C, Boda K, Bertassoni L. Biomaterials for craniofacial bone Regeneration. Dent Clin North Am. 2018;61:1835-56.

https://doi.org/10.1016/j.cden.2017.06.003

PMid:28886771 PMCid:PMC5663293

16. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. PLoS Med. 2021;18:e1003583.

https://doi.org/10.1371/journal.pmed.1003583

PMid:33780438 PMCid:PMC8007028

17. Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, Thomas J. Updated guidance for trusted systematic reviews: A new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019;10:ED000142.

https://doi.org/10.1002/14651858.ED000142

PMid:31643080 

18. Hooijmans CR, Rovers MM, De Vries RBM, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE's risk of bias tool for animal studies. BMC Med Res Methodol. 2014;14:1-9.

https://doi.org/10.1186/1471-2288-14-43

PMid:24667063 PMCid:PMC4230647

19. du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The arrive guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 2020;18:1-12.

https://doi.org/10.1371/journal.pbio.3000410

PMid:32663219 PMCid:PMC7360023

20. Li X, Tang L, Lin YF, Xie GF. Role of vitamin C in wound healing after dental implant surgery in patients treated with bone grafts and patients with chronic periodontitis. Clin Implant Dent Relat Res. 2018;20:793-8.

https://doi.org/10.1111/cid.12647

PMid:30039526 

21. Rowe DJ, Ko S, Tom XM, Silverstein SJ, Richards DW. Enhanced production of mineralized nodules and collagenous proteins in vitro by calcium ascorbate supplemented with vitamin C metabolites. J Periodontol. 1999;70:992-9.

https://doi.org/10.1902/jop.1999.70.9.992

PMid:10505801 

22. Yilmaz C, Erdemli E, Selek H, Kinik H, Arikan M, Erdemli B. The contribution of vitamin C to healing of experimental fractures. Arch Orthop Trauma Surg. 2001;121:426-8.

https://doi.org/10.1007/s004020100272

PMid:11510911 

23. Sarisözen B, Durak K, Dinçer G, Bilgen OF. The effects of vitamins E and C on fracture healing in rats. J Int Med Res. 2002;30:309-13.

https://doi.org/10.1177/147323000203000312

PMid:12166348 

24. Sanbe T, Tomofuji T, Ekuni D, Azuma T, Tamaki N, Yamamoto T. Oral administration of vitamin C prevents alveolar bone resorption induced by high dietary cholesterol in rats. J Periodontol. 2007;78:2165-70.

https://doi.org/10.1902/jop.2007.070181

PMid:17970684 

25. Sanbe T, Tomofuji T, Ekuni D, Azuma T, Irie K, Tamaki N, et al. Vitamin C intake inhibits serum lipid peroxidation and osteoclast differentiation on alveolar bone in rats fed on a high-cholesterol diet. Arch Oral Biol. 2009;54:235-40.

https://doi.org/10.1016/j.archoralbio.2008.11.001

PMid:19110235 

26. Uysal T, Amasyali M, Olmez H, Enhos S, Karslioglu Y, Gunhan O. Effect of vitamin C on bone formation in the expanded inter-premaxillary suture. Early bone changes. J Orofac Orthop. 2011;72:290-300.

https://doi.org/10.1007/s00056-011-0034-3

PMid:21830123 

27. Giordano V, Albuquerque RP, do Amaral NP, Chame CC, de Souza F, Apfel MIR. Supplementary vitamin C does not accelerate bone healing in a rat tibia fracture model. Acta Ortop Bras. 2012;20:10-2.

https://doi.org/10.1590/S1413-78522012000100001

PMid:24453572 PMCid:PMC3718416

28. Choi HK, Kim G-J, Yoo H-S, Song DH, Chung K-H, Lee K-J, et al. Vitamin C activates osteoblastogenesis and inhibits osteoclastogenesis via Wnt/β-catenin/ATF4 signaling pathways. Nutrients. 2019;11:1-20.

https://doi.org/10.3390/nu11030506

PMid:30818817 PMCid:PMC6471534

29. Akça EK, Atalay B, Öner B. Histopathologic and immunohistochemical investigation of the effects of vitamin C on bone healing in rats exposed to nicotine. J Oral Maxillofac Surg. 2020;78:194.e1-14.

https://doi.org/10.1016/j.joms.2019.09.006

PMid:31605679 

30. Gabbay KH, Bohren KM, Morello R, Bertin T, Liu J, Vogel P. Ascorbate synthesis pathway: Dual role of ascorbate in bone homeostasis. J Biol Chem. 2010;285:19510-20.

https://doi.org/10.1074/jbc.M110.110247

PMid:20410296 PMCid:PMC2885230

31. Kim HH, Lee SE, Chung WJ, Choi Y, Kwack K, Kim SW, et al. Stabilization of hypoxia-inducible factor-1α is involved in the hypoxic stimuli-induced expression of vascular endothelial growth factor in osteoblastic cells. Cytokine. 2002;17:14-27.

https://doi.org/10.1006/cyto.2001.0985

PMid:11886167 

32. Tomofuji T, Kusano H, Azuma T, Ekuni D, Yamamoto T, Watanabe T. Effects of a high-cholesterol diet on cell behavior in rat periodontitis. Practitioner. 2005;249:752-6.

https://doi.org/10.1177/154405910508400813

PMid:16040735 

33. Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. J Am Med Assoc. 1999;281:1415-23.

https://doi.org/10.1001/jama.281.15.1415

PMid:10217058 

34. Carinci F, Pezzetti F, Spina AM, Palmieri A, Laino G, De Rosa A, et al. Effect of vitamin C on pre-osteoblast gene expression. Arch Oral Biol. 2005;50:481-96.

https://doi.org/10.1016/j.archoralbio.2004.11.006

PMid:15777530 

35. Nastri L, Moretti A, Migliaccio S, Paoletta M, Annunziata M, Liguori S, et al. Do dietary supplements and nutraceuticals have effects on dental implant osseointegration? A scoping review. Nutrients. 2020;12:268.

https://doi.org/10.3390/nu12010268

PMid:31968626 PMCid:PMC7019951

36. Higuchi T, Kinoshita A, Takahashi K, Oda S, Ishikawa I. Bone Regeneration by Recombinant Human Bone Morphogenetic Protein-2 in Rat Mandibular Defects. An Experimental Model of Defect Filling. J Periodontol. 1999;70:1026-31.

https://doi.org/10.1902/jop.1999.70.9.1026

PMid:10505805 

37. Kustro T, Kiss T, Chernohorskyi D, Chepurnyi Y, Helyes Z, Kopchak A. Quantification of the mandibular defect healing by micro-CT morphometric analysis in rats. J Cranio-Maxillofacial Surg. 2018;46:2203-13.

https://doi.org/10.1016/j.jcms.2018.09.022

PMid:30343871 

38. Liu G, Guo Y, Zhang L, Wang X, Liu R, Huang P, et al. A standardized rat burr hole defect model to study maxillofacial bone regeneration. Acta Biomater. 2019;86:450-64.

https://doi.org/10.1016/j.actbio.2018.12.049

PMid:30605772