Systematic review of preclinical studies on the effect of vitamins on bone regeneration
Keywords:
bone regeneration, vitamin E, vitamin D, vitamin C.Abstract
Introduction: Vitamins are organic substances with biological properties on multiple tissues of the organism, including bone tissue; therefore, they may participate in the process of bone regeneration.
Objective: To evaluate the effect of vitamins on the bone regeneration process in preclinical models of bone defects.
Methods: The following systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The research question was constructed according to the PICO (Population, Intervention, Comparator, Outcome) model, and literature searches were performed in PubMed/Medline, Embase, Web of Science (WOS), Scopus and LILACS databases. Gray literature was also consulted in PROQUEST and Google Scholar. Bone regeneration” was probed as the main outcome.
Results: Twenty-three articles were included for qualitative analysis; subsequently, quality was assessed using the Animal Reseach: Reporting of In Vivo Experiments (ARRIVE) tool and risk of bias was assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE risk of bias tool). The main findings showed the action of vitamins on bone regeneration in induced bone defects in animals; however, data on the parameters analyzed similarly across studies were not retrieved.
Conclusions: Current evidence suggests that vitamin administration promotes bone regeneration; however, further preclinical studies are required to confirm the effect of vitamins on bone defects.
Downloads
References
1. Borrelli J, Pape C, Hak D, Hsu J, Lin S, Giannoudis P, et al. Physiological challenges of bone repair. J Orthop Trauma. 2012;26(12):708-11. DOI: https://doi.org/10.1097/bot.0b013e318274da8b
2. Dimitriou R, Jones E, McGonagle D, Giannoudis P. Bone regeneration: Current concepts and future directions. BMC Med. 2011;9(66):2-10. DOI: https://doi.org/10.1186/1741-7015-9-66
3. Li S, Zhao J, Xie Y, Tian T, Zhang T, Cai X. Hard tissue stability after guided bone regeneration: a comparison between digital titanium mesh and resorbable membrane. Int J Oral Sci. 2021;13(1):37. DOI: https://doi.org/10.1038/s41368-021-00143-3
4. Delfrate G, Mroczek T, Mecca L, Andreis J, Fernandes D, Lipinski L, et al. Effect of pentoxifylline and α-tocopherol on medication-related osteonecrosis of the jaw in rats: Before and after dental extraction. Arch Oral Biol. 2022;137:105397. DOI: https://doi.org/10.1016/j.archoralbio.2022.105397
5. 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(4):290-300. DOI: https://doi.org/10.1007/s00056-011-0034-3
6. Reid I, Bolland M, Grey A. Effects of vitamin D supplements on bone mineral density: A systematic review and meta-Analysis. Lancet. 2014;383(9912):146-55. DOI: http://dx.doi.org/10.1016/S0140-6736(13)61647-5
7. Mohamad S, Shuid A, Mohamed N, Fadzilah F, Mokhtar S, Abdullah S, et al. The effects of alpha-tocopherol supplementation on fracture healing in a postmenopausal osteoporotic rat model. Clinics. 2012;67(9):1077-85. DOI: https://doi.org/10.6061/clinics/2012(09)16
8. Chin K, Ima-Nirwana S. Vitamin C and bone health: evidence from cell, animal and human studies. Curr Drug Targets. 2018;19(5):439-50. DOI: https://doi.org/10.2174/1389450116666150907100838
9. Fujita K, Iwasaki M, Ochi H, Fukuda T, Ma C, Miyamoto T, et al. Vitamin E decreases bone mass by stimulating osteoclast fusion. Nat Med. 2012;18(4):589-94. DOI: https://doi.org/10.1038/nm.2659
10. Melhus G, Solberg L, Dimmen S, Madsen JE, Nordsletten L, Reinholt F. Experimental osteoporosis induced by ovariectomy and vitamin D deficiency does not markedly affect fracture healing in rats. Acta Orthop. 2007;78(3):393-403. DOI: https://doi.org/10.1080/17453670710013988
11. Frank J, Weiser H, Biesalski H. Interaction of vitamins E and K: effect of high dietary vitamin E on phylloquinone activity in chicks. Int J Vitam Nutr Res. 1997 [acceso 27/11/2022];67(4):242-7. Disponible en: https://pubmed.ncbi.nlm.nih.gov/9285253/
12. Shuid A, Mohamad S, Muhammad N, Fadzilah F, Mokhtar S, Mohamed N, et al. Effects of α-tocopherol on the early phase of osteoporotic fracture healing. J Orthop Research.2011;29(11):1732-8. DOI: https://doi.org/10.1002/jor.21452
13. Jiang Q. Natural forms of vitamin E: Metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radic Biol Med. 2014;72:76-90. DOI: http://dx.doi.org/10.1016/j.freeradbiomed.2014.03.035
14. Maruli A, Gunawan B, Jusuf A. The role of vitamin C in enhancement of fracture healing in fracture with periosteal stripping at Sprague-Dawley white rats femur. Indon J Orthop. 2021 [acceso 27/11/2022];41(1):9-14. Disponible en: https://www.neliti.com/publications/90658/the-role-of-vitamin-c-in-enhancement-of-fracture-healing-in-fracture-with-perios
15. Vallibhakara S, Nakpalat K, Sophonsritsuk A, Tantitham C, Vallibhakara O. Effect of vitamin E supplement on bone turnover markers in postmenopausal osteopenic women: a double-blind, randomized, placebo-controlled trial. Nutrients. 2021;13(12):4226. DOI: https://doi.org/10.3390/nu13124226
16. Giordano V, Albuquerque R, do Amaral N, Chame C, de Souza F, Apfel M. Supplementary vitamin C does not accelerate bone healing in a rat tibia fracture model. Acta Ortop Bras. 2012;20(1):10-2. DOI: https://doi.org/10.1590/S1413-78522012000100001
17. 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(1):268. DOI: https://doi.org/10.3390/nu12010268
18. Percie N, Hurst V, Ahluwalia A, Alam S, Avey M, Baker M, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. Br J Pharmacol. 2020;177(16):3617. DOI: https://doi.org/10.1371/journal.pbio.3000411
19. Hooijmans C, Rovers M, de Vries R, Leenaars M, Ritskes-Hoitinga M, Langendam M. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol. 2014;14(1):1-9. DOI: https://doi.org/10.1186/1471-2288-14-43
20. Nguyen T, Eo M, Seo M, Myoung H, Kim S, Lee J. Effects of pentoxifylline and tocopherol on a rat-irradiated jaw model using micro-CT cortical bone analysis. Eur Arch Otorhinolaryngol.2019;276(12):3443-52. DOI: https://doi.org/10.1007/s00405-019-05600-8
21. Seo M, Myoung H, Lee J, Yang H, Woo K, Lee S, et al. Effects of pentoxifylline and tocopherol on an osteoradionecrosis animal model. J Cranio-Maxillofacial Surg. 2020;48(7):621-31. DOI: https://doi.org/10.1016/j.jcms.2020.02.008
22. Akçay H, Kuru K, Tatar B, Şimşek F. Vitamin E promotes bone formation in a distraction osteogenesis model. J Craniofac Surg. 2019;30(8):2315-8. DOI: https://doi.org/10.1097/scs.0000000000005685
23. Mohamad S, Shuid A, Mokhtar S, Abdullah S, Soelaiman I. Tocotrienol supplementation improves late-phase fracture healing compared to alpha-tocopherol in a rat model of postmenopausal osteoporosis: A biomechanical evaluation. Evid Complement Alternat Med. 2012;2012:2-7. DOI: https://doi.org/10.1155/2012/372878
24. Kurklu M, Yildiz C, Kose O, Yurttas Y, Karacalioglu O, Serdar M, et al. Effect of alpha-tocopherol on bone formation during distraction osteogenesis: A rabbit model. J Orthop Traumatol. 2011;12(3):153-8. DOI: https://doi.org/10.1007/s10195-011-0145-z
25. Turk CY, Halici M, Guney A, Akgun H, Sahin V, Muhtaroglu S. Promotion of fracture healing by vitamin E in rats. J Int Med Res. 2004;32(5):507-12. DOI: https://doi.org/10.1177/147323000403200508
26. Durak K, Sonmez G, Sarisozen B, Ozkan S, Kaya M, Ozturk C. Histological assessment of the effect of α-tocopherol on fracture healing in rabbits. J Int Med Res. 2003;31(1):26-30. DOI: https://doi.org/10.1177/147323000303100104
27. Pal S, Khan K, China S, Mittal M, Porwal K, Shrivastava R, et al. Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats. Toxicol Appl Pharmacol. 2016;295:12-25. DOI: https://doi.org/10.1016/j.taap.2016.02.002
28. Aydoğan NH, Özel I, Iltar S, Kara T, Özmeriç A, Alemdaroğlu K. The effect of vitamin D and bisphosphonate on fracture healing: An experimental study. J Clin Orthop Trauma. 2016;7(2):90-4. DOI: https://doi.org/10.1016/j.jcot.2016.01.003
29. Saito M, Shiraishi A, Ito M, Sakai S, Hayakawa N, Mihara M, et al. Comparison of effects of alfacalcidol and alendronate on mechanical properties and bone collagen cross-links of callus in the fracture repair rat model. Bone. 2010;46(4):1170-9. DOI: http://dx.doi.org/10.1016/j.bone.2009.12.008
30. Cao Y, Mori S, Mashiba T, Kaji Y, Manabe T, Iwata K, et al. 1α,25-Dihydroxy-2β (3-hydroxypropoxy) vitamin D3 (ED-71) suppressed callus remodeling but did not interfere with fracture healing in rat femora. Bone. 2007;40(1):132-9. DOI: https://doi.org/10.1016/j.bone.2006.07.023
31. Seo E, Einhorn T, Norman A. 24R,25-dihydroxyvitamin D3: an essential vitamin D3 metabolite for both normal bone integrity and healing of tibial fracture in chicks. Endocrinol. 1997;138(9):3864-72. DOI: https://doi.org/10.1210/endo.138.9.5398
32. Lindgren J, DeLuca H, Mazess R. Effects of 1,25(OH)2D3 on bone tissue in the rabbit: studies on fracture healing, disuse osteoporosis, and prednisone osteoporosis. Calcif Tissue Int. 1984;36(5):591-5. DOI: https://doi.org/10.1007/bf02405372
33. Farhadian N, Miresmaeili A, Azar R, Zargaran M, Moghimbeigi A, Soheilifar S. Effect of dietary ascorbic acid on osteogenesis of expanding midpalatal suture in rats. J Dent (Tehran). 2015 [acceso 27/11/2022];12(1):39-48. Disponible en: https://pubmed.ncbi.nlm.nih.gov/26005453/
34. Sarisözen B, Durak K, Dinçer G, Bilgen O. The effects of vitamins E and C on fracture healing in rats. J Int Med Res. 2002;30(3):309-13. DOI: https://doi.org/10.1177/147323000203000312
35. 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(7):493-501. DOI: https://doi.org/10.1007/s00402-007-0395-7
36. 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(7):426-8. DOI: https://doi.org/10.1007/s004020100272
37. Lindholm T, Sevastikoglou J. The effect of 1alpha-hydroxycholecalciferol on the healing of experimental fractures in adult rats. Acta Orthop Scand. 1978;49(6):485-91. DOI: https://doi.org/10.3109/17453677808993227
38. Garrett I, Boyce B, Oreffo R, Bonewald L, Poser J, Mundy G. Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J Clin Invest. 1990;85(3):632-9. DOI: https://doi.org/10.1172/JCI114485
39. Reilly P, Schiller H, Bulkley G. Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites. Am J Surg. 1991;161(4):488-503. DOI: https://doi.org/10.1016/0002-9610(91)91120-8
40. Chin K, Mo H, Soelaiman I. A review of the possible mechanisms of action of tocotrienol - a potential antiosteoporotic agent. Curr Drug Targets. 2013;14(13):1533-41. DOI: https://doi.org/10.2174/13894501113149990178
41. Chin K, Ima-Nirwana S. The biological effects of tocotrienol on bone: a review on evidence from rodent models. Drug Des Devel Ther. 2015;9:2049-61. DOI: https://doi.org/10.2147/dddt.s79660
42. Smith B, Lucas E, Turner R, Evans G, Lerner M, Brackett D, et al. Vitamin E provides protection for bone in mature hindlimb unloaded male rats. Calcif Tissue Int. 2005;76(4):272-9. DOI: https://doi.org/10.1007/s00223-004-0269-8
43. Hermizi H, Faizah O, Ima-Nirwana S, Ahmad Nazrun S, Norazlina M. Beneficial effects of tocotrienol and tocopherol on bone histomorphometric parameters in Sprague–Dawley male rats after nicotine cessation. Calcif Tissue Int. 2008;84(1):65-74. DOI: https://doi.org/10.1007/s00223-008-9190-x
44. Norazlina M, Ima-Nirwana S, Gapor MT, Khalid BAK. Palm vitamin E is comparable to alpha-tocopherol in maintaining bone mineral density in ovariectomised female rats. Exp Clin Endocrinol Diabetes. 2000;108(4):305-10. DOI: https://doi.org/10.1055/s-2000-7758
45. Chin K, Ima-Nirwana S. The effects of α-tocopherol on bone: a double-edged sword? Nutrients. 2014;6(4):1424. DOI: https://doi.org/10.3390/nu6041424
46. Hosomi A, Arita M, Sato Y, Kiyose C, Ueda T, Igarashi O, et al. Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. Fed Eur Bioch. 1997;409(1):105-8. DOI: https://doi.org/10.1016/S0014-5793(97)00499-7
47. Kasai S, Ito A, Shindo K, Toyoshi T, Bando M. High-dose α-tocopherol supplementation does not induce bone loss in normal rats. PLoS One. 2015;10(7). DOI: https://doi.org/10.1371/journal.pone.0132059
48. Muresan G, Hedesiu M, Lucaciu O, Boca S, Petrescu N. Effect of vitamin D on bone regeneration: a review. Medicin. 2022;58(10). DOI: https://doi.org/10.3390/medicina58101337
49. Zhou J, Wang F, Ma Y, Wei F. Vitamin D3 contributes to enhanced osteogenic differentiation of MSCs under oxidative stress condition via activating the endogenous antioxidant system. Osteoporos Int. 2018;29(8):1917-26. DOI: https://doi.org/10.1007/s00198-018-4547-0
50. Doepfner W. Consequences of calcium and-or phosphorus deficient diets on various parameters of callus formation and on growth rate in young rats. Br J Pharmacol. 1970 [acceso 27/11/2022];39(1):188-9. Disponible en: https://pubmed.ncbi.nlm.nih.gov/5420093/
51. Einhorn T, Bonnarens F, Burstein A. The contributions of dietary protein and mineral to the healing of experimental fractures. A biomechanical Study. J Bone Joint Surg. 1986 [acceso 27/11/2022];68(9):1389-95. Disponible en: https://pubmed.ncbi.nlm.nih.gov/3782211/
52. Franceschi R, Iyer B. Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cells. J Bone Miner Res. 1992;7(2):235-46. DOI: https://doi.org/10.1002/jbmr.5650070216
Downloads
Published
How to Cite
Issue
Section
License
Aquellos autores/as que tengan publicaciones con esta revista, aceptan los términos siguientes: Los autores/as conservarán sus derechos de autor y garantizarán a la revista el derecho de primera publicación de su obra, el cuál estará simultáneamente sujeto a la Licencia de reconocimiento de Creative Commons (CC-BY-NC 4.0) que permite a terceros compartir la obra siempre que se indique su autor y su primera publicación esta revista. Los autores/as podrán adoptar otros acuerdos de licencia no exclusiva de distribución de la versión de la obra publicada (p. ej.: depositarla en un archivo telemático institucional o publicarla en un volumen monográfico) siempre que se indique la publicación inicial en esta revista. Se permite y recomienda a los autores/as difundir su obra a través de Internet (p. ej.: en archivos telemáticos institucionales o en su página web) antes y durante el proceso de envío, lo cual puede producir intercambios interesantes y aumentar las citas de la obra publicada. (Véase El efecto del acceso abierto).
Como Revista Cubana de Investigaciones Biomédicas forma parte de la red SciELO, una vez los artículos sean aceptados para entrar al proceso editorial (revisión), estos pueden ser depositados por parte de los autores, si estan de acuerdo, en SciELO preprints, siendo actualizados por los autores al concluir el proceso de revisión y las pruebas de maquetación.
