Radiographic Evaluation of the Effect of Vitamin D3 Supplementation on Regeneration of Calvarial Bone Defects in Rats

Year 2023, Volume: 13 Issue: 4, 769 - 775, 29.12.2023

Gülce Nil Varlıhan Ömer Birkan Ağralı Hatice Selin Yıldırım Sibel Demirci Delipınar Leyla Kuru Hafize Öztürk Özener

https://doi.org/10.33808/clinexphealthsci.1262852

Abstract

Aim: The present study was aimed to evaluate radiographically the effect of orally administered vitamin D3 on guided bone regeneration in calvarial critical size defects (CSD) in rats.
Methods: Two calvarial CSD were created in 12 male Sprague-Dawley rats. One of the defects was left empty (E defect), while the other one was treated with deproteinized bovine bone graft and collagen-based resorbable membrane (GM-filled defect). Following surgical intervention, rats were randomly assigned into two groups; the control group was administered distilled water, and the test group was treated with 2 µg /kg vitamin D3 by gavage once a day for 8 weeks. Radiological images were obtained from rats on 4th and 8th weeks. The area fraction of newly formed osteoid was determined using Image Fiji Analysis Software.
Results: The percentages of area fraction in the GM-filled defects were statistically higher than the E defects in both study groups at 4th and 8th weeks (p<.0001). In both E and GM defects, the percentage of area fraction was higher at weeks 4 and 8 in the test group compared to the control groups (p<.0001). In comparison to the other groups, the GM-filled defect in the test group had the highest mean percentage of area fraction (p<.0001).
Conclusion: This study demonstrated that healing of CSD could be evaluated by radiography and Vitamin D3 improves bone healing, particularly when guided bone regeneration is used in rats with CSD at the calvaria.

Keywords

bone regeneration, radiography, Vitamin D3

Supporting Institution

This study was supported by grants from Marmara University Scientific Research Projects Coordination Unit

Project Number

TDK-2021-10161

References

• Troeltzsch M, Troeltzsch M, Kauffmann P, Gruber R, Brockmeyer P, Moser N, Rau A, Schliephake H. Clinical efficacy of grafting materials in alveolar ridge augmentation: A systematic review. J Craniomaxillofac Surg. 2016;44:1618-1629. DOI: 10.1016/j.jcms.2016.07.028
• Li Z, Li ZB. Repair of mandible defect with tissue engineering bone in rabbits. ANZ J Surg. 2005;75:1017-1021. DOI: 10.1111/j.1445-2197.2005.03586.x
• Smiler D, Soltan M. The bone-grafting decision tree: a systematic methodology for achieving new bone. Implant Dent. 2006;15:122-128. DOI: 10.1097/01.id.0000217780.69637.cc
• Wessing B, Lettner S, Zechner W. Guided Bone Regeneration with Collagen Membranes and Particulate Graft Materials: A Systematic Review and Meta-Analysis. Int J Oral Maxillofac Implants. 2018;33:87-100. DOI: 10.11607/jomi.5461
• Chiapasco M, Zaniboni M. Clinical outcomes of GBR procedures to correct peri-implant dehiscences and fenestrations: a systematic review. Clin Oral Implants Res. 2009;20 Suppl 4:113-123. DOI: 10.1111/j.1600-0501.2009.01781.x
• Hammerle CH, Jung RE, Feloutzis A. A systematic review of the survival of implants in bone sites augmented with barrier membranes (guided bone regeneration) in partially edentulous patients. J Clin Periodontol. 2002;29 Suppl 3:226-231; discussion 232-223. DOI: 10.1034/j.1600-051x.29.s3.14.x
• Elgali I, Omar O, Dahlin C, Thomsen P. Guided bone regeneration: materials and biological mechanisms revisited. Eur J Oral Sci. 2017;125:315-337. DOI: 10.1111/eos.12364
• Liu J, Kerns DG. Mechanisms of guided bone regeneration: a review. Open Dent J. 2014;8:56-65. DOI: 10.2174/1874210601408010056
• Misch CE, Dietsh F. Bone-grafting materials in implant dentistry. Implant Dent. 1993;2:158-167. DOI: 10.1097/00008505-199309000-00003
• Jung Y, Kim WH, Lee SH, Ju KW, Jang EH, Kim SO, Kim B, Lee JH. Evaluation of New Octacalcium Phosphate-Coated Xenograft in Rats Calvarial Defect Model on Bone Regeneration. Materials (Basel). 2020;13. DOI: 10.3390/ma13194391
• Froum SJ, Wallace SS, Elian N, Cho SC, Tarnow DP. Comparison of mineralized cancellous bone allograft (Puros) and anorganic bovine bone matrix (Bio-Oss) for sinus augmentation: histomorphometry at 26 to 32 weeks after grafting. Int J Periodontics Restorative Dent. 2006;26:543-551.
• Kim S, Chang H, Hwang JW, Kim S, Koo KT, Kim TI, Seol YJ, Lee YM, Ku Y, Lee JH, Rhyu IC. A randomized controlled clinical study of periodontal tissue regeneration using an extracellular matrix-based resorbable membrane in combination with a collagenated bovine bone graft in intrabony defects. J Periodontal Implant Sci. 2017;47:363-371. DOI: 10.5051/jpis.2017.47.6.363
• Park JI, Yang C, Kim YT, Kim MS, Lee JS, Choi SH, Jung UW. Space maintenance using crosslinked collagenated porcine bone grafted without a barrier membrane in one-wall intrabony defects. J Biomed Mater Res B Appl Biomater. 2014;102:1454-1461. DOI: 10.1002/jbm.b.33124
• Sculean A, Nikolidakis D, Schwarz F. Regeneration of periodontal tissues: combinations of barrier membranes and grafting materials - biological foundation and preclinical evidence: a systematic review. J Clin Periodontol. 2008;35:106-116. DOI: 10.1111/j.1600-051X.2008.01263.x
• Kawakami M, Takano-Yamamoto T. Local injection of 1,25-dihydroxyvitamin D3 enhanced bone formation for tooth stabilization after experimental tooth movement in rats. J Bone Miner Metab. 2004;22:541-546. DOI: 10.1007/s00774-004-0521-3
• Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-281. DOI: 10.1056/NEJMra070553
• Adams JS, Liu PT, Chun R, Modlin RL, Hewison M. Vitamin D in defense of the human immune response. Ann N Y Acad Sci. 2007;1117:94-105. DOI: 10.1196/annals.1402.036
• Fischer V, Haffner-Luntzer M, Prystaz K, Vom Scheidt A, Busse B, Schinke T, Amling M, Ignatius A. Calcium and vitamin-D deficiency marginally impairs fracture healing but aggravates posttraumatic bone loss in osteoporotic mice. Sci Rep. 2017;7:7223. DOI: 10.1038/s41598-017-07511-2
• Dvorak G, Fugl A, Watzek G, Tangl S, Pokorny P, Gruber R. Impact of dietary vitamin D on osseointegration in the ovariectomized rat. Clin Oral Implants Res. 2012;23:1308-1313. DOI: 10.1111/j.1600-0501.2011.02346.x
• Hong HH, Chou TA, Yang JC, Chang CJ. The potential effects of cholecalciferol on bone regeneration in dogs. Clin Oral Implants Res. 2012;23:1187-1192. 10.1111/j.16000501.2011.02346.x
• Hong HH, Yen TH, Hong A, Chou TA. Association of vitamin D3 with alveolar bone regeneration in dogs. J Cell Mol Med. 2015;19:1208-1217. DOI: 10.1111/jcmm.12460
• Pryor ME, Susin C, Wikesjo UM. Validity of radiographic evaluations of bone formation in a rat calvaria osteotomy defect model. J Clin Periodontol. 2006;33:455-460. DOI: 10.1111/j.1600-051X.2006.00921.x
• Gomes PS, Fernandes MH. Rodent models in bone-related research: the relevance of calvarial defects in the assessment of bone regeneration strategies. Lab Anim. 2011;45:14-24. DOI: 10.1258/la.2010.010085
• Schmitz JP, Hollinger JO. The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res. 1986:299-308. DOI: 10.1097/00003086-198604000-00036
• Gosain AK, Santoro TD, Song LS, Capel CC, Sudhakar PV, Matloub HS. Osteogenesis in calvarial defects: contribution of the dura, the pericranium, and the surrounding bone in adult versus infant animals. Plast Reconstr Surg. 2003;112:515-527. DOI: 10.1097/01.PRS.0000070728.56716.51
• Agrali OB, Yildirim S, Ozener HO, Kose KN, Ozbeyli D, Soluk-Tekkesin M, Kuru L. Evaluation of the Effectiveness of Esterified Hyaluronic Acid Fibers on Bone Regeneration in Rat Calvarial Defects. Biomed Res Int. 2018;2018:3874131. DOI: 10.1155/2018/3874131
• Vajgel A, Mardas N, Farias BC, Petrie A, Cimoes R, Donos N. A systematic review on the critical size defect model. Clin Oral Implants Res. 2014;25:879-893. DOI: 10.1111/clr.12194
• Bosch C, Melsen B, Vargervik K. Importance of the critical-size bone defect in testing bone-regenerating materials. J Craniofac Surg. 1998;9:310-316. DOI: 10.1097/00001665-199807000-00004
• Gosain AK, Song L, Yu P, Mehrara BJ, Maeda CY, Gold LI, Longaker MT. Osteogenesis in cranial defects: reassessment of the concept of critical size and the expression of TGF-beta isoforms. Plast Reconstr Surg. 2000;106:360-371; discussion 372. DOI: 10.1097/00006534-200008000-00018
• Cooper GM, Mooney MP, Gosain AK, Campbell PG, Losee JE, Huard J. Testing the critical size in calvarial bone defects: revisiting the concept of a critical-size defect. Plast Reconstr Surg. 2010;125:1685-1692. DOI: 10.1097/PRS.0b013e3181cb63a3
• Sohn JY, Park JC, Um YJ, Jung UW, Kim CS, Cho KS, Choi SH. Spontaneous healing capacity of rabbit cranial defects of various sizes. J Periodontal Implant Sci. 2010;40:180-187. DOI: 10.5051/jpis.2010.40.4.180
• Rogers GF, Greene AK. Autogenous bone graft: basic science and clinical implications. J Craniofac Surg. 2012;23:323-327. DOI: 10.1097/scs.0b013e318241dcba
• Abou Fadel R, Samarani R, Chakar C. Guided bone regeneration in calvarial critical size bony defect using a double-layer resorbable collagen membrane covering a xenograft: a histological and histomorphometric study in rats. Oral Maxillofac Surg. 2018;22:203-213. OI: 10.1007/s10006-018-0694-x
• Spicer PP, Kretlow JD, Young S, Jansen JA, Kasper FK, Mikos AG. Evaluation of bone regeneration using the rat critical size calvarial defect. Nat Protoc. 2012;7:1918-1929. DOI: 10.1038/nprot.2012.113
• Shibuya N, Jupiter DC. Bone graft substitute: allograft and xenograft. Clin Podiatr Med Surg. 2015;32:21-34. DOI: 10.1016/j.cpm.2014.09.011
• Canullo L, Trisi P, Simion M. Vertical ridge augmentation around implants using e-PTFE titanium-reinforced membrane and deproteinized bovine bone mineral (bio-oss): A case report. Int J Periodontics Restorative Dent. 2006;26:355-361. DOI: 10.1111/j.1600-0501.2007.01389.x
• Klein MO, Kammerer PW, Gotz H, Duschner H, Wagner W. Long-term bony integration and resorption kinetics of a xenogeneic bone substitute after sinus floor augmentation: histomorphometric analyses of human biopsy specimens. Int J Periodontics Restorative Dent. 2013;33:e101-110. DOI: 10.11607/prd.1469
• Baldini N, De Sanctis M, Ferrari M. Deproteinized bovine bone in periodontal and implant surgery. Dent Mater. 2011;27:61-70. DOI: 10.1016/j.dental.2010.10.017
• Schwarz F, Sager M, Rothamel D, Herten M, Sculean A, Becker J. [Use of native and cross-linked collagen membranes for guided tissue and bone regeneration]. Schweiz Monatsschr Zahnmed. 2006;116:1112-1123. DOI: 10.1097/00008505-199700610-00020
• Bunyaratavej P, Wang HL. Collagen membranes: a review. J Periodontol. 2001;72:215-229. DOI: 10.1902/jop.2001.72.2.215
• Liu SH, Yang RS, al-Shaikh R, Lane JM. Collagen in tendon, ligament, and bone healing. A current review. Clin Orthop Relat Res. 1995:265-278.
• Maiorana C, Beretta M, Battista Grossi G, Santoro F, Scott Herford A, Nagursky H, Cicciu M. Histomorphometric evaluation of anorganic bovine bone coverage to reduce autogenous grafts resorption: preliminary results. Open Dent J. 2011;5:71-78. DOI: 10.2174/1874210601105010071
• Kelly J, Lin A, Wang CJ, Park S, Nishimura I. Vitamin D and bone physiology: demonstration of vitamin D deficiency in an implant osseointegration rat model. J Prosthodont. 2009;18:473-478. DOI: 10.1111/j.1532-849X.2009.00446.x
• Fugl A, Gruber R, Agis H, Lzicar H, Keibl C, Schwarze UY, Dvorak G. Alveolar bone regeneration in response to local application of calcitriol in vitamin D deficient rats. J Clin Periodontol. 2015;42:96-103. DOI: 10.1111/jcpe.12342
• Cignachi NP, Ribeiro A, Machado GDB, Cignachi AP, Kist LW, Bogo MR, Silva RBM, Campos MM. Bone regeneration in a mouse model of type 1 diabetes: Influence of sex, vitamin D3, and insulin. Life Sci. 2020;263:118593. DOI: 10.1016/j.lfs.2020.118593
• Han X, Du J, Liu D, Liu H, Amizuka N, Li M. Histochemical examination of systemic administration of eldecalcitol combined with guided bone regeneration for bone defect restoration in rats. J Mol Histol. 2017;48:41-51. DOI: 10.1007/s10735-016-9705-0
• Zhou C, Li Y, Wang X, Shui X, Hu J. 1,25Dihydroxy vitamin D(3) improves titanium implant osseointegration in osteoporotic rats. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114:S174-178. DOI: 10.1016/j.oooo.2011.09.030
• Cacciafesta V, Dalstra M, Bosch C, Melsen B, Andreassen TT. Growth hormone treatment promotes guided bone regeneration in rat calvarial defects. Eur J Orthod. 2001;23:733-740. DOI: 10.1093/ejo/23.6.733
• Verna C, Dalstra M, Wikesjo UM, Trombelli L, Carles B. Healing patterns in calvarial bone defects following guided bone regeneration in rats. A micro-CT scan analysis. J Clin Periodontol. 2002;29:865-870. DOI: 10.1034/j.1600-051x.2002.290912.x
• Jiang X, Liu J, Li S, Qiu Y, Wang X, He X, Pedersen TO, Mustafa K, Xue Y, Mustafa M, Kantarci A, Xing Z. The effect of resolvin D1 on bone regeneration in a rat calvarial defect model. J Tissue Eng Regen Med. 2022;16:987-997. DOI: 10.1002/term.3345