Does vitamin D have an effect on osseointegration of dental implants? A systematic review

Joscha G Werny, Keyvan Sagheb, Leonardo Diaz, Peer W Kämmerer, Bilal Al-Nawas, Eik Schiegnitz, Joscha G Werny, Keyvan Sagheb, Leonardo Diaz, Peer W Kämmerer, Bilal Al-Nawas, Eik Schiegnitz

Abstract

Purpose: The aim of this study was to systematically review the available evidence to evaluate the efficacy of vitamin D supplementation or vitamin D depletion on the osseointegration of implants in animals and humans.

Methods: The focus questions addressed were "Do vitamin D deficient subjects treated with (dental) implants have an inferior osseointegration than subjects with adequate serum vitamin D level?" and "Do vitamin D supplemented subjects treated with (dental) implants have a superior osseointegration than subjects with adequate serum vitamin D level?" Humans and animals were considered as subjects in this study. Databases were searched from 1969 up to and including March 2021 using different combination of the following terms: "implant", "bone to implant contact", "vitamin D" and "osseointegration". Letters to the editor, historic reviews, commentaries and articles published in languages other than English and German were excluded. The pattern of the present systematic review was customize to primarily summarize the pertinent data.

Results: Thirteen experimental studies with animals as subject, two clinical studies and three case reports, with humans as subjects, were included. The amount of inserted titanium implants ranged between 24 and 1740. Results from three animal studies showed that vitamin D deficiency has a negative effect on new bone formation and/or bone to implant contact (BIC). Eight animal studies showed that vitamin D supplementation has a enhancing effect on BIC and/or new bone formation around implants. Furthermore, enhancing the impact of vitamin D supplementation on the osseointegration of implants in subjects with diabetes mellitus, osteoporosis and chronic kidney disease (CKD) were assessed. Studies and case reports involving human subjects showed that patients with a low serum vitamin D level have a higher tendency to exhibit an early dental implant failure. When supplemented with vitamin D the osseointegration was successful in the case reports and a beneficial impact on the changes in the bone level during the osseointegration were determined.

Conclusions: Vitamin D deficiency seems to have a negative effect on the osseointegration of implants in animals. The supplementation of vitamin D appears to improve the osseointegration in animals with systemic diseases, such as vitamin D deficiency, diabetes mellitus, osteoporosis, and CKD. Slight evidence supports the hypothesis that humans similarly benefit from vitamin D supplementation in terms of osseointegration. Further investigation is required to maintain these assumptions.

Conflict of interest statement

J. G. Werny, K. Sagheb, L. Díaz Agurto, P. W. Kämmerer, B. Al-Nawas and E. Schiegnitz declare no conflicts of interest with respect to the research, authorship, and/or publication of this article. J. G. Werny, K. Sagheb, L. Díaz Agurto, P. W. Kämmerer, B. Al-Nawas and E. Schiegnitz do not have any financial interests, either directly or indirectly, related to the products or information discussed in the paper.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Endogenous synthesis of 1,25 (OH) Vitamin D. DBP: Vitamin D-binding Protein, CYP2R1: Vitamin D 25-hydroxylase, CYP27B1: 1 alpha-hydroxylase
Fig. 2
Fig. 2
Flow chart showing the search strategy that was adopted to identify studies that fulfilled the eligibility criteria. This flow chart was constructed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines
Fig. 3
Fig. 3
Overview concerning the main results of studies carried out with animals. NBF: New bone formation, BIC: Bone to implant contact. Including histological pictures published by Naito et al. 2014 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219862/), no changes have been made to the Figure. Copyright© Naito Y, Jimbo R, Bryington MS, Vandeweghe S, Chrcanovic BR, Tovar N, Ichikawa T, Coelho PG, Wennerberg A. (http://creativecommons.org/licenses/by-nc-nd/3.0/)
Fig. 4
Fig. 4
Overview concerning the main results of clinical studies. ESRD: End-stage renal failure, EDIF: Early dental implant failure. Including orthopantomogram pictures published by Fretwurst et al. 2016 (https://link.springer.com/content/pdf/10.1186/s40729-016-0056-0.pdf), no changes have been made to the figure. Copyright© Tobias Fretwurst, Sebastian Grunert, Johan P. Woelber, Katja Nelson and Wiebke Semper-Hogg (http://creativecommons.org/licenses/by/4.0/).

References

    1. Brånemark PI, Adell R, Breine U, Hansson BO, Lindström J, Ohlsson A. Intra-osseous anchorage of dental prostheses. I. Experimental studies. Scand J Plast Reconstr Surg. 1969;3(2):81–100.
    1. Schroeder A, van der Zypen E, Stich H, Sutter F. The reactions of bone, connective tissue, and epithelium to endosteal implants with titanium-sprayed surfaces. J Maxillofac Surg Februar. 1981;9(1):15–25. doi: 10.1016/S0301-0503(81)80007-0.
    1. Hong H-H, Yen T-H, Hong A, Chou T-A. Association of vitamin D3 with alveolar bone regeneration in dogs. J Cell Mol Med Juni. 2015;19(6):1208–1217. doi: 10.1111/jcmm.12460.
    1. Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK. Effect of high-dose vitamin D supplementation on volumetric bone density and bone strength: a randomized clinical trial. JAMA. 2019;322(8):736–745. doi: 10.1001/jama.2019.11889.
    1. Holick MF. Vitamin D deficiency. N Eng J Med. 2007;357(3):266–281. doi: 10.1056/NEJMra070553.
    1. Laky M, Bertl K, Haririan H, Andrukhov O, Seemann R, Volf I. Serum levels of 25-hydroxyvitamin D are associated with periodontal disease. Clin Oral Invest. 2017;21(5):1553–1558. doi: 10.1007/s00784-016-1965-2.
    1. Antonoglou GN, Knuuttila M, Niemelä O, Raunio T, Karttunen R, Vainio O. Low serum level of 1,25(OH)2D is associated with chronic periodontitis. J Periodontal Res. 2015;50(2):274–280. doi: 10.1111/jre.12207.
    1. Zhan Y, Samietz S, Holtfreter B, Hannemann A, Meisel P, Nauck M. Prospective study of serum 25-hydroxy vitamin D and tooth loss. J Dental Res. 2014 doi: 10.1177/0022034514534985.
    1. Brinker M, O’Connor D, Monla Y, Earthman T. Metabolic and endocrine abnormalities in patients with nonunions. J Orthop Trauma. 2007;21(8):557–570. doi: 10.1097/BOT.0b013e31814d4dc6.
    1. Alkalay D, Shany S, Dekel S. Serum and bone vitamin D metabolites in elective patients and patients after fracture. J Bone Jt Surg Br. 1989;71-B(1):85–87. doi: 10.1302/0301-620X.71B1.2783695.
    1. Lehmann B. The vitamin D3 pathway in human skin and its role for regulation of biological processes. Photochem Photobiol. 2005;81(6):1246–1251. doi: 10.1562/2005-02-02-IR-430.
    1. O’Connor A, Benelam B. An update on UK Vitamin D intakes and status, and issues for food fortification and supplementation. Nutr Bull. 2011;36(3):390–396. doi: 10.1111/j.1467-3010.2011.01918.x.
    1. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87(4):1080S–1086S. doi: 10.1093/ajcn/87.4.1080S.
    1. U.S. Department of Agriculture, Agricultural Research Service. FoodData Central [Internet]. [zitiert 9. März 2021]. Verfügbar unter: .
    1. Halfon M, Phan O, Teta D. Vitamin D: a review on its effects on muscle strength, the risk of fall, and frailty. Biomed Res Int. 2015. Verfügbar unter: .
    1. Kogawa M, Findlay DM, Anderson PH, Ormsby R, Vincent C, Morris HA. Osteoclastic metabolism of 25(OH)-vitamin D3: a potential mechanism for optimization of bone resorption. Endocrinology. 2010;151(10):4613–4625. doi: 10.1210/en.2010-0334.
    1. Atkins GJ, Kostakis P, Pan B, Farrugia A, Gronthos S, Evdokiou A. RANKL expression is related to the differentiation state of human osteoblasts. J Bone Mineral Res. 2003;18(6):1088–1098. doi: 10.1359/jbmr.2003.18.6.1088.
    1. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–58. doi: 10.1210/jc.2010-2704.
    1. Nutrition and bone health: with particular reference to calcium and vitamin D. Report of the Subgroup on Bone Health, Working Group on the Nutritional Status of the Population of the Committee on Medical Aspects of the Food Nutrition Policy. Rep Health Soc Subj (Lond). 1998;49:iii–xvii, 1–24. PMID: 9932291.
    1. Makris K, Sempos C, Cavalier E. The measurement of vitamin D metabolites: part I—metabolism of vitamin D and the measurement of 25-hydroxyvitamin D. Hormones. 2020;19(2):81–96. doi: 10.1007/s42000-019-00169-7.
    1. Schulze-Späte U, Dietrich T, Wu C, Wang K, Hasturk H, Dibart S. Systemic vitamin D supplementation and local bone formation after maxillary sinus augmentation—a randomized, double-blind, placebo-controlled clinical investigation. Clin Oral Implants Res. 2016;27(6):701–706. doi: 10.1111/clr.12641.
    1. Wu Y, Yu T, Yang X, Li F, Ma L, Yang Y. Vitamin D3 and insulin combined treatment promotes titanium implant osseointegration in diabetes mellitus rats. Bone. 2013;52(1):1–8. doi: 10.1016/j.bone.2012.09.005.
    1. Dvorak G, Fügl A, Watzek G, Tangl S, Pokorny P, Gruber R. Impact of dietary vitamin D on osseointegration in the ovariectomized rat. Clin Oral Implant Res. 2012;23(11):1308–1313. doi: 10.1111/j.1600-0501.2011.02346.x.
    1. Liu W, Zhang S, Zhao D, Zou H, Sun N, Liang X. Vitamin D supplementation enhances the fixation of titanium implants in chronic kidney disease mice. PLoS One. 9(4). Verfügbar unter: .
    1. Zhou C, Li Y, Wang X, Shui X, Hu J. 1,25Dihydroxy vitamin D3 improves titanium implant osseointegration in osteoporotic rats. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114(Supplement_5):S174–S178. doi: 10.1016/j.oooo.2011.09.030.
    1. Salomó-Coll O, Val de JEM-S, Ramírez-Fernandez MP, Hernández-Alfaro F, Gargallo-Albiol J, Calvo-Guirado JL. Topical applications of vitamin D on implant surface for bone-to-implant contact enhance: a pilot study in dogs part II. Clin Oral Implants Res. 2016;27(7):896–903. doi: 10.1111/clr.12707.
    1. Cho YJ, Heo SJ, Koak JY, Kim SK, Lee SJ, Lee JH. Promotion of osseointegration of anodized titanium implants with a 1α,25-dihydroxyvitamin D3 submicron particle coating. Int J Oral Maxillofac Implants. 2011;26(6):1225–1232.
    1. Satué M, Monjo M, Ronold HJ, Lyngstadaas SP, Ramis JM. Titanium implants coated with UV-irradiated vitamin D precursor and vitamin E: in vivo performance and coating stability. Clin Oral Implant Res. 2017;28(4):424–431. doi: 10.1111/clr.12815.
    1. Naito Y, Jimbo R, Bryington MS, Vandeweghe S, Chrcanovic BR, Tovar N. The influence of 1α.25-Dihydroxyvitamin D3 coating on implant osseointegration in the rabbit Tibia. J Oral Maxillofac Res. 2014;5(3). Verfügbar unter: .
    1. Akhavan A, Noroozi Z, Shafiei AA, Haghighat A, Jahanshahi GR, Mousavi SB. The effect of vitamin D supplementation on bone formation around titanium implants in diabetic rats. Dent Res J (Isfahan) 2012;9(5):582–587. doi: 10.4103/1735-3327.104877.
    1. 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(6):473–478. doi: 10.1111/j.1532-849X.2009.00446.x.
    1. Vandersteenhoven JJ, DeLustro FA, Bell NH, Turner RT. Osteoinduction by implants of demineralized allogeneic bone matrix is diminished in vitamin D-deficient rats. Calcif Tissue Int. 1988;42(1):39–45. doi: 10.1007/BF02555837.
    1. Pimentel SP, Casarin RC, Ribeiro FV, Cirano FR, Rovaris K, Haiter F. Impact of micronutrients supplementation on bone repair around implants: microCT and counter-torque analysis in rats. J Appl Oral Sci. 2016;24(1):45–51. doi: 10.1590/1678-775720150293.
    1. Nakamura Y, Hayashi K, Abu-Ali S, Naito M, Fotovati A. Effect of preoperative combined treatment with alendronate and calcitriol on fixation of hydroxyapatite-coated implants in ovariectomized rats. J Bone Jt Surg Am. 2008;90(4):824–832. doi: 10.2106/JBJS.G.00635.
    1. Kwiatek J, Jaroń A, Trybek G. Impact of the 25-hydroxycholecalciferol concentration and vitamin D deficiency treatment on changes in the bone level at the implant site during the process of osseointegration: a prospective, randomized, controlled clinical trial. J Clin Med 2021;10(3). Verfügbar unter: .
    1. Guido Mangano F, Ghertasi Oskouei S, Paz A, Mangano N, Mangano C. Low serum vitamin D and early dental implant failure: Is there a connection? A retrospective clinical study on 1740 implants placed in 885 patients. J Dent Res Dent Clin Dent Prospects. 2018;12(3):174–182. doi: 10.15171/joddd.2018.027.
    1. Flanagan D, Mancini M. Bimaxillary full arch fixed dental implant supported treatment for a patient with renal failure and secondary hyperparathyroidism and osteodystrophy. J Oral Implantol. 2015;41(2):e36–43. doi: 10.1563/AAID-JOI-D-13-00188.
    1. Bryce G, MacBeth N. Vitamin D deficiency as a suspected causative factor in the failure of an immediately placed dental implant: a case report. J R Nav Med Serv. 2014;100(3):328–332. doi: 10.1136/jrnms-100-328.
    1. Fretwurst T, Grunert S, Woelber JP, Nelson K, Semper-Hogg W. Vitamin D deficiency in early implant failure: two case reports. Int J Implant Dent. 2020;2. Verfügbar unter: .
    1. Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med. 2006;260(3):245–254. doi: 10.1111/j.1365-2796.2006.01685.x.
    1. Chapuy MC, Schott AM, Garnero P, Hans D, Delmas PD, Meunier PJ. Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group. J Clin Endocrinol Metab. 1996;81(3):1129–1133.
    1. Greene-Finestone LS, Berger C, de Groh M, Hanley DA, Hidiroglou N, Sarafin K. 25-Hydroxyvitamin D in Canadian adults: biological, environmental, and behavioral correlates. Osteoporos Int. 2011;22(5):1389–1399. doi: 10.1007/s00198-010-1362-7.
    1. Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT. Prevalence of Vitamin D inadequacy among postmenopausal north american women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005;90(6):3215–3224. doi: 10.1210/jc.2004-2364.
    1. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81(3):353–373. doi: 10.4065/81.3.353.
    1. Charoenngam N, Shirvani A, Holick MF. The ongoing D-lemma of vitamin D supplementation for nonskeletal health and bone health. Curr Opin Endocrinol Diab Obes. 2019;26(6):301–305. doi: 10.1097/MED.0000000000000508.
    1. Fretwurst T, Wölber JP, Nelson K. Vitamin D zur implantation—Ist ein Screening mit Substitution sinnvoll? Quintessenz Zahnmedizin. 2020;71(5):504–510.
    1. Shahram G, Karl UV, Al-Maawi S. Vitamin D als schlüsselelement für immunabwehr und regeneration. Implantol J. 2020;9:16–22.
    1. Irie MS, Rabelo GD, Spin-Neto R, Dechichi P, Borges JS, Soares PBF. Use of micro-computed tomography for bone evaluation in dentistry. Brazil Dental J. 2018;29(3):227–238. doi: 10.1590/0103-6440201801979.
    1. Vandeweghe S, Coelho PG, Vanhove C, Wennerberg A, Jimbo R. Utilizing micro-computed tomography to evaluate bone structure surrounding dental implants: a comparison with histomorphometry. J Biomed Mater Res B Appl Biomater. 2013;101(7):1259–1266. doi: 10.1002/jbm.b.32938.
    1. Max-Bergmann-Center for Biomaterials, Technische Universität Dresden, Budapester Str. 27, 01062 Dresden, Germany, Bernhardt R, Kuhlisch E, Schulz M, Eckelt U, Stadlinger B. Comparison of bone-implant contact and bone-implant volume between 2D-histological sections and 3D-SRµCT slices. ECM. 2012;23:237–48.

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