Systemic Health and Implant Failure

Implant therapy has become a fundamental component of dental care. Treatment with dental implants has eliminated the need to include contiguous teeth in the treatment plan when only a single tooth requires replacement, and has provided clinicians with a series of options that allow replacement of teeth where before only a removable prosthesis was possible.1Busenlechner D, Fürhauser R, Haas R, Watzek G, Mailath G, Pommer B. Long-term implant success at the Academy for Oral Implantology: 8-year follow-up and risk factor analysis. J Periodontal Implant Sci 2014;44:102-8. http://dx.doi.org/10.5051/jpis.2014.44.3.102

Dental implant therapy has proven to be a remarkably successful clinical procedure, with a recent systematic review with a follow-up of more than 10 years finding a mean survival rate of 94.6% and a mean success rate of 89.7%.2Moraschini V, Poubel LA, Ferreira VF, Barboza Edos S. Evaluation of survival and success rates of dental implants reported in longitudinal studies with a follow-up period of at least 10 years: a systematic review. Int J Oral Maxillofac Surg 2015;44(3):377-88.

A recent systematic review with a follow-up of more than 10 years reported a mean survival rate of 94.6% and a mean success rate of 89.7%.

Complications

The large number of implants placed has meant that implant complications have become more common. Complications include mucosal inflammation (peri-implant mucositis), which untreated can progress to loss of bone support (peri-implantitis) and thereby implant failure.3American Academy of Periodontology. Peri-implant mucositis and peri-implantitis: A current understanding of their diagnoses and clinical implications. J Periodontol 2013;84(4):436-43. In addition, in older patients receiving implants, there is a higher probability of being diagnosed with a systemic/chronic disease or condition. An important concern is the potential impact of these conditions on implant complications and failure.

Systemic diseases and conditions

A recent report examined the association of dental implant failure and systemic diseases/conditions in 6,358 patients, with a follow-up of up to 31 years.4Carr AB, Revuru VS, Lohse CM. Association of systemic conditions with dental implant failures in 6,384 patients during a 31-year follow-up period. Int J Oral Maxillofac Implants 2017;32(5):1153-61. More than twenty systemic diseases/conditions were considered. Epidemiologic, medical and dental data were available for analysis. Implant failure was experienced by 713 patients, with a median time to first failure of 0.6 years. After adjusting for age, gender and follow-up period, none of the systemic conditions were found to increase risk for implant failure.


Figure 1
Systemic conditions/diseases considered in studies.

Other systematic reviews have also failed to find a clear association between systemic disorders and implant failure.5Bornstein MM, Cionca N, Mombelli A. Systemic conditions and treatments as risks for implant therapy. Int J Oral Maxillofac Implants 2009;24(Suppl):12-27.,6Guobis Z, Pacauskiene I, Astramskaite I. General diseases influence on peri-implantitis development: a systematic review. J Oral Maxillofac Res 2016;7(3):e5.,7Clementini M, Rossetti PH, Penarrocha D, Micarelli C, Bonachela WC, Canullo L. Systemic risk factors for peri-implant bone loss: a systematic review and meta-analysis. Int J Oral Maxillofac Surg 2014;43(3):323-34. Additionally, in a retrospective study including more than 200 patients and 1,000 implants, and with a minimum follow-up of at least 20 years and a maximum of 36 years, no differences in survival rates were observed for patients with and without type 2 diabetes, high blood pressure, immunosuppression, hypothyroidism or those taking bisphosphonates.8Chrcanovic BR, Kisch J, Albrektsson T, Wennerberg A. A retrospective study on clinical and radiological outcomes of oral implants in patients followed up for a minimum of 20 years. Clin Implant Dent Relat Res 2017 Dec 6. While the reviews and studies discussed found no associations for systemic diseases overall, this may mask the potential for complications as a result of a single disorder, conflicting findings and potential confounders. It is illustrative to examine specific disorders in greater detail.

Several systematic reviews have failed to find a clear association between systemic disorders and implant failure.

Diabetes mellitus

In a review of 14 studies published between 2000 and August 2015, and at low risk of bias, types 1 and 2 diabetes (DM) were not found to be risk factors for implant failure.9Moraschini V, Barboza ES, Peixoto GA. The impact of diabetes on dental implant failure: a systematic review and meta-analysis. Int J Oral Maxillofac Surg 2016;45(10):1237-45. doi: 10.1016/j.ijom.2016.05.019. Further, in a meta-analysis that included 5 studies, no significant association was found for implant failure and DM,10Chen H, Liu N, Xu X, Qu X, Lu E. Smoking, radiotherapy, diabetes and osteoporosis as risk factors for dental implant failure: a meta-analysis. PLoS One 2013;8:e71955. and in another meta-analysis of 7 studies no direct association was found for implant failure and glycemic level.11Shi Q, Xu J, Huo N, Cai C, Liu H. Does a higher glycemic level lead to a higher rate of dental implant failure?: A meta-analysis. J Am Dent Assoc 2016;147(11):875-81. doi: 10.1016/j.adaj.2016.06.011. Healing and osseointegration have been found to be delayed for patients with poor glycemic control, while similar success rates were observed one year after implant loading for patients with and without DM, including those with poorly-controlled diabetes.12Oates TW Jr, Galloway P, Alexander P, Vargas Green A, Huynh-Ba G5, Feine J, McMahan CA. The effects of elevated hemoglobin A(1c) in patients with type 2 diabetes mellitus on dental implants: Survival and stability at one year. J Am Dent Assoc 2014;145(12):1218-26. doi: 10.14219/jada.2014.93. Implant survival rates for four studies in another review ranged from 92% to 97.2% and 93.2% to 98.8%, respectively, for patients with and without DM.13Naujokat H, Kunzendorf B, Wiltfang J. Dental implants and diabetes mellitus—a systematic review. Int J Implant Dent 2016;2:5. doi: 10.1186/s40729-016-0038-2.
However, further examination of these reviews and studies reveals several issues. Some reviews reported significant study heterogeneity, a lack of high-quality studies, and failure rates across individual studies varied considerably for control and test groups.13Naujokat H, Kunzendorf B, Wiltfang J. Dental implants and diabetes mellitus—a systematic review. Int J Implant Dent 2016;2:5. doi: 10.1186/s40729-016-0038-2.
In addition, conflicting conclusions have been drawn for the influence of glycemic control on implant failure rates, not all studies addressed glycemic control, and definitions for levels of glycemic control varied.13Naujokat H, Kunzendorf B, Wiltfang J. Dental implants and diabetes mellitus—a systematic review. Int J Implant Dent 2016;2:5. doi: 10.1186/s40729-016-0038-2. Only 5 of 22 studies in one review indicated the length of time since patients had been diagnosed with DM with just 2 of 22 studies considering its influence.13Naujokat H, Kunzendorf B, Wiltfang J. Dental implants and diabetes mellitus—a systematic review. Int J Implant Dent 2016;2:5. doi: 10.1186/s40729-016-0038-2. In addition, in two of four studies with a control group evaluating peri-implantitis, an approximately two- to four-fold increased risk was found at 5 and 10 years for patients with DM.13Naujokat H, Kunzendorf B, Wiltfang J. Dental implants and diabetes mellitus—a systematic review. Int J Implant Dent 2016;2:5. doi: 10.1186/s40729-016-0038-2. In contrast, no significant difference in bone resorption at 3 years was found in another study, yet a further study found that less well-controlled glycemic levels were directly related to peri-implantitis.13Naujokat H, Kunzendorf B, Wiltfang J. Dental implants and diabetes mellitus—a systematic review. Int J Implant Dent 2016;2:5. doi: 10.1186/s40729-016-0038-2. Implant survival rates were found to be similar in the first few years following implant placement, and it was concluded that peri-implantitis was subsequently more prevalent in patients with DM and that long-term survival rates are lower for these patients.
In two of four studies with a control group evaluating peri-implantitis, an approximately two- to four-fold increased risk was found at 5 and 10 years for patients with diabetes.
Table 1. Summary data for studies of patients with and without DM
Study Findings
Chen et al, 2013 No statistically significant association found for implant failure and DM.
Oates et al, 2014 Healing and osseointegration were delayed for patients with poor glycemic control. Similar success rates observed 1-year after implant loading, including for patients with poorly-controlled DM.
Moraschini et al, 2016 Types 1 and 2 DM were not risk factors for implant failure.
Naujokat et al, 2016 Similar implant survival rates for patients with well-controlled DM and without DM
Shi et al, 2016 No direct association for implant failure and glycemic level.

Irradiated bone

Conflicting outcomes and conclusions have been reported for implants placed in irradiated bone. In a pooled analysis of 16 studies, a more than two-fold increased risk of implant failure was found for implants placed in irradiated bone.10Chen H, Liu N, Xu X, Qu X, Lu E. Smoking, radiotherapy, diabetes and osteoporosis as risk factors for dental implant failure: a meta-analysis. PLoS One 2013;8:e71955. In addition, an almost three-fold increased risk for implant failure for implants placed in irradiated bone was found in a meta-analysis of 7 studies in a second systematic review, as well as and an almost six-fold risk for implants placed in irradiated bone in the maxilla compared to in the mandible.14Chambrone L, Mandia J Jr, Shibli JA, Romito GA, Abrahao M. Dental implants installed in irradiated jaws: a systematic review. J Dent Res 2013;92(12 Suppl):119S-30S.Other studies have compared survival rates for implants placed at different periods of time post-irradiation, or compared pre- or post-irradiation implant placement. In a review of 10 studies, it was concluded that implant placement less than 12 months after radiotherapy may result in a higher risk of failure.15Claudy MP, Miguens SA Jr, Celeste RK, Camara Parente R, Hernandez PA, da Silva AN Jr. Time interval after radiotherapy and dental implant failure: systematic review of observational studies and meta-analysis. Clin Implant Dent Relat Res 2015;17(2):402-11. doi: 10.1111/cid.12096. Similar implant survival rates were found for dental implants placed pre- and post-irradiation in a systematic review of 19 studies reported between 1990 and 2006,16Colella G, Cannavale R, Pentenero M, Gandolfo S. Oral implants in radiated patients: A systematic review. Int J Oral Maxillofac Impl 2007;22:616-22. as well as in a separate review of articles published between 1990 and 2012.17Nooh N. Dental implant survival in irradiated oral cancer patients: a systematic review of the literature. Int J Oral Maxillofac Implants 2013;28(5):1233-42.

Maxillary implant survival rates were lower than for the mandible when placed prior to radiation therapy.
It is difficult to draw conclusions due to the heterogeneity and variable quality of existing studies, and the lack of robust controlled studies. For example, excluding one study from the meta-analysis in one review reduced the increased risk of implant failure attributed to timing of implant placement from 34% to 8%, two studies involved placement before the stated inclusion period, and selection bias was evident.15Claudy MP, Miguens SA Jr, Celeste RK, Camara Parente R, Hernandez PA, da Silva AN Jr. Time interval after radiotherapy and dental implant failure: systematic review of observational studies and meta-analysis. Clin Implant Dent Relat Res 2015;17(2):402-11. doi: 10.1111/cid.12096. In another review, radiation exposures ranged from 36 to 72 Gy, failure rates for individual studies varied greatly, and it was not reported whether implant placement occurred before or after radiation therapy.10Chen H, Liu N, Xu X, Qu X, Lu E. Smoking, radiotherapy, diabetes and osteoporosis as risk factors for dental implant failure: a meta-analysis. PLoS One 2013;8:e71955. In addition, while higher implant failure rates have been found for patients who received high-dose radiation therapy, high-dose was defined in different studies as >55 Gy, >50 Gy and >45 Gy.17Nooh N. Dental implant survival in irradiated oral cancer patients: a systematic review of the literature. Int J Oral Maxillofac Implants 2013;28(5):1233-42.,18Granström G. Osseointegration in irradiated cancer patients: An analysis with respect to implant failures. J Oral Maxillofac Surg 2005;63:579-85.,19Curi MM, Condezo AFB, Ribeiro KDCB, Cardoso CL. Long-term success of dental implants in patients with head and neck cancer after radiation therapy. Int J Oral Maxillofac Surg 2018 Feb 6. pii: S0901-5027(18)30028-6. doi: 10.1016/j.ijom.2018.01.012. [Epub ahead of print] Considered in total, these studies do, however, suggest that the radiation dose and the method of radiation delivery impacts implant outcomes.
Considered in total, studies suggest that the radiation dose and the method of radiation delivery impacts implant outcomes.

Other Conditions

Systematic reviews have also been conducted in patients with and without osteoporosis.8Chrcanovic BR, Kisch J, Albrektsson T, Wennerberg A. A retrospective study on clinical and radiological outcomes of oral implants in patients followed up for a minimum of 20 years. Clin Implant Dent Relat Res 2017 Dec 6.,20de Medeiros FCFL, Kudo GAH, Leme BG, Saraiva PP, Verri FR, Honório HM, Pellizzer EP, Santiago Junior JF. Dental implants in patients with osteoporosis: a systematic review with meta-analysis. Int J Oral Maxillofac Surg 2018;47(4):480-91.,21Temmerman A, Rasmusson L, Kubler A, Thor A, Quirynen M. An open, prospective, non-randomized, controlled, multicentre study to evaluate the clinical outcome of implant treatment in women over 60 years of age with osteoporosis/osteopenia: 1-year results. Clin Oral Implants Res 2017;28:95-102.,22Giro G, Chambrone L, Goldstein A, Rodrigues JA, Zenóbio E, Feres M, Figueiredo LC, Cassoni A, Shibli JA. Impact of osteoporosis in dental implants: A systematic review. World J Orthop 2015;6(2):311-5. In one recent meta-analysis of 15 studies with a total of almost 9,000 patients and 30,000 implants, no statistically significant differences were found for implant survival at the individual or patient level.20de Medeiros FCFL, Kudo GAH, Leme BG, Saraiva PP, Verri FR, Honório HM, Pellizzer EP, Santiago Junior JF. Dental implants in patients with osteoporosis: a systematic review with meta-analysis. Int J Oral Maxillofac Surg 2018;47(4):480-91. However, nuances are also apparent across studies. Peri-implantitis was evaluated in only one study, and studies did not consistently report whether the onset of osteoporosis preceded or followed dental implant therapy and/if bisphosphonate therapy was initiated before or after implant placement.20de Medeiros FCFL, Kudo GAH, Leme BG, Saraiva PP, Verri FR, Honório HM, Pellizzer EP, Santiago Junior JF. Dental implants in patients with osteoporosis: a systematic review with meta-analysis. Int J Oral Maxillofac Surg 2018;47(4):480-91.,21Temmerman A, Rasmusson L, Kubler A, Thor A, Quirynen M. An open, prospective, non-randomized, controlled, multicentre study to evaluate the clinical outcome of implant treatment in women over 60 years of age with osteoporosis/osteopenia: 1-year results. Clin Oral Implants Res 2017;28:95-102.,22Giro G, Chambrone L, Goldstein A, Rodrigues JA, Zenóbio E, Feres M, Figueiredo LC, Cassoni A, Shibli JA. Impact of osteoporosis in dental implants: A systematic review. World J Orthop 2015;6(2):311-5.,23Dvorak G, Arnhart C, Heuberer S, Huber CD, Watzek G, Gruber R. Peri-implantitis and late implant failures in postmenopausal women: a cross-sectional study. J Clin Periodontol 2011;38:950-5.,24Walter C, Al-Nawas B, Wolff T, Schiegnitz E, Grötz KA. Dental implants in patients treated with antiresorptive medication – a systematic literature review. Int J Impl Dent 2016;2:9.,25Hellstein JW, Adler RA, Edwards B, Jacobsen PL, Kalmar JR, Koka S, Migliorati CA, Ristic H; American Dental Association Council on Scientific Affairs Expert Panel on Antiresorptive Agents. Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: executive summary of recommendations from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 2011;142(11):1243-51. There is limited data available for other systemic/chronic diseases. A 93.7% survival rate was found for implants placed in patients with Sjögren’s syndrome with a mean follow-up of 4 years in a recent systematic review, which was limited to one case study, one prospective and four retrospective studies.26Almeida D, Vianna K, Arriaga P, Moraschini V. Dental implants in SjoÈgren’s syndrome patients: A systematic review. PLoS One 2017;12(12): e0189507. https://doi.org/10.1371/journal.pone.0189507 Further, limited data on implant outcomes is available for patients with cardiovascular disease, and even less for patients with HIV/AIDS, Crohn’s disease, ectodermal dysplasia, lichen planus, scleroderma, or for patients taking immunosuppressants.5Bornstein MM, Cionca N, Mombelli A. Systemic conditions and treatments as risks for implant therapy. Int J Oral Maxillofac Implants 2009;24(Suppl):12-27.,27Paredes V, López-Pintor RM, Torres J, de Vicente JC, Sanz M, Hernández G. Implant treatment in pharmacologically immunosuppressed liver transplant patients: A prospective-controlled study. Clin Oral Implants Res 2018;29(1):28-35.

Conclusions

The results of systematic reviews indicate that “systemic disease” in the broadest sense is not a contraindication to implant therapy, and disorders such as diabetes, irradiated bone and osteoporosis do not disqualify patients from receiving dental implants.

However, as noted, studies in the reviews were heterogeneous, at varying levels of risk of bias, and there is a paucity of truly robust studies. In addition, far fewer studies have evaluated implant success, i.e., an absence of complications, including peri-implantitis. Further, for other conditions there is a lack of, or limited, available data. This issue will become increasingly important as the population ages and more individuals with systemic/chronic diseases could benefit from implant therapy.

It can be concluded that more randomized controlled trials and prospective long-term studies are needed on the impact of a range of systemic conditions, as well as the significance of medical management, comorbidities and other confounding factors on implant therapy.6Guobis Z, Pacauskiene I, Astramskaite I. General diseases influence on peri-implantitis development: a systematic review. J Oral Maxillofac Res 2016;7(3):e5.,10Chen H, Liu N, Xu X, Qu X, Lu E. Smoking, radiotherapy, diabetes and osteoporosis as risk factors for dental implant failure: a meta-analysis. PLoS One 2013;8:e71955.,13Naujokat H, Kunzendorf B, Wiltfang J. Dental implants and diabetes mellitus—a systematic review. Int J Implant Dent 2016;2:5. doi: 10.1186/s40729-016-0038-2.
Implant maintenance protocols were recently introduced that could improve long-term implant outcomes28Bidra AS, Daubert DM, Garcia LT, Kosinski TF, Nenn CA, Olsen JA, Platt JA, Wingrove SS, Chandler ND, Curtis DA. Clinical practice guidelines for recall and maintenance of patients with tooth-borne and implant-borne dental restorations. J Am Dent Assoc 2016;147(1):67-74. and medical management of chronic diseases/conditions continues to evolve. Though not thoroughly examined in the reviews, the relative success of medical management of specific disorders should be a critical factor in determining the best course of treatment for patients. Each patient must be evaluated separately when deciding upon a course of treatment, other health professionals should be consulted, and potential concerns should be discussed with patients.

References

  • 1.Garrido M, Dezerega A, Bordagaray MJ, Reyes M, Vernal R, Melgar-Rodriguez S, et al. C-reactive protein expression is up-regulated in apical lesions of endodontic origin in association with interleukin-6. J Endod. 2015;41(4):464-9.
  • 2.Georgiou AC, Crielaard W, Armenis I, de Vries R, van der Waal SV. Apical periodontitis is associated with elevated concentrations of inflammatory mediators in peripheral blood: A systematic review and meta-analysis. J Endod. 2019;45(11):1279-95 e3.
  • 3.Samuel RO, Gomes-Filho JE, Azuma MM, Sumida DH, de Oliveira SHP, Chiba FY, et al. Endodontic infections increase leukocyte and lymphocyte levels in the blood. Clin Oral Investig. 2018;22(3):1395-401.
  • 4.Berlin-Broner Y, Febbraio M, Levin L. Association between apical periodontitis and cardiovascular diseases: A systematic review of the literature. Int Endod J. 2017;50(9):847-59.
  • 5.Caplan DJ, Chasen JB, Krall EA, Cai J, Kang S, Garcia RI, et al. Lesions of endodontic origin and risk of coronary heart disease. J Dent Res. 2006;85(11):996-1000.
  • 6.Petersen J, Glassl EM, Nasseri P, Crismani A, Luger AK, Schoenherr E, et al. The association of chronic apical periodontitis and endodontic therapy with atherosclerosis. Clin Oral Investig. 2014;18(7):1813-23.
  • 7.Liljestrand JM, Mantyla P, Paju S, Buhlin K, Kopra KA, Persson GR, et al. Association of endodontic lesions with coronary artery disease. J Dent Res. 2016;95(12):1358-65.
  • 8.Virtanen E, Nurmi T, Soder PO, Airila-Mansson S, Soder B, Meurman JH. Apical periodontitis associates with cardiovascular diseases: A cross-sectional study from sweden. BMC Oral Health. 2017;17(1):107.
  • 9.Segura-Egea JJ, Castellanos-Cosano L, Machuca G, Lopez-Lopez J, Martin-Gonzalez J, Velasco-Ortega E, et al. Diabetes mellitus, periapical inflammation and endodontic treatment outcome. Med Oral Patol Oral Cir Bucal. 2012;17(2):e356-61.
  • 10.Segura-Egea JJ, Martin-Gonzalez J, Castellanos-Cosano L. Endodontic medicine: Connections between apical periodontitis and systemic diseases. Int Endod J. 2015;48(10):933-51.
  • 11.Segura-Egea JJ, Martin-Gonzalez J, Cabanillas-Balsera D, Fouad AF, Velasco-Ortega E, Lopez-Lopez J. Association between diabetes and the prevalence of radiolucent periapical lesions in root-filled teeth: Systematic review and meta-analysis. Clin Oral Investig. 2016;20(6):1133-41.
  • 12.Cintra LTA, Estrela C, Azuma MM, Queiroz IOA, Kawai T, Gomes-Filho JE. Endodontic medicine: Interrelationships among apical periodontitis, systemic disorders, and tissue responses of dental materials. Braz Oral Res. 2018;32(suppl 1):e68.
  • 13.Segura-Egea JJ, Cabanillas-Balsera D, Jimenez-Sanchez MC, Martin-Gonzalez J. Endodontics and diabetes: Association versus causation. Int Endod J. 2019;52(6):790-802.
  • 14.Cabanillas-Balsera D, Martin-Gonzalez J, Montero-Miralles P, Sanchez-Dominguez B, Jimenez-Sanchez MC, Segura-Egea JJ. Association between diabetes and nonretention of root filled teeth: A systematic review and meta-analysis. Int Endod J. 2019;52(3):297-306.
  • 15.Perez-Losada FL, Estrugo-Devesa A, Castellanos-Cosano L, Segura-Egea JJ, Lopez-Lopez J, Velasco-Ortega E. Apical periodontitis and diabetes mellitus type 2: A systematic review and meta-analysis. J Clin Med. 2020;9(2).
  • 16.Gupta A, Aggarwal V, Mehta N, Abraham D, Singh A. Diabetes mellitus and the healing of periapical lesions in root filled teeth: A systematic review and meta-analysis. Int Endod J. 2020.
  • 17.Smadi L. Apical periodontitis and endodontic treatment in patients with type ii diabetes mellitus: Comparative cross-sectional survey. J Contemp Dent Pract. 2017;18(5):358-62.
  • 18.Rudranaik S, Nayak M, Babshet M. Periapical healing outcome following single visit endodontic treatment in patients with type 2 diabetes mellitus. J Clin Exp Dent. 2016;8(5):e498-e504.
  • 19.Gomes CC, Guimaraes LS, Pinto LCC, Camargo G, Valente MIB, Sarquis MIM. Investigations of the prevalence and virulence of candida albicans in periodontal and endodontic lesions in diabetic and normoglycemic patients. J Appl Oral Sci. 2017;25(3):274-81.
  • 20.Graetz C, El-Sayed KF, Geiken A, et al. Effect of periodontitis history on implant success: a long-term evaluation during supportive periodontal therapy in a university setting. Clin Oral Investig 2018;22:235-244.
  • 21.Hasanoglu Erbasar GN, Hocaoglu TP, Erbasar RC. Risk factors associated with short dental implant success: a long-term retrospective evaluation of patients followed up for up to 9 years. Braz Oral Res 2019;33:e030.
  • 22.Goncalves Junior R, Pinheiro Ada R, Schoichet JJ, et al. MMP13, TIMP2 and TGFB3 gene polymorphisms in Brazilian chronic periodontitis and peri-implantitis subjects. Braz Dent J 2016;27:128-134.
  • 23.Petkovic-Curcin A, Zeljic K, Cikota-Aleksic B, Dakovic D, Tatic Z, Magic Z. Association of cytokine gene polymorphism with peri-implantitis risk. Int J Oral Maxillofac Implants 2017;32:e241-e248.
  • 24.Costa LC, Fonseca MAD, Pinheiro ADR, et al. Chronic periodontitis and RANKL/OPG ratio in peri-implant mucosae inflammation. Braz Dent J 2018;29:14-22.
  • 25.Heitz-Mayfield LJA, Salvi GE. Peri-implant mucositis. J Periodontol 2018;89 Suppl 1:S257-S266.
  • 26.Schwarz F, Derks J, Monje A, Wang HL. Peri-implantitis. J Periodontol 2018;89 Suppl 1:S267-S290.
  • 27.Farsalinos KE, Voudris V, Poulas K. Are metals emitted from electronic cigarettes a reason for health concern? A risk-assessment analysis of currently available literature. Int J Environ Res Pub Health 2015;12(5):5215-32.
  • 28.Liu X, Lu W, Liao S, Deng Z, Zhang Z, Liu Y, Lu W. Efficiency and adverse events of electronic cigarettes: A systematic review and meta-analysis (PRISMA-compliant article). Medicine (Baltimore) 2018;97(19):e0324. doi: 10.1097/MD.0000000000010324.
  • 29.Cho JH. The association between electronic-cigarette use and self-reported oral symptoms including cracked or broken teeth and tongue and/or inside-cheek pain among adolescents: A cross-sectional study. PLoS One 2017;12(7):e0180506. doi: 10.1371/journal.pone.0180506.
  • 30.National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health. E-Cigarette Use Among Youth and Young Adults: A Report of the Surgeon General [Internet]. Atlanta (GA): Centers for Disease Control and Prevention (US); 2016. Chapter 3, Health Effects of E-Cigarette Use Among U.S. Youth and Young Adults. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538688/.
  • 31.U.S. Food & Drug Administration. Effective and Compliance Dates Applicable to Retailers, Manufacturers, Importers, and Distributors of Deemed Tobacco Products. Available at: https://www.fda.gov/tobacco-products/compliance-enforcement-training/effective-and-compliance-dates-applicable-retailers-manufacturers-importers-and-distributors-deemed.
  • 32.CDC. State Tobacco Activities Tracking and Evaluation (STATE) System. Available at: https://www.cdc.gov/statesystem/factsheets/ecigarette/ECigarette.html.
  • 33.U.S. Food & Drug Administration. FDA News Release. FDA finalizes enforcement policy on unauthorized flavored cartridge-based e-cigarettes that appeal to children, including fruit and mint. January 2, 2020. Available at: https://www.fda.gov/news-events/press-announcements/fda-finalizes-enforcement-policy-unauthorized-flavored-cartridge-based-e-cigarettes-appeal-children.
  • 34.U.S. Food & Drug Administration. Misleadingly Labeled E-Liquids that Appeal to Youth. Available at: https://www.fda.gov/tobacco-products/ctp-newsroom/misleadingly-labeled-e-liquids-appeal-youth.
  • 35.Vape Ban 2021: Home Delivery of Vaping Products in Jeopardy? February 18, 20201. Available at: https://www.vaporvanity.com/vape-ban/
  • 36.Edwards E. Federal flavor ban goes into effect Thursday, but many flavored vape products will still be available. Feb 5, 2020. Available at: https://www.nbcnews.com/health/vaping/federal-flavor-ban-goes-effect-thursday-many-flavored-vape-products-n1130466.
  • 37.Gold J. More vapers are making their own juice, but not without risks. Kaiser Health News, Nov 13, 2019. Available at: https://www.nbcnews.com/health/vaping/more-vapers-are-making-their-own-juice-not-without-risks-n1081496.
  • 38.Gardener H, Elkind MSV. Artificial sweeteners, real risks. Stroke 2019;50:549-51.
  • 39.Serra-Majem L, Raposo A, Aranceta-Bartrina J, Varela-Moreiras G, Logue C, Laviada H, Socolovsky S, et al. Ibero–American consensus on low- and no-calorie sweeteners: Safety, nutritional aspects and benefits in food and beverages. Nutrients 2018;10,:818. doi:10.3390/nu10070818.
  • 40.American Dental Association. Policies and recommendations on diet and nutrition. Available at: https://www.ada.org/en/advocacy/current-policies/diet-and-nutrition.
  • 41.Hayes M, Brady P, Burke FM, Allen PF. Failure rates of class V restorations in the management of root caries in adults – a systematic review. Gerodontology. 2016 Sep;33((3)):299–307.
  • 42.Cazzolla AP, De Franco AR, Lacaita M, Lacarbonara V. Efficacy of 4-year treatment of icon infiltration resin on postorthodontic white spot lesions. Case Reports 2018;2018:bcr-2018-225639.
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