Review Article

Effects of Periodontal Therapy on Systemic Markers in Healthy Patients

Rachana Hegde*
Department of Periodontology, Roseman University of Health Sciences College of Dental Medicine, USA


*Corresponding author: Rachana Hegde, Department of Periodontology, Roseman University of Health Sciences College of Dental Medicine, USA


Published: 22 Jun, 2017
Cite this article as: Hegde R. Effects of Periodontal Therapy on Systemic Markers in Healthy Patients. J Dent Oral Biol. 2017; 2(8): 1055.

Abstract

Objectives: Periodontitis is associated with increased in inflammatory markers, especially cytokines and these inflammatory markers in turn have been observed in individuals with various systemic diseases. Periodontal therapy has also been believed to induce bacteremia and is thought to be a risk factor for distant site infections such as infective endocarditis in susceptible individuals. There are also reports of deleterious effects of blood loss following a periodontal surgery. However, there is conflicting data that reflects lack of evidence suggesting strong causal association between periodontal therapy and its effects on inflammatory marker, bacteremia and blood loss. This literature review will assess systemic effects (cytokines, bacteremia and blood loss) of invasive periodontal therapy and dental implants in systemically healthy individuals.
Methods: A comprehensive MEDLINE/PubMed literature search was conducted in January 2012 on systemic effects of surgical periodontal therapy and dental implant therapy. Of the 227 articles identified from literature; 23 articles were identified as highly relevant for the purposes of this literature review and the findings of these selected articles are summarized based on the intervention received.
Results: Inflammatory markers, TNF-α, IL-6, CRP and fibrinogen, significantly increase up to 24 h. After periodontal therapy and reaches its baseline levels after 1 month. Circulating PMNs, erythrocytes and Hemoglobin decreases after therapy and returns to baseline levels at 7 days. Transient bacteremia in the range of 3.3% to 80.9% was found in patients undergoing periodontal therapy. This transient bacteremia was reported to increase significantly during the point of maximum trauma to the soft tissues. Despite individual variation of the extent, invasiveness and duration of periodontal surgery, blood loss after routine periodontal therapy remains below 500 ml.
Conclusion: This literature review identifies anecdotal reports on incidence of cardiovascular and other systemic events following periodontal treatment. It further concludes that the relationship between periodontal treatment, bacteremia and inflammatory markers is dynamic and not completely understood. Further research is required to understand the causative model of post periodontal therapy systemic events.


Introduction

Chronic periodontitis is defined as an infectious disease resulting in inflammation within the supporting tissues of the teeth, progressive attachment, and bone loss. It is characterized by pocket formation and/or gingival recession [1]. Although it is a disease that is initiated by bacteria and their components like lipopolysaccharide, host defense plays an important role in the pathogenesis and disease progression. Various pathogenic products stimulate a variety of host cells resulting in the expression of inflammatory cytokines. Subsequent cascade of events and alteration in host immune response leads to increased inflammatory cell recruitment and tissue destruction.
It is now known that people with periodontitis have increased systemic levels of acute phase proteins, plasma antibody levels, coagulation factor, total white blood cell count, neutrophils, C reactive protein (CRP), and cytokines such as INF-gamma (Interferon gamma), TNF-α (Tumor necrosis Factor-Alpha), IL (Interleukin)-1β, IL-2 and IL-6 [2-6]. Heightened inflammatory markers have been reported in patients with cardiovascular disease [7,8], adverse pregnancy outcomes [9], diabetes [10] and respiratory disease [11]. Periodontal disease has hence been epidemiologically associated with these adverse systemic outcomes.
Periodontal therapy has also been believed to induce bacteremia, which is considered a risk factor for distant site infections such as infective endocarditis in susceptible individuals. This led to the present American Heart Association recommendations of antibiotic prophylaxis before dental procedures [12]. These recommendations are based on data concerning surrogate measures of risk such as invasiveness of a dental procedure and degree of periodontal disease at surgical site. However, there is conflicting data that reflects lack of evidence suggesting strong causal association between dental procedure-induced bacteremia and infective endocarditis [13]. It is hypothesized that other factors such as host immune and inflammatory response may play a role in determining the systemic effects of invasive dental procedures [14].
The purpose of the present literature review is to assess the systemic effects of invasive periodontal therapy and dental implants in systemically healthy individuals.


Figure 1

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Figure 1
Changes in circulating levels of TNF-a, IL-6, CRP and Fibrinogen and leucocyte differential counts at 1, 7 and 30 days after periodontal therapy [3]. N=55 at each time point. Analysis performed by ANOVA for repeated measures. * P<0.01, * P<0.001.

Methods

To obtain information on systemic effects of surgical periodontal therapy and dental implant therapy, a comprehensive MEDLINE/ PubMed literature search was conducted in January 2017 using the phrases “Systemic effects of periodontal or implant surgery and inflammatory markers or cytokines or plasma proteins” and “Periodontal therapy and Bacteremia”. The literature searches yielded 327 articles published to date that were available in English; the author reviewed the abstracts from these 327 articles and selected a subset, attempting to meet the following criteria:
Study design
Randomized clinical trials or prospective studies.
Subjects
Healthy adults with no known systemic complications. Studies that did not report the patients being systemically healthy were not included in this review.
Sample size
More than 10 patients. Articles reporting on single center experience; case reports were not included of the 327 articles identified from literature; there were few articles that were repeated in multiple searches and the actual number of unique articles is less than 327. Based on the above inclusion criteria, 33 articles were identified as highly relevant for the purposes of this literature review and Table 1 and 2 summarizes the findings of these selected articles literature.


Summary of Literature Review

D’Aiuto et al. [3] found that TNF-α, IL-6, CRP and fibrinogen significantly increases and reaches its peak 24 h (Day 1) after periodontal therapy, however it starts decreasing after 24 h and reaches its baseline levels only after 1 month. They also found that the PMNs decreased significantly 24 h after treatment and erythrocytes and hemoglobin level remained lower than normal levels even at day 7 after the treatment. The group later concluded that during the acute response to periodontal therapy, there was a broad concordance between markers of inflammation and endothelial function. Figure 1 summarizes the findings.
Similarly, Ide et al. [26] measured the inflammatory markers immediately after the treatment and found increased levels of both IL-6 and TNF-alpha within 60 min to 120 min post treatment, but no significant difference in the measured levels were noted by the same group at 6 weeks. Ushida et al. [31] found this effect to be greater in patients treated with full mouth debridement compared to quadrant wise mechanical debridement and hence recommended evaluating the risks and benefits of full mouth debridement in patients with higher circulating levels of these markers i.e., people at high risk for cardiovascular events. However, Bahrani et al. [14] found no significant differences in any of the cytokine levels between baseline and 1 h post extraction. But, they also reported that their subjects had high variability in baseline cytokine levels and their study lacked the power (n=41) to identify the existing differences in cytokine levels.


Table 1

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Table 1
Summary of effects on cytokines after periodontal therapy.

Table 2

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Table 2
Summary of bacteremia after periodontal and implant surgery.

Summary

Bacteremia occurs when bacteria enter the bloodstream transiently and can be detected by laboratory blood culture techniques. Numerous papers were found in literature citing the incidence of bacteremia after daily procedures including chewing and tooth brushing. However, very few papers were found emphasizing the association between bacteremia and periodontal surgery. Also, it was difficult to differentiate between the treatment groups “scaling and root planning” and “periodontal surgery”, since little information was available on the invasiveness of the “scaling and root planning” procedure. For the sake of completeness of this review, non-surgical periodontal procedure like full mouth scaling and root planning with sub gingival curettage are included in this review.
Bacteremia was found in patients undergoing periodontal therapy in the range of 3.3% to 80.9%. However, most studies concluded that this bacteremia is transient in nature and increases significantly during the point of maximum trauma to the soft tissues.


Discussion

Following periodontal therapy, cascade of events occur that include bacteremia, increased circulating inflammatory markers and blood loss. It is empirical to understand the interaction between these factors to identify a new causal model of association between oral therapy and incidence of adverse systemic events like infective endocarditis.


Inflammatory Markers and Bacteremia

While bacteremia does occur as result of periodontal surgery, it is also evident that “everyday” procedures like chewing and tooth brushing also results in bacteremia [28]. Most of the literature available measures the percentage prevalence of bacteremia and not the intensity. The intensity of the inocula of disseminated bacteria found in humans is lower than the intensity of bacteremia that has been shown to be an important factor in the genesis of experimental animal endocarditis [38]. Hence, argument in the favor of periodontal manipulation being the cause of cardiovascular events still remains unproven.
It is also evident from the current review that there is a transient increase in the inflammatory markers especially IL-6, TNF-α and CRP after periodontal therapy. It is proposed that the mechanisms that lead to this increased systemic inflammatory burden in otherwise healthy individuals include: (a) the local, infection driven production of inflammatory mediators (IL-1, IL-6) “dumped” into systemic circulation [39,40]. (b) the ability of the periodontal pathogens and/ or their toxins to disseminate and thus induce a distant inflammatory response [41,42]. (c) a combination of the above.


Bacteremia and Blood Loss

A correlation was found between the duration of oral surgery, amount of blood loss and bacteremia. When the amount of blood loss was more than 50 ml and the duration of surgery exceeded 100 min, the incidence of bacteremia was higher [43]. There was a statistically significant difference in the incidence of blood cultures positive for organisms at both shorter (<3 min, P=0.04) and longer (>6 min, P=0.04) surgery times [44]. On the contrary, Takai et al. [45] found that there was no association between degree of surgical invasion and bacteremia. They concluded in their clinical trial of 237 patients that any transoral incision produces bacteremia, the risk increases if the site is infected.


Conclusion

The results from this literature review indicate that there are anecdotal reports on incidence of cardiovascular and other systemic events following periodontal treatment. The relationship between periodontal treatment, bacteremia and inflammatory markers is dynamic but not completely understood. Further research is required to understand this interplay and its effects on systemic health.


References

  1. Caton JG, Greenwell H, Mahanonda R, Williams R, Zappa U, Claffey N, et al. Consensus report: dental plaque-induced gingival diseases Jack G. Ann Periodontol. 1999;4(1):18-9.
  2. Wu T, Trevisan M, Genco RJ, Falkner KL, Dorn JP, Sempos CT. Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. Am J Epidemiol. 2000;151(3):273-82.
  3. D'Aiuto F, Ready D, Tonetti MS. Periodontal disease and C-reactive protein-associated cardiovascular risk. J Periodontal Res. 2004;39(4):236-41.
  4. Loos BG, Craandijk J, Hoek FJ, Wertheim-van Dillen PM, van der Velden U. Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients. J Periodontol. 2000;71(10):1528-34.
  5. Kweider M, Lowe GD, Murray GD, Kinane DF, McGowan DA. Dental disease, fibrinogen and white cell count; links with myocardial infarction? Scott Med J. 1993;38(3):73-4.
  6. Noack B, Genco RJ, Trevisan M, Grossi S, Zambon JJ, De Nardin E. Periodontal infections contribute to elevated systemic C-reactive protein level. J Periodontol. 2001;72(9):1221-7.
  7. Wu T, Trevisan M, Genco RJ, Dorn JP, Falkner KL, Sempos CT. Periodontal disease and risk of cerebrovascular disease: the first national health and nutrition examination survey and its follow-up study. Arch Intern Med. 2000;160(18):2749-55.
  8. Morrison HI, Ellison LF, Taylor GW. Periodontal disease and risk of fatal coronary heart and cerebrovascular diseases. J Cardiovasc Risk. 1999;6(1):7-11.
  9. Offenbacher S, Katz V, Fertik G, Collins J, Boyd D, Maynor G, et al. Periodontal infection as a possible risk factor for preterm low birth weight. J Periodontol. 1996;67(10):1103-13.
  10. Grossi SG, Genco RJ. Periodontal disease and diabetes mellitus: a two-way relationship. Ann Periodontol. 1998;3(1):51-61.
  11. Hayes C, Sparrow D, Cohen M, Vokonas PS, Garcia RI. The association between alveolar bone loss and pulmonary function: the VA dental longitudinal study. Ann Periodontol. 1998;3(1):257-61.
  12. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, et al. Prevention of infective endocarditis: guidelines from AHA. Circulation. 2007;116:1736-54.
  13. Lockhart PB, Loven B, Brennan MT, Fox PC. The evidence base for the efficacy of antibiotic prophylaxis in dental practice. J Am Dent Assoc. 2007;138(4):458-74.
  14. Bahrani-Mougeot FK, Thornhill M, Sasser H, Marriott I, Brennan MT, Papagerakis S, et al. Systemic host immuno-inflammatory response to dental extractions and periodontitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106(4):534-41.
  15. Taylor B, Tofler G, Morel-Kopp MC, Carey H, Carter T, Elliott M, et al. The effect of initial treatment of periodontitis on systemic markers of inflammation and cardiovascular risk: a randomized controlled trial. Eur J Oral Sci. 2010;118(4):350-6.
  16. Caúla AL, Lira-Junior R, Tinoco EM, Fischer RG. The effect of periodontal therapy on cardiovascular risk markers: a 6-month randomized clinical trial. J Clin Periodontol. 2014;41(9):875-82.
  17. Kamil W, Al Habashneh R, Khader Y, Al Bayati L, Taani D. Effects of nonsurgical periodontal therapy on C-reactive protein and serum lipids in Jordanian adults with advanced periodontitis. J Periodontal Res. 2011;46(5):616-21.
  18. Li X, Tse HF, Yiu KH, Li LS, Jin L. Effect of periodontal treatment on circulating CD34(+) cells and peripheral vascular endothelial function: a randomized controlled trial. J Clin Periodontol. 2011;38(2):148-56.
  19. Leite AC, Carneiro VM, Guimarães Mdo C. Effects of periodontal therapy on C-reactive protein and HDL in serum of subjects with periodontitis. Rev Bras Cir Cardiovasc. 2014;29(1):69-77.
  20. George AK, Janam P. The short-term effects of non-surgical periodontal therapy on the circulating levels of interleukin-6 and C-reactive protein in patients with chronic periodontitis. J Indian Soc Periodontol. 2013;17(1):36-41.
  21. D'Aiuto F, Nibali L, Parkar M, Suvan J, Tonetti MS. Short-term effects of intensive periodontal therapy on serum inflammatory markers and cholesterol. J Dent Res. 2005;84(3):269-73.
  22. D'Aiuto F, Parkar M, Andreou G, Brett PM, Ready D, Tonetti MS. Periodontitis and atherogenesis: causal association or simple coincidence? J Clin Periodontol. 2004;31(5):402-11.
  23. D'Aiuto F, Nibali L, Mohamed-Ali V, Vallance P, Tonetti MS. Periodontal therapy: a novel non-drug-induced experimental model to study human inflammation. J Periodontal Res. 2004;39(5):294-9.
  24. Elter JR, Hinderliter AL, Offenbacher S, Beck JD, Caughey M, Brodala N, et al. The effects of periodontal therapy on vascular endothelial function: a pilot trial. Am Heart J. 2006;151(1):47.
  25. Forner L, Larsen T, Kilian M, Holmstrup P. Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation. J Clin Periodontol. 2006;33(6):401-7.
  26. Ide M, McPartlin D, Coward PY, Crook M, Lumb P, Wilson RF. Effect of treatment of chronic periodontitis on levels of serum markers of acute-phase inflammatory and vascular responses. J Clin Periodontol. 2003;30(4):334-40.
  27. Ide M, Jagdev D, Coward PY, Crook M, Barclay GR, Wilson RF. The short-term effects of treatment of chronic periodontitis on circulating levels of endotoxin, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6. J Periodontol. 2004;75(3):420-8.
  28. Rahman AU, Rashid S, Noon R, Samuel ZS, Lu B, Borgnakke WS, et al. Prospective evaluation of the systemic inflammatory marker C-reactive protein in patients with end-stage periodontitis getting teeth replaced with dental implants: a pilot investigation. Clin Oral Implants Res. 2005;16(1):128-31.
  29. Taylor BA, Tofler GH, Carey HM, Morel-Kopp MC, Philcox S, Carter TR, et al. Full-mouth tooth extraction lowers systemic inflammatory and thrombotic markers of cardiovascular risk. J Dent Res. 2006;85(1):74-8.
  30. Tonetti MS, D'Aiuto F, Nibali L, Donald A, Storry C, Parkar M, et al. Treatment of periodontitis and endothelial function. N Engl J Med. 2007;356(9):911-20.
  31. Ushida Y, Koshy G, Kawashima Y, Kiji M, Umeda M, Nitta H, et al. Changes in serum interleukin-6, C-reactive protein and thrombomodulin levels under periodontal ultrasonic debridement. J Clin Periodontol. 2008;35(11):969-75.
  32. Yamazaki K, Honda T, Oda T, Ueki-Maruyama K, Nakajima T, Yoshie H, et al. Effect of periodontal treatment on the C-reactive protein and proinflammatory cytokine levels in Japanese periodontitis patients. J Periodontal Res. 2005;40(1):53-8.
  33. Asi KS, Gill AS, Mahajan S. Postoperative bacteremia in periodontal flap surgery, with and without prophylactic antibiotic administration: A comparative study. J Indian Soc Periodontol. 2010;14(1):18-22.
  34. Castillo DM, Sánchez-Beltrán MC, Castellanos JE, Sanz I, Mayorga-Fayad I, Sanz M, et al. Detection of specific periodontal microorganisms from bacteraemia samples after periodontal therapy using molecular-based diagnostics. J Clin Periodontol. 2011;38(5):418-27.
  35. Kinane DF, Riggio MP, Walker KF, MacKenzie D, Shearer B. Bacteraemia following periodontal procedures. J Clin Periodontol. 2005;32(7):708-13.
  36. Lafaurie GI, Mayorga-Fayad I, Torres MF, Castillo DM, Aya MR, Barón A, et al. Periodontopathic microorganisms in peripheric blood after scaling and root planing. J Clin Periodontol. 2007;34(10):873-9.
  37. Piñeiro A, Tomás I, Blanco J, Alvarez M, Seoane J, Diz P. Bacteraemia following dental implants' placement. Clin Oral Implants Res. 2010;21(9):913-8.
  38. Bahn SL, Goveia G, Bitterman P, Bahn AN. Experimental endocarditis induced by dental manipulation and oral streptococci. Oral Surg Oral Med Oral Pathol. 1978;45(4):549-59.
  39. Offenbacher S, Farr DH, Goodson JM. Measurement of prostaglandin E in crevicular fluid. J Clin Periodontol. 1981;8(4):359-67.
  40. Graves DT. The potential role of chemokines and inflammatory cytokines in periodontal disease progression. Clin Infect Dis. 1999;28(3):482-90.
  41. Herzberg MC, Weyer MW. Dental plaque, platelets, and cardiovascular diseases. Ann Periodontol. 1998;3(1):151-60.
  42. Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ. Identification of periodontal pathogens in atheromatous plaques. J Periodontol. 2000;71(10):1554-60.
  43. Okabe K, Nakagawa K, Yamamoto E. Factors affecting the occurrence of bacteremia associated with tooth extraction. Int J Oral Maxillofac Surg. 1995;24(3):239-42.
  44. Lockhart PB. An analysis of bacteremias during dental extractions. A double-blind, placebo-controlled study of chlorhexidine. Arch Intern Med. 1996;156(5):513-20.
  45. Takai S, Kuriyama T, Yanagisawa M, Nakagawa K, Karasawa T. Incidence and bacteriology of bacteremia associated with various oral and maxillofacial surgical procedures. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;99(3):292-8.