The effect of subantimicrobial-dosedoxycycline periodontal therapy on serum biomarkers of systemic inflammation: A randomized, double-masked, placebo-controlled clinical trial

Journal of the American Dental Association

Volumn 142, Issue 3, 2011, Pages 262-273

  Payne, Jeffrey B ^a   Golub, Lome M ^b   Stoner, Julie A ^c   Lee, Hsi Ming ^b   Reinhardt, Richard A ^a   Sorsa, Timo ^d   Slepian, Marvin J ^e  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^b STONY BROOK UNIVERSITY   (United States)

^c UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER   (United States)

^d UNIVERSITY OF HELSINKI   (Finland)

^e UNIVERSITY OF ARIZONA   (United States)

Author keywords

C reactive protein; Doxycycline; High density lipoprotein cholesterol; Inflammation; Matrix metalloproteinases; Periodontitis; Serum inflammatory biomarkers

Indexed keywords

ANTIINFECTIVE AGENT; AUTACOID; C REACTIVE PROTEIN; DOXYCYCLINE; GELATINASE B; HIGH DENSITY LIPOPROTEIN CHOLESTEROL;

ARTICLE; BLOOD; CHRONIC PERIODONTITIS; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CORONARY ARTERY DISEASE; DOUBLE BLIND PROCEDURE; FEMALE; HUMAN; METABOLIC BONE DISEASE; MIDDLE AGED; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL;

ANTI-BACTERIAL AGENTS; BONE DISEASES, METABOLIC; C-REACTIVE PROTEIN; CHOLESTEROL, HDL; CHRONIC PERIODONTITIS; CORONARY DISEASE; DOUBLE-BLIND METHOD; DOXYCYCLINE; FEMALE; HUMANS; INFLAMMATION MEDIATORS; MATRIX METALLOPROTEINASE 9; MIDDLE AGED;

EID: 79953861737     PISSN: 00028177     EISSN: None     Source Type: Journal    
DOI: 10.14219/jada.archive.2011.0165     Document Type: Article

References (43)

1. Libby P. Inflammation in atherosclerosis. Nature 2002;420(6917): 868-874. (Pubitemid 36019640)
2. Montecucco F, Mach F. Common inflammatory mediators orchestrate pathophysiological processes in rheumatoid arthritis and atherosclerosis. Rheumatology (Oxford) 2009;48(1):11-22.
3. Craig RG, Yip JK, So MK, Boylan RJ, Socransky SS, Haffajee AD. Relationship of destructive periodontal disease to the acutephase response. J Periodontal 2003;74(7):1007-1016.
4. Friedewald VE, Kornman KS, Beck JD, et al.; American Journal of Cardiology; Journal of Periodontology. The American Journal of Cardiology and Journal of Periodontology Editors' Consensus: periodontitis and atherosclerotic cardiovascular disease. Am J Cardiol 2009;104(1):59-68.
5. Rossouw JE, Anderson GL, Prentice RL, et al.; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288(3):321-333.
6. Rees M, Stevenson J; British Menopause Society Council. Primary prevention of coronary heart disease in women. Menopause Int 2008;14(1):40-45.
7. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342(12):836-843. (Pubitemid 30165206)
8. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002; 347(20):1557-1565. (Pubitemid 35315836)
9. Blankenberg S, Rupprecht HJ, Poirier O, et al.; AtheroGene Investigators. Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation 2003;107(12):1579-1585.
10. Ridker PM, Danielson E, Fonseca FA, et al.; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359(21): 2195-2207.
11. Golub LM, Lee HM, Ryan ME, Giannobile WV, Payne J, Sorsa T. Tetracyclines inhibit connective tissue breakdown by multiple nonantimicrobial mechanisms. Adv Dent Res 1998;12(2):12-26.
12. Golub LM, Lee HM, Stoner JA, et al. Subantimicrobial-dose doxycycline modulates gingival crevicular fluid biomarkers of periodontitis in postmenopausal osteopenic women. J Periodontal 2008; 79(8):1409-1418.
13. Moses MA, Harper J, Folkman J. Doxycycline treatment for lymphangioleiomyomatosis with urinary monitoring for MMPs. N Engl J Med 2006;354(24):2621-2622. (Pubitemid 43882375)
14. O' DeIl JR, Elliott JR, Mallek JA, et al. Treatment of early seropositive rheumatoid arthritis: doxycycline plus methotrexate versus methotrexate alone. Arthritis Rheum 2006;54(2):621-627. (Pubitemid 43228640)
15. Meier CR, Derby LE, Jick SS, Vasilakis C, Jick H. Antibiotics and risk of subsequent first-time acute myocardial infarction. JAMA 1999;281(5):427-431. (Pubitemid 29069440)
16. Golub LM, Greenwald RA, Thompson RW. Antibiotic use and risk of myocardial infarction. JAMA 1999;282(21):1997-1998.
17. Brown DL, Desai KK, Vakili BA, Nouneh C, Lee HM, Golub LM. Clinical and biochemical results of the metalloproteinase inhibition with subantimicrobial doses of doxycycline to prevent acute coronary syndromes (MIDAS) pilot trial. Arterioscler Thromb Vase Biol 2004;24(4):733-738. (Pubitemid 38451612)
18. Payne JB, Stoner JA, Nummikoski PV, et al. Subantimicrobial dose doxycycline effects on alveolar bone loss in post-menopausal women. J Clin Periodontal 2007;34(9):776-787.
19. Reinhardt RA, Stoner JA, Golub LM, et al. Efficacy of subantimicrobial dose doxycycline in post-menopausal women: clinical outcomes (published correction appears in J Clin Periodontal 2007;34[12]:1097.
20. J Clin Periodontal 2007;34(9):768-775.
21. Golub LM, Lee HM, Stoner JA, et al. Doxycycline effects on serum bone biomarkers in post-menopausal women. J Dent Res 2010;89(6):644-649.
22. Walker C, Puumala S, Golub LM, et al. Subantimicrobial dose doxycycline effects on osteopenic bone loss: microbiologic results. J Periodontal 2007;78(8):1590-1601.
23. Tuomainen AM, Nyyssönen K, Laukkanen JA, et al. Serum matrix metalloproteinase-8 concentrations are associated with cardiovascular outcome in men. Arterioscler Thromb Vase Biol 2007;27(12):2722-2728. (Pubitemid 350158928)
24. Prikk K, Maisi P, Pirilä E, et al. Airway obstruction correlates with collagenase-2 (MMP-8) expression and activation in bronchial asthma. Lab Invest 2002;82(11):1535-1545. (Pubitemid 35332912)
25. Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika 1986;73(l):13-22.
26. Lan KKG, DeMets DL. Discrete sequential boundaries for clinical trials. Biometrika 1983;70(3):659-663.
27. Pocock SJ. Clinical trials with multiple outcomes: a statistical perspective on their design, analysis, and interpretation. Control Clin Trials 1997;18(6):530-545. (Pubitemid 27520841)
28. Chang MK, Binder CJ, Torzewski M, Witztum JL. C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sei U S A 2002;99(20):13043-13048.
29. Shah PK, Falk E, Badimon JJ, et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques: potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation 1995; 92(6):1565-1569.
30. Garvin P, Nilsson L, Carstensen J, Jonasson L, Kristenson M. Circulating matrix metal]oproteinase-9 is associated with cardiovascular risk factors in a middle-aged normal population. PLoS One 2008;3(3):e1774.
31. Fukuda D, Shimada K, Tanaka A, et al. Comparison of levels of serum matrix metalloproteinase-9 in patients with acute myocardial infarction versus unstable angina pectoris versus stable angina pectoris. Am J Cardiol 2006;97(2):175-180. (Pubitemid 43139231)
32. Tüter G, Kurtis B, Serdar M, et al. Effects of scaling and root planing and sub-antimicrobial dose doxycycline on oral and systemic biomarkers of disease in patients with both chronic periodontitis and coronary artery disease. J Clin Periodontal 2007;34(8):673-681.
33. Yaras N, Sariahmetoglu M, Bilginoglu A, et al. Protective action of doxycycline against diabetic cardiomyopathy in rats. Br J Pharmacol 2008;155(8):1174-1184.
34. Catan JG, Ciando SG, Blieden TM, et al. Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis. J Periodontal 2000;71(4):521-532. (Pubitemid 30602323)
35. Beiden A, Ainola M, Hukkanen M, Gürgan C, Sorsa T, Konttinen YT. MMPs, IL-I, and TNF are regulated by IL-17 in periodontitis. J Dent Res 2007;86(4):347-351.
36. Giannopoulou C, Kamma JJ, Mombelli A. Effect of inflammation, smoking and stress on gingival crevicular fluid cytokine level. J Clin Periodontal 2003;3(X2):145-153. (Pubitemid 38019410)
37. Teng YT, Sodek J, McCulloch CA. Gingival crevicular fluid gelatinase and its relationship to periodontal disease in human subjects. J Periodontal Res 1992;27(5):544-552.
38. Sorsa T, Tervahartiala T, Leppilahti J, et al. CoUagenase-2 (MMP-8) as a point-of-care biomarker in periodontitis and cardiovascular diseases: therapeutic response to non-antimicrobial properties of tetracyclines (published online ahead of print Oct. 16, 2010). Pharmacol Res 2011;63(2):108-113. doi:10.1016-yj.phrs.2010.10.005.
39. Mayer C, Gruber HJ, Landi EM, et al. Rosuvastatin reduces interleukin-6-induced expression of C-reactive protein in human hepatocytes in a STAT3- and C/EBP-dependent fashion. Int J Clin Pharmacol Ther 2007;45(6):319-327. (Pubitemid 46895050)
40. Joshipura KJ, Wand HC, Merchant AT, Rimm EB. Periodontal disease and biomarkers related to cardiovascular disease. J Dent Res 2004;83(2):151-155. (Pubitemid 41713800)
41. Elliott P, Chambers JC, Zhang W, et al. Genetic loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA 2009;302(1):37-48.
42. Islam MM, Franco CD, Courtman DW, Bendeck MP. A nonantibiotic chemically modified tetracycline (CMT-3) inhibits intimai thickening. Am J Pathol 2003;163(4):1557-1566. (Pubitemid 37175102)
43. Scarabelli TM, Staphanou A, Pasini E, et al. Minocycline inhibits caspase activation and reactivation, increases the ratio of XIAP to smac/DIABLO, and reduces the mitochondrial leakage of cytochrome C and smac/DIABLO. J Am Coll Cardiol 2004;43(5): 865-874. (Pubitemid 38296490)