1

Presented by Jo-Anne Jones RDH

President RDH Connection Inc wwwjo-annejonescom jjonesjo-annejonescom

Synopsis Are we still treating periodontal disease as an infection when leading authorities have redefined periodontitis as an inflammatory disease Is our practice compliant with the newly published 2015 JADA guidelines The link between periodontal disease and systemic health is becoming increasingly clear and is the benchmark of innovative healthcare delivery Long running ongoing chronic disease such as periodontal disease tips the bodyrsquos balance towards chronic inflammation Inflammation often being referred to as the lsquosilent killerrsquo is one of the hottest topics of research The latest research surrounding the oral systemic link is both startling and compelling What if we now could slow down the destruction caused by chronic inflammation and impact not only oral health but systemic health We have the ability to change lives through the power of our message and the science of our treatment

Learning Outcomes 1 Recognize the role of the inflammatory pathway in initiating disease states within the body 2 Elevate understanding and treatment of periodontal disease as an inflammatory rather than an infectious disease 3 Incorporate new therapeutic modalities and communication strategies to enhance treatment outcomes

References Vujicic M Israelson H Antoon J Kiesling R Paumier T Zust M A profession in transition J Am Dent Assoc 2014 Feb145(2)118-21 Economic Report to the Dental Profession November 2013 Prepared by R K House amp Associates Offenbacher S Beck JD Changing Paradigms in the Oral Disease-Systemic Disease Relationship J Periodontol June 2014761-764 Jones JD Summary of the 2015 JADA Evidence-based Guidelines on the Non-surgical Treatment of Chronic Periodontitis Oral Health Dec 2015

THE SILENT KILLER Understanding and Addressing the Inflammatory Pathway Why another course on the oral-systemic link FACT The information has been redefining our understanding of how inflammation is at the very core of todayrsquos complex prevalent and deadly diseases FACT Moderate to severe chronic periodontitis has significant systemic implications FACT The AAP has redefined periodontal disease as an inflammatory disease with far reaching effects FACT We need to reconsider our therapeutic endpoints to ensure that the impact of oral disease does not continue to threaten overall health FACT We need to meet the needs of todayrsquos population

SCIENCE MEETS THE DEMOGRAPHIC We OWN This Defining of a healthcare professional ldquoAn occupation whose core element is work based upon the mastery of a complex body of knowledge and skillshellipto be used in the service of others Professions and their members are accountable to those served and to society Society rewards health professionalshellipthis status however comes with professional obligationsrdquo

Self-Evaluation Rate Your Present Periodontal Therapy Program

1 How satisfied are you with your present periodontal therapy program 2 Are you receiving predictable outcomes 3 What do you feel would elevate your periodontal program to the next level 4 How are you addressing the inflammatory component of periodontal disease 5 Do you have an evidence based risk assessment program in place 6 Do you feel your medical history update is uncovering sufficient information to fully address the needs of your dental hygiene client 7 Do you have adequate resources to educate your client about the oral-systemic link

2

Notes

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

References amp Resources

Jones JD Golub LM Gu Y et al Is periodontitis an infectious or inflammatory disease Oral Hyg May 2015 Donley T Golub LM Jones JD et al Addressing the inflammatory response in periodontal and related systemic disease Oral Health Periodontics Fall 2015 httpswwwcdhacapdfsProfessionResourcesDisease_Link_Articlepdf Roifman I Beck PL Anderson TJ et al Chronic inflammatory disease and cardiovascular risk a systematic review Can J Cardiol 2011 Mar-Apr27(2)174-82 httpswwwcdhacapdfsProfessionResourcesDisease_Link_Articlepdf Danesh J Whincup P Walker M et al Low grade inflammation and coronary heart disease prospective study and updated meta-analyses BMJ 200032(7255)199-204 Hansson GK Inflammation atherosclerosis and coronary artery disease N Eng J Med 2005352(16)1685-95

8 What treatment modalities have you incorporated into your periodontal therapy program in order to reduce the bacterial burden 9 What treatment modalities have you incorporated into your periodontal therapy program in order to address the host response 10 What are your determinants and criteria for referring to a periodontist

1 Understand the Most Current and Compelling Research Related to the Oral Systemic Link Cardiovascular Disease

Two pathways

3

Notes

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

References amp Resources

Jones JD Golub LM Gu Y et al Is periodontitis an infectious or inflammatory disease Oral Hyg May 2015 Donley T Golub LM Jones JD et al Addressing the inflammatory response in periodontal and related systemic disease Oral Health Periodontics Fall 2015 Danesh J Whincup P Walker M et al Low grade inflammation and coronary heart disease prospective study and updated meta-analyses BMJ 200032(7255)199-204 Hansson GK Inflammation atherosclerosis and coronary artery disease N Eng J Med 2005352(16)1685-95 httpwwwsurgicalrestorativecomarticles201302the-link-between-periodontitis-and-cardiovascular-disease-a-briehtml wwwhypertensioncaen Guidelines Hypertension Canada ndash 13585 (Normal blood pressure) httpwwwcdhoorgAdvisoriesCDHO_Advisory_Hypertensionpdf (p 21 22) httpswwwdiabetescaCDAmediadocumentspublications-and-newslettersadvocacy-reportscanada-at-the-tipping-point-policy-backgrounder-englishpdf Diabetes in Canada Facts and figures from a public health perspective Public Health Agency of Canada wwwpublichealthgcca Boyd LD Giblin L Chadbourne D Bidirectional relationship between diabetes mellitus and periodontal disease State of the evidence Can J Dent Hygiene 201246 no293-102

Cardiovascular Disease Clinical Considerations for Dental Hygiene Practice

Is it mandatory to take my clientrsquos blood pressure Definition of Hypertension

A condition where blood pressure persistently exceed specified limits

One of the leading health problems in Canada preceding stroke heart attack kidney failure dementia and sexual dysfunction

More than 1 in 5 Canadians currently suffer from hypertension with a lifetime risk of 90

Often asymptomatic referred to lsquosilent killerrsquo Responsibility of Todayrsquos Dental Hygienist

Important to have a baseline as part of initial assessment

Requirement of blood pressure to be taken when medical history indicates a need

Ensure client is not being placed at risk before initiating dental hygiene treatment

If clientrsquos history is clear a registrant is encouraged to take a baseline assessment prudent and proactive to periodically monitor as often asymptomatic

Diabetes in Canada

The Facts on Diabetes FACT Approximately 3 million Canadians with diabetes increase of over 70 in the last decade Estimated by 2020 1 in 3 Canadians will be living with diabetes or prediabetes FACT Periodontal disease is listed as the 6th complication FACT 82 of diabetic patients with severe periodontitis experienced the onset of one or more major cardiovascular cerebrovascular or peripheral vascular events compared to only 21 of diabetics without periodontitis

4

Notes

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

References amp Resources

Fowler MJ Microvascular and Macrovascular Complications of Diabetes Clinical Diabetes 200826(2)77-82 Manuchehf-Pour M et al Comparison of neutrophil chemotactic response in diabetic patients with mild and severe periodontal disease J Periodontol 198152410-415 McMullen JA et al Neutrophil chemotaxis in individuals with advanced periodontal disease and a genetic predisposition to diabetes mellitus J Periodontol 198152167-173 Tunes RS Foss-Freitas MC Nogueira-Filho G et al Impact of Periodontitis on the Diabetes-Related Inflammatory Status JCDA August 2010 httpswwwdiabetescaCDAmediadocumentspublications-and-newslettersadvocacy-reportscanada-at-the-tipping-point-policy-backgrounder-englishpdf httpwwwperioorgnode501 (Milestones July 2013) httpwwwperioorgnode501 (Milestones July 2013)

Understanding the Oral-Systemic Link Diabetes Research supports that infectious and inflammatory processes increase insulin resistance resulting in hyperglycemia Hyperglycemia (elevated blood glucose) diminishes the ability of WBC neutrophils in particular to track adhere and kill bacteria Diabetes increases risk through an amplified inflammatory response and depressed wound healing elevated blood glucose leads to elevated glucose levels in GCF hindering wound healing capacity of fibroblasts GCF contains elevated concentrations of cytokines producing higher levels of MMPs that promote tissue destruction and disease severity Diabetes Clinical Considerations for Dental Hygiene Practice

A diabetes management program should involve on-going comprehensive periodontal assessments Independent association between moderate to severe periodontitis and increased risk for development or progression of diabetes AAP and EFP Consensus Reporthelliprdquoperiodontal interventions may provide beneficial effects on diabetes outcomes in some patients so regular comprehensive periodontal evaluations should be part of an ongoing diabetes management programrdquo Solicit feedback regarding diabetic status bull Type 1 2 or pre-diabetic or familial history What is their blood

glucose target What were the results of their last A1c test bull What was their blood glucose level the morning of the

appointment What times of the day are best for scheduled appointments

Understanding the Oral-Systemic Link between Obesity and Periodontal Disease

A pro-inflammatory state exists in obesity as a result of the release of several cytokines and hormones from adipose tissue into systemic circulation similar cytokines are released into circulation in periodontal disease

A person with a BMI of 30 or more is generally considered obese research is debating whether BMI waist circumference (WC) or both should be used to determine disease risk

Obesity is a major risk factor for a number of chronic diseases including type 2 diabetes hypertension cardiovascular disease metabolic syndrome liver disease musculoskeletal disease reproductive abnormalities and cancer Recent studies have reported an association between obesity and periodontitis

5

Notes

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

References amp Resources

httpwwwdiabetescaclinical-practice-educationclinical-practice-guidelines Genco RJ Grossi SC Ho A et al A proposed model linking inflammation to obesity diabetes and periodontal infections J Periodontol 20057611(Suppl) 2075-84 Yoshihiro Iwamoto Fusanori Nishimura et al The Effect of Antimicrobial Periodontal Treatment on Circulating Tumor Necrosis Factor-Alpha and Glycated Hemoglobin Level in Patients with Type 2 Diabetes J Periodontal72774-778 2001 Pischon N Heng N Bernimoulin J et al Obesity Inflammation and Periodontal Disease J Dent Res 2007 66400 Twells LK Gregory DM Reddigan J Midodzi WK Current and predicted prevalence of obesity in Canada a trend analysis CMAJ Open 2014 Jan-Mar2(1) E18-E26 Genco RJ Grossi SC Ho A et al A proposed model linking inflammation to obesity diabetes and periodontal infections J Periodontol 20057611(Suppl) 2075-84 Saito T Shimazaki Y Koga T et al Relationship between upper body obesity and periodontitis J Dent Res 20018071631-36 Scannapieco FA Bush RB Paju S Associations between periodontal disease and risk for nosocomial bacterial pneumonia and chronic obstructive pulmonary Disease A systematic review Ann Periodontol 20038(1)54-69 Azarpazhooh A Leake JL Systematic review of the association between respiratory diseases and oral health J Periodontol 200677(9)1465-82

Studies prove that a high prevalence of PD can be expected among obese adults

Obesity Rates in North America

Between 1985 and 2011 the prevalence of overweight adults increased by 21 to 336 and obesity increased 200 from 61 to 183 Respiratory Disease Biological Link between Periodontal Disease and Respiratory Disease Possible mechanisms for presence of oral bacteria in pathogenesis of respiratory invasions include

Dental plaque may serve as a reservoir for pulmonary pathogens responsible for aspiration pneumonia in high risk patients

Enzymes associated with periodontal disease may facilitate adherence of respiratory pathogens to the mucosal tissues in the oral cavity and ultimate in the airways

Hydrolytic enzymes associated with periodontal disease pathogens may destroy salivary pellicles and reduce their host defense capabilities

Cytokines and other inflammatory mediators originating from the periodontal tissues may alter respiratory epithelium resulting in pathogen adherence and colonization

Rheumatoid Arthritis (RA) Understanding the Oral-Systemic Link with Rheumatoid Arthritis

Periodontal disease (PD) is an infection characterized by chronic inflammation and may ultimately lead to tooth loss

Rheumatoid arthritis (RA) is a chronic disease characterized by inflammation of the synovium of the joints and may ultimately lead to destruction of the joint

o RA begins with inflammation of the synovial membranehelliplymphocytes neutrophils and other inflammatory cells migrate into the joint and release inflammatory chemicals that destroy body tissues

Chronic inflammatory mediators are shared by both these diseases and this has prompted researchers to investigate the possibility of a relationship between RA and PD

RA Clinical Consideration for Dental Hygiene Practice

45 million or 1 in 6 Canadians aged 15 years and older report having arthritis By 2031 approximately 7 million Canadians 1 in 5 are expected to have arthritis

Pregnancy (PLBW) Understanding the Oral Systemic Link with Pregnancy (PLBW) bull1 in 10 infants born are considered to be preterm improvements in neonatal intensive care medicine have improved the survival rate however rate of premature delivery has steadily climbed since the 1950rsquos bullOther risk factors include race smoking alcohol and drug use lower socioeconomic status and lower education more than frac14 of all complicated pregnancies occur for no apparent reason

6

Notes

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

References amp Resources

Agado B Bowen D Periodontal disease and respiratory disease A systematic review of the evidence Can J Dent Hygiene 2012 46 no 103-114 Scannapieco FA Role of oral bacteria in respiratory infection J Periodontol 199970793-802 Scannapieco F The Relationship between Respiratory Diseases and Periodontal Diseases Dent Today July 2003 Saini R Saini S Sharma S Periodontitis A Risk Factor to Respiratory Diseases Lung India 2010 July ndash Sept 27(3) 189 Page RD Offenbacher S Schroeder HE et al Advances in the pathogenesis of periodontitis summary of developments clinical implications and future directions Periodontol 2000 1997141216-48 Marieb EN Hoehn K Anatomy and Physiology 4th Ed San Francisco Pearson Benjamin Cummings 2008289-39 Bartold PM Marshall RI Haynes DR Periodontitis and rheumatoid arthritis A review J Periodontol 20067611(Suppl)2066-74 Mecado FB Marshall RI Bartold PM Inter-relationships between rheumatoid arthritis and periodontal disease J Clin Periodontol 2003309761-72 Mercado FB Marshall RI Bartold PM Is there a relationship between rheumatoid arthritis and periodontal disease J Clin Periodontol 200027(4)267-72 wwwarthritisca httpwwwstatcangccapub82-625-x2011001article11457-enghtm

Periodontal disease may contribute by presenting an infectious inflammatory ongoing challenge to the fetus

Feb 2015 Statement During normal pregnancy the placenta invades the surrounding uterine tissue and provides an exchange of nutrients and waste between mother and fetus via the umbilical cord As pregnancy progresses amniotic fluid levels containing prostaglandin E2 (PGE2) and inflammatory cytokinesmdashtumor necrosis factor (TNF-α) and interleukin 1(IL-1β)mdashsteadily rise to reach the threshold that induces labor Thus normal labor and delivery are induced by inflammatory signaling One theory for the association between periodontal diseases and preterm birth is that women with periodontitis a bacterial infection exhibit an increase in fluid mediator levels and inflammatory cytokines which can trigger labor prematurely Furthermore an increase in other markers of inflammation such as C-reactive protein (CRP) has been associated with an elevated risk for preeclampsia and intrauterine growth restriction

Osteoporosis Biological Link between Periodontal Disease and Osteoporosis In periodontal disease chronic oral inflammation results in

destruction of oral bone and periodontal ligament Increased production of cytokines IL-6 stimulate osteoclast

activity and promote bone resorption Similar mechanism may contribute to osteoporosis Evidence indicates there is an association between the two

diseases Common risk factors age genetics estrogen deficiency calcium

and Vitamin D deficiency alcohol intake and smoking Alzheimerrsquos Disease Understanding the Systemic Link between Alzheimerrsquos and Periodontal Disease

Alzheimerrsquos disease (AD) is a degenerative disease of the brain characterized by neurofibrillary tangles and the accumulation of beta amyloid plaques

A strong positive correlation was found between midlife C-reactive protein levels a marker of inflammation and the risk of developing AD The chronic nature of oral infections such as

7

Notes

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

References amp Resources

Lopez N Periodontal Therapy May Reduce the Risk of Preterm Low Birth Weight in Women with Periodontal Disease A randomized Controlled Trial Journal of Periodontology August 2002 Vol 73 No 8 Pages 911-924 Offenbacher S Beck JD Jared HL et al Effects of periodontal therapy on rate of preterm delivery a randomized controlled trial Obstet Gynecol 2009 Sep114(3)551-9 Offenbacher S Dillow K Reduce the risk of adverse pregnancy outcomes Dimensions of Dental Hygiene Feb 2015 httpwwwdimensionsofdentalhygienecom201502_FebruaryFeaturesReduce_the_Risk_of_Adverse_Pregnancy_Outcomesaspx Haram K Mortensen JH Wollen AL Preterm delivery an overview Acta Obstet Gynecol Scand 200382687ndash704 Madianos PN Bobetsis YA Offenbacher S Adverse pregnancy outcomes (APOs) and periodontal disease pathogenic mechanisms J Clin Periodontol 201340S170ndashS180 Herrera JA Parra B Herrera E et al Periodontal disease severity is related to high levels of C-reactive protein in pre-eclampsia J Hypertens 2007251459ndash1464 wwwdimensionsofdentalhygienecom201502_FebruaryFeaturesReduce_the_Risk_of_Adverse_Pregnancy_Outcomesaspx Wactawski-Wende J Periodontal diseases and osteoporosis Association and mechanisms Ann Periodontol 20016(1)197-208 Chesnut CH III The relationship between skeletal and oral bone mineral density An overview Ann Periodontol 20016(1)193-196 wwwelseviercomaboutpress-releasesresearch-and-journalsamyloid-formation-may-link-alzheimer-disease-and-type-2-diabetes Schmidt R Schmidt H Curb JD et al Early inflammation and dementia a 25-year follow-up study of the Honolulu-Asia Aging Study Ann Neurol 200252(2)168-74 Rivere GR Riviere KH Smith KS Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimerrsquos disease Oral Microbiol Immunol 200217(2)113-18

periodontitis may further amplify the mechanisms that lead to the onset or progression of AD

It is possible that periodontal pathogens may directly invade the central nervous system via systemic circulation oral Treponema may have reached the brain via the trigeminal nerve

Recognize the Role of the Inflammatory Pathway in Initiating Disease States within the Body

FACT The Common Link ndash Inflammation Todayrsquos diseases of influence are linked by the inflammatory

pathway Periodontal disease is the most common chronic inflammatory

disease known to mankind Living longer consequences of Western lifestyle adding to

todayrsquos inflamed body Elevate Understanding and Treatment of Periodontal Disease as an Inflammatory Disease Wersquove Lost the Battlehellipwhen we focus on reducing the bacterial component only we do not achieve the reduction of the host response Inflammation and destruction continues placing healing repair and systemic health in jeopardy

FACT American Academy of Periodontology Statement

Todayrsquos Periodontal Therapy Program Objective Traditional clinical periodontal examination includes assessment

of already existing damage to periodontal tissues as well as measure of periodontal inflammation

Cost effective simple method in determining the location and severity of diseased periodontal tissues

However in predicting future periodontal breakdown or even just quantifying current disease activityhellipespecially inflammation these methods are far from ideal

Oral inflammatory load (OIL) not pocket depths or periodontal pathogenic bacteria explains the linkages with systemic disease

FACT Call to Action for Dental Hygienists ldquoIf we in dentistry are indeed healers it is imperative for us to take a different approach the goal is to help patients become and remain inflammation-freerdquo Dr Tim Donley

8

Notes

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

References amp Resources

Doering H Tenenbaum HC Glogauer M Oral inflammatory load ndash a new concept for the understanding of oral Disease Oral Health October 201464-68 httpwwwdentalproductsreportcomdentalarticle5-things-consider-regarding-connection-between-stroke-and-inflammation T Van Dyke C Serhan A Novel Approach to Resolving Inflammation Oral and the Whole Body Health200642-45 D Graves Cytokines That Promote Periodontal Tissue Destruction J Periodontol (Suppl) 20081585-1591 Goldstep F Periodontal Inflammation Simplified Oral Health Dec 20138 ndash 17 TIME Magazine article httpwwwinflammationresearchfoundationorginflammation-scienceinflammation-detailstime-cellular-inflammation-article

Understand and Apply the 2015 JADA Guidelines into Clinical Practice and Treatment Delivery

1 Adequate Management of Risk Factors

Oral Science Risk Questionnaire

Philips Oral Healthcare CARE tool (Customized Assessment and Risk Evaluator) web-based client interview and integration of risk management program into dental hygiene clinical practice httpswwwphilipcarecom

2 Adequate Bacterial Reduction

Biofilm leads to bacteremia

Onset of bacteremia initiates inflammatory response

Systemic involvement Solutions for Effective Client Self-Care wwworalsciencecom wwworalhealthboutiquecom 3 Address Host Response Periodontal Inflammation and Destruction

Cytokines are an intermediate mechanism between bacterial stimulation and tissue destruction may also be produced by fibroblasts and osteoblasts

The host response is the major contributing factor for chronic maladaptive periodontal disease A deficient host response initiates the chronic condition and response that leads to further tissue breakdown

Bacteria initiate periodontitis They are essential but insufficient What is required is a susceptible host

Primary etiologic basis for periodontal disease is bacterial however the excessive host inflammatory response or inadequate resolution of inflammation is critical to the pathogenesis of periodontitis

Host Modulation Low-dose doxycycline (LDD) Medical and Dental Benefits About 30 years ago Golub et al discovered that doxycycline had the unexpected ability to inhibit host-derived tissue-destructive enzymes known as MMPs by mechanisms unrelated to the antibacterialantibiotic properties of these drugs These enzymes when present in pathologically-excessive levels are largely responsible for degrading collagen fibers and mediating bone resorption related to various medical and dental diseases Over the past decade this novel non-antimicrobial LDD has been tested in patients with medical disorders which excessive MMPs and inflammatory mediators play a role

9

Notes

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

________________________________________

References amp Resources

Stoner JA Golub LM Payne JB Probing depth a poor predictor of clinical attachment level changes J Dent Res 2015 (94 Spec Is)Abstract 1670 Smiley CJ Tracy SL Abt E et al Systematic review and meta-analysis on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts JADA 2015146(7)508-524 Proceedings of the 1996 World Workshop in Periodontics Lansdowne Virginia July 13-17 1996 Ann Periodontol 199611-947 Goldstep F Periodontal Inflammation Simplified Oral Health Dec 20138 ndash 17 T Van Dyke C Serhan A Novel Approach to Resolving Inflammation Oral and the Whole Body Health200642-45 Smiley CJ Tracy SL Abt E et al Evidence-based clinical practice guideline on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts JADA 2015146(7)525-535 Golub LM Lee HM Lehrer G et al Minocycline reduces gingival collagenolytic activity during diabetes preliminary observations and a proposed new mechanism of action J Periodontol Res 1983 18516-526 Walker SG Golub LM Host modulation therapy for periodontal disease Subantimicrobial-dose doxycycline medical as well as dental benefits Oral Health October 2012 Sub-antimicrobial Dose Doxycycline (SDD) Study Listing at end of handout

Therapeutic Benefit of Inhibiting Collagen Breakdown Inhibit breakdown of collagen in diseased joint (synovial) tissues

reducing severity of symptoms in ARTHRITIS Inhibit breakdown of collagen in connective tissues around

CANCER cells reduced local invasiveness and metastasis Protect collagen ldquocaprdquo stabilizing cholesterol-rich arterial

plaques reduced risk for MYOCARDIAL INFARCTION amp STROKE Reduce diagnostic biomarkers of skeletal bone resorption for

POST MENOPAUSAL OSTEOPOROSIS with no effect on biomarkers of bone formation

Reduce blood levels of Hemoglobin A1C after SDD + SRP for DIABETICS

Periostat Mechanism of Action Periostat will help to reduce the over-production of collagenase (enzymes responsible for the destruction of collagen) and osteoclasts (bone cell responsible for the resorption of bone) that are present in overabundance during a chronic prolonged amp destructive inflammatory response This exaggerated inflammatory response is common among inflammatory diseases such as periodontitis cardiovascular disease and rheumatoid arthritis Therefore Periostat when used (BID) for 6 to 9 months will help to modulate the chronic prolonged amp destructive inflammatory response into a normal amp healthy inflammatory response process

10

ldquoMy client doesnrsquot want to take any more medicationsrdquo KEY TALKING POINTS __________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

ldquoIrsquom concerned with my client experiencing side effects from taking an antibiotic for so longrdquo KEY TALKING POINTS __________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

ldquoMy client doesnrsquot have any real medical concerns at this timerdquo KEY TALKING POINTS __________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

ldquoMy client comes in regularly has effective self-care measures Insurance covers a 3 month maintenance interval There is still inflammation present however I donrsquot feel he needs Periostatrdquo KEY TALKING POINTS __________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

11

12

13

Empower the Client through the Provision of Resources to Understand the Oral Systemic Connection CDHA httpwwwcdhacapdfsOralCareEducational_Resources_6pdf httpwwwcdhacapdfsprofessionresourcesFactSheet_WholeBody_Cpdf Colgate Professional wwwcolgateprofessionalcomprofessional-educationoral-systemic-health wwwcolgateprofessionalcomProfessionalv1enuslocale-assetsdocsOSH-CardiovascularHealth-Healthy-Mouth-Healthy-Bodypdf CDHO Knowledge Network httpwwwcdhoorgknowledge+networkasp American Academy of Periodontology Consumer Site httpwwwperioorgconsumerother-diseases Whatrsquos Your Real Age wwwrealagecom Oral Systemic Link Professional and Public Information wwworalsystemiclinkpro wwworalsystemiclinknet

Product References For the complete monography httpwwworalsciencecaenproductsperiostathtml Clinical Resources Oral Science Products Curaprox Perio Patch Plaque Finder Gengigel 1-888-442-7070 wwworalsicencecom wwworalhealthboutiquecom (product purchase online) Certain products available in London Drugs Shoppers Drug Mart Thank you for your time and participation If there is anything further that I may assist you with in regards to todayrsquos presentation please do not hesitate to contact me Jo-Anne Jones RDH jjonesjo-annejonescom wwwjo-annejonescom copy 2016 All rights reserved RDH Connection Inc No part of this publication may be reproduced distributed or transmitted in any form or by any means including photocopying recording or other electronic or mechanical methods without the prior written permission of the author

10

ldquoMy client doesnrsquot want to take any more medicationsrdquo KEY TALKING POINTS __________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

ldquoIrsquom concerned with my client experiencing side effects from taking an antibiotic for so longrdquo KEY TALKING POINTS __________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

ldquoMy client doesnrsquot have any real medical concerns at this timerdquo KEY TALKING POINTS __________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

ldquoMy client comes in regularly has effective self-care measures Insurance covers a 3 month maintenance interval There is still inflammation present however I donrsquot feel he needs Periostatrdquo KEY TALKING POINTS __________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

__________________________________________________________________________________________________

11

12

13

Empower the Client through the Provision of Resources to Understand the Oral Systemic Connection CDHA httpwwwcdhacapdfsOralCareEducational_Resources_6pdf httpwwwcdhacapdfsprofessionresourcesFactSheet_WholeBody_Cpdf Colgate Professional wwwcolgateprofessionalcomprofessional-educationoral-systemic-health wwwcolgateprofessionalcomProfessionalv1enuslocale-assetsdocsOSH-CardiovascularHealth-Healthy-Mouth-Healthy-Bodypdf CDHO Knowledge Network httpwwwcdhoorgknowledge+networkasp American Academy of Periodontology Consumer Site httpwwwperioorgconsumerother-diseases Whatrsquos Your Real Age wwwrealagecom Oral Systemic Link Professional and Public Information wwworalsystemiclinkpro wwworalsystemiclinknet

Product References For the complete monography httpwwworalsciencecaenproductsperiostathtml Clinical Resources Oral Science Products Curaprox Perio Patch Plaque Finder Gengigel 1-888-442-7070 wwworalsicencecom wwworalhealthboutiquecom (product purchase online) Certain products available in London Drugs Shoppers Drug Mart Thank you for your time and participation If there is anything further that I may assist you with in regards to todayrsquos presentation please do not hesitate to contact me Jo-Anne Jones RDH jjonesjo-annejonescom wwwjo-annejonescom copy 2016 All rights reserved RDH Connection Inc No part of this publication may be reproduced distributed or transmitted in any form or by any means including photocopying recording or other electronic or mechanical methods without the prior written permission of the author

11

12

13

Empower the Client through the Provision of Resources to Understand the Oral Systemic Connection CDHA httpwwwcdhacapdfsOralCareEducational_Resources_6pdf httpwwwcdhacapdfsprofessionresourcesFactSheet_WholeBody_Cpdf Colgate Professional wwwcolgateprofessionalcomprofessional-educationoral-systemic-health wwwcolgateprofessionalcomProfessionalv1enuslocale-assetsdocsOSH-CardiovascularHealth-Healthy-Mouth-Healthy-Bodypdf CDHO Knowledge Network httpwwwcdhoorgknowledge+networkasp American Academy of Periodontology Consumer Site httpwwwperioorgconsumerother-diseases Whatrsquos Your Real Age wwwrealagecom Oral Systemic Link Professional and Public Information wwworalsystemiclinkpro wwworalsystemiclinknet

Product References For the complete monography httpwwworalsciencecaenproductsperiostathtml Clinical Resources Oral Science Products Curaprox Perio Patch Plaque Finder Gengigel 1-888-442-7070 wwworalsicencecom wwworalhealthboutiquecom (product purchase online) Certain products available in London Drugs Shoppers Drug Mart Thank you for your time and participation If there is anything further that I may assist you with in regards to todayrsquos presentation please do not hesitate to contact me Jo-Anne Jones RDH jjonesjo-annejonescom wwwjo-annejonescom copy 2016 All rights reserved RDH Connection Inc No part of this publication may be reproduced distributed or transmitted in any form or by any means including photocopying recording or other electronic or mechanical methods without the prior written permission of the author

12

13

Empower the Client through the Provision of Resources to Understand the Oral Systemic Connection CDHA httpwwwcdhacapdfsOralCareEducational_Resources_6pdf httpwwwcdhacapdfsprofessionresourcesFactSheet_WholeBody_Cpdf Colgate Professional wwwcolgateprofessionalcomprofessional-educationoral-systemic-health wwwcolgateprofessionalcomProfessionalv1enuslocale-assetsdocsOSH-CardiovascularHealth-Healthy-Mouth-Healthy-Bodypdf CDHO Knowledge Network httpwwwcdhoorgknowledge+networkasp American Academy of Periodontology Consumer Site httpwwwperioorgconsumerother-diseases Whatrsquos Your Real Age wwwrealagecom Oral Systemic Link Professional and Public Information wwworalsystemiclinkpro wwworalsystemiclinknet

Product References For the complete monography httpwwworalsciencecaenproductsperiostathtml Clinical Resources Oral Science Products Curaprox Perio Patch Plaque Finder Gengigel 1-888-442-7070 wwworalsicencecom wwworalhealthboutiquecom (product purchase online) Certain products available in London Drugs Shoppers Drug Mart Thank you for your time and participation If there is anything further that I may assist you with in regards to todayrsquos presentation please do not hesitate to contact me Jo-Anne Jones RDH jjonesjo-annejonescom wwwjo-annejonescom copy 2016 All rights reserved RDH Connection Inc No part of this publication may be reproduced distributed or transmitted in any form or by any means including photocopying recording or other electronic or mechanical methods without the prior written permission of the author

13

Empower the Client through the Provision of Resources to Understand the Oral Systemic Connection CDHA httpwwwcdhacapdfsOralCareEducational_Resources_6pdf httpwwwcdhacapdfsprofessionresourcesFactSheet_WholeBody_Cpdf Colgate Professional wwwcolgateprofessionalcomprofessional-educationoral-systemic-health wwwcolgateprofessionalcomProfessionalv1enuslocale-assetsdocsOSH-CardiovascularHealth-Healthy-Mouth-Healthy-Bodypdf CDHO Knowledge Network httpwwwcdhoorgknowledge+networkasp American Academy of Periodontology Consumer Site httpwwwperioorgconsumerother-diseases Whatrsquos Your Real Age wwwrealagecom Oral Systemic Link Professional and Public Information wwworalsystemiclinkpro wwworalsystemiclinknet

Product References For the complete monography httpwwworalsciencecaenproductsperiostathtml Clinical Resources Oral Science Products Curaprox Perio Patch Plaque Finder Gengigel 1-888-442-7070 wwworalsicencecom wwworalhealthboutiquecom (product purchase online) Certain products available in London Drugs Shoppers Drug Mart Thank you for your time and participation If there is anything further that I may assist you with in regards to todayrsquos presentation please do not hesitate to contact me Jo-Anne Jones RDH jjonesjo-annejonescom wwwjo-annejonescom copy 2016 All rights reserved RDH Connection Inc No part of this publication may be reproduced distributed or transmitted in any form or by any means including photocopying recording or other electronic or mechanical methods without the prior written permission of the author

14

Medical History Update Client Name _________________________________________________ Date ______________________________ Recent research indicates a strong relationship between the mouth and the body Since we now know how closely they are related we are going to be asking you some questions about your family history and your overall health that we may not have asked you about before This additional information will assist us in providing the best possible care to maintain your oral health and overall wellness Any changes in your health since your last dental visit Yes No If yes please list __________________________________________________________________________________________________ What medications are you taking _____________________________________________________________________ __________________________________________________________________________________________________ Any changes in medication dosage or medications Yes No If yes please list __________________________________________________________________________________________________ __________________________________________________________________________________________________ What over the counter or lsquoherbalnaturalrsquo supplements are you taking on a regular basis Please list __________________________________________________________________________________________________ Are you taking any bisphosphonates in the past or presently Yes No If yes please provide details __________________________________________________________________________________________ Do you have a persistent sore throat hoarseness ear ache or feeling of something being caught in your throat Yes No If yes please provide details Have you had any surgery or been hospitalized since your last visit Yes No If yes please explain ________________________________________________________________________________ Are you being treated for any medical problem presently Yes No If yes please explain _______________________________________________________________________________ Have you ever taken antibiotics prior to having your teeth cleaned or before dental work Yes No If yes please explain _______________________________________________________________________________ Any allergies to drugs food metal or latex Yes No If yes please list __________________________________________________________________________________ History of illness or disease in family If yes please explain _______________________________________________________________________________ Have you been diagnosed with diabetes Type I Type II Pre-diabetes Diet-controlled Medication controlled Under control Yes No Have you had any heart problems or a knee hip or prosthetic joint replacement Yes No If yes provide details _____________________________________________________________________________ Have you had a bone mineral density test Yes No Results ____________________________________ Female clients Are you pregnant Yes No On a scale of 1 to 10 (10 being highest) how would you rate your general health at this time __________________ How would you rate your level of stress presently Low Moderate High On a scale of 1 to 10 (10 being highest) how closely related is the health of your mouth to your overall health in your opinion ________________

15

References Subantimicrobial Dose Doxycycline (SDD) 1 Caton J Ryan ME Clinical studies on the management of periodontal diseases utilizing subantimicrobial dose doxycycline (SDD) Pharmacol Res 2011 Feb63(2)114-20 2 Ashley RA Clinical trials of a matrix metalloproteinase inhibitor in human periodontal disease SDD Clinical Research Team Ann N Y Acad Sci 1999 Jun 30878335-46 3 Lee JY Lee YM Shin SY Seol YJ Ku Y Rhyu IC Chung CP Han SB Effect of subantimicrobial dose doxycycline as an effective adjunct to scaling and root planing J Periodontol 2004 Nov75(11)1500-8 4 Preshaw PM Host response modulation in periodontics Periodontol 2000 20084892-110 5 Caton JG Ciancio SG Blieden TM et al Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis J Periodontol 200071521-32 6 Caton JG Ciancio SG Blieden TM Bradshaw M Crout RJ Hefti AF Massaro JM Polson AM Thomas J Walker C Subantimicrobial dose doxycycline as an adjunct to scaling and root planing post-treatment effects J Clin Periodontol 2001 Aug28(8)782-9 7 Preshaw PM Hefti AF Bradshaw MH Adjunctive subantimicrobial dose doxycycline in smokers and non-smokers with chronic periodontitis J Clin Periodontol 2005 Jun32(6)610-6 8 Novak MJ Johns LP Miller RC et al Adjunctive benefits of subantimicrobial dose doxycycline in the management of severe generalized chronic periodontitis J Periodontol 200272762-9 9 Mohammad AR Preshaw PM Bradshaw MH Hefti AF Powala CV Romanowicz MAdjunctive subantimicrobial dose doxycycline in the management of institutionalized geriatric patients with chronic periodontitis Gerodontology 2005 Mar22(1)37-43 10 Gu Y Walker C Ryan ME PayneJB Golub LM Non-antibacterial tetracycline formulations clinical applications in dentistry and medicine J Oral Microbiol 20124 doi 103402jomv4i019227 11 Novak MJ Dawson DR 3rd Magnusson I Karpinia K Polson A Polson A Ryan ME Ciancio S Drisko CH Kinane D Powala C Bradshaw M Combining host modulation and topical antimicrobial therapy in the management of moderate to severe periodontitis a randomized multicenter trial J Periodontol 2008 Jan79(1)33-41 12 Preshaw PM Hefti AF Novak MJ Michalowicz BS Pihlstrom BL Schoor R Trummel CL Dean J Van Dyke TE Walker CB Bradshaw MH Subantimicrobial dose doxycycline enhances the efficacy of scaling and root planing in chronic periodontitis a multicenter trial J Periodontol 2004 Aug75(8)1068-76 13 ODell JR Elliot JR Mallek JA Mikuls TR Weaver CA Glickstein S et al Treatment of early seropositive rheumatoid arthritis doxycycline plus methotrexate alone Arthritis Rheum 200654621-7 14 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 Vasc Biol 2004 Apr24(4)733-8 15 Tuumlter G Kurtiş B Serdar M Aykan T Okyay K Yuumlcel A Toyman U Pinar S Cemri M Cengel A Walker SG Golub LM 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 Periodontol 2007 Aug34(8)673-81 16 Bench TJ1 Jeremias A Brown DL Matrix metalloproteinase inhibition with tetracyclines for the treatment of coronary artery disease Pharmacol Res 2011 Dec64(6)561-6 17 Payne JB Golub LM Stoner JA Lee HM Reinhardt RA Sorsa T Slepian MJ The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation a randomized double-masked placebo-controlled clinical trial J Am Dent Assoc 2011 Mar142(3)262-73 18 Reinhardt RA Stoner JA Golub LM et al Efficacy of subantimicrobial dose doxycycline in postmenopausal women clinical outcomes J Clin Periodontol 200734768-75 19 Golub LM Lee HM Stoner JA et al Subantimicrobial dose doxycycline modulates gingival crevicular fluid biomarkers of periodontitis in postmenopausal osteopenic women J Periodontol 2008791409-18 20 Walker C Puumala S Golub LM et al Subantimicrobial dose doxycycline effects on osteopenic bone loss microbiologic results J Periodontol 2007781590-601 21 Payne JB Stoner JA Nummikoski PV Reinhardt RA Goren AD Wolff MS Lee HM Lynch JC Valente R Golub LM Subantimicrobial dose doxycycline effects on alveolar bone loss in post-menopausal women J Clin Periodontol 2007 Sep34(9)776-87 22 Engebretson SP Hey-Hadavi J Sub-antimicrobial doxycycline for periodontitis reduces hemoglobin A1c in subjects with type 2 diabetes a pilot study Pharmacol Res 2011 Dec64(6)624-9 23 Engebretson SP Hyman LG Michalowicz BS Schoenfeld ER Gelato MC Hou W Seaquist ER Reddy MS Lewis CE Oates TW Tripathy D Katancik JA Orlander PR Paquette DW Hanson NQ Tsai MY The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons with type 2 diabetes and chronic periodontitis a randomized clinical trial JAMA 2013 Dec 18310(23)2523-32 24 Golub LM Lee HM Stoner JA Reinhardt RA Sorsa T Goren AD Payne JB Doxycycline effects on serum bone biomarkers in post-menopausal women J Dent Res 2010 Jun89(6)644-9 25 Ryan ME Lee HM Bookbinder MIC et al Treatment of genetically susceptible patients with a subanmicrobial dose of doxycycline Dent Res 200079608 (abstract 3719)

Note This does not comprise a complete listing of studies related to LDD

15

References Subantimicrobial Dose Doxycycline (SDD) 1 Caton J Ryan ME Clinical studies on the management of periodontal diseases utilizing subantimicrobial dose doxycycline (SDD) Pharmacol Res 2011 Feb63(2)114-20 2 Ashley RA Clinical trials of a matrix metalloproteinase inhibitor in human periodontal disease SDD Clinical Research Team Ann N Y Acad Sci 1999 Jun 30878335-46 3 Lee JY Lee YM Shin SY Seol YJ Ku Y Rhyu IC Chung CP Han SB Effect of subantimicrobial dose doxycycline as an effective adjunct to scaling and root planing J Periodontol 2004 Nov75(11)1500-8 4 Preshaw PM Host response modulation in periodontics Periodontol 2000 20084892-110 5 Caton JG Ciancio SG Blieden TM et al Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis J Periodontol 200071521-32 6 Caton JG Ciancio SG Blieden TM Bradshaw M Crout RJ Hefti AF Massaro JM Polson AM Thomas J Walker C Subantimicrobial dose doxycycline as an adjunct to scaling and root planing post-treatment effects J Clin Periodontol 2001 Aug28(8)782-9 7 Preshaw PM Hefti AF Bradshaw MH Adjunctive subantimicrobial dose doxycycline in smokers and non-smokers with chronic periodontitis J Clin Periodontol 2005 Jun32(6)610-6 8 Novak MJ Johns LP Miller RC et al Adjunctive benefits of subantimicrobial dose doxycycline in the management of severe generalized chronic periodontitis J Periodontol 200272762-9 9 Mohammad AR Preshaw PM Bradshaw MH Hefti AF Powala CV Romanowicz MAdjunctive subantimicrobial dose doxycycline in the management of institutionalized geriatric patients with chronic periodontitis Gerodontology 2005 Mar22(1)37-43 10 Gu Y Walker C Ryan ME PayneJB Golub LM Non-antibacterial tetracycline formulations clinical applications in dentistry and medicine J Oral Microbiol 20124 doi 103402jomv4i019227 11 Novak MJ Dawson DR 3rd Magnusson I Karpinia K Polson A Polson A Ryan ME Ciancio S Drisko CH Kinane D Powala C Bradshaw M Combining host modulation and topical antimicrobial therapy in the management of moderate to severe periodontitis a randomized multicenter trial J Periodontol 2008 Jan79(1)33-41 12 Preshaw PM Hefti AF Novak MJ Michalowicz BS Pihlstrom BL Schoor R Trummel CL Dean J Van Dyke TE Walker CB Bradshaw MH Subantimicrobial dose doxycycline enhances the efficacy of scaling and root planing in chronic periodontitis a multicenter trial J Periodontol 2004 Aug75(8)1068-76 13 ODell JR Elliot JR Mallek JA Mikuls TR Weaver CA Glickstein S et al Treatment of early seropositive rheumatoid arthritis doxycycline plus methotrexate alone Arthritis Rheum 200654621-7 14 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 Vasc Biol 2004 Apr24(4)733-8 15 Tuumlter G Kurtiş B Serdar M Aykan T Okyay K Yuumlcel A Toyman U Pinar S Cemri M Cengel A Walker SG Golub LM 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 Periodontol 2007 Aug34(8)673-81 16 Bench TJ1 Jeremias A Brown DL Matrix metalloproteinase inhibition with tetracyclines for the treatment of coronary artery disease Pharmacol Res 2011 Dec64(6)561-6 17 Payne JB Golub LM Stoner JA Lee HM Reinhardt RA Sorsa T Slepian MJ The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation a randomized double-masked placebo-controlled clinical trial J Am Dent Assoc 2011 Mar142(3)262-73 18 Reinhardt RA Stoner JA Golub LM et al Efficacy of subantimicrobial dose doxycycline in postmenopausal women clinical outcomes J Clin Periodontol 200734768-75 19 Golub LM Lee HM Stoner JA et al Subantimicrobial dose doxycycline modulates gingival crevicular fluid biomarkers of periodontitis in postmenopausal osteopenic women J Periodontol 2008791409-18 20 Walker C Puumala S Golub LM et al Subantimicrobial dose doxycycline effects on osteopenic bone loss microbiologic results J Periodontol 2007781590-601 21 Payne JB Stoner JA Nummikoski PV Reinhardt RA Goren AD Wolff MS Lee HM Lynch JC Valente R Golub LM Subantimicrobial dose doxycycline effects on alveolar bone loss in post-menopausal women J Clin Periodontol 2007 Sep34(9)776-87 22 Engebretson SP Hey-Hadavi J Sub-antimicrobial doxycycline for periodontitis reduces hemoglobin A1c in subjects with type 2 diabetes a pilot study Pharmacol Res 2011 Dec64(6)624-9 23 Engebretson SP Hyman LG Michalowicz BS Schoenfeld ER Gelato MC Hou W Seaquist ER Reddy MS Lewis CE Oates TW Tripathy D Katancik JA Orlander PR Paquette DW Hanson NQ Tsai MY The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons with type 2 diabetes and chronic periodontitis a randomized clinical trial JAMA 2013 Dec 18310(23)2523-32 24 Golub LM Lee HM Stoner JA Reinhardt RA Sorsa T Goren AD Payne JB Doxycycline effects on serum bone biomarkers in post-menopausal women J Dent Res 2010 Jun89(6)644-9 25 Ryan ME Lee HM Bookbinder MIC et al Treatment of genetically susceptible patients with a subanmicrobial dose of doxycycline Dent Res 200079608 (abstract 3719)

Note This does not comprise a complete listing of studies related to LDD