Oral and Whole Body Health

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• Mouth - Body CONNECTIONS • The Facts and Fictions of INFLAMMATION • PREGNANCY and PERIODONTAL DISEASE • Linking DIABETES, OBESITY and INFECTION • Reflections from a SURGEON GENERAL • HEALTH POLICY of the Future • Blurring the DOCTOR-DENTIST Barrier

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INTRODUCTION » OUR MOUTHS, OURSELVES As the relationship between the mouth and the rest of the body becomes clearer, it is changing the way dentists, doctors and patients view oral health. 3 BY SHARON GUYNUP INVADERS AND THE BODY’S DEFENSES Gum disease illustrates how local infections may have systemic consequences. 6 BY PHILIP E. ROSS HEART HEALTH IN THE INFLAMMATION AGE Arterial plaques, once thought to be fatty deposits, are a result of the inﬂ ammatory process. 12 BY PETER LIBBY THE THREE-WAY STREET ORAL AND WHOLE BODY HEALTH Two decades of biomedical and dental detective is published by SCIENTIFIC AMERICAN, INC., 415 Madison Avenue, New York, work have linked obesity, diabetes and periodontal NY 10017-1111. Copyright © 2006 disease. by SCIENTIFIC AMERICAN, INC. All rights reserved. No part of this issue may BY ROBERT J. GENCO be reproduced by any mechanical, photographic or electronic process, 18 or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted or INTERVIEW » otherwise copied for public or private use without written BUZZ TALK WITH permission of the publisher. MARJORIE K. JEFFCOAT

Subscription inquiries for The Dean of the University of Pennsylvania School of SCIENTIFIC AMERICAN MAGAZINE: Dental Medicine on the facts and ﬁ ction surrounding U.S. and Canada (800) 333-1199; oral health’s relationship to the rest of the body. Other (515) 248-7684

23 CREDIT b SCIENTIFIC AMERICAN PRESENTS: ORAL + WHOLE BODY HEALTH PROTCTOR & GAMBLE A custom publication produced ORAL AND WHOLE BODY HEALTH in collaboration with CREST and ORAL-B

WHAT EVERY WOMAN NEEDS TO KNOW Growing evidence suggests that poor oral hygiene during pregnancy can adversely affect the health of newborns. BY STEVEN OFFENBACHER 24 AS THE BODY AGES When it comes to the complications of oral disease, the elderly are particularly vulnerable. BY FRANK A. SCANNAPIECO 30

INSIGHTS » ORAL HEALTH AROUND THE WORLD Maurizio Tonetti, an oral health professional who has worked in four different countries, offers some thoughts on the future of global oral health. 35

PUBLIC POLICY & ORAL HEALTH » A WHOLE NEW GAME Governments, insurers, clinicians and the public must all recognize the changing face of dental medicine. BY SHEILA RIGGS 36

INTERVIEW » DISCUSSION WITH DAVID SATCHER The former U.S. surgeon general reflects on his landmark report that put oral health on the national agenda and the policy steps that still need to be taken.

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A custom publication produced in A NOVEL APPROACH TO collaboration with CREST & ORAL-B INFLAMMATION PROJECT MANAGEMENT Understanding how the body “turns off” infl ammation Publication and Media Director : may yield new treatments for periodontal disease Jeremy Abbate and other infl ammatory conditions. Editorial Director: Sharon Guynup BY THOMAS E. VAN DYKE Features Editor: Larry Katzenstein 42 & CHARLES N. SERHAN Art Director: Jeff Mellin Illustrators: Matt Collins, Tami Tolpa, Keith Kasnot Custom Photography: John Soares PATH TO PREVENTION » Production Consultant: Richard Hunt MOUTHFUL OF BUGS Copy Editor: Michael Battaglia Pathogenic bacteria are a way of life. Research: Anna Kline So, too,must be brushing and fl ossing. BOARD OF ADVISERS BY ROBERT H. KAGAN Robert J. Genco: Distinguished Professor, Department of Oral Biology, 46 School of Dental Medicine, State University of New York at Buffalo Jim Beck: Distinguished Professor, Department of Dental Ecology, School INTERVIEW » of Dentistry, The University of North Carolina at Chapel Hill THE ADA’S TAKE Marjorie K. Jeffcoat: Dean, University of How the American Dental Association, the world’s Pennsylvania School of Dental Medicine leading dental organization, views the growing Steven Offenbacher: Director, Center for Oral and Systemic Diseases, University connections between a healthy mouth and a healthy of North Carolina at Chapel Hill body — a conversation with Daniel M. Meyer. Maurizio Tonetti: Chair, Division of 49 Periodontology, University of Connecticut School of Dental Medicine Thomas E. Van Dyke: Professor, Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine A Message from the AMERICAN ACADEMY OF PERIODONTOLOGY SCIENTIFIC AMERICAN EDITORS & PROJECT STAFF THE AMERICAN ACADEMY OF PERIODONTOLOGY (AAP) congratulates Procter & Gamble Editor In Chief: John Rennie Professional Oral Health, Scientific American and all of the contributors to this special Executive Editor: Mariette DiChristina Managing Editor: Ricki L. Rusting supplement for providing in-depth and balanced information on the association between News Editor: Philip M. Yam periodontal diseases and general health conditions. Special Projects Editor: Gary Stix Senior Editor: Michelle Press The AAP has been a leader in tracking periodontal and systemic research for over a decade. Editors: Mark Alpert, Steven Ashley, The research results to date have been promising, and the prospect that periodontal Graham P. Collins, Steve Mirsky, George Musser, Christine Soares treatment may signifi cantly improve general health outcomes is exciting. However, there is Art Director: Ed Bell still a great deal to learn about the impact of periodontal infection and infl ammation on Associate Publisher, Production: general health. Additional research into these complex associations is essential if patients William Sherman Production Manager: Christina Hippeli are to reap the benefi ts of improved health. Prepress and Quality Manager: Silvia Given the potential impact on diabetes, pre-term low birthweight, cardiovascular disease De Santis Director of Ancillary Products: Diane and other conditions, we believe this research merits the investment and should be prioritized McGarvey by the National Institutes of Health and other funding agencies. Associate Publisher, Circulation: Simon Aronin The Academy and its member periodontists are proud to collaborate to advance oral and Circulation Director: Christian Dorbandt systemic health. Readers are encouraged to visit www.perio.org for more information about General Manager: Michael Florek Business Manager: Marie Maher periodontists and periodontal health. President and Chief Executive Offi cer: Gretchen G. Teichgraeber Vice President and Managing Director, — KENNETH A. KREBS, D.M.D. International: Dean Sanderson President, American Academy of Periodontology Vice President: Frances Newburg CREDIT CREDIT d SCIENTIFIC AMERICAN PRESENTS: ORAL + WHOLE BODY HEALTH PROTCTOR & GAMBLE INTRODUCTION

OUR MOUTHS, OURSELVES As the interrelationship between the mouth and the rest of the body becomes clearer, dental professionals, doctors and patients will need to rethink the term “oral health”

BY SHARON GUYNUP

ORAL AND WHOLE BODY HEALTH 3 S I N C E T I M E I M M E M O R I A L , people have struggled to maintain adequate oral health. As far back as a.d. 250, Kemetic Egyptians used myrrh and other antiseptic herbs to treat infected gums. The Nubians that dwelt in the Nile River valley two centuries later drank beer as a palliative for unhealthy teeth; it may have worked well, as it was brewed from grain contaminated with the same bacteria that produces tetracycline.

Lengthening teeth and receding gums have historically “oral-systemic link” emerges almost daily. For example, in been considered a consequence of surviving into adulthood. May 2006 it was announced at an American Society for Mi- (In his 1852 novel The History of Henry Esmond, Esq., Wil- crobiology meeting that researchers have identifi ed genes in liam Thackary used the expression “long in the tooth” to certain oral bacteria that allow the organisms to invade and describe a middle-aged person.) The few teeth that didn’t de- infect human arterial cells. This certainly expands to the cay in youth usually loosened with the passing years, as the discussion of the possible biologic pathways that might link tissues supporting them were eroded by periodontal disease. the mouth and the heart (or other parts of the body). Addi- Those teeth ultimately fell out. tionally, this year will see the results of two major studies Today, people are living longer, and gum disease has sup- examining the relationship between oral disease and preg- planted tooth decay as the most common cause of tooth loss nancy complications in expectant mothers. in adults. The disease affects about 80 percent of Americans So what exactly is the connection between what happens over age 65, according to the American Dental Association. in your mouth and your overall health? Some of the millions At the turn of the last millennium, then–U.S. surgeon gen- of bacteria that lurk in our mouths (numbering more than all eral David Satcher called periodontal disease the “silent the cells in our bodies) are the primary culprits—along with epidemic” in his landmark report, Oral Health in America. the subsequent infl ammation they cause. These microrgan- Given the state of public health, good oral hygiene may prove isms form complex colonies of sticky plaque. This tenacious to be more critical than just preserving your smile. A grow- plaque — what microbiologists call a “biofi lm” — is com- ing body of research suggests that periodontal disease may posed of durable, coral reef–like structures, building up at the play a role in a variety of systemic health problems as wide gum line and in between teeth. ranging as diabetes, respiratory illness, pregnancy complica- Some of the approximately 500 species of bacteria in your tions, and heart disease. mouth are not innocuous fl ora. They cause gingivitis, infect- It is this body of research—and the attendant health pol- ing gums. Your immune system steps in to fi ght these invad- icy implications it engenders—that is the subject of this cus- ers—gums become infl amed, and may bleed when you brush. tom publication from Scien- tific American, Oral and Whole Body Health, pro- The fi elds of dentistry and medicine have traditionally duced with the generous support of the Procter & Gam- been worlds apart. But in light of the growing evidence ble Company. Here we pres- pointing to links between oral and whole body health, this ent, for the benefi t of both separation of disciplines is slowly beginning to change. health professionals and patients, the latest pieces in the ever-growing puzzle of oral disease’s connection to systemic Interestingly, if this same type of infection appeared on a per- health. You’ll hear from some of the pioneering researchers son’s arm or another body part, they would no doubt go run- themselves about their ongoing explorations into the mouth- ning to the doctor for treatment—but bleeding, tender gums body relationship. are often ignored. Like any new area of scientifi c inquiry, some data paint a Untreated, this tenderness progresses into full-blown peri- very clear picture while other results are still inconclusive. odontitis, and here the immune system shows its dark side. Several studies, for example, have found that blood-sugar This simmering infl ammation ulcerates gums and summarily levels in diabetics with periodontal disease were signifi cant- destroys the soft tissue and bone that anchors your teeth. It ly reduced when the patients’ gum disease was treated. Oth- also sends infl ammatory substances throughout the body. ers, like the ones examining the connection between peri- Researchers are discovering that out-of-control infl amma- odontal disease and heart conditions, have not yet uncovered tion may prove to be the engine that drives an ever-growing a defi nitive causal relationship. But new information on this list of greatly feared, chronic illnesses from clogged arteries

4 ORAL AND WHOLE BODY HEALTH and heart attacks to arthritis and cancer. This infl ames on their Web site, mation link is just one of a number of hypotheses ex- warning: “if you or plaining how chronic oral infection may trigger or someone you know intensify systemic diseases. had periodontal dis- Another concern is that the microbial ecosystem in ease, diagnosed or your mouth doesn’t just stay there. Stealthy, virulent undiagnosed, and ei- bacteria overgrow in infl amed gum tissues; with each ther ignored or treat- bite of food or stroke of a toothbrush, some of those ed unsuccessfully, microbes can seep into your bloodstream, traveling to before or during the distant parts of your body. The question is: can they set same time as any of the up shop elsewhere and cause harm? It is known that some mentioned systemic dis- of these bad bugs, when inhaled, can cause pneumonia, par- eases, you may be eligible ticularly in the elderly. Some are also able to move through arter- for damages caused by these ies to the uterus and have been found in the placenta. systemic diseases.” Although BUGS WITH STAYING POWER: an extreme example, it embod- clearly the mouth is in many ways the “gateway” to the Once thought to be a mere ies the confusion and hype sur- rest of the body. However, this connection is often overlooked. congregation of pathogens, rounding this topic and under- dental plaque is now known to In the U.S., the fi elds of dentistry and medicine have tradition- be a dynamic – and tenacious – scores the need for objective, ally been worlds apart. But in light of the growing evidence microbiological community credible analysis. And it ig- pointing to links between oral and whole body health, this called a biofilm. nores the fact that oral disease separation of disciplines is slowly beginning to break down. is complex. The notion that dentists care for only gums and teeth, while For example, changing hormone levels can cause fl are-ups doctors look after everything else is being rethought. in women during pregnancy and while premenstrual—or in There is a dawning realization that often it is a dentist or perio- those taking oral contraceptives. Other medications can also dontist who fi rst discovers a larger health problem, because of make gums more susceptible to infection, including antihis- what they see in a patient’s mouth—and that doctors need to look tamines, antidepressants, cancer drugs, steroids, and espe- at more than the tonsils when a patient opens wide and says “ah.” cially those that cause “dry mouth,” disrupting the mouth’s For example, diabetics tend to develop periodontal disease at three bacterial ecosystem. Genetic, microbial, immunological and to four times the rate of nondiabetics. If a dental professional sees environmental factors infl uence both the risk and progression gum infl ammation in someone who brushes and fl osses regu- of infection. For example, the American Academy of Peri- larly, they need to ask, “Have you checked your blood sugar odontology says that perhaps one third of Americans may be lately?” Or, conversely, the doctor of a patient with uncontrolled genetically susceptible—making them up to six times more blood sugar may need to refer them to a dental professional. likely to develop periodontal disease. It could be that in some There is already a ripple effect in some sectors of the insur- cases these same factors or susceptibility might independent- ance industry. Some insurers are fi nding it more cost-effective ly cause harm elsewhere in the body, creating a mere illusion to include periodontal treatment among covered services for of oral-systemic causality. diabetics and pregnant women. But if additional research so- Of course, one of the most important differences between lidifi es the links between gum disease and other chronic ill- periodontal disease and other systemic conditions is that the nesses, sweeping changes will be needed to provide access to former has a known cause and is quite treatable. Dental profes- care. This will be crucial for the segments of society—the poor sionals should never lose sight of the fact that they are address- and the elderly—who are most at risk for oral disease as well as ing a disease that signifi cantly contributes to disability and a conditions such as heart disease and diabetes. It is a huge public lack of well-being in the population. This fact alone makes it health issue: periodontal treatment and prevention can cost important to treat this condition, regardless of whether it might between $100 and $1,000 annually per patient. contribute to other serious illnesses. And although no one Over the past few years, newspapers, magazines and oth- should overstate the oral-systemic link, proffers Robert Genco, er national media outlets have hyped numerous stories about a professor of oral medicine and microbiology at the Univer- the possible systemic health risks of periodontal disease as sity at Buffalo, no one should underestimate what can happen well as infl ammation’s general link to a broad range of dis- if it’s ignored, either. While the mouth’s relationship to the rest eases. Some articles have greatly exaggerated or oversimpli- of the body will certainly be a matter of public health, of patient fi ed the connection, enough so that the expression “fl oss or awareness and of the changing roles among caregivers, it will die” has become a standing joke among researchers. fi rst and foremost be a matter of science. • Even some opportunistic law fi rms have jumped on the

PREVIOUS PAGE PHOTO: JOHN SOARES MOUTH IMAGES: CLIPART.COM COLLAGE ILLUSTRATION: JEFF MELLIN bandwagon. One in Arizona solicits potential malpractice cas- SHARON GUYNUP is editorial director of Oral and Whole Body Health.

ORAL AND WHOLE BODY HEALTH 5 > >

Gum disease illustrates how local infections may have systemic consequences

INVADERBY PHILIP E. ROSSS & THE BODY’S DEFENSES

IF EVER THERE WAS A MAGIC BULLET —a drug so discriminating that it attacked

microbes while sparing healthy tissue— it would be the monoclonal antibody, a human-tuned

form of an immune molecule honed by eons of natural selection. Yet, as the world learned

this spring, when such an antibody nearly ic effects are nowhere better illustrated than killed several subjects in a British clinical in chronic gum disease. Although it origi- trial, even these drugs can cause serious side nates in a bacterial assault, some two thirds effects. No one should have been too sur- of the damage is caused by the infl ammatory prised; the natural immune response also response to the perceived invader. What is causes damage, which is why it fully mobi- worse, inflammation somehow communi- lizes—in a process called inflammation— cates itself to distant points, explaining the only when the enemy is at the gates. possible association of gum disease with oth- In recent years, a lot of media attention er conditions: adult-onset (or type 2) diabe- has been lavished upon the process of infl am- tes, premature birth, stroke and cardiovascu- mation (including a cover story in Time mag- lar disease. However infection travels from azine on this “silent killer”) as researchers the mouth to infl ame distant organs, it is continue to uncover evidence linking it with clear that it turns the body against itself. In other serious diseases. Whether or not in- the words of the cartoon character Pogo, fl ammation turns out to be the “holy grail” of “We have met the enemy and he is us.” medicine is yet to be seen. But infl ammation’s Only a handful of the more than 500 spe- >>problem of friendly fi re and potential system- cies of bacteria that live in the mouth are 6 ORAL AND WHOLE BODY HEALTH S

INFECTION AND INFLAMMATION in the mouth have been linked to a variety of systemic conditions, including pregnancy complications, type 2 diabetes, heart disease and stroke. While recent national media coverage spotlighting inﬂ ammation has spawned much interest in the topic, more research is needed to uncover exactly how infection and inﬂ ammation affect the body. JOHN SOARESJOHN

ORAL AND WHOLE BODY HEALTH 7 A PRIME LOCATION MOUTH The hard, non-shedding surface of the teeth and the nutrient- rich, oxygen-poor environment of the mouth provide ideal INVADERS conditions for the growth of oral bacteria. They easily attach themselves to the tooth and gum. Of the over 500 The Progression of microorganisms that live in dental plaque, only a handful have Periodontal Disease been implicated in gum disease.

implicated in gum disease. They are par- dead and dying neutrophils, and any the ligaments that anchor teeth in their ticularly hard to eradicate because they cellular detritus that may litter the bat- sockets, loosening them until they at last form biofilms: tough, many layered, tlefi eld. Meanwhile, the macrophages fall out. Nowadays this happens less fre- mineral encrusted communities. Hud- secrete fatty acids and interleukin-1 quently; the patient notices the bleeding dling in the deepest layers are the oxygen- (IL-1), a primary regulator of infl am- and goes to a dentist. The dentist or den- shunning, or anaerobic, bacteria that ap- matory and immune responses, as well tal hygienist scrapes away infl ammation- pear to cause the most damage. as tumor necrosis factor alpha (TNF␣), riddled material and treats the infection When bacteria come in contact with a protein that heightens infl ammation. with antibiotics. Treatment, however, gums, they secrete toxins that break The resulting mayhem may be likened cannot prevent the influx of bacteria. down gum lining, creating a tiny ulcer. to urban warfare, with immune sol- The disease will recur if the patient does The body’s bloodhounds, the neutro- diers running from house to house, not stick to a rigorous routine of brush- phil cells, then attack these invaders. If tossing in grenades, spraying rooms ing, fl ossing, rinsing and dental clean- they keep the biofi lm at bay, the battle with machine-gun fi re, all before ask- ings. And although the damage in peri- reaches a standoff, termed gingivitis. If, ing who is friend and who is foe. No odontal disease is primarily the result of however, the bacteria continue to ad- wonder the tissue breaks down. The the infl ammatory process, it can only be vance into the gums, the immune sys- ulcers sink deeper into the gum, creat- prevented or treated by addressing the tem signals a higher state of alert, mo- ing a “periodontal pocket”; full-blown bacterial biofilm that is infecting the bilizing macrophages (Greek for “big periodontitis begins. gums. What is worse, the chance of early eaters”). These white blood cells swal- If the disease is allowed to progress, detection is lessened in those who are low bacteria, along with the gorged, the advancing infl ammation eats away most vulnerable—smokers. Just as to-

8 ORAL AND WHOLE BODY HEALTH TENACIOUS BUGS A HEATED STRUGGLE Oral bacteria are particularly hard to eradicate because they form Continued defensive strikes by the immune system heighten tough, many-layered, mineral-encrusted communities, known as infl ammation as specialized white blood cells (macrophages, biofi lms. If untreated, these biofi lms become lodged in the gingival as well as others) secrete infl ammatory substances. This crevices around the tooth. The immune system launches a defensive intense infl ammation can ultimately break down gum tissue, strike against these bacterial invaders by dispatching neutrophils. creating a periodontal pocket — the beginning of full-blown The fi rst signs of infl ammation (redness, swelling) begin to appear. periodontal disease.

bacco smoke irritates the gums, height- neutrophils have trouble homing in on tomb fat in situ, creating atherosclerot- ening infl ammation, it also tends to mask bacteria, showering them with chemical ic plaque. This buildup, combined with telltale bleeding. grenades called superoxides. “But instead infl ammation, fattens the arterial wall, Other factors that predispose people of destroying bacteria, they destroy the gradually restricting blood fl ow to tis- to gum disease include bad oral hygiene periodontal ligament that ties the tooth to sues. Sometimes, for reasons that are and an unlucky bequeathal of genes. the jaw,” says Charles N. Serhan, profes- not well understood, the thin layer of One very invasive form of periodontal sor of anesthesiology at Harvard Medical tissue covering the plaque ruptures, disease is found in just 0.1 percent of School. “It’s like rheumatoid arthritis, an spurring clots to form in a matter of Americans, a distribution that indicates autoimmune disease where a lot of the minutes, often triggering a heart attack a genetic component. People with these degradation of the synovium [the lining of or stroke. This is why the most com- and other predisposing genes must work the joints] is done by neutrophils.” Serhan mon fi rst symptom of heart disease is extra hard to care not only for their is looking for ways to shut down this ex- sudden death. teeth but even for the artifi cial implants cessive immune response. If infection in the gums not only pre- that may replace those teeth. Periodon- When infl ammation strikes sites far cedes infl ammation in the arteries, but tal disease can strike the tissues sur- from the gums, it progresses there much encourages it, the question is how does rounding implants as well. as it does in the mouth. In the lining of it happen. One theory holds that bacte- Genetic variation is of particular in- the heart’s arterial wall, for instance, ria are the primary vehicles in commu- terest because it may illuminate the mech- macrophages engulf whatever detritus nicating disease; another lays the blame anisms that underlie all varieties of peri- they find, including fatty particles. on proinfl ammatory chemicals that leak

MATT COLLINS MATT odontal disease. In one invasive form, When the macrophages die, they en- out of the gums and into the blood-

ORAL AND WHOLE BODY HEALTH 9 stream. Direct infl ammation currently valve. What if a similar weakness ex- sidered innocuous. Yet critics of the holds sway, particularly in the popular ists in the arterial lining? bacterial-cause theory point out that press. Still, there is evidence supporting Researchers have, in fact, found oral bacteria survive poorly in the both theories, and each may explain traces of oral bacteria in arterial plaque. bloodstream. They also note that proin- part of the problem. Yet as critics of the infection theory flammatory chemicals demonstrably Oral bacteria can get into the blood- point out, the method they used to iden- leak from the gums into the bloodstream. Robert Genco, a professor of tify the bacteria—a highly potent DNA stream, adding to the body’s infl amma- oral medicine and microbiology at the amplification tool—cannot tell how tory burden. In a test tube, proinfl am- University at Buffalo, took moment-by- many bacteria were present in the matory agents from one group of cells moment blood tests in healthy patients plaque or whether any of them were can spark a response in another group. undergoing routine teeth cleaning. The alive when they entered it. Injecting proinfl ammatories into ani- bacterial count spiked when cleaning be- Paul Ewald, an evolutionary biolo- mals also produces such a response. gan, then fell back to normal less than a gist at the University of Louisville, has Some argue that these chemicals alone minute after it was over—that is how fast been a leading advocate of the role of can explain the association of gum dis- the body’s immune system rousts such infectious agents in chronic illnesses. ease and systemic illness. invaders. Yet in people with periodontal He argues that gum disease fi ts into the Here is how it might play out. Imag- disease, such bacterial inundations of the evolutionary model he has devised be- ine that there is some small irritation in blood occur every time a loosened tooth cause it is chronic, widespread and of the wall of the coronary artery, per- moves in its socket, providing many op- great antiquity, and therefore cannot be haps the result of chemicals absorbed portunities for a stray bacterium to relo- simply the result of defective genes. from cigarette smoke or car exhaust. If cate to some distant location. “If it were just a case of the immune the overall infl ammatory burden is low, Oral bacteria, once established else- system going haywire, you’d think that then perhaps these sites will remain where in the body, are bad news. Genco natural selection would have weeded it quiescent. If, however, proinfl amma- injected Porphymonas gingivalis, a out,” he says. “But if you are looking at tory chemicals have leached from the main culprit in periodontal disease, un- actual combat between the immune sys- periodontal pocket into the blood- der the skin of rodents and found that it tem and [an] infectious agent, you’d ex- stream, it might heighten local infl ammation in the artery, beginning the process of atherosclerosis. If infection in the gums not only precedes How do the two theories stack up? It infl ammation in the arteries, but encourages it, is not easy to say from the evidence now the question is how does it happen? in hand, which comes mainly from ob- serving correlations between gum disease and other diseases; either or both of invariably produced fatal infections. “It pect it to be an evolutionary arms race, the proposed mechanisms could be re- causes gross necrosis of skin and under- one that would never stabilize.” That sponsible. Take the evidence linking lying tissue; if you inject into the belly, same arms race would have tuned the periodontal disease with premature the intestines will be exposed,” he says. bacteria to a high pitch of virulence and birth, which could be caused by the in- A rare, analogous condition has been invasiveness, hence their ferocious be- fection reaching the uterus or, alterna- seen in humans, in which a dental infec- havior when ensconced in another part tively, by the release into the bloodstream tion spreads down the neck to the area of the body. of such proinfl ammatories as prostaglan- surrounding the carotid artery, where it Biologists are now investigating the din E2, a drug used by obstetricians to digests tissue. possibility that many chronic illnesses, induce labor. There is also evidence that Perhaps the most persuasive exam- once attributed to other causes, may in oral disease destabilizes blood sugar con- ple of a secondary infection from oral fact stem from infection. Several strik- trol in diabetic patients, although the sources comes from patients who have ing examples have been demonstrated mechanism remains unclear. It is known mitral valve heart defects. Such pain the past two decades: Stomach ulcers, that high blood sugar contributes to gum tients are warned to take antibiotics long attributed to stress, spicy food and disease and that all kinds of stress badly before their dental appointments so genes, turn out to derive, almost always, impact diabetic control. Periodontal dis- that tooth cleaning will not send bac- from the bacterium Helicobacter pylori. ease may put stress on the body by teria to infect or inflame the valve, Cervical cancer, it is now known, can spreading bacteria, increasing the in- which could destroy it or produce clots develop only in women who have been fl ammatory burden, or both. that might block arteries. The critical infected by certain varieties of the hu- So, too, many treatments whose suc- element here is the vulnerability of the man papillomavirus (HPV), long con- cess may seem to confi rm one theory or

10 ORAL AND WHOLE BODY HEALTH INFLAMMATORY MOLECULES produced locally in tissue can get into the bloodstream and travel throughout the body. The inflammation-causing bacteria can also infect blood FIGHTING INVADERS and travel to distant points.

THE IMMUNE SYSTEM INCLUDES, among other components, antimicrobial molecules and various phagocytes (cells that ingest and destroy pathogens). These cells, such as dendritic cells and macrophages, also activate an inﬂ ammatory response, secreting proteins called cytokines that trigger an inﬂ ux of more defensive cells from the blood.

another turn out to be hard to interpret. We need interventionist studies to learn Genco notes that “the insurance com- Aspirin, an anti-infl ammatory, is used whether treating oral disease unmistak- panies are driven by economics, and to reduce the risk of heart attack, but ably shows a preventative benefi t against even though the science isn’t absolutely again, no one can say that this proves heart disease. Such trials are needed to there yet, they are taking action.” that infl ammation, pure and simple, is justify any public investment in such The smart money, therefore, is bet- the culprit. It could be that aspirin mere- treatment, and several are now planned ting on healthy gums. To keep them that ly limits clotting. and in line for funding. way, there are no magic bullets, no What is needed are large clinical tri- In the meantime, insurance compa- chemicals that can be added to drinking als in which patients are divided, at ran- nies—which are used to basing policies water, as fl uoride was added to stave off dom, into two groups: one that gets on purely actuarial data—are respond- tooth cavities. There is no substitute for treatment for periodontal disease, an- ing. This year, Aetna Dental announced brushing, fl ossing and regular dental other that gets a placebo. Two such stud- the results of a study of policyholders visits. It should be easier to justify than ies are trying to determine whether such that had both dental and health insur- in the past, for the dentist’s or hygien- treatment alleviates the risk of prema- ance. It showed that treating periodon- ist’s ministrations may turn out to pro- ture birth in women with gum disease. tal disease in heart patients lowered the tect not only your teeth, but, quite pos- Another is testing whether antibiotic total cost of treating both conditions. sibly, the rest of you as well. • treatment can alleviate heart disease. Yet, even here, one must beware of the pos- PHILIP E. ROSS, a former SCIENTIFIC AMERICAN contributing editor, is currently the online sibility that antibiotics themselves may editor of IEEE Spectrum, t h e m a g a z i n e o f t h e I n s t i t u t e o f E l e c t r i c a l a n d E l e c t r o n i c

TAMI TOLPA exert a subtle anti-inﬂ ammatory effect. Engineers. He has written for Forbes and Red Herring.

ORAL AND WHOLE BODY HEALTH 11 It is clear that inflammation is linked to heart disease, and that one of the body’s most common sources of inflammation is periodontal disease. Does poor oral health contribute to heart disease risk? Although the jury is still out while scientists investigate this link, here is what we know about inflammation’s role in atherosclerosis. | BY PETER LIBBY HeartHealth IN THE INFLAMMATIONAGE

ONLY A DECADE AGO, most physicians would have confi dently described sometimes fail. It also highlights the need for better prevention, detection atherosclerosis as a plumbing problem: Fat-laden gunk gradually builds up on and treatment. In industrialized nations, deaths from heart attacks and artery walls. If a deposit (plaque) grows large enough, it closes off an affected strokes exceed those from cancer—and they are also becoming more prevalent “pipe,” preventing blood fl ow. Eventually, Such research has established in- in developing countries. the blood-starved tissue dies. If that fl ammation’s key role in atherosclerosis. happens in the heart or the brain, a heart This process—the same one that causes IGNITING TROUBLE attack or stroke occurs. infected cuts to become swollen, hot we know that inflammation symp- Few believe that tidy explanation and painful—underlies everything from toms refl ect a pitched struggle on a mi- anymore. Twenty years of research show the creation of plaques to their growth croscopic battlefield. After sensing that arteries bear little resemblance to and rupture. (rightly or wrongly) a microbial inva- pipes. They contain living cells that When microbes invade, infl amma- sion, certain types of white blood communicate with one another and tion (literally meaning “on fi re”) fi ghts cells—the immune system’s frontline their environment. They also partici- infection. But with atherosclerosis, in- warriors—convene in the threatened pate in the development of the fatty de- fl ammation proves harmful; our own tissue. There they secrete chemicals to posits that grow within vessel walls— defenses bombard us with friendly fi re, limit infection: oxidants that damage few which actually shrink vessels to a just as they do in lupus and other auto- invaders and signaling molecules (in- pinpoint. Most heart attacks and many immune disorders. This revised picture cluding proteins called cytokines) that strokes stem from interior plaques that resolves two disturbing mysteries: why orchestrate the activities of defensive rupture suddenly, spawning a blood clot many heart attacks strike without warn- cells. Their presence in tissue signifi es

that blocks blood ﬂ ow. ing and why preventative therapies an inﬂ ammatory response. >> COLLINS MATT

12 ORAL AND WHOLE BODY HEALTH

CROSS-SECTION OF HEALTHY INFLAMMATION’S MANY ROLES CORONARY ARTERY INFLAMMATION—a central player in atherosclerosis—occurs when white blood cells, the body’s ﬁ rst line of defense against infec- Blood channel tion, invade and become active in tissue. These diagrams depict atherosclerotic plaque growth in a coronary Intima artery; the close-ups highlight some inﬂ ammatory processes triggered by elevated Media low-density lipoprotein (LDL) in the blood. Adventitia

LOL

T cell Endothelial 1 cell 2 Monocyte Adhesion Scavenger Foam Blood channel molecule receptor cell 3 INTIMA Modiﬁ ed LOL Chemokine Plaque Thrombus

4 5 Microphage Inﬂ ammatory Elastic tissue mediators

MEDIA Smooth muscle cells

BIRTH OF A PLAQUE PLAQUE PROGRESSION Excess LDL accumulates in Monocytes mature into active The macrophages display Infl ammatory artery walls, undergoing macrophages in the intima; “scavenger receptors” to help molecules trigger further 1 chemical changes. Modified 2 with T cells, they produce 3 ingest modified LDLs; 4 plaque growth. A fibrous cap LDLs stimulate endothelial cells to infl ammatory mediators, including macrophages feast on them, fi lling develops over the lipid core when the display adhesion molecules, which cytokines that carry signals with frothy, fatty droplets. These molecules induce smooth muscle capture circulating monocytes (key between immune system cells and “foam cells” combine with T cells, cells to migrate to the intima surface, players in infl ammation) and T cells factors that promote cell division. comprising the fatty streak—early multiplying and producing a tough, (immune cells). Endothelial cells atherosclerotic plaque. fibrous matrix that glues cells also secrete “chemokines,” luring together. The cap makes the plaque snared cells into the intima. larger and walls it off from the blood.

Cholesterol studies on both animals As LDLs accumulate, their lipids mature into active macrophages, ready and cultured cells have elaborated in- oxidize—a corrosive process similar to to unleash their weapons against the fl ammation’s role in atherosclerosis. Sci- the one that rusts pipes. Cells in the body’s enemies. These warriors set about entists have long known that although blood vessel wall react to these changes clearing perceived invaders from vessel we need cholesterol, excessive amounts by calling for reinforcements from the walls. Scavenger receptor molecules cap- clog arteries. But until recently, no one body’s defense system. Adhesion mole- ture modifi ed LDL particles and help knew how this happened. Low-density cules on the endothelial cells that line macrophages “eat” them—until they’re lipoprotein (LDL)—also known as bad vessels latch like Velcro onto mono- so full of fatty droplets that they look cholesterol—is composed of fatty mol- cytes, infl ammatory cells that normally foamy under a microscope, giving them ecules (lipids) and protein. Its job: trans- circulate in the blood, attaching them to their “foam cell” nickname. port cholesterol (another lipid) from its artery walls. Endothelial and smooth T lymphocytes (a type of white blood source in the liver and intestines to other muscle cells inside vessels then secrete cell) also attach themselves to artery organs. The trouble begins when LDLs chemokines—chemicals that attract walls, releasing cytokines that intensify from the blood collect in the intima, the monocytes. Much as hounds track the infl ammation. The fi rst visible athero- interior wall of an artery. At low concen- scent of their prey, more monocytes fol- sclerotic lesion, a yellow “fatty streak,” trations in the blood, LDLs can pass in low the chemical trail into the intima. is a mix of foamy macrophages and T and out of the intima; in excess, LDLs Stimulated by chemokines and other lymphocytes. These lesions are a precur-

become stuck in the cell matrix. substances, the monocytes multiply and sor of the complex plaques that later dis- KASNOTKEITH

14 ORAL AND WHOLE BODY HEALTH PLAQUE RUPTURE sel surface. Once there, they form a fi - channel. This also explains why bypass Foam cells secrete inflammatory brous covering over the original plaque. surgery or therapies such as angioplasty substances that weaken the cap, 5 digesting matrix molecules and damaging Underneath this cap, some foam cells or stents that widen obstructed arteries smooth muscle cells that normally repair it. die, releasing their load of lipids. can ease angina—yet often fail to pre- Foam cells may produce tissue factor, a potent Atherosclerotic plaques usually ex- vent a heart attack. Even when blocked clot-promoter. If the plaque ruptures, a clot forms. A large clot can halt blood fl ow to the pand outward, not inward to block an arteries are treated, they often clog up heart, causing a heart attack—the death of artery’s blood-carrying channel. When again fairly quickly—it seems that the cardiac tissue. they do push in, blood fl ow to tissues is treatment itself elicits a robust infl am- restricted, especially when arteries matory response. Thrombus would normally expand. During exer- Matrix-degrading enzyme cise or stress, blood fl ow through a com- BEYOND BAD CHOLESTEROL Cytokines that disrupt smooth promised heart artery fails to meet the several other atherosclerosis risk fac- muscle cells Fibrous increased demand. This causes angina tors exhibit intriguing infl ammatory fea- cap pectoris, a feeling of tightness or pres- tures: diabetes, for instance, elevates sure usually under the breastbone. Nar- blood sugar levels, which can enhance rowing in other arteries can cause pain- LDL’s infl ammatory properties. Smoking ful cramping of the calves or buttocks causes oxidants to form, possibly hasten- during exertion. ing LDL oxidation—and fostering arterial infl ammation even in people with CAUSING CRISES average LDL levels. Obesity contributes only about 15 percent of heart at- to diabetes and vascular infl ammation. tacks are caused by large plaques that Conversely, high-density lipoprotein block arteries. Autopsies have shown (HDL) seems benefi cial; as levels of this that most attacks occur after a plaque’s “good cholesterol” decline, the likeli- fi brous cap ruptures, prompting a blood hood of suffering a heart attack goes up. clot to develop over the break. Infl amma- HDL may achieve its benefi cial effects tion makes the cap vulnerable. My labo- in part by reducing infl ammation, be- ratory found that when stimulated by cause along with cholesterol, HDL infl ammatory chemicals, macrophages transports antioxidant enzymes that secrete enzymes that degrade a cap’s break down oxidized lipids. strong collagen fi bers and stop smooth Given infl ammation’s usual respon- CUTAWAY VIEW OF ARTERY AFFLICTED BY ATHEROSCLEROSIS muscle cells from extruding fresh colla- sibility in the body—blocking and elim- gen to repair and maintain it. inating infectious agents—biologists Clots form when blood seeps have wondered whether arterial infec- through a fi ssure in a cap and coagu- tions might contribute to infl ammation fi gure arteries. Many Americans begin lates. Although our bodies produce sub- in the arteries. Recent studies suggest plaque buildup as early as their teens. stances that can prevent or degrade that atherosclerosis can develop in the blood clots, infl amed plaques release absence of infection. However, circum- FUELING PLAQUE GROWTH chemicals that impede this clot-busting stantial evidence suggests that certain when an inflammatory response in, machinery. If a clot does clear naturally microorganisms, such as herpes viruses say, a scraped knee successfully blocks or with medication, the healing process or the bacterium Chlamydia pneumoni- infection, macrophages release molecules may kick in once again, restoring the ae could induce or aggravate atheroscle- that promote healing. A “healing” pro- cap but also enlarging the plaque by rosis. C. pneumoniae appears in many cess is also part of the chronic, low-level forming scar tissue. Considerable evi- atherosclerotic plaques—and can trig- infl ammation that operates in athero- dence suggests that plaques grow in fi ts ger infl ammatory responses. sclerosis. But instead of restoring artery and starts as infl ammation comes and Infections might also act from a dis- walls, the process perversely remodels goes and as clots emerge and dissolve. tance, in an “echo effect.” When the them, generating a bigger plaque. This new picture of atherosclerosis body fi ghts infections, infl ammatory me- Recently, biologists have learned explains why many heart attacks seem diators can escape into the blood and that both macrophages and cells within to come from out of the blue. Plaques travel to distant sites. Because the mouth an inflamed vessel wall secrete sub- that rupture may not protrude very far can be a source of chronic infection, re- stances that create a kind of scar tissue. into a blood channel—and may not searchers are exploring the potential im- Smooth muscle cells migrate to the ves- cause angina or appear on images of the pact of gum disease. Infection from peri-

ORAL AND WHOLE BODY HEALTH 15 EVALUATING THE DATA: Could Periodontal Disease Increase the Risk for Cardiovascular Disease? BY KAUMUDI JOSHIPURA

HEART DISEASE AND PERIODONTAL DISEASE have several loss-induced dietary things in common. One of them is infl ammation, which both narrows changes (e.g., shunning coronary arteries and breaks down the tissues that hold teeth in fruits, vegetables and place. Could periodontal disease increase your risk for developing dietary fiber) that heart disease, perhaps due to bacterial pathogens or infl ammatory increase heart risks. chemicals carried by the blood from the mouth to the heart? If so, The link between the could you reduce your heart disease risk by preventing or treating two diseases may periodontal disease? derive from factors that Research suggests that there may be links between the two influence both. For conditions. Animal studies in particular offer provocative evidence example, cigarette that certain biologic pathways might allow one disease to infl uence smoking is a major risk the other. Periodontal bacteria are found in the plaque deposits that factor for heart disease narrow coronary arteries; inducing periodontal disease in rabbits and for periodontal causes plaque accumulations in their coronary arteries. disease, and a genetic Other evidence comes from observational human studies. The susceptibility to largest such study, the National Health and Nutrition Examination inflammation might Survey (NHANES), involved 10,000 Americans between the ages of 18 cause someone to develop both diseases (see chart). and 74. It found that people with periodontal disease were much more Although periodontal disease seems to be associated with heart likely to be diagnosed with heart disease than those without disease, more studies are needed before we can say with certainty periodontal disease. that one disease actually causes the other. Meanwhile, everyone Not all studies have yielded similar results. For example, my colleagues should be conscientious about treating gum disease, but it is not yet and I examined a group of health care professionals and failed to fi nd an clear that doing so will protect you from heart disease. • overall association. Interestingly, our study and several others did detect a signifi cant association between tooth loss (often a result of severe KAUMUDI JOSHIPURA is director of the Division of Dental Public periodontal disease) and heart disease. So the “connection” between Health at the University of Puerto Rico and also teaches at Har- periodontal disease and heart disease may be indirect, involving tooth- vard University. odontal disease pumps a continuous fl ow measuring the heat of blood vessels (be- tion’s ability to ward off infection out- of bacteria and cytokines into the blood- cause heat normally accompanies in- weighed its drawbacks. Today, as we live stream. Bacteria also produce toxins that fl ammation); and altering existing im- longer, exercise less, eat too much, and can trigger infl ammatory responses. Cy- aging technologies, such as MRI or CT smoke, many of us suffer from infl am- tokines and bacterial toxins can stimu- scans, to improve their ability to peer mation’s dark side—including its ability late the white cells in atherosclerotic inside vessel walls. Scientists are trying to contribute to atherosclerosis and other plaques, prompting plaque growth or to develop molecular imaging tech- chronic disorders. Scientists continue to rupture. Despite these links between in- niques to “visualize” biological process- pursue a deeper understanding of infection and atherosclerosis, current clin- es such as infl ammation, looking be- fl ammation’s role in atherosclerosis, and ical evidence does not support the use of yond the anatomical features of blood to decipher the intricate interactions that antibiotics to prevent recurrent compli- vessels. Geneticists are hunting for genes ignite and drive the infl ammatory pro- cations following a heart attack. that predispose some people to chronic cesses in the arteries. These insights inflammation and atherosclerosis so should enable us to make further inroads TOWARD EARLY DETECTION they can seek more aggressive monitor- against a disease with growing world- noninvasive methods for identifying ing and treatment. wide impact that causes extensive dis- vulnerable plaques might help pinpoint For most of human history, infl amma- ability and takes far too many lives. • at-risk individuals who lack warning signs of potential heart attack or stroke. PETER LIBBY, who earned his M.D. from the University of California, San Diego, is chief of Ideas include testing for elevated levels cardiovascular medicine at Brigham and Women’s Hospital, Mallinkrodt Professor of of C-reactive protein, a substance in the Medicine at Harvard Medical School, and co-editor of Heart Disease, a classic cardiology blood that signifi es acute infl ammation; textbook (W.B. Saunders, 2001).

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Two decades of biomedical and dental detective work have linked obesity, diabetes and periodontal disease BY ROBERT J. GENCO

IN THE EARLY 1960S,

researchers from the National Institutes of Health (NIH) journeyed to the parched desert

lands of the Gila River Indian Community in central Arizona to study the health of the Pima

Indians. In the course of routine medical exams, they made a startling discovery: the Pima people proved to be fatter than any other group of people on Earth except for the Paciﬁ c Nauru islanders. Nearly half of those over the age of 35 had type 2, or adult-onset diabetes, eight times the national average. In order to survive in the desert, it seems that their thrifty genes may have evolved to carefully conserve fat through times of drought and famine. After World War II, when the tribe changed their traditional diet to an American one, their fat intake rose from about 15 percent to a whopping 40 percent of calories—and their genetic evolution backﬁ red. >>

18 ORAL AND WHOLE BODY HEALTH 2003 EDWARD S. CURTIS’S “THE NORTH AMERICAN INDIAN,” HISTORY INTERRUPTED: When Arizona’s Pima Indians adopted a fatty American diet, their thrifty desert genes backﬁ red. Almost half of adults over 35 developed type 2 diabetes—and also contracted severe gum disease at twice the normal incidence. NORTHWESTERN UNIVERSITY LIBRARY, LIBRARY, UNIVERSITY NORTHWESTERN

ORAL AND WHOLE BODY HEALTH 19 2 diabetes research from our studies both on the Pimas and on the population of Erie County in New York State, along with research from around the globe—Japan, Brazil, Chile, Finland, Slovenia and other nations. In nearly all of the studies, it was found that diabetics suffered from more severe periodontal disease that often appeared years or even decades before it did in the general population—and once a diabetic patient had periodontal disease, their sugar control worsened and they suffered further complications, including nerve damage and kidney disease. We combined the results of these studies and formulated a hypothesis that we and others could begin testing. This informational mosaic has given us a reasonable understanding of how obesity and diabetes are linked to infections such as periodontal disease. It also revealed a potential explanation of why IN 1983, H. was healthy. Three years later, she suffered from out-of-control type 2 diabetes and diabetes is a signifi cant risk factor for severe gum disease, with abscesses ulcerating her gums and loose, shifted teeth. oral infection and infl ammation—and why it often leads to periodontal disease As the NIH studies continued over clinics.) Diabetics fared the worst, with at a much earlier age than normal. Pa- the following decades, the researchers twice the normal incidence of gum dis- tients with type 2 diabetes are twice as delved into other health issues including ease—and much more severe oral infec- prone to periodontal disease as nondia- kidney problems and heart disease. They tion than nondiabetic patients. betics, all other factors being equal. also suspected that there might be a In 1983 we examined H, a 32 year- An important piece of this puzzle higher than normal incidence of gum old woman who was extremely over- emerged 10 years ago during the Erie disease. In 1981 the Dental Institute weight, but otherwise quite healthy. In County study, conducted in metropoli- asked me to assess the periodontal health her follow-up exam two years later we tan Buffalo, N.Y. We discovered that of the Pimas. At that time, I was in the were shocked to discover that her health obesity and periodontal disease were re- midst of clinical studies at the University had deteriorated precipitously: she suf- lated. We collected information on both at Buffalo Periodontal Disease Research fered from uncontrolled type 2 diabetes the general and oral health of 1,250 Center examining the body’s response to and had developed advanced gum dis- adults. After statistical adjustment for bacterial infection in the mouth—so I ease. Abscesses ulcerated her gums, and other periodontal risk factors including welcomed the opportunity to examine a her teeth were loose and had shifted out age, gender, socioeconomic status, smok- very different population. I spent three of position, leaving large gaps between ing, diabetes and dental plaque, the rela- days at the Gila River reservation con- her front teeth. Under normal circum- tionship remained strong: obesity ap- ducting several dozen clinical exams. stances, the progression of this condi- pears to be an independent risk for peri- Never before had I seen such severe, un- tion would have taken 15 to 20 years to odontal disease. Investigations by Nabil treated periodontal disease. reach that level of infection. Bissada and his colleagues at Case West- In 1982 we established our fi rst den- Her case sparked a question that we ern University in Cleveland and by Toshi- tal clinic in a trailer on the reservation, couldn’t answer. Could there possibly yuki Saito of Kyushu University in Fu- run by Dr. Marc Shlossman, and initi- be a connection between obesity, diabe- kuoka, Japan, mirrored our fi ndings. ated a study to track the Pimas’ oral tes and oral infection? It took 21 years Another important clue surfaced in health. Since then, we have examined of medical and dental detective work, the mid-1990s that helped to explain the 3,600 people, giving checkups every piecing together data from many sourc- role obesity plays in infection. We learned two years. (Regular dental care was es, to understand this triangular rela- that fat tissue is not only a repository for provided by the reservation’s dental tionship. We gathered the results of type fat cells but is increasingly viewed as a

20 ORAL AND WHOLE BODY HEALTH metabolically active endocrine organ. Scientists at the Dana Farber Institute in Boston found that fat tissue in the “obese mouse,” a species bred to be fat the DIABETIC in and diabetic, produced a protein called tumor necrosis factor (TNF). Fat cells produce and secrete several proteins— the DENTAL CHAIR like TNF—that act in a hormonelike BY BRIAN L. MEALEY fashion, regulating the intake and ex- penditure of energy. These proteins, CURRENTLY, 20.8 MILLION Americans New research suggests that periodontal called proinfl ammatory cytokines, are have diabetes, according to the American disease can also affect a diabetic patient’s powerful substances that mediate and Diabetes Association. About one third of ability to control his or her blood sugar regulate the body’s infl ammatory pro- those with the disease are unaware that levels, and can contribute to diabetic cess. The obese mice carried toxic con- they have it, and of those who have been complications such as heart and kidney centrations of cytokines—immune re- diagnosed, only a little more than half disease. Infl ammatory diseases of many sponse molecules—in their blood. have it under control. kinds—including those that affect the Human fat cells pump out tumor Diabetes is a disease where the body mouth—can increase insulin resistance. In necrosis factor alpha (TNF␣), which does not produce or properly use insulin, people with type 2, increased resistance kills tumors and triggers production of a hormone made in the pancreas. Insulin caused by gum disease can make blood other proinfl ammatory cytokines. But “unlocks” cells, allowing sugars derived sugar harder to control. However, it also has a dark side: it can cause in- from carbohydrates and other food to periodontal treatment reduces the level of sulin resistance and high blood sugar enter. Sugar is the basic fuel for cells, inflammation in the tissues around the levels (common diabetic symptoms) providing energy for daily life. teeth, thereby improving blood sugar and break down bone as well as acti- There are two types of diabetes: In control in many diabetics. vate endothelial cells that line blood type 1 diabetes, the pancreas no longer Thus, care of patients with diabetes vessels, which can lead to heart disease makes insulin. Sugar cannot enter the poses a particular challenge to dental professionals. Diabetes often worsens and stroke. Interleukin-6 (IL-6), an im- cells and builds up in the bloodstream. In oral health, particularly that of the gum mune protein, is another product of hu- type 2, the pancreas does not produce tissues and bone, which, in turn, man fat cells. Like TNF␣, it dissolves enough insulin, or the hormone does not function properly at the cellular level, a deteriorates blood sugar control. The bones and causes infl ammation—and condition called insulin resistance. In this patient and dental professional must work prompts the liver to secrete C-reactive case, too, sugar is locked out of the cells, together to stop this vicious cycle before protein, whose presence signals high so it builds up in the blood. In both types of it begins by being attentive to daily oral risk for heart attack. These are just two diabetes, cells may be starved for energy. hygiene: brushing and flossing, getting of the dozen or more cytokines pro- Over time, high blood sugar can damage regular oral health checkups, and properly duced by human fat tissue. vision, even causing blindness. It can also treating periodontal disease early on. • This relentless release of cytokines trigger kidney failure, nerve damage and into the bloodstream provides a possi- heart disease, and in people with diabetes BRIAN L. MEALEY is director of the ble explanation of how obesity intensi- wounds heal poorly. Periodontics Postgraduate Program fi es infections, including periodontal Diabetes also increases the risk for at the University of Texas Health disease. The diverse colonies of bacte- periodontal disease, an infectious Science Center at San Antonio ria that fl ourish in the mouth spark the process that inflames gum tissues, infl ammatory response that is so de- causing them to bleed; it also destroys structive to gum tissue. The infection the bone and soft tissues that support intensifi es as gum tissue produces its teeth. While periodontal disease occurs in own cytokines. At the same time, fat nondiabetic people, too, gum disease tissue churns out cytokines that travel is more common and more severe throughout the body. This cytokine in diabetics. Dentists monitor their overload heightens the overall infl am- diabetic patients closely for these matory response, causing great tissue oral conditions and may refer damage. Infected gums become chron- patients to a periodontist (gum ically infl amed, the bone around the specialist) to diagnose and teeth dissolves, and the teeth loosen treat periodontal disease. and eventually fall out.

ORAL AND WHOLE BODY HEALTH 21 One of these, adiponectin, regulates insulin response and inhibits infl amma- OBESITY tion inside blood vessels. We need greater understanding of this and other regu- latory chemicals manufactured both in fat tissue and in other parts of the body that could mitigate the chronic infl ammation and insulin resistance sparked by cytokines. We believe that the triangular inter- DIABETES PERIODONTAL action among obesity, type 2 diabetes DISEASE and periodontal disease is mediated by the cytokines produced by both fat tissue throughout the body and by infected gums. More research is needed to evaluate other infl uences, like the impact of A TRIANGULAR RELATIONSHIP: Obesity can intensify infections, such as periodontal disease; cytokines diet and the importance of genetics on produced by fat cells are known to trigger insulin resistance, which can lead to type 2 diabetes. infl ammation and susceptibility to the Diabetes, in turn, is known to increase the risk for periodontal disease. New research suggests that aforementioned conditions. A more periodontal disease can affect a diabetic patient’s ability to control blood sugar levels. complete understanding should help physicians and dental professionals em- To test this hypothesis, we exam- acerbate more dangerous, tenacious oral ploy treatments or preventive measures ined blood test results from the Erie infections, their presence also helps ex- to reduce the onset of diabetes and its Country study subjects. All those who plain why obesity is such a serious risk potentially life-threatening complica- suffered from periodontal disease had factor for diabetes and cardiovascular tions such as heart and kidney disease. elevated levels of soluable receptors for disease: TNF␣ and other cytokines are Addressing obesity in the manage- TNF␣ in their blood, but levels were known to trigger insulin resistance. This ment of diabetes or periodontal disease highest in seriously overweight patients. can ultimately lead to full-blown type 2 is clearly important—as is tandem treat- Over the last decade, a large body of diabetes, which spikes blood sugar lev- ment in patients who have both condi- research from laboratories and clinics els and elevates fats in the blood. This tions. Studies show that periodontal in many countries has highlighted the condition contributes to complications treatment leads to improved blood sug- role of TNF␣ and other cytokines in of diabetes, including heart, kidney and ar control. Because periodontal disease damaging tissue—and in predisposing retinal disease, along with susceptibility in diabetics leads to a higher rate of an individual to diabetes. TNF␣ trig- to infection, and other complications. complications, such as cardiovascular gers certain cells to produce tissue- or It seems that infl ammation creates a disease and diabetic kidney disease, we bone-dissolving enzymes. Other cyto- triangular interaction between obesity, strongly suggest aggressive treatment kines induce infl ammation by increas- diabetes and periodontal disease: Obe- and prevention of periodontal disease in ing the amount of blood leaked from sity is a risk factor for both type 2 dia- patients with diabetes as part of the vessels and by stimulating the release of betes and periodontal infection, and overall management of not only their toxic substances (such as reactive oxy- diabetes also heightens risk for gum dis- oral health, but their diabetic state. gen species) from infl ammatory cells in ease. Infl ammation links all three, trig- Current treatments for periodontal the region, damaging tissue. Another gered by the proinfl ammatory cytokines disease are effective. If maintained, re- kind summons phagocytic cells to the manufactured by fat tissue and pro- currence can be, by and large, prevent- site of the infection that then envelop duced locally by gum infection. ed—and of all the ways to mitigate dia- and “devour” perceived invaders. At But fat tissue is complex, and further betes risk in the fi rst place, good oral later stages of infl ammation, antibodies studies will likely illuminate the role of hygiene is much easier to maintain than (proteins that target and destroy spe- other substances secreted by these cells. strict diet or exercise regimens. • cific bacteria and viruses) form. Al- though they are usually protective, they ROBERT J. GENCO has studied periodontology and its relation to wider health conditions can also turn against cells, as in autoim- for over 30 years. He attended the University at Buffalo School of Dentistry and earned mune disorders. a Ph.D. in immunology from the University of Pennsylvania. He is currently a distin- But proinflammatory cytokines guished professor at the University at Buffalo and vice provost and director of the Uni- manufactured by fat cells don’t only ex- versity’s Offi ce of Science, Technology Transfer and Economic Outreach.

22 ORAL AND WHOLE BODY HEALTH INTERVIEW

SCIENTIFIC AMERICAN: Most of the buzz about the oral-systemic link has been among research- >>ers. What should consumers or patients know about this topic at this stage?

JEFFCOAT: The consumer needs to know three things: First, oral disease is a disease like any other—and in and of itself is deserving of treatment. Number two, everything in the body is connected. Having a chronic infection is a serious problem that you should not ignore. It can indeed make you systemically sick. Three, patients should not think that treating periodontal disease will guarantee them lifetime health, but it is one step they can take to be healthier overall. Consumers have to understand that all the data is not yet in. We cannot deﬁ nitively say if

BUZZ TALK with eventually all curriculums will address this MARJORIE K. JEFFCOAT issue is some way or another. So the patients, in your opinion, that would THE DEAN OF THE UNIVERSITY OF PENNSYLVANIA SCHOOL OF DENTAL MEDICINE benefi t most from this data would be expectant mothers? Right now, yes—pregnant wom- – A PIONEERING DENTAL RESEARCHER HERSELF – ADDRESSES THE FACTS AND en and diabetics. Although we have smaller FICTIONS ABOUT ORAL HEALTH’S RELATIONSHIP TO THE REST OF THE BODY studies on diabetics than we do on expectant mothers, we do know that any untreated infection in a diabetic can affect glucose control. So treatment will affect one’s susceptibility to the best information possible. We’re already treating oral infection and oral infl ammation is other diseases—heart disease, stroke, diabe- starting to see changes in reimbursement for a reasonable thing to do until all the studies tes, etc. We do know that it is one risk factor for some of these things. Insurance companies have fi nished. preterm birth. But people act on these correla- are taking notice. Cigna and others now cover tions because they want to feel they have con- periodontal treatment during pregnancy. It’s What about the elderly and some of the data trol of their health. Professionals do, too. They a business decision; they feel it will help save linking oral disease with respiratory problems want to provide every possible treatment money in the long run. in patients who are in intensive care units or avenue for the patient. hospitals? Getting care to these populations Do you hear a lot of misinformation? I do. Some is still the biggest challenge. Often in a nursing As a prominent researcher you must have a people want information because they’ve home there are extra costs for dental care. lot of people asking you about this topic? heard a little bit about this topic—and some Family members who monitor their elders’ All the time. I don’t know how many phone will believe anything they read on the Internet. care should be made aware of the importance calls I took today—from patients, from doc- Some media outlets do not provide the whole of good oral care. For many, it will help to tors, from drug companies, from the media. story or all of its complexities. reduce the risk of getting pneumonia. They want to know the real scoop: what we really know at this time. How is this topic – the mouth’s relationship Are consumers becoming more skeptical of to the rest of the body – affecting dental health messages they see or read about in the Has this issue spawned more collaboration education? I think more [dental] schools media? We have two highly distinct popula- between the fi elds of dentistry and medicine? are integrating total health into their cur- tions: the “worried well” —those who are Yes. And I have found that collaboration riculum. Dental education can be a contro- always looking for ways to improve their health, between the two fi elds comes quite easily. It is versial topic, and I think some schools will and those who are skeptical of everything they very important that both disciplines take own- probably not adopt this whole-body see or read—this population is very hard to deal

JEFF MELLIN JEFF ership of these issues so that patients can get approach for some time. But I do feel that with in terms of getting messages across. •

ORAL AND WHOLE BODY HEALTH 23 WHAT EVERY WOMAN NEEDS TO KNOW

Growing evidence suggests that poor oral hygiene during pregnancy can adversely affect the health of newborns

BY STEVEN OFFENBACHER

24 ORAL AND WHOLE BODY HEALTH JOHN SOARESJOHN

ORAL AND WHOLE BODY HEALTH 25 In 1981 Judith F. was referred to me for periodontal care. She was very upset, having just discovered why her front teeth were shifting: she had been diagnosed with severe gum disease. Her dentist had explained to her that periodontal disease is sometimes a “silent” infection that may be pain- less and without symptoms until very late in the disease process. She had also recently miscarried after having a very difﬁ cult time conceiving. She recounted how her gums had ﬂ ared up after she became pregnant, which prompted her to go to the dentist.

As crazy as it might have sounded at the time, she was convinced that the simmering infection in her gums was somehow related to her pregnancy complications.

I suspected that her intuition may erated by oral bacteria. The result: at low mothers with untreated periodontal have been correct—but told her that doses, about 15 percent miscarried and disease who were also being tracked. we really did not know scientifi cally 30 percent of the surviving offspring These fi ndings provided the rationale whether periodontal disease could were abnormally small. When given high for the National Institute of Dental and cause pregnancy problems. However, I doses, 100 percent of the mothers mis- Craniofacial Research to support two did tell her that both her obstetrician carried. We later induced gum disease in multicentered, randomized clinical tri- and I were in agreement that any infec- pregnant hamsters. Overall, the result- als. One of these, the Obstetrics and tion during pregnancy is a potential ing babies weighed 18 percent less than Periodontal Therapy (OPT) Study at the cause for concern. normal. We also found elevated levels of University of Minnesota, led by Bryan Just before Judith came to me, my prostaglandin-E2 (PGE2) in the ham- Michalowicz, tracked the pregnancies of laboratory had begun what would be- sters’ placentas—similar to the human more than 800 pregnant women follow- come a 25-year scientifi c inquiry explor- physiological response to preterm deliv- ing gum disease treatment. The second ing the potential role of periodontal dis- ery and low-weight births. This chemical trial, run by our group at the University ease in pregnancy complications. This is produced as a response to infection; it of North Carolina at Chapel Hill, is en- research has included a multitude of lab- mediates infl ammation in both the pla- titled MOTOR (Maternal Oral Therapy oratory experiments, animal studies, centa and the fetus—and also can induce to Reduce Obstetric Risk) and will ulti- and randomized human clinical trials. labor. Around that time, obstetrics re- mately follow 1,800 women. The fi nd- Today, growing evidence supports search had linked PGE2 to premature ings from these large, randomized and the concept that gum infection may in- and low-weight SGA (small for gesta- controlled trials should ultimately prove deed play a role in pregnancy complica- tional age) births. whether or not gum disease can cause tions, possibly inducing miscarriage and In a landmark paper published in pregnancy complications. Earlier esti- premature birth as well as inhibiting the 2002, Nestor Lopez in Chile reported mates from pilot studies suggest that up growth and development of the unborn the results of his study of 400 pregnant to 18 percent of all preterm births may child. Clearly, there are many causes for women with periodontal disease: half be attributable to gum disease. problems that can arise during pregnan- had scaling and root planing periodon- Unfortunately, pregnancy complica- cy; but it now appears that with addi- tal treatment during pregnancy; the tions are far too common, with about tional research, oral infection might be other half were treated after their ba- one in 10 babies being born too early in added to the list of possible risk factors. bies were born. Just 1.8 percent of the the U.S.—nearly double the rate of oth- From a public health perspective, what is treated women gave birth early, com- er industrialized countries. Improve- most important is that periodontal dis- pared with 10.1 percent in the delayed ments in prenatal care and neonatal in- ease is both preventable and treatable. treatment group. tensive care medicine have improved As a clinician who is trying to help pa- Marjorie Jeffcoat at the University the survival rates of these babies, but tients, I know that it is critical to identify of Alabama also saw similar benefi ts in the rate of premature delivery has new causes of disease —and to fi nd ways a study of 123 mothers with periodon- steadily climbed since the 1950s. The to prevent them. tal disease. After treatment, their rate failure to prevent preterm deliveries is In one of our earliest experiments at of preterm delivery (earlier than 37 due in part to the fact that we do not Emory University in 1981, we gave ham- weeks) was 4.1 percent, compared with understand all of the risk factors, which sters intravenous doses of the toxins gen- 13.7 percent in another group of 733 include race, smoking, alcohol and drug

26 ORAL AND WHOLE BODY HEALTH use, low income, and poor education, among others. More than one quarter of all complicated pregnancies occur for no known reason. Periodontal disease may contribute to the common problems of pregnancy by presenting an infectious, infl ammatory challenge to the fetus: when bacteria or their products slip through the placenta and reach the baby, they trigger an immune and infl ammatory response—which stresses the fetus. Since pregnancy is such a critical time for human development, this could potentially have debilitating effects on an infant’s health, creating problems that could last a lifetime. Infections are thought to account for between 30 and 50 percent of all premature deliveries. Maternal infections during pregnancy, especially when they spark a fever, have long been known to cause miscarriage, premature birth and babies that are born abnormally small for their gestational age. This is attributed to the fact that bacteria or viruses in the bloodstream trigger the production of infection-fighting chemicals that threaten the “mother- child unit” and impair fetal growth and development. The chemicals and hor- BREAKING THOUGH: When oral bacteria in the mother’s blood mones that mediate the infl ammatory breaches the placenta and reaches response can also dilate the cervix and the fetus, it triggers an immune and trigger uterine contractions, leading to infl ammatory response, stressing the unborn child. Infections may preterm labor. account for up to 50 percent of But it’s not just infection and bacte- premature births. rial products that pose a threat—infl ammation does, too. Inside the placenta, sclerotic damage to heart arteries: the infl ammation in the mother. At fi rst, the membranes normally remain intact, vessels shrink and do not function prop- thought of a linkage between a distant holding the fetus suspended in amniotic erly, compromising the fl ow of blood oral infection and pregnancy complica- fluid until just hours before delivery and nutrients to the fetus, and impair- tions was considered “preposterous,” but when the water “breaks” to start labor. ing growth. Abnormal blood fl ow in the accumulating scientifi c evidence is unveil- However, infl ammation can make these placenta can also result in an imbalance ing its biological plausibility. membranes more fragile; their early rup- in the mother’s blood pressure, causing The increase in hormonal activity ture often initiates preterm labor. preeclampsia, a mild kidney malfunc- during pregnancy can cause gums to When the placenta becomes in- tion that can lead to life-threatening bleed more easily and may promote bac- fl amed, structural changes occur that convulsions. This condition can only be terial overgrowth. This bleeding is not can endanger the fetus and shorten ges- cured by delivering the baby. normal and signals ulceration between tation. Studies in mice have shown that It now seems that oral infection may the tooth and gum. In full-blown peri- placental infl ammation causes edema be one of a number of factors that can odontal disease, the infected area around and kills off tissue. It also can cause produce these pregnancy complications. all 32 teeth becomes a huge ulcerated changes to the intertwined fetal/mater- Any oral disease, from mild gingivitis to area—about the size of the palm of your

MATT COLLINS MATT nal blood vessels that resemble athero- severe periodontitis, causes infection and hand. These infected areas no longer

ORAL AND WHOLE BODY HEALTH 27 HAVE INFECTION, WILL TRAVEL: Bacteria from dental plaque can enter the bloodstream through small ulcers in the gum and can then travel throughout the body. The increase in hormonal activity during pregnancy can cause gums to bleed more easily and promote bacterial overgrowth. have the natural skin barrier between the caused at least 10,000 miscarriages and to the organisms that normally live in bacteria in dental plaque and the moth- stillbirths, and more than 20,000 babies our mouths with the fi rst human fi nd- er’s bloodstream. Bacteria enter the blood were born with birth defects. Rubella ings being reported in 2001. Studies and travel to the placenta, which normal- was fi rst identifi ed as a cause of birth on mice reported in 2002 and later ly blocks penetration to the fetus. defects several decades ago when re- studies in rabbits proved that oral bac- For many years, doctors believed searchers discovered the virus fl oating in teria could cross the placenta and that the environment inside the uterus amniotic fl uid and that fetuses carried reach the fetus. Some recent work by was relatively isolated and protected, antibodies to it—proving that the virus Dr. Yiping W. Han at Case Western with few organisms passing to the pla- had indeed entered the placenta to infect Reserve University demonstrated in centa or the fetus. But this infection bar- the growing baby inside. 2006 that maternal oral bacteria have rier can be breached by a few organisms, We conducted studies at U.N.C., been found in human amniotic fl uid including the rubella virus. A rubella Chapel Hill to learn whether unborn providing proof of transmission. This

(German measles) outbreak in 1964-65 babies would show antibody responses strongly suggested fetal infection in COLLINS MATT

28 ORAL AND WHOLE BODY HEALTH this study—but proving transmission cert to trigger labor contractions, rup- not involve infection. In fact, there to the fetus of a large population of ture the amniotic sac, and impair blood may be underlying conditions, expo- oral bacteria will be diffi cult, as babies fl ow in the placenta. So the onset of la- sures or genetic traits that predispose are not born in a sterile environment. bor is actually a naturally occurring in- mothers to abnormal pregnancy out- About eight years ago, we found that flammatory response—the mother’s comes. Some of these risk factors may in utero exposure to the mother’s oral body uses infl ammation to “reject” the also predispose mothers to periodon- bacteria is a fairly common event. Re- baby—but labor can be triggered early tal disease, such as susceptibility to search conducted by Phoebus Madianos by the abnormal presence of these in- severe infl ammation. Nevertheless, the in our lab, published in 2001, showed fl ammatory chemicals. progression of periodontal disease that contact with enough periodontal This mechanism—a silent infection during pregnancy can result in fetal bacteria to induce a fetal immune re- leading to fetal inflammation—may exposure—and trigger a fetal infl am- sponse resulted in a two- to three-fold also provide a possible explanation for matory response—which may increase increase in risk for preterm delivery. the Barker hypothesis, developed in the the risk for pregnancy complications. It appears that if the magnitude of early 1900s by David Barker and his The potential importance of these exposure is low, either because of a mild colleagues in Southampton, England. linkages on health care costs and fam- infection or effective protection from They followed the health of low birth ily well-being have not been lost on the mother’s antibodies, then the fetus weight babies and discovered that pre- health insurance companies; some is shielded from these bacteria. But if maturity harms health later in life. It now provide coverage for periodontal oral bacteria cross the placental barrier seems that defi cits in a baby’s fetal and care during pregnancy. early in gestation, the probability that infant growth “programs in” risk fac- Although we do not yet have they will cause problems is much higher tors for adult diseases and a lifetime of enough evidence to say unequivocally than if the security breach occurs late- various disabilities and impairments, that periodontal infections can cause term. For example, about 28 percent of including diabetes, high blood pressure adverse pregnancy outcomes, the data all unborn babies are exposed to the and cardiovascular disease. Preterm ba- supporting this idea are mounting Campylobacter rectus (or C. rectus) bies are particularly prone to long-term quickly. According to our research, bacteria—but evidence of exposure to disability, because their respiratory and when oral bacteria breaches the the bacteria is found in 52 percent of neurological systems are especially im- “armed guard” of the placenta and infants born before 32 weeks gestation pacted by premature birth—and the reaches the fetus, that baby’s risk of (eight weeks early). earlier the delivery, the greater the risk being born early rises to 2.8 times that When an unborn child’s immune of long-term conditions such lung dis- of an unexposed baby. Perhaps in the system kicks in to fi ght off those bacte- ease, asthma, mental retardation, cere- future a vaccine will be developed to ria, the risk for preterm delivery in- bral palsy and impaired cognitive func- combat these organisms. But in the creases between four- and seven-fold, tion. Preterm babies are also at high risk meantime, the good news is that we after adjusting for traditional obstetric for neonatal death. know how to prevent and manage risk factors. Elevated levels of the chem- Studies in our laboratory demon- periodontal disease—and treatment icals and hormones that regulate the im- strated in 2004 that when pregnant mice can be provided safely during preg- mune-inflammatory system create a were exposed to the C. rectus oral bac- nancy to improve a mother’s oral toxic in utero environment that stresses teria, brain damage in their offspring health, reducing infection and infl am- the fetus. It was once thought that the was similar to that seen in conditions mation that may harm her unborn mother’s body determined when labor such as cerebral palsy and mental retar- child. An increased dialogue among kicked in, but we now know that the dation, which can be caused by in utero expectant mothers, their obstetricians baby also contributes to the timing of infections. But clearly, more research is and their dental professionals to diag- delivery. Stress may cause the fetus’s ad- needed, as animal models do not always nose, prevent and manage maternal renal glands to produce the hormones refl ect what happens in humans. oral infections appears to be a promis- that help precipitate its own delivery. Certainly, there are many reasons ing strategy for optimizing maternal At birth, these babies’ umbilical cord for pregnancy complications that do health during pregnancy. • blood carries higher-than-normal levels of C-reactive protein, a marker of in- STEVEN OFFENBACHER is director for Oral and Systemic Diseases and a distinguished fl ammation which refl ects liver activity professor at the Department of Periodontology, School of Dentistry at the University of in both mother and child. Other chemi- North Carolina at Chapel Hill. He researches the mechanisms of periodontitis-associ- cals, like PGE2 and TNF␣ (tumor ne- ated pregnancy complications, risk factors for periodontitus, and bone regeneration. crosis factor alpha), mediate the body’s He holds D.D.S. Doctor of Dental Surgery and Ph.D. Biochemistry degrees from Virginia infl ammatory response and act in con- Commonwealth University.

ORAL AND WHOLE BODY HEALTH 29 When it comes to the complications of oral disease, the elderly are particularly vulnerable AS THE BODYAGES In the U.S., periodontal disease affects an estimated one in 10 adults, and one in five over the age of 65. It is the leading cause of tooth loss in adults. But emerging evidence linking periodontal disease to serious health problems, particularly in the elderly, is making diagnosis and treatment even more crucial. | BY FRANK A. SCANNAPIECO

E V E L Y N J O N E S , an 89-year-old woman, came to my offi ce last year for a rowed and thickened the vessels carrying blood to her lungs, making her heart routine dental cleaning. She lived in a local nursing home and had not been to a work harder and causing fl uid to build up in her lungs. dentist in over a year. Aside from high blood pressure, which was being treated with After treatment with calcium channel blockers, which increase blood and diuretics, she apparently had no other oxygen fl ow to the heart, her condition medical problems. A dental exam re- improved. But on her third day in the vealed red, swollen gums and several hospital she developed a fever and loose teeth. cough, which proved to be pneumonia. Mrs. Jones said she’d had a cold and She was placed on antibiotics. Two days felt tired. She also appeared short of later, lung cultures revealed that her breath, light-headed, and complained of pneumonia had been caused by the in- chest pain. I took her blood pressure, testinal bacterium Escherichia coli, which was elevated. Suspecting that she which was also found in her blood. She might have a heart problem, I urged her was switched to a different antibiotic on to see a physician immediately. Her day six, but her condition worsened. caregiver drove her from my offi ce to She experienced kidney failure on day the hospital, where she was admitted seven, and died on day nine. Believe it with a diagnosis of pulmonary hyper- or not, Mrs. Jones’s poor oral health

tension: high blood pressure had nar- may have contributed to her death.» SOARES JOHN

30 ORAL AND WHOLE BODY HEALTH HEALTHY MOUTH, HEALTHY BODY: Maintaining proper oral health is important at any age. Diseases that threaten the elderly can be exacerbated by poor oral care.

ORAL AND WHOLE BODY HEALTH 31 Over the past several decades, researchers have found that tooth and gum health may infl uence the health of the entire body. Their provocative studies have shown that gum disease may increase a person’s risk for heart attack, stroke, diabetes and—as in Mrs. Jones’s case—pneumonia. These fi ndings are especially pertinent to older people, because the likelihood of developing oral disease increases with age. Oral bacteria can contaminate a How poor oral health might affect ventilator tube overall health still is being actively inves- tigated. Some researchers theorize that when the gums bleed, bacteria from the mouth enters the bloodstream and mi- grates to other parts of the body where they trigger health problems. For example, some heart valve infections are clearly linked to recent dental work. Among people with heart valve problems, oral Bacteria can grow on bacteria that enter the blood may attach the tube and make to the valves, causing a potentially fatal their way to the lungs infl ammatory disease called endocarditis. As a preventive measure, dentists since the 1950s have routinely prescribed antibiotics to patients with valve problems before even the simplest of procedures, such as a routine cleaning or fi lling a cavity. To see if oral health might be associated with heart disease, in 1989 a team of Finnish investigators studied 100 recent heart attack patients and a similar number of closely matched people without a history of heart disease. The heart patients had substantially worse dental health, including a much higher prevalence of periodontal disease, than the control subjects. This fi nding sparked considerable interest. Numerous follow- up studies conducted since then have mostly supported a link between periodontal disease and an increased risk for heart disease. Other research has found a similar association between periodontal disease and stroke. Both heart attack and stroke are caused by atherosclerosis, the buildup of fatty deposits within the arteries that channel blood to the heart and brain. AN INFECTIOUS PATH: When patients are hooked to a ventilator, their risk of pneumonia can increase With evidence now showing that infl am- 20-fold, making it the leading killer among hospital-acquired infections. Oral bacteria in dental plaque mation helps fuel atherosclerosis, re-

can “jump” to the tube and begin to grow on it, eventually making their way down into the lungs. searchers are exploring whether cyto- COLLINS MATT

32 ORAL AND WHOLE BODY HEALTH alveolar bone that supports the also more vulnerable to periodon- ORAL DISEASE & teeth. Researchers are exploring tal destruction. Lifestyle factors how alveolar bone is lost—and such as cigarette smoking and low OSTEOPOROSIS how it may be connected to osteo- calcium intake as well as the BY JEAN WACTAWSKI-WENDE porosis and body-wide bone loss. effects of aging may also put indi- Because osteoporosis is a sys- viduals at greater risk for low bone temic disease, it may affect bones density and loss of alveolar bone. IS BONE LOSS from oral infec- sometimes makes comparison in the mouth in a number of ways. Ongoing studies will provide tion associated with osteoporo- and interpretation difﬁ cult. Bone loss around teeth may occur further insight into the interaction sis? Research on osteoporosis How does bone loss occur? independent of oral inﬂ ammation. of osteoporosis and periodontal >>and oral bone loss has shown a Bones are living, growing tissues Osteoporosis may lead to more bone loss, which will be increas- fairly consistent relationship, that undergo con- including a recent University at stant remodeling in Buffalo study that linked osteo- response to the porosis and periodontal disease, stress placed upon which caused loss of both oral them. About 10 per- bone and teeth—especially in cent of the body’s women aged 70 years and older. total bone mass is But other types of studies have “remodeled” each produced inconsistent results, or year—removed and have revealed no connection at then replaced. Cells all. This is due, in part, to study called osteoclasts design variation. For example, lay on the bone sur- several negative studies have face, breaking down included subjects in their 40s and existing bone in a 50s, when osteoporosis and low process known as resorption. Their rapid breakdown of alveolar bone ingly important in the prevention bone density prevalence is low. counterparts, osteoblasts, then after oral bacteria invades. of these two very prevalent disor- Assessment of both osteoporosis secrete collagen and minerals to Systemic factors that affect ders in older Americans. • and periodontal disease can also lay down new, replacement bone. bone remodeling may also modify differ across studies, which In osteoporosis, there is an how local tissues respond to peri- JEAN WACTAWSKI-WENDE imbalance: Either too much bone odontal infection. Specifically, is associate chair of the is resorbed or too little bone is people with overall bone loss are Department of Social and formed. This skeletal disorder known to have increased system- Preventive Medicine at decreases the quality, density wide production of cytokines the State University of (amount) and strength of bone, (specifically IL-1 and IL-6) that New York at Buffalo. which becomes abnormally may impact bone quality through- porous and spongy, and fractures out the body—including the easily. According to the National bones of the oral cavity. Osteoporosis Foundation, an esti- Periodontal infection, in turn, mated 10 million Americans have increases local cytokine produc- the disease; almost 34 million tion that boosts local osteoclast more have low bone mass. Three activity—accelerating alveolar quarters of these are women. bone loss. Periodontitis, a bacterial infec- Both osteoporosis and gum dis- tion in the mouth, is the primary ease share a number of risk fac- cause of tooth loss in adults. It tors. Individuals with a genetic destroys both gum tissue and the predisposition to bone loss are JOHN SOARES

ORAL AND WHOLE BODY HEALTH 33 kines and other infl ammatory chemicals in those people living in nursing homes oral cancers. Researchers hypothesize from diseased gums may travel through or admitted to the hospital. that bacterial toxins, enzymes and the the blood and contribute to the problem. Chronic obstructive pulmonary dis- chemicals involved in infl ammation may In Mrs. Jones’s case, excess dental ease (COPD), which limits the fl ow of cause mutations in human cells that lead plaque and periodontal disease may air into the lungs, is also associated with to uncontrolled growth and, ultimately, have set the stage for nosocomial (hospi- poor oral hygiene and periodontal dis- cancer. This work is still in its infancy, tal-acquired) pneumonia, a leading ease. COPD usually stems from long- but results so far are provocative. cause of death among older Americans. term cigarette smoking and can involve One recent study on the health status Elderly, institutionalized people like a spectrum of conditions, including em- of a cross-section of the U.S. population Mrs. Jones are at particular risk for de- physema and chronic bronchitis. People included an assessment of the oral health of more than 13,000 people. People diag- Clearly, more dedicated efforts to keep gums nosed with periodontal disease had a sig- healthy may reap health dividends far beyond nifi cantly higher risk of also having oral cancer compared with those who had improving oral health and keeping your teeth. healthy gums, even after controlling for age, a history of smoking and other fac- veloping pneumonia while hospitalized with COPD are at increased risk for tors that might have skewed the results. because, along with other factors, they periodontal disease, which, when pres- Finally, periodontal disease has also tend to have poor oral hygiene. So when ent, seems to cause lung function to de- been associated with rheumatoid arthri- they enter the hospital, their dental teriorate further. Because smoking is tis (RA), an autoimmune disease that plaque—the bacterial biofi lm that forms also a major risk factor for periodontal infl ames joints and can cause destruc- on teeth—is more likely to become colo- disease, it is diffi cult to separate the tion of cartilage, bone and ligaments. nized by the disease-causing bacteria roles that each of them plays in COPD. The two diseases share some basic char- that lurk in hospitals. The swallowing Preliminary studies by my colleagues acteristics: both the gum tissues affect- diffi culty that often accompanies old and me indicate that, while smoking is ed by periodontal disease and the joints age also increases the amount of bacte- clearly the major cause of COPD, peri- affected by RA contain similar cyto- ria in the mouth—it is not washed away odontal disease may exacerbate it. kines and growth factors. These chemi- by saliva, increasing the likelihood that Other systemic diseases that affect cals promote the dissolution of bone, a it and other oral debris will inadvertent- older individuals may also be infl uenced problem shared by both diseases. This ly be inhaled into the lungs. by oral health status. For example, osteo- suggests the presence of a common un- This risk is magnifi ed if a mechani- porosis disproportionately affects post- derlying inflammatory mechanism. cal ventilator is needed to assist patients menopausal women, thinning bones and People with advanced R A are known to who cannot breathe on their own by often leading to bone fracture. Periodon- be at increased risk for developing peri- pumping air into the lungs via a tube tal disease apparently does not increase odontal problems—and vice versa. inserted into the mouth or nose. Venti- one’s vulnerability to osteoporosis, but Clearly, more dedicated efforts to lated patients are up to 20 times more people with the latter appear to face an keep gums healthy may reap health divi- likely to develop pneumonia than those increased risk of developing oral disease dends far beyond improving oral health breathing on their own. Oral bacteria and tooth loss. My colleague Jean Wac- and retaining your teeth. The good news can grow on the tube and travel into the tawski-Wende and our research group at is that controlling and even preventing lungs. Not surprisingly, between 10 and the University at Buffalo have found a periodontal disease is possible through 25 percent of these patients develop ven- strong and consistent association be- relatively low-tech means: daily brushing tilator-associated pneumonia (VAP), tween osteoporosis and periodontal dis- and fl ossing, plus regular trips to your making it the leading cause of death ease that causes both tooth and jawbone dentist’s offi ce for cleanings and check- from hospital-acquired infections. loss—especially among women ages 70 ups. Knowing that maintaining oral hy- Improving oral hygiene among the and older [see box on page 33]. giene could help prevent more serious institutionalized elderly would be a cost- Oral infection and the gum infl am- conditions may be just the incentive both effective way to reduce the risk of pneu- mation it causes may also contribute to young and old need to make it a habit. • monia caused by bacteria in the mouth. More than a dozen studies have shown FRANK A. SCANNAPIECO studies oral microbiology and the interface between oral and that simple measures, such as super- systemic health—specifi cally, the role of oral conditions in the process of respiratory vised toothbrushing and regular use of infection. He is professor and chair of the Department of Oral Biology, School of Dental antibacterial mouthwashes, can reduce Medicine at the State University of New York at Buffalo. He has been engaged in dental by more than half the risk of pneumonia research and education for over 20 years.

34 ORAL AND WHOLE BODY HEALTH INSIGHTS ORAL HEALTH

problem and the recommendation of effective AROUND THE WORLD and accessible interventions or preventive measures. WITH PROFESSIONAL EXPERIENCE IN FOUR DIFFERENT Also, in Western society, these messages are likely to reach the portion of the COUNTRIES – THE UNITED STATES, ITALY, SWITZERLAND AND THE population that could benefit least. The UNITED KINGDOM, MAURIZIO TONETTI, CHAIR OF THE people you reach with these messages are the ones whose “health IQ,” or health DIVISION OF PERIODONTOLOGY AT THE UNIVERSITY OF awareness, is so developed that they are CONNECTICUT HEALTH SCIENCES CENTER HAS A TRULY GLOBAL unlikely to be the ones harboring massive undetected disease. PERSPECTIVE ON ORAL HEALTH. HERE HE OFFERS A FEW INSIGHTS ON ORAL HEALTH AND SYSTEMIC DISEASE: ON CHANGES AT THE WORLD HEALTH ORGANIZATION (WHO) ON ORAL HEALTH: ON EDUCATION AND THE CONVERGENCE OF very, very few resources, but the usefulness Historically, before a relatively recent DENTISTRY AND MEDICINE: A common of what they are doing is limited by the fact reorganization in the 1990s, oral health was biomedical curriculum is much more that there is no coordination or consistent part of a WHO branch that focused on >>prevalent in Europe than in the U.S. Until methodology being employed. In Europe we infections. Now, they have placed it with 1980, in most countries, dentistry was a have been—and in other areas of the world we chronic noncommunicable diseases. They medical specialty, so you became a physician, are still—at the level of pilot [studies] have grouped together areas where risk and then specialized in dentistry—rather involving a few hundred patients. The building factors of the population base are similar than, say, cardiology or orthopedics. So, the blocks to be able to do the real clinical trial are because they think this is the best way to foundation of dentistry in the majority of there. Now it’s time to do the real studies. We fight these diseases; many countries are European countries has very, very deep need to focus efforts and develop a vision in following this approach. medical roots. In the United States most order to make a coordinated research effort dental schools have their own faculty happen. ON ORAL HEALTH IN EUROPE: Europe is not a teaching such courses as anatomy, homogeneous reality. You have countries that pharmacology and biology. In Europe it’s not ON PRESS COVERAGE OF THE ORAL are responsive to the needs of populations: like this. There is a biomedical science faculty CONNECTIONS TO OVERALL HEALTH: they have public health systems that are that includes medicine and dentistry. In Europe we have been much more cautious probably the envy of the world—probably, I A strong biomedical curriculum is needed than in the U.S. We have kept the dental would say, better than the U.S. But Europe, not only because of the possible systemic profession very well informed by making sure being made of 25 states these days, has a implications of oral diseases, but also that these topics are discussed at professional wider discrepancy of care than between, say, because of the fact that people are living meetings, but by and large we have not had Connecticut—which is probably one of the longer. So all of a sudden, dentistry has major press releases on the topic. Over the states with the best access to dental care and become an important component of life last two years there has been an increased best health policy in the U.S.—and Louisiana, expectancy, of the well-being of people. awareness, and the media has started to or rural Alabama. Health care is a state issue, communicate. I think this is perhaps a better not a European Union issue. Oral health care ON RESEARCH ADDRESSING THE ORAL- approach than the U.S. media in traditional EU countries is generally good, SYSTEMIC LINK OUTSIDE THE U.S.: There’s lots hype; wait until you have but signiﬁ cant disparities among the various of enthusiasm and attention, but unfortunately enough data and then countries and disadvantaged groups and all of this has translated into fragmented go to the people. Ideally, individuals exist. As in the U.S., in Europe the efforts. There is no body, no organization communication should major burden of oral disease is to be found in a that has been able to catalyze and focus include both the minority of the population. • research activity in places as diverse as Africa, the Far East, Europe—even within Europe—and in the United States. “The foundation of dentistry in the We are missing a tremendous majority of European countries has opportunity because there are lots of people around the world that very, very deep medical roots.” are doing research with COURTESY OF THE UNIVERSITY OF CONNECTICUT OF UNIVERSITY THE OF COURTESY

ORAL AND WHOLE BODY HEALTH 35 SUSAN HAD CAREFULLY MONITORED HER HEALTH IN

the months leading up to the delivery of her ﬁ rst child. She visited her obstetrician

for regular checkups, downed prenatal vitamins every morning, and stopped

smoking. Although she worked full daughter, she wondered what had gone time, she made sure to get plenty of rest. wrong. Her baby had arrived just eight Many of her friends at work were par- months into her pregnancy. ents and they gave her advice daily, tell- Susan is not alone. According to the ing her: keep exercising; don’t jog, swim March of Dimes, each day 1,300 babies instead; don’t eat too many tuna fi sh in the U.S. are born prematurely for rea- sandwiches. One thing she heard over sons linked to specifi c risk factors like and over again—an old wives’ tale, re- smoking or high blood pressure. And if ally—was that she shouldn’t go to the emerging research proves true, peri- dentist because of “x-rays in the air.” So odontal (gum) disease will be a new ad- Susan skipped her annual dental check- dition to that list. In fact, if the bacteria up even though she was concerned by and infl ammation from gum infection how her gums bled when she brushed do indeed play a role in preterm deliver- her teeth. Everyone assured her that this ies—as well as other conditions such as was normal. pneumonia, stroke, heart disease and As she lay in her hospital bed after diabetes—the reverberations across our the premature delivery of her tiny little health care system will be seismic and transformative. “Medically necessary dentistry” will become the new slogan PUBLIC POLICY & ORAL HEALTH: of our time. A WHOLE NEW

Governments, insurers, clinicians & the public must all recognize the changing face of dental medicine. BY SHEILA RIGGS

36 ORAL AND WHOLE BODY HEALTH The generations-old barriers that in- between what we know and what we cious information through the lens of a advertently disconnect the mouth from do when it comes to an issue that cross- primary care physician. the body in terms of patient care are sub- es unusually hardened divides in our Dentists are usually the most acces- stantial. Most of our physicians and den- health care system? sible members of the medical team. Typ- tists are trained in different schools, ically, Americans visit their dentist twice practice in different settings, and receive A WHOLE NEW GAME a year for preventive care. According to payment through different systems. let us assume that all the research link- Dr. Michael Glick, editor of The Journal When your physician asks you to “open ing periodontal disease to many of our of the American Dental Association, wide,” he or she is examining your nation’s most prevalent and costly chron- “Dentists can play an important role in throat, not your mouth. Meanwhile, ic health conditions reaches the same the primary prevention of cardiovascu- your dentist focuses on saving your teeth conclusion: the presence of active oral lar disease…and refer patients for more and gums; he or she doesn’t necessarily disease causes system-wide complica- in-depth evaluation.” view periodontal treatment as a way to tions, and treatment and prevention will Referrals will come more easily when prevent inflammation that can cause improve overall health. Our whole per- dentists and physicians train together in harm throughout the rest of your body. ception of dentistry will need to change, classrooms. It is also crucial that they It takes an average of 17 years be- as will its role in our health care system. work side by side in clinical settings dur- fore Americans benefit from new In this new paradigm, dentists ing graduate school, for example, co- knowledge gained from medical re- should be recognized as the physicians treating a pregnant patient. Deﬁ ning and search, according to Carolyn Clancy, of one part of the body, not just the sur- implementing a uniﬁ ed primary care team M.D., director of the Maryland-based geons of a perfect smile. Dentists take from day one in school will create a pow- Agency for Healthcare Research and blood pressures and health histories as erful new norm. Team members should Quality. This rais- well as gather insights from their pa- include physicians, nurses, pharmacists, es an important tients on risk factors impacting oral dentists and dental hygienists to question: How health, like tobacco use and soda con- both demystify the oral cavity for long will the sumption. Now they physicians and to empower the time lapse be must view this pre- work of the dental team. >> JOHN SOARESJOHN

ORAL AND WHOLE BODY HEALTH 37 Curriculum changes, however, are If our assumption about periodontal health plans in their “pay for perfor- not suffi cient. This new knowledge ulti- disease proves true, such “pay for performance programs”: insurance companies mately must translate into the everyday mance” programs should also include pay physicians a bonus for meeting or practices of physicians and dentists and teeth cleaning and dental care. Likewise, exceeding treatment metrics. be covered by insurance companies— when the federal government tracks how Another standard component of dis- and there are precedents. Numerous many Americans with diabetes receive ease management is a program that con- “quality improvement initiatives” related essential monitoring and care in their an- nects pregnant Minnesotans or those suf- to medical care are currently underway nual National Healthcare Quality Re- fering from chronic conditions with a reg- istered nurse. In regular checkup phone It takes an average of 17 years before calls, their nurse helps them improve lifestyle habits and coordinate care. These Americans benefi t from medical research. same nurses could also educate their patients on the importance of dental care. in clinics and hospitals nationwide. port, a new dental component will need Currently, more than 250,000 pa- These initiatives implement standardized to be added to their survey. tients with diabetes, heart disease and treatment guidelines to insure that pa- other conditions are enrolled by two tients receive proper care. They also es- MINNESOTA AS A PRACTICE FIELD medical insurance companies who al- tablish who is responsible for carrying minnesota, a state known for its health ready partner with one of Minnesota’s out each step outlined by these new care reform, may be the ideal place to largest dental insurers, Delta Dental. guidelines. Hospitals and clinics using launch this revolution. All the major Broadening dental coverage for these these new initiatives are examining their stakeholders currently working to im- populations with fewer co-pays would protocols to make sure no step in patient prove the quality of the state’s health encourage preventive care. care is overlooked. For example, patients care are in place—and they are capable Employers, consumers and innovators hospitalized with a heart attack should of getting this new research into prac- are also active in health improvement ef- begin beta-blocker therapy (medication tice sooner rather than later. Included in forts in Minnesota. Companies are acting that lightens the heart’s workload) with- this group are educators, health care to lower health care expenses, which have in seven days of discharge. New proto- professionals, insurers, employers, con- spiraled dramatically upward over the cols dictate who is responsible for issuing sumers and entrepreneurs. past decade: The cost to employers in the prescription. On the educational front, the deans 2003 for a healthy newborn’s two-day These efforts are frequently spon- of the University of Minnesota’s medical, hospital stay was about $1,700, while a sored by insurance companies or em- dental, pharmacy, nursing and public premature or underweight baby’s average ployers. Using fi nancial incentives, they health schools are discussing joint classes 24.2-day stay was around $77,000, ac- speed the time it takes for new research and a linked curriculum. “We are work- cording to the March of Dimes. on health care practices to become ev- ing through the details of launching on- An employer coalition called the eryday patient treatment. They must campus and clinic-based educational op- Buyers Health Care Action Group is in now also be injected with a healthy portunities, like at the Rice Memorial place to encourage and reward improve- dose of dentistry, which would recon- Hospital in Willmar,” said Patrick Lloyd, ment initiatives in Minnesota’s health fi gure programs to include gum disease dean of the School of Dentistry. care. Recently, they issued a report com- as a preventable risk factor for several Another important initiative is the paring the performance of the state’s common health problems. Minnesota-based Institute for Clinical health plans in both clinical areas (such Some very large employers now di- Systems Improvement (ICSI), a health as prevention and chronic disease man- rectly pay bonuses to doctors; the insurance–funded think tank that estab- agement) and in administrative prac- “Bridges to Excellence” diabetes care lishes guidelines for medical treatment tices (like extending personal digital as- program is one example. General Elec- and improved care. For over a decade, sistant devices to physicians and nurse tric and other companies provide a bo- ICSI has worked with virtually every practitioners). In the future, employer nus of $80 per patient to physicians medical group and hospital system coalitions should evaluate insurers’ ef- who meet National Committee for throughout the state, designing ways to forts to encourage their employees with Quality Assurance standards in caring implement the best clinical practices. chronic conditions to seek dental care. for their diabetic employees, with a fo- ICSI’s “collaboratives” are currently in But it could be the entrepreneurs at cus on improving patients’ blood sugar place to improve care to pregnant wom- one of Minnesota’s 450 medical device levels, blood pressure and cholesterol en and to those suffering from diabetes companies that offer the best solutions. levels. This saves employers about $350 and heart disease. The standards created For example, one company is developing a year per patient. by these collaboratives are rewarded by a topical liquid for use by dentists that

38 ORAL AND WHOLE BODY HEALTH said Christopher H. Fox, executive director of the International and American Associations for Dental Research. “While the cost for these trials is high, it is pennies compared to the lifelong treatment costs for low birth weight babies or for patients with cardiovascular disease.” The landmark government report issued in 2000, “Oral Health in Ameri- ca: A Report of the Surgeon General,” made a similar call for future research. When Medicare was established in 1965, Congress made a blanket exclu- sion of dental care. Medicaid coverage varies state to state, but adult periodontal services are covered in just nine states, according to a U.S. Government Ac- countability Offi ce report to Congress. So although the poor and the elderly have some of the highest occurrences of heart conditions and diabetes, there is little public assistance available for periodontal treatment, which costs between $100 and $1,000 per year depending on its severity. In developed countries, 44 to 57 percent of adults have moderate periodontitis; 7 to 15 percent have an advanced form of the disease. In their 2003 “Public Health Impli- cations of Chronic Periodontal Infec- THE BURDEN OF DISEASE: Poor oral health impacts individuals and whole communities and results tions in Adults” report, the Centers For in pain, suffering, impairment of function and reduced quality of life. According to the World Health Disease Control and Prevention (cdc) Organization (WHO), oral disease is the fourth most expensive condition to treat in most industrialized countries. As more research links oral health to overall health, policymakers will need to address suggested restructuring benefi ts to pro- new models of prevention and treatment. vide dental infection control services to Medicaid and Medicare recipients. If disrupts plaque biofi lm, removing the tional policymakers should fund studies preventing and treating periodontal dis- harmful effects of the bacteria that cause to confi rm whether periodontal disease ease does indeed avert preterm deliver- periodontal disease in the fi rst place. is indeed a risk factor for often prevent- ies and decrease the illness burden of Ongoing research into oral-systemic able “medical” conditions that affect Americans with diabetes and heart dis- health links will certainly spawn much millions of Americans. “In order to ease, covering dental treatment for more development among product mak- move from uncovering an association adults in our public entitlement health ers and life sciences companies. between periodontal disease and various programs should be considered. In the end, these solutions will be systemic diseases and conditions, to ac- So that the next time Susan is preg- necessary to change the cultures of the tually demonstrating causality, large- nant, there will be a brand-new member medical and dental practices to embrace scale clinical trial research is needed,” on her health care team—her dentist. • the new research fi ndings on the con- nectedness of the mouth to the body. SHEILA RIGGS received her dental degree (D.D.S.) from the University of Iowa College of Dentistry and went on to earn her doctorate of medical sciences (D.M.Sc.) in oral epide- FEDERAL GOVERNMENT’S ROLE miology from Harvard University. She was recently appointed president and CEO of THE FEDERAL GOVERNMENT also has Delta Dental Plan of Minnesota, one of the largest dental benefi t providers in the upper “skin in this game” both as a primary Midwest, which serves more than 3.3 million individuals at 8,500 Minnesota-based funder of medical research and as the companies and is leading the effort to integrate the latest dental and medical research

MATT COLLINS COLLINS MATT provider of Medicaid and Medicare. Na- into its dental offerings.

ORAL AND WHOLE BODY HEALTH 39 INTERVIEW

THE FORMER U.S. SURGEON GENERAL REFLECTS ON HIS is mounting evidence. We still don’t have that definitive, long-term study because SEMINAL REPORT THAT PUT ORAL HEALTH ON THE NATIONAL those take a long time, but more and more AGENDA, AND THE POLICY STEPS THAT STILL NEED TO BE TAKEN studies support the associations. And I don’t mean just public education. Clearly, in the future, it will be critical that SCIENTIFIC AMERICAN: “Oral Health in America” report—and how did it help mobilize efforts medical students, dental students, nurs- was a landmark report. What factors com- for better oral care and greater awareness? ing students and public health students be pelled you to issue it? Both in the public and private sector, we’ve educated about the significance of oral >> seen increased focus on oral health, funding disease as it relates to systemic disease— SATCHER: I think the request from the oral programs and educating the population. The and about some of the things we can do to health community, including dentists and National Center for Dental and Craniofacial intervene. others, had probably been there for many Research at NIH (National Institutes of Health) has now In light of continued evidence linking oral funded several and systemic health, is the mandate to Centers of Excel- address socioeconomic differences in oral DISCUSSION with lence on oral health health care access even more pressing? r e s e a r c h . I n t h e I think it is. Our report stated that 20 percent DAVID SATCHER private sector, the of the population now suffers more than 80 Robert Wood John- percent of oral health disease. About one son Foundation fund- third of the elderly, by the time they’re 65, years. When I got to Washington—having ed 19 dental schools to develop outreach are edentulous. We know that periodontal come from the CDC (Centers for Disease programs into communities around them. disease is more common in African-American Control and Prevention)—I was especially Other foundations have also focused men in general, and that it’s more common in concerned about areas that had not been increased attention on oral health. smokers. So I think we’re now in a position to dealt with, like mental health and oral health, The other thing that I appreciate is that begin to target populations [who are most and obesity. So oral health was very high on it’s led to new partnerships between doc- adversely affected]. our list because it had been neglected by the tors and dentists and other oral health pro- surgeon general’s ofﬁ ce. We tried to make it fessionals. I think [the report] rejuvenated Many people without health care might go to very clear that this was not about the dental the ﬁ eld in many ways. a dentist, whereas they may not have had a profession, it was about oral health, and that medical checkup in some years. What kind of oral health was everybody’s business— As more evidence comes in linking oral responsibility should fall on the dental pro- everybody who was concerned about health health to other medical conditions, what fession in those cases, where perhaps and health care. further efforts do you feel need to be taken, they’re treating a diabetic patient that also

Were there speciﬁ c issues around oral health that were of particular concern at that time, “We tried to make it very clear that this was not both to you and to the medical and dental com- about the dental profession, it was about oral munities? Well, one issue was disparities in health. If you go back to the “Healthy People health, and that oral health was everybody’s 2010” report that we released in January business—everybody who was concerned about 2000, we looked at two major areas. One was health and health care.” the quality of life of people as they get older; one of those issues was edentulousness in either clinical practice, public education has gum disease? Well, I think diabetes is a (tooth loss). The second was the issue of dis- or policy? I think in all of those areas there good example, because the association with parities in health among different racial and is a need for enhanced education and com- periodontal disease is probably most clear. ethnic groups. I don’t think there is any area munication about the magnitude of the Since we know that people with diabetes are that demonstrates health disparities more problem of oral disease—and its signifi- at greater risk for oral health disease, coun- than oral health—there are 108 million cance. Especially when you begin to tie peri- seling patients about being tested for diabe- Americans who lack dental insurance. odontal disease to low birth weight or tes [or making sure that their diabetes is adverse pregnancy outcomes, increased under control] is important. The education Since that time, what steps have been taken risk for diabetes or cardiovascular disease about diet that dentists give is important for toward addressing the issues outlined in the and stroke. Those are the ones where there both the health of the mouth and for the over-

40 ORAL AND WHOLE BODY HEALTH all health of a person with diabetes: increasing fruits and vegetables, and decreasing sweets, meats and calories. Dentists, by focusing on the mouth, have an opportunity to look at what’s happening to the whole person. And by partnering with the health professional, they can work to make sure that the [patient] gets the care that he or she deserves. I was thinking about the role that dentists are playing in helping people [to] quit smoking, because they focus on how their teeth and gums look when they smoke. And so, in recent years a major avenue for smoking cessation has been to get dentists involved. I think that these [medical-dental] partnerships are being forged both ways. The mouth is an important mirror and a window to the body: it’s not just what is going on in the mouth, it’s what’s reflected in the mouth about the state of health of the body.

What other comments do you have that you think would be good for both dental professionals and the general public to hear? The overriding message that came out of that report is the importance of access to oral health care; the fact that so many Americans don’t have access to oral health care is a major concern ... and that it disproportionately impacts low income families and minor- ities. Hopefully, as a nation, we should be moving towards universal access to oral health, as well as health care in general. I know that there were some states that sig- niﬁ cantly increased their Medicaid coverage for oral health after our report. [But] many of those states, after they had budget problems, cut back Medicaid again, which, of course, hurt all aspects of health care. •

DAVID SATCHER completed his four-year term as the 16th surgeon general of the United States in February 2002. He also served as assistant secre- tary for health from February 1998 to January 2001, making him only the second person in history to have held both posi- tions simultaneously COURTESY OF THE MOREHOUSE SCHOOL OF MEDICINE

ORAL AND WHOLE BODY HEALTH 41 RESEARCH SNAPSHOT:

A Novel Approach to Resolving Inflammation

Understanding how the body naturally “turns off” infl ammation may yield new sible to rein in runaway infl ammation treatments for periodontal disease and other infl ammatory conditions and the tissue destruction it causes. We and our colleagues have identi- By Thomas E. Van Dyke and Charles N. Serhan fi ed powerful compounds, produced naturally by the body, that put the brakes on the infl ammatory response. cientists have known for almost 50 years If we can manufacture these novel anti-infl ammatory chemicals and use that periodontal disease is caused by bacterial infections. However, them as medicines, they might offer safe and effective treatments—not the tissue damage that occurs in periodontal disease—destruction only for periodontal disease but also S for heart disease, arthritis, Alzheim- of the bone and ligaments that hold that periodontal disease results er’s disease and other health problems teeth in place—cannot entirely be ex- mainly from the body’s failure to where chronic infl ammation appears plained by the action of infecting or- turn off its infl ammatory response to to play an important role. ganisms. Instead, the real culprit seems infection. The result is chronic in- Much of our work on infl amma- to be the patient’s own infl ammatory fl ammation, which causes much of tion in periodontal disease has fo- response to that infection. the tissue damage that we observe in cused on its cause: the immune reac- Infl ammation evolved as a pro- periodontal disease. tion that the body mounts against in- tective response to infection and to Why, for some of us, does this infection. This attack triggers the classic traumas such as wounds and insect fl ammatory response to oral bacteria signs of infl ammation including heat, bites. Yet infl ammation can also be persist rather than subside? The an- redness, swelling and pain. We’ve deleterious—especially when it per- swer may lie in our genes: Studies indi- been particularly interested in the in- sists, instead of fading away as it cate that much of our susceptibility to nate immune response—the body’s should. Our research collaboration periodontal disease is genetically infl u- fi rst line of defense. This response is over the past nine years indicates enced. But fortunately, it may be pos- initiated by neutrophils, a type of white blood cell crucially important in eliminating infectious organisms CAN GUM DISEASE CAUSE HEART DISEASE? by engulfi ng them through a process called phagocytosis—which literally SEVERAL PROVOCATIVE STUDIES suggest that people with periodontal disease have an means “cell eating.” increased risk of heart disease. To further investigate this link, we induced periodontal As they congregate at the site of disease in rabbits by tying a thread around some of their teeth and treating their gums infection or trauma, neutrophils se- and teeth with a bacterium known to cause periodontitis in humans. Six weeks later, crete “proinfl ammatory” chemicals after the rabbits had developed periodontal disease, we examined their major blood that cause the fi rst, or acute, phase of vessels. The rabbits with periodontal disease had much more atherosclerosis—fatty infl ammation. Normally, in the next plaque deposits in their major blood vessels—than the healthy control rabbits. step, neutrophils cease their chemical onslaught and infl ammation subsides. But which component of periodontal disease—the infection or the infl ammation— But in periodontal disease there is a was the culprit? To fi nd out which had caused the atherosclerosis, we once again glitch: neutrophils continue churning tried inducing periodontal disease. This time, besides ordinary rabbits, we used out proinflammatory chemicals, “infl ammation-resistant” rabbits that we genetically engineered with Larry Chan which create a complex, chronic le- (Baylor Medical College) to have abnormally high lipoxin levels in their blood. The sion that destroys the gum and bone resistant rabbits not only failed to develop periodontal disease—their arteries were almost completely free of plaque, compared with the nonresistant rabbits holding teeth in place. that developed periodontal disease. Clearly, infl ammation’s failure to enter its last or “resolution” phase can This study adds to mounting evidence that periodontal disease may contribute to have serious consequences. This fi nal atherosclerosis. It further suggests that periodontal infl ammation plays a key role in the potential periodontal disease–heart disease connection. — TVD

42 ORAL AND WHOLE BODY HEALTH TODAY’S ANTI-INFLAMMAT ORY DRUGS target only specific aspects of ly cause infl ammation—and typical ng so. TRAUMA OR INFECTIONharmful triggersside effects the early in doiphase of infl ammationAspirin, (“go” traffi ibuprofen c lights). Herande, ara-other lammatory chidonic acid isnonsteroi converteddal to proinflanti-inf ammatory ple, curb mediators leukotrienedrugs (NSAIDs), B4 (LTB 4for) and exam prosta- uction while glandin E2 (PGEprosta2) that glandincause edema, prod fever and sers’ risk for pain. Later, elevatedincrea PGEsing2 levels u help resolve inflammation bygastrointestinal stimulating production bleeding. of By enzymes that formcontrast, anti-infl ammatonaturallyry lipoxins occurring ounds, (“stop” traffi c lights),infl ammat whichion-resol are alsoving generated comp within blood vesselssuch as via resolvins platelet-neutrophil and lipoxins, affect interactions. The fi aspects nal step ofi inflammation. They all n halting infl ammation is the switchcreate of familiesa coordinated in lipid medicellulara- and brings tors from proinflammatorymolecular responseto resolvins that and alt. Drugs protectins. Exudateinf neutroplammathilsion biosynthesize to a h these two chemicalmimicking families these from natural ome compounds,ga-3 great fatty acids in the nowdiet. in development, offer potential for treat ing infl ammation s “naturally” and without side effect TAMI TOLPA

ORAL AND WHOLE BODY HEALTH 43 RESEARCH SNAPSHOT:

phase has traditionally been consid- tion, then it is lipoxins that can be ered a passive event—a petering out considered the “red lights” that help of immune activity that paled in com- bring infl ammation to a halt. parison to the acute phase’s neutro- The synthesis of these infl amma- phil attack. That assumption re- tion-stopping compounds starts late quired drastic revision after one of us in the acute infl ammatory response. (Serhan) carried out the fi rst system- Before that, infl ammation is in full atic study of the natural history of swing: enzymes from platelets and infl ammation by examining infl am- other cells attracted to the area me- matory pus in skin lesions of rabbits tabolize arachidonic acid (a major and mice. fatty acid in cell membranes) to create We observed that neutrophils, leukotrienes and other proinfl amma- which lead the white cell onslaught tory compounds. Then, once these during infl ammation’s acute phase, infl ammatory chemicals have crowd- secrete two compounds well known ed together, an abrupt shift occurs, UPPER PHOTO shows infl ammation and erosion for provoking infl ammation and at- and enzymes induced in neutrophils of gums in rabbits with periodontitis. In lower photo, topical resolvin prevents infl ammation and tracting additional white cells to the convert arachidonic acid into infl am- tissue destruction of periodontitis. area: leukotriene B4, followed by mation-dampening lipoxins. The in- prostaglandin E2. But at the end of fl ammatory response ceases as lipox- the acute phase, we saw something ins increase in quantity at the expense tis, cardiovascular disease and other surprising: neutrophils stopped se- of proinfl ammatory compounds. infl ammatory conditions. We now sus- creting classic infl ammatory chemi- pect that the resolvins formed from cals and instead began collaborating serhan recently discovered yet omega-3s may in part account for the with other cells to synthesize com- another family of infl ammation-re- anti-infl ammatory properties of these pounds that halted infl ammation. solving compounds that we’ve dietary fatty acids. We dubbed these anti-infl amma- dubbed “resolvins.” In contrast to li- The actions of lipoxins and re- tory compounds lipoxins, since they poxins, whose starting material is solvins in the body are similar but were derived from the lipids (fatty ac- arachidonic acid, the resolvins are not identical. Their net effect is to ids) released from neutrophils’ cell derived from fatty acids in the diet— rapidly halt infl ammation and mini- membranes and from other cells that specifi cally from omega-3 fatty acids mize tissue damage. Furthermore, congregate early in infl ammation. If that are especially plentiful in fi sh. taking aspirin results in more potent it is prostaglandins and leukotrienes Several well-designed clinical stud- and longer-lasting lipoxins and re- that give the “green light” that ac- ies indicate that diets rich in omega-3s solvins [see box on page 45]. celerates tissue injury and infl amma- help in treating and preventing arthri- In our federally funded Special- ized Center for Oral Infl ammation A N T I - I N F L A M M A T O R Y D R U G S and Resolution, we are studying how target only specific aspects of the structure of resolvins gives them inflammation—and typically their potent anti-infl ammatory abil- cause harmful side effects in doing so. Ibuprofen and other ity. Based on our fi ndings, we rea- nonsteroidal anti-infl ammatory soned that the topical application of drugs (NSAIDs), for example, curb lipoxins and resolvins as medicines prostaglandin production while might prove useful in treating or even increasing users’ risk for gastro- preventing inflammatory diseases intestinal bleeding. By contrast, naturally occurring inflamma- like periodontitis. We also wondered tion-resolving compounds, such if these compounds might help as resolvins and lipoxins, affect against other inflammatory prob- all aspects of infl ammation. They lems such as cardiovascular disease create a coordinated cellular and and the complications of diabetes. molecular response that brings inflammation to a halt. Drugs To test resolvins’ ability to prevent mimicking these natural com- periodontitis, we chose an established pounds could potentially treat inflammation “naturally” and without side effects.

44 ORAL AND WHOLE BODY HEALTH REVVING UP LIPOXINS AND RESOLVINS WITH ASPIRIN model of human gum infection—the rabbit model. We tied silk thread ASPIRIN’S POTENT ANTI-INFLAMMATORY PROPERTIES were recognized soon after it was around certain rabbit teeth to trap bac- introduced a century ago. But not until many decades later did Sir John Vane, Sune Bergström teria and then added a disease-causing and Bengt Samuelsson—in research for which they shared a 1982 Nobel Prize—discover human bacterium, Porphyromonas how aspirin actually works. Aspirin blocks the enzyme COX-2. This provides relief by gingivalis, to induce periodontitis. Af- preventing arachidonic acid in cell membranes from being converted into prostaglandins— ter dividing the rabbits into two groups, the chemical messengers that cause the pain and swelling of infl ammation. we swabbed a resolvin-containing so- By blocking the COX-2 enzyme, aspirin and lution on the gums of one group and an similar drugs do a good job of shutting off the inactive solution on the gums of the prostaglandins that fuel the early, acute phase other. The results were striking: rab- of infl ammation. But they may also set the stage bits receiving the topical resolvin solu- for chronic infl ammation by hindering the body’s tion were completely protected against own attempt to heal: As the illustration on page periodontitis, whereas the placebo 43 shows, prostaglandins are vital for producing group developed severe gum disease the lipoxins that help to resolve infl ammation. [see photos on page 44]. This suggests a better strategy for quelling infl ammation: Instead of halting acute infl ammation, focus instead on helping the body in its effort to resolve the infl ammatory response. to further explore this connection When we swallow aspirin, it not only inhibits COX-2 but also modifi es its action. Research between infl ammation and suscepti- by one of us (C.S.) has shown that aspirin-modifi ed COX-2 catalyzes the production of “new bility to disease, we studied genetically and improved” resolvin and lipoxin compounds that have more potent and longer-lasting engineered rabbits that have elevated anti-infl ammatory effects than the naturally occurring variety. levels of lipoxins when their white These previously unappreciated aspects of aspirin’s activity may help researchers blood cells are activated. These rabbits develop truly anti-inflammatory compounds that would not just muffle acute also have a very low incidence of ath- infl ammation but would actively resolve infl ammation and heal wounds. These drugs erosclerosis [see box on page 42] in would be especially useful against periodontal disease, heart disease and other their major vessels. We tried to pro- important health problems that arise from chronic infl ammation. duce gum disease in these “infl ammation-resistant” rabbits using the same — TVD silk thread and bacteria technique described above. With their elevated levels of circulating lipoxins, these rabbits flammatory drugs are the NSAIDs ing inflammation rather than just proved resistant to periodontitis. (nonsteroidal anti-inflammatory turning off one or another individual While we know that bacteria drugs), which include naproxen, ibu- infl ammatory pathway [see sidebar causes periodontal disease, it now ap- profen and many other compounds. on page 44]. In addition, these natu- pears that its progressive form may be The NSAIDs short-circuit just one in- ral compounds would be expected to primarily driven by infl ammation— flammatory pathway (the one that produce few side effects. which could alter the way this condi- converts arachidonic acid into prosta- Our studies have shown that lipox- tion is controlled and treated. In peo- glandins). Moreover, NSAIDs cause ins and resolvins may be ideally suited ple susceptible to periodontal disease, thousands of deaths annually in the for treating periodontal disease. • for example, topical application of li- U.S., mainly due to gastrointestinal poxins or resolvins could possibly bleeding. Other, more powerful anti- THOMAS E. VAN DYKE studies the resolution prevent or lessen its severity. infl ammatory drugs, such as Remicade of infl ammation as a therapeutic is a professor target. He More broadly, our research has for treating rheumatoid arthritis, do so in the Department of Peri- odontology and Oral Biology at shown that infl ammation involves the by dampening the immune response, Boston Univer- sity’s Goldman School of Dental Medicine, coordinated response of a large num- which may increase vulnerability to in- directs the Clinical Research Center, and is ber of biochemical pathways. But to- fections as well as to cancer. associate director at the BU School cine General of Medi- day’s anti-infl ammatory drugs defuse By contrast, lipoxins and re- Clinical Research Center. only one pathway or another and can solvins might offer major advantages CHARLES N. SERHAN studies the cellular be risky to use. Consider two exam- over existing anti-inflammatory molecular mechanisms that resolve infl tion. He holds amma- ples: by far the largest class of anti-in- drugs. They act by “centrally” defus- the Gelman Professorship Harvard Medical School, at is a senior biochem- ist and an endowed distinguished at Brigham and Women’s Hospital. scientist is also chairman and professor Dr. Serhan of oral medi cine, infection and immunity at the Harvard - School of Dental Medicine. ORAL AND WHOLE BODY HEALTH 45 PATH TO PREVENTION

of Pathogenic bacteria are a way of life. So, too, must MOUTHFUL BUGS be brushing and ﬂ ossing. | BY ROBERT H. KAGAN

THE MOUTH IS A CAULDRON OF BUGS. die for bacteria to fi nd inroads: diseases, such On average, some 500 species sit in the oral as diabetes, can decrease the ability of the im- cavity going about their daily business as mune system to respond effectively to bacteria, their hosts sleep, talk, chew and swallow. and this can tilt the balance toward the latter, “Bacteria are lurking in the tongue, nasal cav- triggering the beginnings of oral disease. Lo- ity, tonsil area, gingival pockets [and] fl oat- calized neglect—not taking adequate care in- ing in saliva,” explains John C. Gunsolley, a side the mouth—can also lead to pathogenic professor in the department of periodontics bacterial overgrowth. This can occur when at Virginia Commonwealth University in periodontal pathogens such as Actinobacillus Richmond. “Our skin has bacteria on it, actinomycetemcomitans, Prophyromonas we’re never completely sterile. Swab any ex- gingivalis or Tannerella forsythia begin to in- ternal portion of the body, you will fi nd bac- crease their presence in the mouth and over- teria. It’s nothing to be alarmed at. It’s what colonize soft tissue. When these bacteria ex- nature is.” pand in the pockets of the gums, they can trig- The body is constantly fi ghting these bac- ger redness and infl ammation from gingivitis, teria, and healthy bodies are able to keep them a warning sign for possible progression to peri- at bay. When our immune systems stop re- odontitis and the destruction of gum tissue sponding, however, our bodies become bacte- and bone that can result. rial buffets. Within a day or two of dying, Eliminating pathogenic bacteria complete- bodies start to smell, Gunsolley says. That’s ly might make the mouth safe from periodon- the bacteria taking over. But we don’t have to tal disease, Gunsolley explains.>> Experiments adapted from vintage illustration provided by Clipart.com JEFF MELLIN MELLIN JEFF

46 ORAL AND WHOLE BODY HEALTH ORAL AND WHOLE BODY HEALTH 47 BATTLING BACTERIA AND INFLAMMATION Home Care Chemotherapeutic • Brushing & Flossing • Chlorhexidine • Stannous ﬂ ouride • Cetylpyridium chloride Professional Care • Essential oils • Scaling and root planing • Triclosan • Flap surgery • Antimicrobial inserts • Grafts (BONE, SOFT TISSUE) into pockets • Tissue regeneration surgery • Systemic antibiotics • Bone (OSSEOUS) surgery

ORAL ARSENAL: A variety of interventions are available to combat infection and infl ammation in the mouth. have been done with rats where peri- pathogenic bacteria that populate a pa- and root planing as well as placing anti- odontal pathogens were eliminated from tient’s mouth and how much damage microbial inserts into gum pockets, or parts of the mouth, and the rats resisted they might do. Gunsolley points out additional interventions [see box above]. attempts to induce periodontitis as long that although there are no good metrics But fi rst and foremost, Gunsolley em- the areas stayed bacteria-free. But even- or devices to measure a mouth’s bacte- phasizes, is good mechanical oral hy- tually, bacteria fi nd their way back into rial load, the body’s response to bacte- giene: brushing and fl ossing. This, ulti- the mouth, as humans (and rats) have ria is effective in determining treat- mately, is the ideal way to disrupt plaque, bacterial reservoirs that make it impos- ments. If a mouth appears healthy, with especially at the gum line. sible to completely eliminate the mi- no infl ammation or redness, then the Traci Portnoff, D.M.D., in private crobes for extended periods of time. The main indication is mechanical: brush- practice in Westborough, Mass., and a practical issue, then, is one of balance: ing and fl ossing. Both brushing, wheth- former instructor in oral medicine at oral disease can often be avoided or kept er with a manual or electronic tooth- the Harvard School of Dental Medi- at bay if the number of bad bacteria are brush, and fl ossing break up plaque— cine, agrees: “The bottom line is if kept in check, Gunsolley says. the mass of bacteria and food that forms [someone is] not brushing, they are not a biofi lm, which coats tooth and gum doing anything. You need physical ZEN AND THE ART OF MOUTH surfaces. The goal is break up biofi lm stimulation.” While Portnoff certainly MAINTENANCE on a daily basis before it adheres, Gun- employs advanced technologies to deal keeping microbes in check is an on- solley says. with indications of gingivitis or peri- going practice, and a goal met by two The next level of treatment is often odontal disease from pathogenic bac- main approaches: mechanically sweep- chemotherapeutic, where chemicals in teria, her fi rst line of defense and most ing away bacteria so they cannot take mouthwashes or antiplaque agents in important battle cry to patients re- root in the mouth, and reducing their some toothpastes are used to nonselec- mains the same. “Our main focus is numbers through chemical means. The tively combat bacteria in the mouth. hygiene instruction,” she emphasizes. level of bacteria in a mouth will deter- This decreases the number of pathogen- “There’s no substitute for the brushing mine the types of tools to use under ic bacteria and thus reduces infl amma- and fl ossing.” • adapted from vintage illustration provided by Clipart.com each approach. tion. If there is serious gingivitis or peri- A first step in addressing oral hy- odontal disease, then other treatments ROBERT H. KAGAN is a science writer

giene is to determine the amount of are generally added, including scaling based in Boston, Mass. MELLIN JEFF

48 ORAL AND WHOLE BODY HEALTH INTERVIEW

DANIEL M. MEYER, ASSOCIATE EXECUTIVE DIRECTOR OF THE component of some of these conditions, or it DIVISION OF SCIENCE AT THE AMERICAN DENTAL ASSOCIATION, may be a minor component. Whether or not treating oral health condi- SPEAKS WITH SCIENTIFIC AMERICAN ABOUT ORAL HEALTH, ETHICS, tions will affect systemic health depends on AND THE STATE OF THE SCIENCE LINKING GUM INFECTION WITH the disease—and we’ll know more about that as future research unfolds. Until we have OTHER SERIOUS DISEASES. [intervention] studies, where we can measure results in consideration of other variables SCIENTIFIC AMERICAN: What is the ADA’s need to be clarifi ed. It would be naive of us to that may infl uence health, I think we have to (American Dental Association) position on think that the mouth is separate from the rest be guarded in treatment recommendations. >>the science behind the possible links of the body; the mouth is an excellent location But treating oral conditions such as periodon- between periodontal disease tal disease has its own undisput- and other systemic conditions? ed benefi ts and may have broader systemic health outcomes. DANIEL M. MEYER: The ADA is a sci- I think it’s going to be decades ence-based organization. It’s had THE ADA’S TAKE before we fully understand car- a rich history of basing its poli- How the world’s leading dental diovascular diseases. And again, I cies, clinical recommendations organization views the growing think we have to be very cautious and guidance for providers, about any of the oral health rela- patients and the public on sound connections between a healthy tionships, because they may pale scientifi c principles. Oftentimes, mouth and a healthy body. in comparison to other risk fac- the science is there and clearly tors. But good oral health makes sets a sense of direction, but at sense, is appropriate to all cases, times we need more information. As far as oral- to diagnose, prognose, treat and intervene on and contributes to good general health. systemic relationships, we’re dealing with a whole host of disease processes. Oral health new discoveries and new scientifi c informa- has to be a part of general health care, so it’s You make a good point. Regardless of peri- tion. The burden of proof of a causal relation- not too early. odontal health’s relation to your heart, it still ship is not yet met; but research is ongoing is important for your mouth and your teeth. and it looks promising. Infl ammatory process- Which of the possible links do you feel are We want patients to be focused on good oral- es in the oral cavity could play a role in causing stronger and which do you feel will need con- health and oral hygiene, but we also want problems in other parts of the body. siderably more research before there are any them to take care of their bodies. » It’s important that we distinguish between strong conclusions either way? The relation- sound science and pseudoscience—and ship to cardiovascular disease is less clear. between causal relationships and casual rela- Regarding the relationships to preterm births, “Fundamental to it all, good oral health makes sense, it is appropriate to all cases, and certainly good oral health does contribute to good general health.”

tionships. We want to make sure that every- depending on what studies you’re reading... one has the best scientific information to we’re getting varying results. Bacteria and make good treatment and clinical care deci- various health conditions can coexist, but sions that will improve the quality of life and we’re talking about bacteria that not only exist health for our patients. in the oral cavity but may exist in other parts of the body as well. Whether or not they result Do you feel that it’s too early for there to be in a cause-and-effect relationship or inﬂ uence clinical implications or do you feel that the relative risk remains unclear. These diseases evidence is solid enough in any of these areas are complex. Some have multiple risk factors— to change either medical or dental care? behaviors, genetic conditions and predis- Obviously there is a relationship between oral posing factors, including environmental health and general health. Other relationships issues. So oral health can be a major

ORAL AND WHOLE BODY HEALTH 49 As more evidence links the health of the mouth an opportunity to work together with the AMA, s o m e p e o p l e a n d b y t h e m e d i a a t t i m e s . to the health of the body, do you feel the role to share information, to update the public and I don’t know who coined the phrase, but it of the dentist needs to change, and if so, how? the profession on where we are at this time. does lend itself to the misconception that all I do. I think the role of the dentist, as well as We didn’t want to overstate relationships, but you have to do is fl oss and you won’t die. any health care provider, needs to evolve as we didn’t want to understate them, either. research evolves, expanding as information If the role of the dentist does indeed need to becomes available. In all of medicine and den- You mentioned that there is a lot of misinfor- shift to incorporate risk for—let’s choose tistry, the role of the provider has changed mation. What are some examples? There are pregnancy outcomes—what would that mean considerably over the last several decades. I those that would say that some of these are regarding liabilities for dentists? We will have see the dentist becoming much more integral causal relationships, that there is a direct to wait and see. We’re treating individuals, to the general health care team. Dentists gen- relationship between oral bacteria, and, for often with a host of prior medical conditions. erally treat healthy, ambulatory patients example, cardiovascular disease. That hasn’t People are living longer now, taking a variety of rather than affl icted or debilitated patients so been demonstrated yet. There are still con- medications, many of which interact or cause they can be involved in early intervention, flicting studies that call into question the dry mouth—which can cause other oral and early diagnosis, risk assessment and disease strength of some of these relationships. Our health complications. So with care comes the concern for side effects and risks. You have to We’ve had patients calling up thinking that they can weigh the benefi ts against the risks. We are treating patients for complex diseases, but treat their heart conditions by simply going in and perhaps we don’t fully understand all of the having their teeth cleaned or scale and root planed. health implications, or all of the side effects, or all of the interactions. Along with that there management of many diseases, and [they concern is to keep things in the proper per- certainly are medical and legal risks. can] refer those individuals to appropriate spective—so when someone goes to a physi- health care providers. For example, to help cian or a dentist, that the level of care is con- Which in the U.S. is a big issue. We are per- detect cardiovascular conditions it would be sistent with the quality and strength of sci- haps the most litigious society in the world. benefi cial for dentists to do blood pressure entifi c evidence. Right. And so, are dentists preyed upon? Yes. screenings, and we’re looking at new tech- Are health care providers preyed upon? Are nologies like salivary diagnostics. The chemi- Are there any other obvious myths around patients preyed upon? Yes. And so that’s cals that you see in blood should also be periodontal disease and general health that always a concern. detected in saliva, and although this technol- come to mind? There are misconceptions that ogy needs to be refi ned, it allows dentists to need to be addressed. We’ve had patients call- Do you think this new data could create a more be part of the early diagnostic team. We need ing up thinking that they can prevent or treat complex legal matrix? It’s already been brought to take more of a medical approach to some of heart conditions by simply going in and having to our attention. There are lawyers’ Web sites these conditions, and to align ourselves with their teeth cleaned or scaled and root planed. saying, “If you’ve ever had a history of peri- other health care providers to address them. odontal disease... and if you have any of the Getting your teeth cleaned wouldn’t be the following conditions, then you may be eligible Is the ADA promoting a closer relationship magic bullet there. No, it wouldn’t be. We’ve for legal action.” Does concern us? Obviously with the medical community? We are. We’re had people call up asking, “If I brush my we don’t want harm done to patients, but we working very closely with the American teeth with this certain toothpaste, will that also recognize that there are individuals who Medical Association, a variety of health orga- help cure my heart disease?” No. Could uti- may take advantage of the fact that some of nizations including the American College of lizing an appropriate toothpaste improve these issues are still evolving. We don’t yet Obstetricians and Gynecologists, the oral health? Yes. Is oral health a component know everything that we need to, and with that American Academy of Periodontology, and of general health? Yes. We do know how comes a level of risk and a real need to enlight- various professional and research organiza- proper oral hygiene, proper lifestyles can en the public and the profession on relevant tions to address these issues collectively. influence health—and oral health; but to care—and the need for more research. make huge extrapolations? We’re very con- Specifically, the AMA and ADA had co-orga- cerned about that. Does the ADA have a specific program or nized a press event on periodontal disease. regimen approving dental care/dental proce- What prompted that? The concern is that there I’ve heard a number of researchers use the dures for specifi c problems? Yes. If you go to is a lot of misinformation. We were receiving expression “fl oss or die,” and I’ve wondered ada.org, you’ll see that we do provide guid- many requests from the public about these where it originated. That mentality does ance on a whole host of topics related to relationships and were concerned that they frighten me a bit because some things that patient/provider safety—including oral-sys- be put into proper perspective. We saw this as are said facetiously are taken to heart by temic relationships. •

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