Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR Dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with 3 dental practice-based research networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95% CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased 4-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment >2 years; suppuration and dental extractions were independent risk factors for ONJ.

Dental risk factors for osteonecrosis of the jaws: a CONDOR case-control study.

BACKGROUND: Reports of osteonecrosis of the jaw (ONJ) have associated this lesion to treatment with bisphosphonates (BPs) and dental procedures. In this study, we investigated the association of specific dental diagnoses and procedures with ONJ among patients with past BP use. METHODS: Dentists from three practice-based research networks provided ONJ cases and controls (1:3). Data gathered from patients and dental offices with two respective standard questionnaires included demographic, medical, pharmaceutical, and dental information. Diagnoses and procedures up to 3 years prior to ONJ (prior to interview for controls) were analyzed within risk strata, defined by BP use and cancer status, using interaction terms within conditional logistic regression models. RESULTS: We enrolled 191 ONJ cases and 573 controls from 119 dental offices. Among participants who had used only oral BP, extraction was the only dental risk factor for ONJ (odds ratio (OR) = 12, p = 0.01). Suppuration was also more prevalent in cases (18 %) than in controls (9 %), but not statistically significant (OR = 9, p = 0.06). Among participants who had not used either oral or IV BP (a majority of whom received radiation therapy to the head and neck), suppuration was the only dental risk factor for ONJ (prevalence = 34 % for cases and 8 % for controls; OR = 7, p = 0.01). The prevalence of extractions in this group was also higher, but not statistically significant (44 vs 10 %; OR = 3). Limited power precludes definitive findings among participants exposed to IV BP. CONCLUSIONS: Among patients taking oral BP, extraction was the only dental procedure associated with subsequent ONJ development CLINICAL RELEVANCE: Results of this study suggest that routine dental procedures are not associated with development of ONJ in patients exposed to BPs.

Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with three dental Practice-based Research Networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95%CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased four-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment > 2 years; suppuration and dental extractions were independent risk factors for ONJ.

Dietary carbohydrates and dental-systemic diseases.

Two contradictory hypotheses on the role of dietary carbohydrates in health and disease shape how dental-systemic associations are regarded. On one side, Cleave and Yudkin postulated that excessive dietary fermentable carbohydrate intake led-in the absence of dental interventions such as fluorides-first to dental diseases and then to systemic diseases. Under this hypothesis, dental and systemic diseases shared-as a common cause-a diet of excess fermentable carbohydrates. Dental diseases were regarded as an alarm bell for future systemic diseases, and restricting carbohydrate intake prevented both dental and systemic diseases. On the opposite side, Keys postulated the lipid hypothesis: that excessive dietary lipid intake caused systemic diseases. Keys advocated a diet high in fermentable carbohydrate for the benefit of general health, and dental diseases became regarded as local dietary side effects. Because general health takes precedence over dental health when it comes to dietary recommendations, dental diseases became viewed as local infections; interventions such as fluorides, sealants, oral hygiene, antimicrobials, and dental fillings became synonymous with maintaining dental health, and carbohydrates were no longer considered as a common cause for dental-systemic diseases. These opposing dietary hypotheses have increasingly been put to the test in clinical trials. The emerging trial results favor Cleave-Yudkin's hypothesis and may affect preventive approaches for dental and systemic diseases.

Systemic antibiotics and tooth loss in periodontal disease.

Systemic antibiotics have been recommended for the treatment of destructive periodontal disease. Our goal was to relate antibiotic use for medical or dental reasons to subsequent tooth loss in a cohort of 12,631 persons with destructive periodontal disease. After adjustment for age, smoking, and other confounders, the dispensing of antibiotics for 1-13 days, 14-20 days, or 21 or more days was not associated with reduced tooth loss [Adjusted rate ratio (RR) = 1.0; 95% Confidence Interval (CI) = 0.8-1.1; RR = 1.2; 95% CI = 0.9-1.4, and RR =1.2, 95% CI =1.0-1.3, respectively]. Numerous subgroup analyses were consistent with these overall null findings, with two exceptions: Longer courses of tetracyclines were associated with reduced tooth loss among persons receiving periodontal care, and penicillin was associated with reduced tooth loss among persons with more severe disease. Long-term, larger randomized trials are needed to provide evidence that antibiotics reduce tooth loss when used in the management of destructive periodontal disease.

Secular trends in socio-economic disparities in edentulism: USA, 1972-2001.

For health care planning and policy, it is important to determine whether socio-economic disparities in edentulism, an ultimate marker of oral health, have improved over time. The aim of this study was to investigate the socio-economic disparities in edentulism between 1972 and 2001. Representative samples of the United States population, 25-74 years old, were obtained from NHANES I (1972), III (1991), and 1999-2002. Differences in the edentulism prevalence between high and low socio-economic positions (SEP) were compared. Differences in edentulism prevalence remained stable over approximately three decades (p = 0.480), being 10.6 percentage points in 1972, 12.1 percentage points in 1991, and 11.3 percentage points in 2001. Exploratory subgroup analyses suggested that disparities decreased for those individuals reporting a dental visit in the prior year and those reporting never having smoked. In conclusion, the absolute prevalence difference in edentulism between low and high socio-economic positions has remained unchanged over the last three decades.

Spurious associations in oral epidemiological research: the case of dental flossing and obesity.

BACKGROUND: Individuals with increased oral health awareness may also have increased general health awareness, and vice versa. Such associations between oral and general health awareness has the potential to induce spurious associations in oral epidemiological research. OBJECTIVE: To assess the extent to which oral self-care patterns and general health awareness are confounded, we investigated the association between flossing and obesity, two lifestyle factors that are unlikely to be causally related. METHODS: A cross-sectional study of 1497 individuals presenting for an initial periodontal exam by the specialist. Self-reported flossing behaviors and body mass index (BMI) categories were related using logistic regression models. RESULTS: After adjustment for confounding variables, lack of daily flossing was associated in a dose-dependent way with morbid obesity (odds ratio (OR), 20.3; 95% confidence interval (CI), 2.7-154.0), obesity (OR, 2.1; 95% CI, 1.5-2.9), and being overweight (OR, 1.7; 95% CI, 1.3-2.2). When restricting to never smokers, a significant relationship between obesity and lack of flossing remained. CONCLUSION: The strong associations between two causally unrelated oral and general lifestyle characteristics indicate that simplistic epidemiologic methodology is unlikely to provide insights into causal mechanisms of oral diseases or oral-systemic relationships.

Statin use and tooth loss in chronic periodontitis patients.

BACKGROUND: Statins have anti-inflammatory and bone stimulating properties that may positively affect chronic periodontitis. Our objective in this study was to evaluate whether statin use by chronic periodontitis patients had a beneficial impact on tooth loss. METHODS: In a retrospective cohort study (N patients = 1,021; mean follow-up = 7.1 years), dental records were merged with pharmacy data. Any statin use during 3 years, statin use during each of 3 consecutive years (regular use), and any statin use during the first 3 years after the initial periodontal exam were evaluated as predictors of tooth loss using negative binomial regression models with adjustment for potential confounding factors. RESULTS: Any statin use during 3 years was not associated with tooth loss rate in the year subsequent to the 3-year period (rate ratio [RR] = 1.00; 95% confidence interval [CI] = 0.56 to 1.81). Regular statin use during 3 years was associated with a non-significant 37% reduced tooth loss rate in the year subsequent to the 3-year period (RR = 0.63; 95% CI = 0.32 to 1.25). Any statin use during the first 3 years after the initial periodontal exam was associated with a 48% decreased tooth loss rate in year 4 and subsequent years (RR = 0.52; 95% CI = 0.29 to 0.95). CONCLUSIONS: Our findings were mixed for an association of statin use with reduced tooth loss in chronic periodontitis patients. Lack of control for some potential confounders, particularly smoking, and evaluation of different patterns of statin usage hamper the interpretation of the results. Exploration of these findings in additional epidemiological studies may be worthwhile.

Bias induced by self-reported smoking on periodontitis-systemic disease associations.

Non-causal associations between periodontitis and systemic diseases may be spuriously induced by smoking because of its strong relationship to both. The goal of this study was to evaluate whether adjustment for self-reported smoking removes tobacco-related confounding and eliminated such spurious confounding. Using NHANES III data, we evaluated associations between attachment loss and serum cotinine after adjustment by self-reported number of cigarettes smoked. Cotinine, a metabolite of nicotine, should not be related to attachment loss, if self-reported smoking captures the effect of tobacco on attachment levels. Adjustment for self-reported cigarette smoking did not completely remove the correlation between attachment loss and serum-cotinine level (r = 0.075, n= 1507, p = 0.003). Simulation studies indicated similar results for time-to-event data. These findings demonstrate the difficulty in distinguishing the effects of periodontitis from those of smoking with respect to a smoking-related outcome. Future studies should report results of analyses on separate subcohorts of never-smokers and smokers.

A hidden periodontitis epidemic during the 20th century?

OBJECTIVES: Increasing evidence suggests a strong causal link between smoking and periodontitis. The goal of this study was to impute how the secular changes in smoking prevalence during the 20th century impacted the advanced periodontitis incidence in the US. METHODS: Epidemiological analyses based on US prevalence data of advanced periodontitis and smoking, and predictions of future smoking prevalence. RESULTS: Assuming other risk factors for periodontitis remained constant, we estimated that the incidence of advanced periodontitis decreased by 31% between 1955 and 2000. The changes in smoking habits, and consequently the changes in periodontitis incidence, depended strongly on education and gender. Between 1966 and 1998, we estimated a 43% decreased periodontitis incidence among college-educated individuals versus only an 8% decrease among individuals with less than a high school education. Between 1955 and 1999, we estimated a 41% decrease among males versus a 14% decrease among females. By the year 2020, the incidence of advanced periodontitis may decrease 43% from its level in 1955. CONCLUSIONS: A periodontitis epidemic fueled by smoking remained hidden for most of the 20th century. Because this epidemic was hidden, it distorted our understanding of the treatment and etiology of periodontitis. The socioeconomic polarization of this epidemic will dictate alterations in patterns of periodontal care.

Does chronic periodontitis cause coronary heart disease? A review of the literature.

BACKGROUND: Chronic periodontitis, or CP, has been associated with coronary heart disease, or CHD. This article reviews the available prospective CP-CHD evidence. LITERATURE REVIEWED: In nine cohort studies, CP was associated with a 15 percent greater risk of developing CHD. Conclusions from individual studies depended on study characteristics. Summary risk estimates for studies controlling for smoking intensity (five of nine studies) or health awareness (two of nine studies) or studies with more than 600 CHD events (three of nine studies) suggest that CP is either not at all or weakly associated with CHD. Summary risk estimates for the studies that did not control for these factors or that examined an insufficient number of CHD events reported a weak increase in CHD risk associated with CP (20 percent greater). These data suggest that the CP-CHD associations observed in smaller studies are due to insufficient control for lifestyle differences. In addition, one cohort study reported that edentulous people had a CHD risk similar to that of people with CP. Therefore, the plausibility of dental infection elimination affecting CHD risk appears limited. SUMMARY: Current evidence supporting a causal CP-CHD link is weak. Rigorous methodological and analytical control of lifestyle factors such as smoking will be required to elucidate whether the CP-CHD disease association is either small or nonexistent. CLINICAL IMPLICATIONS: Cigarette smoking destroys both oral and systemic health. Because of this strong common causal factor, oral and systemic health are linked. Dentistry should continue to play an important role in implementing smoking prevention and cessation programs.

Fractal dimension on dental radiographs.

OBJECTIVES: (1) To compare fractal dimension (FD) from periapical radiographs with FD from panoramic radiographs; (2) to correlate FD with cortical thickness and morphology; and (3) to correlate FD with a reported history of osteoporotic fractures. METHODS: Information on fracture and smoking history was obtained by a telephone interview with 281 elderly (>60 years of age) patients who had periapical and panoramic radiographs exposed on the same date. FD was measured in several locations on both types of radiograph. Mandibular cortical thickness and morphology were obtained from the panoramic radiograph. RESULTS: FD measured in the mandible was lower than FD in the maxilla. Same-jaw measurements had a higher correlation than same-side measurements. FD measured on panoramic radiographs was lower than FD from periapical radiographs. There was a negative correlation between cortical thickness and FD. FD was higher in subjects with more mandibular cortical porosities and resorption. The mean panoramic FD from subjects with a history of osteoporotic fractures was significantly higher, after adjusting for smoking, gender, age, height and weight. CONCLUSIONS: FD measured on panoramic radiographs is lower than FD measured on periapical radiographs. FD is higher in both types of radiograph in subjects with a thinner, severely eroded mandibular cortex and a history of osteoporotic fractures. This study confirms other reports that FD increases when bone mass decreases. In addition, it suggests that panoramic radiographs can be used as a possible alternative for the measurement of FD to periapical radiographs.

Case-control study on self-reported osteoporotic fractures and mandibular cortical bone.

OBJECTIVES: The purpose of this case-control study was to determine whether the radiographic appearance of the mandibular cortical bone in patients who were elderly and noninstitutionalized was related to a self-reported history of osteoporotic fractures. STUDY DESIGN: Patients who had a billing statement at the School of Dentistry dated between 1993 and 1996, who were older than 60, and who had a panoramic radiograph were invited to be interviewed regarding fracture history (circumstances and year of fracture) and risk factors for osteoporosis. Cases (n = 93) were individuals reporting osteoporotic fractures (fractures occurring after minor impact). Controls (n = 394) were individuals reporting traumatic fractures (n = 105) or no fractures (n = 289). Blinded to case-control status, we evaluated the mandibular cortex on a panoramic radiograph and classified them as normal (even and sharp endosteal margin), moderately eroded (evidence of lacunar resorption or endosteal cortical residues), or severely eroded (unequivocal porosity). In addition, cortical thickness was measured below the mental foramen. RESULTS: After adjustment for potentially confounding factors, the odds ratio for an osteoporotic fracture associated with moderately eroded and severely eroded mandibular cortices was 2.0 (95% CI, 1.2 to 3.3) and 8.0 (95% CI, 2.0 to 28.9), respectively. After adjusting for all potentially confounding factors, we found that the cortex was 0.54 mm (or 12%) thinner in subjects with an osteoporotic fracture compared with controls (95% CI, 0.25 to 0.84 mm). CONCLUSIONS: Subjects with a self-reported history of osteoporotic fractures tend to have increased resorption and thinning of the mandibular lower cortex.

A survey of endpoint characteristics in periodontal clinical trials published 1988-1992, and implications for future studies.

Endpoints are conditions or events that are associated with individual study subjects and that are used to assess treatment efficacy. 2 types of endpoints can be distinguished: "true" endpoints (reflect unequivocal evidence of tangible benefit to the patient) and "surrogate" endpoints (usually a measure of disease process). The purpose of this study was to survey four aspects of endpoint usage in randomized controlled trials (RCT's) on the treatment of periodontitis: (1) the typical number of endpoints per RCT, (2) the proportion of RCTs using the same endpoint, (3) the proportion of RCTs using true endpoints, and (4) whether treatment choice influenced endpoint choice. 92 publications (1988-1992) reporting on 82 RCT's were identified. The typical number of endpoints per RCT was 6 (range: 1-28). The 3 most frequently used endpoints were mean probing depth (78% of the trials), mean probing attachment level (66%), and the plaque index (37%). In total, 153 distinct surrogate endpoints were defined. Most of these were used infrequently; over 80% of the 153 endpoints were used in fewer than 5 of the 82 trials. No trials used tooth loss as a true endpoint. In the design of an RCT, treatment choice influenced surrogate endpoint choice. Surrogate endpoints based on re-entry surgery were exclusively used for regenerative procedures and microbiological surrogate endpoints were mostly used for RCT's on anti-microbials. The conclusion is that the typical RCT used multiple surrogate endpoints, some of which were used infrequently by other trials. Such endpoint usage characteristics are suitable for exploratory RCTs (designed to identify active treatments or to elucidate treatment mechanisms). The question is raised as to whether periodontal research has reached the point of needing properly designed definitive studies, whose purpose it would be to provide unequivocal evidence of tangible benefits to the patient by the various treatments. If a need for definitive randomized controlled trials is perceived, then the use of (multiple) surrogate endpoints as primary outcomes should be questioned. Surrogate endpoint usage has led to both false positive and false negative conclusions in other chronic disease studies. Endpoint selection and validation in RCTs may be an important element in resolving controversies about periodontal treatments.

Configurational differences in six skeletal landmarks in surgically treated and nonsurgically treated Class II patients.

Nongrowing patients with full-cusp Class II malocclusions can be treated with or without orthognathic surgery. The purposes of this retrospective study were to observe if skeletal factors influence treatment decisions and to investigate whether a discriminant analysis based on skeletal landmarks can be used to approximate the clinician's decisions. Information was obtained from the records of 44 postmenarchal women with a full-cusp Class II occlusion. Orthognathic surgery was suggested for 23 (52%) of the patients. They were on average 7 years older and presented with a greater maxillomandibular disharmony than the patients treated without surgery. Evaluation of the spatial relationships between the anatomic points by means of multidimensional scaling revealed that the shape of the triangle between articulare, supramentale (point B), and subspinale (point A) differed significantly between groups. For 33 of the 44 patients (75%), the clinician's decisions coincided with a linear discriminant function based on the spatial relationship of subspinale, supramentale, and articulare. These findings suggest that age as well as skeletal configuration played a role in the orthodontist's decision to use surgical or nonsurgical treatment.

Metronidazole in periodontitis: reduced need for surgery.

A considerable amount of circumstantial evidence indicates that most forms of periodontitis are due to the presence or dominance of a finite number of bacterial species in the subgingival plaque. Almost all of the putative pathogens are anaerobic species, indicating that most forms of periodontitis could be diagnosed as anaerobic infections. In this double-blind investigation, patients with elevated proportions or levels of spirochetes in 2 or more plaque samples, i.e., 60% spirochetes, were randomly assigned to receive either metronidazole, 250 mg 3 x a day for 1 week, or placebo (positive-control) after the completion of all debridement procedures. When the patients were re-examined 4 to 6 weeks later, the patients in the metronidazole group (n = 15) exhibited a highly significant (p less than 0.01) reduction in probing depth and apparent gain in attachment levels relative to the patients (n = 18) in the positive-control group about those teeth that initially had probing depths of 4 to 6 mm. This pattern was also observed about teeth that initially had probing depths greater than or equal to 7 mm. This reduction in probing depths and apparent gain in attachment was associated with a significant reduction in the need for periodontal surgery in the metronidazole-treated patients (difference 8.4 teeth per patient) compared to the positive-control patients (2.6 teeth per patient). These clinical improvements in the metronidazole group were associated with significantly lower proportions of spirochetes, selenomonads, motile rods, and P. intermedius, and a significantly higher proportion of cocci in the plaques. These findings indicate that systemic metronidazole, when given after all the root surface debridement is completed, leads to additional treatment benefits, including a reduced need for surgery, beyond that which can be achieved by debridement alone.

Effects of metronidazole on periodontal treatment needs.

Periodontitis, a common cause of tooth loss in adult populations, is an inflammatory response to the overgrowth of anaerobic organisms such as spirochetes and bacteroides and, in some cases, micro-aerophilic organisms in the subgingival plaque. In the present investigation, using a double-blind clinical design, we sought to determine whether 1 week of metronidazole treatment plus debridement of the tooth surfaces was superior to 1 week of placebo treatment plus debridement (positive control) in reducing the subsequent amount of periodontal surgery given to the patients. Thirty-nine patients were randomly assigned to either the metronidazole or placebo (positive control) groups. All patients were given the necessary scaling and root planing and were unsupervised in their usage of the medication. After the completion of this treatment, they were reexamined and it was found that the metronidazole regimen caused a significant reduction in surgical needs of about 5 teeth per patient compared to the positive control (difference before and after treatment 8.3 +/- 6.8 teeth metronidazole versus 2.9 +/- 4.8 positive control, P = 0.007). The difference between groups was maintained during the 2 to 3 years' recall period. Metronidazole had a significant effect on the site specific reduction of spirochetes: 90% of the sites in the metronidazole group versus 64% in the positive-control group had a decrease in the percentage of spirochetes (P less than 0.05). We conclude that systemic metronidazole given 250 mg tid for 7 days in conjunction with debridement of the tooth surfaces can significantly reduce the need for periodontal surgery compared to the standard regimen which included only debridement.

The utility of the BANA test for monitoring anaerobic infections due to spirochetes (Treponema denticola) in periodontal disease.

Treponema denticola, Porphyromonas gingivalis, and Bacteroides forsythus each possesses an enzyme(s) that hydrolyzes the synthetic substrate benzoyl-DL-arginine-naphthylamide (BANA). The presence of these organisms in a subgingival plaque sample can be determined by the ability of the plaque to hydrolyze BANA. In the present study, we describe the usefulness of the BANA test at various stages of a clinical trial of the efficacy of metronidazole in the treatment of periodontal disease. A BANA-positive test was significantly associated with high levels and proportions of spirochetes in the plaque, so that it provided information comparable with that which could be obtained by a microscopic examination of the plaque. Patients with such anaerobic spirochetal infections were randomly assigned to a group receiving either metronidazole or placebo (250 mg, three times a day) for one week and whose teeth were scaled and root-planed. The advantages of the decision that metronidazole be used were apparent from the comparison with the results obtained in the patients who received only the scaling and root planing. The initially BANA-positive teeth in the patients treated with metronidazole, scaling, and root planing gained attachment and exhibited a significant reduction in the need for periodontal surgery, when compared with the BANA-positive teeth in the patients who received only placebo, scaling, and root planing. After the conclusion of this therapy, those teeth with persistent BANA-positive plaques had significantly higher proportions and levels of spirochetes than did the teeth with BANA-negative plaques.(ABSTRACT TRUNCATED AT 250 WORDS)