Keita Asai

Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study.

This study estimated the cumulative incidence and risk ratio for osteonecrosis of the jaw (ONJ) after tooth extraction in patients with and without administration of bisphosphonates (BP) and identified potential risk factors for bisphosphonate-induced osteonecrosis of the jaw (BIONJ). A cohort study was conducted in all patients undergoing tooth extraction at a university hospital in Japan from April 2006 to June 2009. Of 3216 patients, 126 had BP administration, of whom 5 (3.9%, 95% confidence interval (CI): 1.2-9.2) developed ONJ, versus 1 (0.032%, 95% CI: 0.00081-0.18) among 3090 patients without BP administration. BP administration was associated with the development of ONJ after tooth extraction, with an unadjusted risk ratio of 122.6 (95% CI: 14.4-1041.8). When stratified by age and route of BP administration, the risk ratio for ONJ patients aged 65 years or older with intravenous BP administration compared to those without was 200.2 (95% CI: 23.8-1679.4, P<0.001). Patients receiving BP showed a significant association between the incidence of BIONJ and alveolar bone loss score. The risk of ONJ is higher in patients with than without BP administration, particularly intravenous administration. Severe periodontitis might be a risk factor for BIONJ.

Risk of osteomyelitis of the jaw induced by oral bisphosphonates in patients taking medications for osteoporosis: A hospital-based cohort study in Japan

Oral bisphosphonates (BPs) represent the first line of prevention and treatment for osteoporosis. However, several studies have reported osteonecrosis of the jaw (ONJ), also known as osteomyelitis of the jaw (OMJ), as a side effect of these drugs. Although absolute risk is suggested to be low, information to date on the relative risk or attributable risk has in fact been limited. Here, we estimated risk of oral BPs for OMJ in osteoporosis patients taking oral BPs compared with other osteoporosis drugs. Using an electronic medical records retrieval system and manual confirmation of OMJ, we conducted a retrospective cohort study of patients taking medications for osteoporosis at Kyoto University Hospital between November 2000 and October 2010. To evaluate relative risks of oral BPs for OMJ, logistic regression analysis was performed and odds ratios (ORs) and 95% confidence interval (CIs) were estimated. In addition, sensitivity analyses were performed according to hierarchical diagnosis. A total of 4129 patients (59.6%) were prescribed BPs while 2794 (40.3%) received other osteoporosis drugs. Absolute risk for OMJ was estimated to range from 0.46% to 0.99% (95% CIs: 0.25-0.66 to 0.69-1.2) among patients receiving oral BPs and 0.071% to 0.17% (95% CIs: 0-0.17 to 0.022-0.33) among patients receiving other osteoporosis drugs. The attributable risks of oral BPs for OMJ were estimated to range from 0.38% to 0.81% (95% CIs: 0.38-0.39 to 0.80-0.81). ORs (95% CIs) adjusted for confounding factors were 5.0 (1.9-12.9) to 6.0 (1.3-26.1) for confirmed cases only. In terms of absolute and attributable risks, the risk of oral BPs for OMJ is considered to be less than 1% in patients with osteoporosis. However, oral BPs may increase the risk of OMJ compared with patients treated with other osteoporosis medications and the risk of side effects should be kept in mind.

Mastication and Risk for Diabetes in a Japanese Population: A Cross-Sectional Study

Background Associations between mastication and insufficient nutrient intake, obesity, and glucose metabolism have been shown in previous studies. However, the association between mastication and diabetes has not been clarified. Our objective was to examine the association between mastication, namely masticatory performance or rate of eating, and diabetes in a population-based cohort. Methods We conducted a cross-sectional study of the association between mastication and diabetes in the Nagahama Prospective Cohort Study, an ongoing study which recruits citizens of Nagahama City in Shiga Prefecture, central Japan. 2,283 male and 4,544 female residents aged 40–74 years were enrolled from July 2009 to November 2010. Masticatory performance was evaluated by spectrophotometric measurement of color changes after masticating color-changeable chewing gum. Categorical rate of eating (fast, intermediate or slow) was self-assessed using a questionnaire. Results 177 males (7.7%) and 112 (2.4%) females were diagnosed with diabetes. We divided participants into four groups by quartile of masticatory performance, namely Q1 (lowest), 2, and 3 and 4 (highest). Compared to the lowest performance group, the multivariable adjusted odds ratio (OR) of diabetes was 0.91 (95% confidence interval (CI), 0.58–1.4) in Q2, 0.77 (95% CI, 0.48–1.2) in Q3, and 0.53 (95% CI, 0.31–0.90) in the highest group in males, and 1.2 (95% CI, 0.73–2.0), 0.95 (95% CI, 0.54–1.6) and 0.56 (95% CI, 0.30–1.0) in females. We also estimated ORs of diabetes by rate of eating. Compared to the fast eating group, ORs in males were 0.87 (95% CI, 0.61–1.2) in the intermediate group and 0.38 (95% CI, 0.16–0.91) in the slow group, and ORs in females were 0.92 (95% CI, 0.59–1.4) and 1.5 (95% CI, 0.73–3.0). Conclusions These findings support the hypothesis that higher masticatory performance and slow eating prevent the occurrence of diabetes.

A pragmatic method for electronic medical record-based observational studies: developing an electronic medical records retrieval system for clinical research

Objective The use of electronic medical record (EMR) data is necessary to improve clinical research efficiency. However, it is not easy to identify patients who meet research eligibility criteria and collect the necessary information from EMRs because the data collection process must integrate various techniques, including the development of a data warehouse and translation of eligibility criteria into computable criteria. This research aimed to demonstrate an electronic medical records retrieval system (ERS) and an example of a hospital-based cohort study that identified both patients and exposure with an ERS. We also evaluated the feasibility and usefulness of the method. Design The system was developed and evaluated. Participants In total, 800 000 cases of clinical information stored in EMRs at our hospital were used. Primary and secondary outcome measures The feasibility and usefulness of the ERS, the method to convert text from eligible criteria to computable criteria, and a confirmation method to increase research data accuracy. Results To comprehensively and efficiently collect information from patients participating in clinical research, we developed an ERS. To create the ERS database, we designed a multidimensional data model optimised for patient identification. We also devised practical methods to translate narrative eligibility criteria into computable parameters. We applied the system to an actual hospital-based cohort study performed at our hospital and converted the test results into computable criteria. Based on this information, we identified eligible patients and extracted data necessary for confirmation by our investigators and for statistical analyses with our ERS. Conclusions We propose a pragmatic methodology to identify patients from EMRs who meet clinical research eligibility criteria. Our ERS allowed for the efficient collection of information on the eligibility of a given patient, reduced the labour required from the investigators and improved the reliability of the results.

Periodontitis and Porphyromonas gingivalis in Preclinical Stage of Arthritis Patients

Purpose To determine whether the presence of periodontitis (PD) and Porphyromonas gingivalis (Pg) in the subgingival biofilm associates with the development of rheumatoid arthritis (RA) in treatment naïve preclinical stage of arthritis patients. Methods We conducted a prospective cohort study of 72 consecutive patients with arthralgia who had never been treated with any anti-rheumatic drugs or glucocorticoids. Periodontal status at baseline was assessed by dentists. PD was defined stringently by the maximal probing depth≧4 mm, or by the classification by the 5th European Workshop in Periodontology (EWP) in 2005 using attachment loss. Up to eight plaque samples were obtained from each patient and the presence of Pg was determined by Taqman PCR. The patients were followed up for 2 years and introduction rate of methotrexate (MTX) treatment on the diagnosis of RA was compared in patients with or without PD or Pg. Results Patients with PD (probing depth≧4mm) had higher arthritis activity (p = 0.02) and higher risk for future introduction of MTX treatment on the diagnosis of RA during the follow up than patients without PD (Hazard ratio 2.68, p = 0.03). Arthritis activity and risk for MTX introduction increased with the severity of PD assessed by EWP, although not statistically significant. On the other hand, presence of Pg was not associated with arthritis activity (p = 0.72) or the risk for MTX introduction (p = 0.45). Conclusion In treatment naïve arthralgia patients, PD, but not the presence of Pg, associates with arthritis activity and future requirement of MTX treatment on the diagnosis of RA.

Tooth Loss and Atherosclerosis The Nagahama Study

Several epidemiologic studies have suggested that oral disease is a risk factor for cardiovascular disease (CVD). However, whether a clinically significant association exists between the 2 disorders remains controversial. Here, we investigated the association between tooth loss, as an indicator of oral disease, and arterial stiffness, as a marker of atherosclerosis, in Japanese adults. Cross-sectional data were collected for 8,124 persons aged 30 to 75 y with no history of tooth loss for noninflammatory reasons, such as orthodontic treatment, malposition, and trauma. Participants received a comprehensive dental examination and extensive in-person measurements of CVD risk factors, and arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). We examined the association between CAVI and tooth loss using general linear models with adjustment for age, sex, body mass index, smoking status, hemoglobin A1c, and a history of insulin or hypoglycemic medication depending on the model. In addition, we performed an analysis that included interaction terms of the centered variables tooth loss, sex, and age. The results of the multiple regression analysis that included the interaction terms detected that the relationship between CAVI and tooth loss was dependent on sex, with only men showing a positive correlation (β for interaction = 0.04; 95% confidence interval, 0.02–0.06). The findings from this study suggest that a linear relationship exists between tooth loss and degree of arterial stiffness and that the association differed depending on sex.

The novel association between red complex of oral microbe and body mass index in healthy Japanese: a population based cross-sectional study.

Microbiota has been thought to be one of important environmental factors for obesity or Type 2 diabetes mellitus. Among oral microbe, Porphyromonas gingivalis, Treponema denticola and Tannellera forsythia are known as risk factors, so called red complex, for periodontitis. Red complex could also be a risk factor for obesity. However, recent study indicated that obesity was not improved by periodontal therapy. Thus, we performed a cross sectional study to reveal the association of oral microbe with body mass index in a healthy population. Healthy individuals were randomly recruited. The infections of oral microbe were identified by Taqman polymerase chain reaction. The relationships between number of red complex and body mass index or waist circumference were analyzed. Two hundred and twenty-two apparently healthy Japanese were enrolled. BMI and waist circumference as well as age, periodontitis, number of brushing teeth were significantly associated with the number of red complex after adjusting covariance. The effect size of body mass index or waist circumference was 0.023 (p = 0.028) or 0.024 (p = 0.024), respectively. Body mass index and waist circumference were independently associated with the number of red complex among apparently healthy Japanese. The current observation implies the possibility that oral microbe was associated with obesity in healthy population.

Assessing anteroposterior basal bone discrepancy with the Dental Aesthetic Index

OBJECTIVE To investigate dental appearance and cephalometric features, using a sample of orthognathic and/or orthodontic patients. A special interest was to identify the relationship of the Dental Aesthetic Index (DAI) with anteroposterior basal bone discrepancy (APBBD) and cephalometric indicators. MATERIALS AND METHODS A full sample of 159 patients in two Japanese hospitals was used. Each patient was assessed with a preorthodontic dental cast and cephalometric radiography. RESULTS Malocclusion with APBBD was more prevalent among high DAI subjects (P  =  .034, OR  =  1.04, 95% CI: 1.00-1.08), Class III malocclusion patients (P  =  .048, OR  =  2.32, 95% CI: 1.01-5.34) and male patients (P  =  .008, OR  =  2.96, 95% CI: 1.33-6.61). Participants scoring 88 points (the highest score in this sample) of the DAI had 16.84 times the risk of APBBD of those who scored 17 points (the lowest score in this sample). Patients with APBBD presented with a greater adjusted ANB angle (t  =  -8.10, P < .001) and a larger adjusted A-B/NF appraisal (t  =  -9.65, P < .001). The SNA angle (P < .001), the SNB angle (P  =  .002), the adjusted ANB angle (P  =  .001), and the adjusted A-B/NF appraisal (P  =  .035) were associated with DAI scores in cubic regression models. CONCLUSION This study has demonstrated a relationship between the DAI and APBBD. Feasibility of using the adjusted ANB angle and the adjusted A-B/NF appraisal to assess severity of APBBD has been confirmed. The DAI may provide a supportive method to evaluate orthognathic needs. Future investigations are indicated.

Mouth breathing, another risk factor for asthma: The Nagahama Study

Allergic rhinitis, a known risk factor for asthma onset, often accompanies mouth breathing. Mouth breathing may bypass the protective function of the nose and is anecdotally considered to increase asthma morbidity. However, there is no epidemiological evidence that mouth breathing is independently associated with asthma morbidity and sensitization to allergens. In this study, we aimed to clarify the association between mouth breathing and asthma morbidity and allergic/eosinophilic inflammation, while considering the effect of allergic rhinitis.

Risk factors and indices of osteomyelitis of the jaw in osteoporosis patients: results from a hospital-based cohort study in Japan.

Background Several studies have reported osteomyelitis of the jaw (OMJ) as a side effect of bisphosphonates (BPs), and the risk of oral BPs has been recently clarified. However, other systemic risk factors of OMJ remain unclear. Importantly, the possibility of risk classification based on the clinical characteristics of patients has not been explored. Here, we clarified risk factors of OMJ and evaluate the predictive accuracy of risk indices in osteoporosis patients. Methods We performed sub-analysis using a database developed for a retrospective cohort study in patients taking medications for osteoporosis at Kyoto University Hospital. Risk indices for OMJ were constructed using logistic regression analysis, and odds ratios (OR) for OMJ cases and 95% confidence intervals (CI) were estimated. Potential risk factors included in the statistical analysis were age; sex; diabetes; use of oral BPs, corticosteroids, cancer chemotherapy, antirheumatic drugs, and biologic agents; and their interactions. Risk indices were calculated by the sum of potential risk factors of an individual patient multiplied by the regression coefficients. The discriminatory power of the risk indices was assessed by receiver operating characteristic (ROC) analysis. Results In analysis of all patients, oral BPs (OR: 4.98, 95% CIs: 1.94-12.75), age (OR: 1.28, 95% CI: 1.06-1.60) and sex-chemotherapy interaction (OR: 11.70, 95% CI: 1.46-93.64) were significant risk factors of OMJ. Areas under the ROC curves of these risk indices provided moderate sensitivity or specificity regardless of group (0.683 to 0.718). Conclusions Our data suggest that oral BP use, age, and sex-chemotherapy are predictors of OMJ in osteoporosis patients. The risk indices are moderately high, and allow the prediction of OMJ incidence.