Claudine Tsao's research while affiliated with University of Melbourne and other places

PURPOSE Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent but morbid and potentially serious condition associated with antiresorptive and antiangiogenic therapies. Although MRONJ can be prevented by optimizing oral health, management of established cases is supportive and remains challenging. Teriparatide, an osteoanabolic agent that improves bone healing in preclinical studies and in chronic periodontitis, represents a potential treatment option. PATIENTS AND METHODS In a double-blind, randomized, controlled trial, 34 participants with established MRONJ, with a total of 47 distinct MRONJ lesions, were allocated to either 8 weeks of subcutaneous teriparatide (20 µg/day) or placebo injections, in addition to calcium and vitamin D supplementation and standard clinical care. Participants were observed for 12 months, with primary outcomes that included the clinical and radiologic resolution of MRONJ lesions. Secondary outcomes included osteoblastic responses as measured biochemically and radiologically and changes in quality of life. RESULTS Teriparatide was associated with a greater rate of resolution of MRONJ lesions (odds ratio [OR], 0.15 v 0.40; P = .013), and 45.4% of lesions resolved by 52 weeks compared with 33.3% in the placebo group. Teriparatide was also associated with reduced bony defects at week 52 (OR, 8.1; P = .017). The incidence of adverse events was balanced between groups, including nausea, anorexia, and musculoskeletal pain, most of mild severity. CONCLUSION Teriparatide improves the rate of resolution of MRONJ lesions and represents an efficacious and safe treatment for it.

This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the effectiveness of chlorhexidine-containing oral products (toothpastes, mouthrinses, varnishes, gels, gums and sprays) in adults on reducing dental caries rates as compared with topical fluoride treatments, placebo or no treatment. To assess if there are optimum parameters of administration of chlorhexidine-containing oral products (e.g. form, concentration, frequency). To examine whether the effect of chlorhexidine-containing oral products is influenced by the level of caries in the population. To describe reported adverse effects, their rate of occurrence and potential to interfere with treatment. It is recognised that studies included in the review of effectiveness may not provide a comprehensive summary of adverse effects. The following null hypotheses will be tested. There is no difference in caries rates between adults using chlorhexidine-containing products compared with topical fluoride treatments, placebo or no treatment. There is no difference in caries rates between adults using chlorhexidine-containing products according to different parameters of administration (form, concentration, frequency).

PURPOSE: To investigate the role of oral health, including periodontitis, as a risk factor for bisphosphonate-associated jaw osteonecrosis (ONJ). MATERIALS AND METHODS: This cross-sectional study compared cases with an ONJ history to controls. All had a history of bisphosphonate treatment for malignancy. Participants underwent oral examination, gingival crevicular fluid (GCF) sampling, and phlebotomy. Serum was analyzed for biochemical parameters, bone markers, and immunoglobulin G titers against 4 periodontitis-associated bacteria. Cytokine levels were determined in GCF using a multiplex assay. RESULTS: Caries development was comparable between groups. Periodontitis was significantly associated with ONJ using the US National Center for Health Statistics periodontitis definition (P = .002), at least 1 site with a probing depth of at least 4 mm (P = .003), and the percentage of sites per participant with a probing depth of 4 to 5 mm (P = .044). Immunoglobulin G titer against Porphyromonas gingivalis and GCF interleukin-1β level were also significantly associated with ONJ (P = .018 and P = .044, respectively). CONCLUSION: In participants with a history of bisphosphonate treatment for malignancy, periodontitis was associated with ONJ when measured using clinical parameters, serum immunoglobulin G titers against P gingivalis, and GCF interleukin-1β levels, suggesting that periodontitis and associated bacteria are potentially important in ONJ pathophysiology.

Objective: This study aims to assess the influence of the clinical experience of the examiner and the diagnostic threshold of the radiographic grading system on the reproducibility and diagnostic accuracy for approximal caries lesions. Method: 200 standardized digital bitewing radiographs pairs were sampled from those taken during a caries clinical trial in adolescents. All radiographs were scored using the Pitts grading system, which allowed both enamel and dentine lesions to be scored at two depths and included a method for scoring caries when overlaps were present. Three experienced dentists (clinical trial radiograph reviewer, clinical trial examiner, paediatric dentist) were trained and calibrated in the grading system prior to its use. Scoring was undertaken in a dedicated room with controlled lighting, a calibrated monitor and custom-built database. Sensitivity, specificity and the area (Az) under the ROC curve were calculated at D1 (enamel) and D3 (dentine) thresholds. Consensus grading by all examiners was used as a gold standard. Result: 4800 proximal surfaces (4d to 7m) were assessed. Prevalence of enamel and dentine lesions were 12.6% and 2.3%, respectively, < 1% had fillings and 3.6% had unreadable overlap. Kappa values between each examiner and the consensus were 0.84, 0.85 and 0.83. At the D1 threshold, sensitivity values were 0.75, 0.76 and 0.89; specificity values were 0.99, 0.99 and 0.96 and Az values were 0.87, 0.88 and 0.93. At the D3 threshold, sensitivity values were 0.70, 0.82 and 0.75; specificity values were 1.00, 1.00 and 1.00; and Az values were 0.85, 0.90 and 0.88. Conclusion: The reproducibility of radiographic scoring for approximal caries using the Pitts grading system was excellent at both the D1 and D3 thresholds. Random effects modelling approach which utilizes the ordinal scale of the grading system and can other covariates will also be discussed.

Bisphosphonates are drugs that suppress bone turnover and are commonly prescribed to prevent skeletal related events in malignancy and for benign bone diseases such as osteoporosis. Bisphosphonate associated jaw osteonecrosis (ONJ) is a potentially debilitating, yet poorly understood condition. A literature review was undertaken to review the dental clinical implications of bisphosphonates. The present paper briefly describes the postulated pathophysiology of ONJ and conditions with similar clinical presentations. The implications of bisphosphonates for implantology, periodontology, orthodontics and endodontics are reviewed. Whilst bisphosphonates have potential positive applications in some clinical settings, periodontology particularly, further clinical research is limited by the risk of ONJ. Prevention and management are reviewed, including guidelines for reducing cumulative intravenous bisphosphonate dose, cessation of bisphosphonates prior to invasive dental treatment or after ONJ development, and the use of serum beta-CTX-1 in assessing risk. In the context of substantial uncertainty, the implications of bisphosphonate use in the dental clinical setting are still being determined.

Unlabelled: There is currently little reliable and quantifiable compliance data reported for preventive trials of oral disease. During a two-year, school-based caries clinical trial of sugar-free chewing gum, strategies to promote compliance with a gum-chewing protocol were implemented and outcomes measured. Methods: Over a 28-month period 2720 subjects, aged 11½-13½ at baseline, were recruited from 29 secondary colleges in Melbourne, Australia. Subjects were required to chew gum (test or control) for 10 min 3× daily, including once during a supervised school chewing session. The main compliance promotion strategies were regular school visits, regular provision of information and performance feedback and reimbursement. Compliance was measured using supervised school chewing logs, self-report paper diaries and returned unused home-use gum. The primary compliance outcome was the percentage of supervised school sessions attended by the subject over a 24-month period. Results: Overall supervised session attendance was 63.9 ± 17.6%. There was no significant difference between control and test groups in supervised session attendance. Average diary return rate was 76%, with final diary returns of 84%. Data from diaries were not considered sufficiently robust to analyse and report. The return rate for unused home-use gum was poor. Conclusions: This research highlights the importance of: (1) dedicated compliance trial personnel in an adequate ratio to trial subjects; (2) inclusion in protocols of direct methods of measuring compliance; (3) prompt analysis of compliance data; (4) piloting of compliance data collection tools and (5) self-report paper diaries having questionable feasibility as a compliance data collection tool.

Orthodontic patients have an increased risk of white-spot lesion formation. A clinical trial was conducted to test whether, in a post-orthodontic population using fluoride toothpastes and receiving supervised fluoride mouthrinses, more lesions would regress in participants using a remineralizing cream containing casein phosphopeptide- amorphous calcium phosphate compared with a placebo. Forty-five participants (aged 12-18 yrs) with 408 white-spot lesions were recruited, with 23 participants randomized to the remineralizing cream and 22 to the placebo. Product was applied twice daily after fluoride toothpaste use for 12 weeks. Clinical assessments were performed according to ICDAS II criteria. Transitions between examinations were coded as progressing, regressing, or stable. Ninety-two percent of lesions were assessed as code 2 or 3. For these lesions, 31% more had regressed with the remineralizing cream than with the placebo (OR = 2.3, P = 0.04) at 12 weeks. Significantly more post-orthodontic white-spot lesions regressed with the remineralizing cream compared with a placebo over 12 weeks.

This study investigated, using digital bitewing radiography, the progression and regression of approximal caries in adolescent subjects chewing a sugar-free gum containing 54 mg CPP-ACP relative to the identical gum without CPP-ACP. 2,720 subjects from 29 schools were randomly assigned to one of the two gums and were instructed to chew their assigned gum for 3 x 10 min/day, with one session supervised on school days, over the 24-month study period. Standardized digital bitewing radiographs were taken at the baseline and 24-month clinical examinations for each subject. The radiographs, scored by a single examiner, were assessed for approximal surface dental caries at both the enamel and dentine level. Surface level transitions were scored using a transition matrix. Caries progression or regression was analysed using proportional-odds ordered logistic regression modelling of the transition scores at the tooth surface level. There was a statistically significant difference in the frequency distributions of the transition scores between the two gum groups (OR = 0.82, p = 0.03). For subjects chewing the CPP-ACP gum the odds of a surface experiencing caries progression were 18% less than those of a surface experiencing caries progression for subjects chewing the control gum. In conclusion, the 54 mg CPP-ACP sugar-free gum significantly slowed progression and enhanced regression of approximal caries relative to a control sugar-free gum in a 24-month clinical trial.