Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial.

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.

Oral health risk factors for bisphosphonate-associated jaw osteonecrosis.

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-1ß 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-1ß levels, suggesting that periodontitis and associated bacteria are potentially important in ONJ pathophysiology.

Compliance in a school-based caries clinical trial of a sugar-free chewing gum.

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.