Controversial Aspects of Diagnostics and Therapy of Idiopathic Condylar Resorption: An Analysis of Evidence- and Consensus-Based Recommendations Based on an Interdisciplinary Guideline Project.

Idiopathic condylar resorption (ICR), though a rare event, is associated with severe detrimental sequelae for the patient. To date, the etiology remains unknown, and treatment strategies are highly controversial. Therefore, the aim of this study is to present an analysis of the consensus- and evidence-based approach to ICR by a German interdisciplinary guideline project of the AWMF (Association of the Scientific Medical Societies in Germany). Following a systematic literature search, including 56 (out of an initial 97) publications, with a predominantly low level of evidence (LoE), two independent working groups (oral and maxillofacial surgery and interdisciplinary, respectively) voted on a draft comprising 25 recommendations in a standardized anonymized and blinded Delphi procedure. While the results of the votes were relatively homogeneous, the interdisciplinary phase required a significantly higher number of rounds (p < 0.001). Most of the controversial recommendations were related to initial imaging (with consensus on CT/CBCT as the current diagnostic standard for imaging), pharmacotherapy (no recommendation due to lack of evidence), discopexy (no recommendation possible due to low LoE) and timing of orthognathic surgery (with consensus on two-staged procedures after invasive TMJ surgery, except for single-stage procedures if combined with total joint reconstruction). Overall, the Delphi procedure resulted in an interdisciplinary guideline offering the best possible evidence- and consensus-based expertise to date in the diagnosis and treatment of ICR.

Controversial Aspects of Diagnostics and Therapy of Arthritis of the Temporomandibular Joint in Rheumatoid and Juvenile Idiopathic Arthritis-An Analysis of Evidence- and Consensus-Based Recommendations Based on an Interdisciplinary Guideline Project.

Introduction: Due to potentially severe sequelae (impaired growth, condylar resorption, and ankylosis) early diagnosis of chronic rheumatic arthritis of the temporomandibular joint (TMJ) and timely onset of therapy are essential. Aim: Owing to very limited evidence the aim of the study was to identify and discuss controversial topics in the guideline development to promote further focused research. Methods: Through a systematic literature search, 394 out of 3771 publications were included in a German interdisciplinary guideline draft. Two workgroups (1: oral and maxillofacial surgery, 2: interdisciplinary) voted on 77 recommendations/statements, in 2 independent anonymized and blinded consensus phases (Delphi process). Results: The voting results were relatively homogenous, except for a greater proportion of abstentions amongst the interdisciplinary group (p < 0.001). Eighty-four percent of recommendations/statements were approved in the first round, 89% with strong consensus. Fourteen recommendations/statements (18.2%) required a prolonged consensus phase and further discussion. Discussion: Contrast-enhanced MRI was confirmed as the method of choice for the diagnosis of TMJ arthritis. Intraarticular corticosteroid injection is to be limited to therapy-refractory cases and single injection only. In adults, alloplastic joint replacement is preferable to autologous replacement. In children/adolescents, autologous reconstruction may be performed lacking viable alternatives. Alloplastic options are currently still considered experimental.

[Management of medication-related osteonecrosis of the jaw-a review of recent study results in comparison to established strategies]. / Management von medikamentenassoziierten Kiefernekrosen ­ Ergebnisse einer Literaturanalyse neuester Studien im Vergleich zu bewährten Strategien.

BACKGROUND: Antiresorptive agents are some of the most frequently used drugs worldwide, with indications in osteology and oncology. They are generally well tolerated and display a favorable safety profile. A potentially severe unwanted side effect is medication-related osteonecrosis of the jaw (MRONJ). PURPOSE OF THIS REVIEW: This review summarizes the latest developments in etiology, diagnosis, and treatment of MRONJ, and compares new insights with established algorithms. METHODS: A systematic review of relevant studies exploring diagnostic methods, prospective management trials, and innovative studies on the pathogenesis of MRONJ published between 2016 and 2021 was performed. The study quality was assessed using the MINORS (methodological index for non-randomized studies) rating score. RESULTS AND DISCUSSION: The prevalence of MRONJ in patients undergoing treatment with antiresorptive drugs for oncological reasons is remarkable (2-12%). MRONJ prevalence in patients receiving antiresorptive drugs for the treatment of osteoporosis is much lower (0.1-1%). MRONJ treatment should be initiated early and involve a surgical approach. MRONJ treatment is safe and predictable, with long-term success rates of more than 85%.

Risk factors associated with onset of medication-related osteonecrosis of the jaw in patients treated with denosumab.

OBJECTIVES: While risk factors of bisphosphonate (BP) associated osteonecrosis of the jaw have been properly analyzed, studies focusing on risk factors associated with denosumab (DNO) are sparse. The purpose of this study was to identify risk factors influencing the onset of medication-related osteonecrosis of the jaw (MRONJ) in patients receiving antiresorptive treatment (ART) with DNO by comparing patients suffering from MRONJ and patients without MRONJ. Multiple variables were evaluated including the impact of a previous BP intake. MATERIALS AND METHODS: A retrospective single-center cohort study with patients receiving DNO was conducted. One-hundred twenty-eight patients were included and divided into three groups: I (control, n = 40) receiving DNO with absence of MRONJ; group II (Test 1, n = 46), receiving DNO with presence of MRONJ; and group III (Test 2, n = 42) sequentially receiving BP and DNO with presence of MRONJ. Patients' medical history, focusing on the identification of MRONJ risk factors, was collected and evaluated. Parameters were sex, age, smoking habit, alcohol consumption, underlying disease (cancer type, osteoporosis), internal diseases, additional chemo/hormonal therapy, oral inflammation, and trauma. RESULTS: The following risk factors were identified to increase MRONJ onset significantly in patients treated with DNO: chemo/hormonal therapy (p = 0.02), DNO dosage (p < 0.01), breast cancer (p = 0.03), intake of corticosteroids (p = 0.04), hypertension (p = 0.02), diabetes mellitus (p = 0.04), periodontal disease (p = 0.03), apical ostitis (p = 0.02), and denture use (p = 0.02). A medication switch did not affect MRONJ development (p = 0.86). CONCLUSIONS: Malignant diseases, additional chemotherapy, DNO dosage, and oral inflammations as well as diabetes mellitus and hypertension influence MRONJ onset in patients treated with DNO significantly. CLINICAL RELEVANCE: Patients receiving ART with DNO featuring aforementioned risk factors have a higher risk of MRONJ onset. These patients need a sound and regular prophylaxis in order to prevent the onset of MRONJ under DNO treatment.

Infection as an Important Factor in Medication-Related Osteonecrosis of the Jaw (MRONJ).

Medication-related osteonecrosis of the jaw (MRONJ) has become a well-known side effect of antiresorptive, and antiangiogenic drugs commonly used in cancer management. Despite a considerable amount of literature addressing MRONJ, it is still widely accepted that the underlying pathomechanism of MRONJ is unclear. However, several clinical and preclinical studies indicate that infection seems to have a major role in the pathogenesis of MRONJ. Although there is no conclusive evidence for the infection hypothesis yet, available data have shown a robust association between local infection and MRONJ development. This observation is very critical in order to implement policies to reduce the risk of MRONJ in patients under antiresorptive drugs. This critical review was conducted to collect the most reliable evidence regarding the link between local infection and MRONJ pathogenesis.

Autofluorescence-guided surgery for the treatment of medication-related osteonecrosis of the jaw (MRONJ): a retrospective single-center study.

OBJECTIVE: Medication-related osteonecrosis of the jaw (MRONJ) has become a serious concern for patients under antiresorptive treatment, especially in the oncological setting. Different approaches have been described in the management of MRONJ, including innovative autofluorescence-guided surgery. However, until now, there has been a lack of data regarding the outcome. In this study, we evaluated the efficacy of minimally invasive autofluorescence-guided resection in MRONJ. STUDY DESIGN: Seventy-five patients with 82 lesions were included in this retrospective, single-center study. All included patients were diagnosed with MRONJ according to the American Association of Oral and Maxillofacial Surgeons guidelines and underwent autofluorescence-guided surgery with a minimum follow-up of 3 months. The primary outcome was complete integrity of the mucosa and absence of bone exposure. RESULTS: The MRONJ stages were stage 0 (3.7%), stage 1 (3.7%), stage 2 (75.6%), and stage 3 (17%). Overall, complete mucosal healing of all lesions after the first surgery was 81.7% (67 of 82), whereas it was 90.2% (74 of 82) after revision surgery. CONCLUSIONS: The study showed that autofluorescence-guided surgery is a safe and successful treatment option that can be considered for all stages of MRONJ.

The Type of Antiresorptive Treatment Influences the Time to Onset and the Surgical Outcome of Medication-Related Osteonecrosis of the Jaw.

PURPOSE: Few data exist focusing on differences in the time to disease onset and the success rates in patients suffering from medication-related osteonecrosis of the jaw (MRONJ) dependent on their different antiresorptive treatment. The purpose of this study was to analyze and compare these variables for patients treated with bisphosphonate (BP) or denosumab (DNO) and for patients who switched the antiresorptive drug (BP/DNO). PATIENTS AND METHODSS: A retrospective single-center cohort study with patients suffering from MRONJ was conducted. The predictor variable was the antiresorptive treatment, the outcome variables were 1) time to onset of MRONJ (time of antiresorptive treatment to MRONJ diagnosis) and 2) treatment success (mucosal integrity 12 months postoperatively). The other variables include data on demographic, underlying disease, MRONJ stage, and trigger events. Cox and logistic regression, Phi-coefficient, Cramer's V, and Kruskal-Wallis tests were applied. RESULTS: One hundred thirty-two patients were included and divided into 3 groups: group I (BP) n = 45 patients, n = 59 lesions; group II (BP/DNO) n = 42 patients, n = 71 lesions; and group III (DNO) n = 45 patients, n = 62 MRONJ lesions. Treatment success and time to onset differed significantly between the groups: success rates in group I BP (84.7%) were significantly lower (P = .04) than in group II BP/DNO (91.5%, P = .12) and group III DNO (90.3%, P = .35). The onset was significantly earlier in group III DNO (median 2.0 years, Q0.25: 1.49, Q0.75: 2.98; confidence interval 95%: 1.93 to 2.83) than in group II BP/DNO (median 4.07 years, Q0.25: 1.64, Q0.75: 6.70; confidence interval 95%: 3.55 to 5.68) and group I BP (median 3.86 years, Q0.25: 1.69, Q0.75: 6.46; confidence interval 95%: 3.43 to 5.87). CONCLUSIONS: The different antiresorptive drugs show distinctive characteristics of time to onset and treatment success with the lowest success rates in the BP group and the earliest onset in the DNO group. The switch of the antiresorptive therapy (BP to DNO) did not influence the outcome variables negatively.

A Drug Holiday Reduces the Frequency and Severity of Medication-Related Osteonecrosis of the Jaw in a Minipig Model.

Treatment of medication-related osteonecrosis of the jaw (MRONJ) is challenging and no clear consensus has been achieved. This study investigated preventive measures recommended for tooth extractions under antiresorptive (AR) treatment and the role of discontinuation of AR therapy to avoid the onset of MRONJ in a minipig model. Thirty-six Göttingen minipigs were divided into four groups. Group 1 (negative control): tooth extractions but no zoledronate (ZOL). Group 2 (positive control): weekly ZOL infusions for 12 weeks followed by tooth extractions without wound management followed by 8 weeks of ZOL treatment. Group 3: weekly ZOL infusions for 12 weeks followed by tooth extractions; surgical wound management (resection of sharp bone edges, mucoperiosteal coverage); and continuation of ZOL infusions for 8 weeks plus antibiotic treatment. Group 4: 12 weeks of ZOL infusions followed by a drug holiday for 6 weeks. Tooth extractions with preventive wound management followed by antibiotic treatment for 8 weeks but no ZOL infusions. Jawbones were subjected to macroscopic, radiological (CT and micro-CT) and histopathological investigations. No clinical cases of MRONJ were observed in the negative group, in the positive control all animals developed MRONJ. Group 3 developed MRONJ in 83% of cases. With a drug holiday, 40% developed MRONJ in areas of tooth extraction. This is the first large animal model that reduces the occurrence of MRONJ following tooth extraction by the implementation of a drug holiday combined with antibiotic prophylaxis and smoothening of sharp bony edges. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..

Differences between auto-fluorescence and tetracycline-fluorescence in medication-related osteonecrosis of the jaw-a preclinical proof of concept study in the mini-pig.

OBJECTIVES: Fluorescence-guided bone surgery is a well-established technique in the treatment of medication-related osteonecrosis of the jaw. No histopathological evidence for bone auto-fluorescence is currently available, and thus, any differences from tetracycline-fluorescence remain unclear. Therefore, the goals of this study were to find out if macroscopic and histological differences occur between the auto- and tetracycline-fluorescence in the delineation of viable and necrotic jawbone in the mini-pig. MATERIALS AND METHODS: According to the proof of concept, osteonecrosis was provoked in eight Göttingen minipigs. Pigs were divided into two groups (AF group: no fluorochrome label; TF group: tetracycline label). Delineation of necrosis and viable bone was evaluated in vivo and in vitro macro-/microscopically, correlated to fluorescence properties and compared between the two study groups. RESULTS: No macroscopic and microscopic clinical differences were seen in fluorescence between the AF and TF groups. Macroscopic and microscopic viable bone fluoresced green, whereas necrotic bone showed no or only pale fluorescence in both groups. The auto-fluorescence was attributable to the arrangements and structure of collagen and the cell-filled bone lacunae. CONCLUSION: Neither in vivo nor in vitro macroscopically differences are apparent between the auto-fluorescence and the tetracycline-fluorescence of bone. The auto-fluorescence is attributable to the arrangements and structure of collagen and the cell-filled bone lacunae. Tetracycline-fluorescence is a mixture of tetracycline (at the bone edges with increased bone formation) and large components of auto-fluorescence. CLINICAL RELEVANCE: Because auto-fluorescence is easy to apply, reproducible, and does not rely on the subjective impression of the surgeon, it promises to be an important standardized alternative to tetracycline-labeled MRONJ therapy.

Is the conservative non-surgical management of medication-related osteonecrosis of the jaw an appropriate treatment option for early stages? A long-term single-center cohort study.

PURPOSE: No consensus has been reached regarding the best treatment option for early-stage lesions in medication-related osteonecrosis of the jaw (MRONJ). The purpose of the present study was to evaluate the long-time outcomes of conservative non-surgical management in stage I patients with underlying malignant disease. MATERIALS AND METHODS: We designed and implemented a retrospective cohort study and enrolled, between 2008 and 2018, a sample of patients with the indication for non-surgical conservative treatment stage I lesions. The primary outcome variable was treatment success defined as mucosal integrity without signs of infection. Secondary outcomes were: (i) worsening stage, (ii) necessity for surgical intervention over time, and (iii) discontinuation of antiresorptive therapy. RESULTS: The sample included 75 patients with 92 lesions. Eight lesions showed full mucosal coverage, whereas 84 continued with exposed jaw bone (91.3%). Of the treatment-resistent 84 lesions, 67 presented a worsening stage shift over time. Indication for surgical intervention was set in 57 lesions. Of all lesions, 28 developed highly advanced necrotic bone destruction. Antiresorptive medication was paused in all evaluated patients after the first diagnosis of MRONJ. CONCLUSION: Conservative non-surgical therapy in MRONJ stage I leads to a healing in rare cases. Conservative management might be a good option to preserve symptoms in patients either unwilling to undergo surgery or in those whose reduced general condition does not allow surgery. Early and consequent surgical advances should be performed throughout all stages of the disease to prevent the possibility of silent disease progression with the risk of large-scale bone loss.

Medication-related osteonecrosis of the jaw: Prevention, diagnosis and management in patients with cancer and bone metastases.

Medication-related osteonecrosis of the jaw (MRONJ) is primarily an adverse side effect of denosumab or bisphosphonates (particularly when used at high doses to prevent skeletal-related events [SREs] in patients with cancer and bone metastases) or possibly anti-angiogenic cancer treatment. While the implementation of preventive measures over recent years has reduced the risk of MRONJ in patients with bone metastases due to cancer, it is imperative to balance the risk of MRONJ against the beneficial effects of treatment with denosumab or bisphosphonates on the skeletal health of patients. Despite growing awareness of MRONJ within the medical community, there is a lack of large-scale, prospective clinical studies in this rapidly evolving field. Discussing preventive measures with patients and implementing them, both before and during treatment with bisphosphonates or denosumab, is the best option to reduce the risk of MRONJ. In particular, avoiding bone trauma and preventing and treating dental infections before and during denosumab or bisphosphonate therapy is crucial to minimize the risk of MRONJ. If MRONJ develops, conservative (non-surgical) treatment can provide symptom relief, but achieving mucosal closure remains challenging. When management of symptoms and mucosal healing are the ultimate goals of therapy, or after failure of conservative treatment, a surgical approach may be beneficial. This critical review, based on a best-evidence review of currently available literature, provides clear practical guidelines to help to prevent, manage and treat MRONJ. Overall, a multidisciplinary, pragmatic approach to MRONJ should be adopted, prioritizing patient's quality of life and management of their skeletal malignant disease.

Further development of the MRONJ minipig large animal model.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious and potentially severe side effect of antiresorptive therapy with bisphosphonates or denosumab. Recently, a large animal minipig MRONJ model was introduced which led to early necrotic lesions in the majority of extraction sites after bisphosphonate administration. The aim of this project was to modify the preoperative cumulative bisphosphonate dose (zoledronate) and hereby firstly to demonstrate the reliability and reproducibility of the established model. Secondly, the MRONJ lesions should be carefully investigated using clinical and µCT as well as detailed histological analyses. Twelve 1.5-year-old Göttingen minipigs were divided into three groups. In group 1 (n = 3) minipigs received weekly doses of zoledronate intravenously (0.05 mg/kg bodyweight) for 20 weeks. No interventions were performed. In group 2 (n = 6) animals received the identical zoledronate dosage as animals in group 1 and tooth extractions of two premolars (PM 2 and 4) in each jaw (maxilla and mandible) were performed after 12 weeks. Group 3 (n = 3) served as tooth extraction only control (no zoledronate administrations). The jaw-bones were subjected to detailed macroscopic, radiological and histological investigations. All extraction sites (24/24) in animals of group 2 showed clinical, radiological and histological signs of MRONJ (mainly stage II), whereas no bone necrosis was found in group 3. Animals of group 1 and group 2 showed further MRONJ lesions in areas where infections (periodontitis) were present. This is the first large animal model to show a 100% incidence of MRONJ at all extraction sites in bisphosphonate pretreated animals (group 2). In addition, in this preclinical model for MRONJ it is shown that tooth extractions are not mandatory for a MRONJ manifestation. MRONJ also developed in areas of gingival or periodontal infections.

Does cefuroxime alter fracture healing in vivo? A micro-computertomographic, biomechanical, and histomorphometric evaluation using a rat fracture model.

Cefuroxime is widely used for antibiotic prophylaxis in orthopedic surgery. However, a recent study indicated a dose-dependent reduction in osteoblast function in vitro. Nevertheless, cell culture might not sufficiently imitate the complex process of bone remodeling. As data concerning possible in vivo interactions of cefuroxime on fracture healing are completely missing, we investigated the following hypothesis: Does Cefuroxime impair bone healing in vivo? Therefore, 34 male Wistar rats were randomised to cefuroxime-treated or control groups, a Kirschner wire was inserted into right femora and closed transverse fractures were produced. Twenty-one days later, the structural properties of the fracture callus in the early fracture healing phase were evaluated via a combination of micro-CT (µCT), biomechanics and histology. µCT demonstrated similar values in the cefuroxime and control group (e.g., callus volume: 67.19 ± 14.90 mm3 vs. 55.35 ± 6.74 mm3 , p = 0.12; density: 635.48 ± 14.81 mg HA/cm3 vs. 647.87 ± 13.01 mg HA/cm3 , p = 0.16). Biomechanically, similar values were again determined between the groups, in terms of both maximum load (77.65 ± 41.82 vs. 78.54 ± 20.52, p = 0.95) and stiffness (122.44 ± 81.16 vs. 123.74 ± 60.08, p = 0.97). Histological findings were consistent with the radiographic results. Thus, no relevant differences between the cefuroxime and control groups could be found and the reported negative effects on osteoblasts in vitro were not confirmed in vivo by using standard concentrations of cefuroxime. In conclusion, cefuroxime can reasonably be recommended in a clinical setting as an antibiotic therapy when fracture healing is involved. However, supraphysiological doses were not evaluated, which may be present when cefuroxime is used as an additive to bone cement and released over time. Therefore, future studies should evaluate the in vivo effects of prolonged high cefuroxime doses on implant incorporation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2282-2291, 2017.

A biomechanical, micro-computertomographic and histological analysis of the influence of diclofenac and prednisolone on fracture healing in vivo.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) have long been suspected of negatively affecting fracture healing, although numerous disputes still exist and little data are available regarding diclofenac. Glucocorticoids interfere in this process over a similar and even broader mechanism of action. As many previously conducted studies evaluated either morphological changes or biomechanical properties of treated bones, the conjunction of both structural measures is completely missing. Therefore, it was our aim to evaluate the effects of diclofenac and prednisolone on the fracture callus biomechanically, morphologically and by 3-dimensional (3D) microstructural analysis. METHODS: Femura of diclofenac-, prednisolone- or placebo-treated rats were pinned and a closed transverse fracture was generated. After 21 days, biomechanics, micro-CT (µCT) and histology were examined. RESULTS: The diclofenac group showed significantly impaired fracture healing compared with the control group by biomechanics and µCT (e.g. stiffness: 57.31 ± 31.11 N/mm vs. 122.44 ± 81.16 N/mm, p = 0.030; callus volume: 47.05 ± 15.67 mm3 vs. 67.19 ± 14.90 mm3, p = 0.037, trabecular thickness: 0.0937 mm ± 0.003 vs. 0.0983 mm ± 0.003, p = 0.023), as confirmed by histology. Biomechanics of the prednisolone group showed obviously lower absolute values than the control group. These alterations were confirmed in conjunction with µCT and histology. CONCLUSIONS: The inhibiting effects of both substances were not only mediated by absolute parameters (e.g. breaking load, BV), but we have shown, for the first time, that additional changes occurred in the microstructural bony network. Especially in patients at risk for delayed bone healing (arteriosclerosis, diabetes mellitus, smoking), the administration of these drugs should be weighed carefully.

Fluorescence-guided surgery for the treatment of medication-related osteonecrosis of the jaw: A prospective cohort study.

INTRODUCTION: The delineation of the necrotic bone is a crucial step in the surgical treatment of medication-related osteonecrosis of the jaw (MRONJ). Several different approaches have been described including the innovative technique of fluorescence-guided surgery. However, until now there is a lack of data regarding the outcome. Therefore, the aim of the present study is to investigate the long-term success rates of fluorescence-guided surgery in the treatment of MRONJ. PATIENTS AND METHODS: 54 Patients were prospectively assigned for surgical treatment of medication-related osteonecrosis of the jaw using fluorescence-guided surgery. Patients received doxycycline 100 mg twice a day for at least seven days preoperatively. Surgical treatment of MRONJ included complete removal of necrotic bone, which was monitored using the visual enhanced lesion scope (Velscope), followed by smoothening sharp bony edges and meticulous wound closure. Procedure success was assessed as postoperative maintenance of full mucosal coverage without pain, infection or bone exposure during regular follow-up. RESULTS: The study included a total of 54 patients (32 female and 22 male, mean age 71.4 ± 9.2 years). In the last follow-up an intact mucosa and absence of exposed bone, pain or signs of infection was identified in 47 of 54 patients (87%) and 56 of 65 lesions (86.2%) after first surgery using fluorescence-guidance. In 4 patients with 6 lesions a second fluorescence-guided surgery was necessary to achieve complete mucosal closure. Respectively, including the case with second surgical attempt 51 of 54 patients (94.4%) and 62 of 65 lesions (95.4%) showed complete mucosal healing. CONCLUSION: The study shows that fluorescence-guided surgery is a safe and successful treatment option which can be considered for all stages of MRONJ. The technique seems also promising for MRONJ cases under denosumab.

Ibandronate treatment of diffuse sclerosing osteomyelitis of the mandible: Pain relief and insight into pathogenesis.

PURPOSE: Diffuse sclerosing osteomyelitis of the mandible (DSO) is a rare and poorly understood disease. Current treatment protocols, including steroid or analgesic medication and corticotomies, show poor or frustrating outcome results and are accompanied by potentially severe side effects. The aim of this study was to determine whether there is a beneficial role of infusions with nitrogen-containing bisphosphonates (ibandronate) in acute conditions of DSO. MATERIAL AND METHODS: Eleven patients were enrolled in the study. In acute conditions of treatment-resistant DSO, single-shot infusions of ibandronate (6 mg) were administered. Pain levels were documented 10 days before and after the infusion on a visual analogue scale (VAS). Patients were monitored regularly. RESULTS: Of the 11 patients, 10 showed a distinct improvement in pain (based on VAS scores) within 48-72 h after infusion. The pain levels of the patients were significantly lower after ibandronate infusions (p < 0.01). The majority of patients were free or almost free of complaints over the following months. Four of the 11 patients returned for repeated infusions. At the time of writing, no severe side effects have been observed, and in particular there has been no case of medication-related jaw osteonecrosis. CONCLUSION: We conclude that single-shot bisphosphonate infusions on demand are promising treatment alternatives in acute DSO. Single-shot bisphosphonate infusions of ibandronate were well tolerated and resulted in distinct, long lasting improvement in subjective pain levels based on VAS scores.

Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: A trigger for BRONJ development?

INTRODUCTION: Scientific debate outlines tooth extraction as a potential trigger for the onset of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Therefore, the aim of this study was to investigate the outcome of tooth extractions in patients receiving bisphosphonate therapy. PATIENTS AND METHODS: A retrospective cohort study was performed on patients with a history of oral or intravenous bisphosphonate administration and tooth extraction between 2007 and 2013 in a single university hospital oral and maxillofacial surgical unit. In all patients, extractions were performed according to the guidelines of the German Society of Oral and Maxillofacial Surgery. The outcome variable was the onset of typical BRONJ signs during postoperative follow-up. RESULTS: In 72 subjects (53 female, 19 male; mean age 67.5 years) receiving oral (n = 27) and/or intravenous (n = 45) bisphosphonates due to malignant tumor (n = 43) or osteoporosis (n = 29), 216 tooth extractions were performed. The mean duration of intake was 36.2 months. In 67 out of 72 patients (93.1%) and 209 out of the 216 extraction sites the postoperative course was uneventful and the wounds healed without complications. Three of the 72 patients (4.2%) developed osteonecrosis of the jaw in four of the 216 extraction sites (1.9%). Duration and route of administration, oral hygiene and steroid intake were identified as potential risk factors for the development of BRONJ. CONCLUSION: Tooth extraction in patients receiving bisphosphonates can be performed in a safe and predictable way, even in high-risk patients, when performed according to established guidelines. It is not tooth extractions themselves, but rather prevailing infectious conditions that may be a key risk factor for the development of BRONJ.

A dental myth bites the dust--no observable relation between the incidence of dental abscess and the weather and lunar phase: an ecological study.

BACKGROUND: Anecdotal reports assert a relationship between weather and lunar activity and the odontogenic abscess (OA) incidence, but this relationship has not been validated. Therefore, the present study investigated the relationship between oral pain caused by OA and a variety of meteorological parameters and cyclic lunar activity. METHODS: The records of all dental emergency patients treated at the AllDent Zahnzentrum Emergency Unit in Munich, Germany during 2012 were retrospectively reviewed. Patients with oral pain who were diagnosed with OA and treated surgically (n = 1211) were included in the analysis. The OA incidence was correlated to daily meteorological data, biosynoptic weather analysis, and cyclic lunar activity. RESULTS: There was no seasonal variation in the OA incidence. None of the meteorological parameters, lunar phase, or biosynoptic weather class were significantly correlated with the OA incidence, except the mean barometric pressure, which was weakly correlated (rho = -0.204). The OA incidence showed a decreasing trend as barometric pressure increased (p < 0.001). On multiple linear regression, the barometric pressure accounted for approximately 4% of the OA incidence. CONCLUSION: There is no evidence supporting a correlation between the incidence of odontogenic abscess and the weather and lunar activities.

Treatment perspectives for medication-related osteonecrosis of the jaw (MRONJ).

The medication-related osteonecrosis of the jaw (MRONJ) is believed to be a therapy-resistant entity. Although the application of the recommended conservative and surgical treatment regimens have returned variable success rates, the increased awareness and experience with MRONJ suggests that surgical therapy can halt the progression of the disease, thereby allowing a histology-based diagnosis of the osteonecrosis. Surgical treatment protocols can achieve success rates of over 90% and novel techniques such as the visualization of bone fluorescence can assist in the intra-operative delineation of the osteonecrosis and standardize the procedure.