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Objective: To review the available prospective literature on hyperbaric oxygen (HBO) therapy for periodontal conditions. Materials and methods: A comprehensive electronic and manual search was performed to identify clinical studies on adult patients who underwent hyperbaric oxygen therapy for periodontal treatments. A systematic literature search was conducted in PubMed, Cochrane, and Dentistry Oral Sciences Source databases. Results: Fourteen articles were included in the final literature review, of which five were RCTs and 11 were prospective clinical studies. Four studies discussed HBO as an adjunct to nonsurgical treatment of periodontitis, eight reported on HBO and osteoradionecrosis, and one examined HBO in bisphosphonate-related necrosis of the jaws. Conclusions: HBO has shown superior efficacy compared to antibiotics as a prophylactic measure in preventing osteoradionecrosis (ORN) in patients with a history of high mandibular irradiation. Clinicians should consider referring such patients for HBO therapy before and after tooth extractions. However, for the surgical excision of existing ORN lesions, HBO therapy does not yield significant benefits but does not negatively impact outcomes either. Regarding the treatment of periodontitis patients, the variability among studies prevents definitive conclusions. HBO therapy as an adjunct to SRP in periodontitis treatment produces mixed results. Clinical relevance: This study’s clinical relevance lies in its exploration of the potential benefits of HBO for periodontal conditions. Also, it provides clinicians with insights into when and how to integrate HBO therapy into their treatment approaches, particularly for patients with a history of irradiation and those undergoing complex dental procedures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the preventive effect of ozonated oil on the development of MRONJ-like lesions at tooth extraction sites in rats submitted to zoledronic acid treatment. Materials and methods: Twelve rats were divided into two groups. Each rat received an injection of zoledronic acid solution once a week for 5 weeks before having its upper first molar extracted. In group 1, the clotted socket was maintained, while in the group 2, the socket was treated with ozonated oil for 10 min/day during 3 days. After euthanasia, block resection was performed for histological analysis. Necrotic bone was defined as the area of the bone with empty osteocyte lacunae and vital bone as the area with osteocyte-occupied lacunae. Results: There was no statistically significant difference between the groups in the average area of vital bone (p = 0.2248) and the average area of necrotic bone (p = 0.1208). However, the average area of vital bone in group 1 was smaller (24.1 ± 2.9 cells/cm2) than in group 2 (26.8 ± 4.2 cells/cm2), and the average area of necrotic bone in group 1 was higher (7.0 ± 2.5 cells/cm2) than in group 2 (4.0 ± 1.1 cells/cm2), indicating that ozonated oil may reduce the development of osteonecrosis. Conclusions: Our findings suggest that ozonated oil might prevent MRONJ-like lesions at tooth extraction sites in rats submitted to a disease induction protocol. Further research should be conducted to confirm this hypothesis. Clinical relevance: MRONJ has been reported as a complication of surgical dental procedures, and there are currently no predictable preventive therapies. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this present study was to evaluate the efficiency of the growth factors delivered by concentrated growth factor (CGF) on the healing process of osteoporotic patients with medication-related osteonecrosis of the jaws (MRONJ). Methods: This randomized controlled study was composed of osteoporotic female patients who were treated with oral bisphosphonates (BPs) and diagnosed with MRONJ. For the CGF group, each patient was treated with a local application of CGF at the surgical site after removing the necrotic bone, while the surgical area was primarily closed as traditional surgical therapy for the control group. The patients underwent clinical examinations for 6 months postoperatively to check the presence of infection and dehiscence. Results: Complete healing was achieved in 19 patients of 28 patients (mean age: CGF group, 73.57 ± 5.1; control group, 73.64 ± 5.49) diagnosed with MRONJ. There was no significant difference in post-op healing data between groups during healing periods (p > 0.05). In the CGF group (n = 14) in three cases, bone exposure without infection was detected, and one of them showed a recurrent infection. In the control group (n = 14) in six cases, bone exposure without infection was detected, and three of them also showed recurrent infection. Conclusion: Although our results were not statistically significant, our findings suggest that the local application of CGF appears to be an effective approach to the surgical treatment of MRONJ in osteoporosis patients by improving tissue regeneration. Clinical relevance: A specific treatment protocol to manage MRONJ is still controversial. This study justifies that CGF can be used in combination with surgical treatment. [ABSTRACT FROM AUTHOR]

Objectives: The aim of our study was to describe microbial flora associated with MRONJ and characterize the susceptibility of pathogens to help guide an effective empiric antibiotic treatment in these patients. Materials and methods: A retrospective, single-center analysis was performed, using 116 bone samples from 98 patients. The bone samples were homogenized and subjected to routine culture methods. Growing bacteria were differentiated to the species level using whole-cell mass spectrometry and subjected to susceptibility testing. Results: A highly diverse microbial flora was detected in necrotic bone, with a simultaneous presence of two or more bacterial species in 79% of all patients. In at least 65% of samples, gram-negative isolates were detected. Therefore, bacterial species resistant against β-lactamase inhibitors were present in at least 70% of all patients. Conclusions: The empiric choice of antibiotics in MRONJ patients should consider the high rate of gram-negative bacteria and resistance against β-lactam antibiotics. Clinical relevance: According to recent guidelines and recommendations, systemic antibiotic treatment is a key component in the treatment of all stage 2 and 3 MRONJ patients. We recommend using fluoroquinolones for empiric treatment and emphasize the use of bacterial cultivation and susceptibility testing to enable an effective antibiotic treatment. [ABSTRACT FROM AUTHOR]

Objective: To estimate boxcounting fractal dimension in a standardized approach in CBCT images of the mandible and maxilla in a group of patients with MRONJ in comparison to a healthy control group. Material and methods: From our records, a study group consisting of 80 maxillary and mandibular CBCTs in 77 cases of patients having MRONJ was collected. The control group consisted of 84 mandibular and maxillary CBCTs in a total of 78 patients. Using the boxcounting method, fractal dimension (FD) was estimated in a standardized fashion either cranially to the apex of the canine (maxilla) or beneath the tooth apices of the lower molars in the bone area above the mandibular canal (mandible). Intra-observer reproducibility of the FD-measurements was assessed by 6 repeated measurements in 10 individuals. FD values were correlated to age and sex of the individuals as well as to region of interest (ROI) sizes. Results: FD in the study group (1.684 ± 0.051) was roughly 3.5 % lower than in the control group (1.745 ± 0.026, p < 0.0001). Sex and age had a significant (p < 0.001) influence on FD values in the study group, yet not in the control group. FD values increased with age (study group, spearman-rho: 0.2895, p < 0.05) and also ROI size (both groups, p < 0.0001). Reproducibility was good (intra-class correlation coefficient (ICC): 0.87). Conclusions: Fractal dimension as assessed by boxcounting seems to be a good descriptor for MRONJ in jaw bones. Influence of age and sex on the outcome values needs to be further investigated in future studies. Clinical relevance: CBCTs could be assessed with respect to FD to obtain an overview of the disease status of MRONJ patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: A central role of infections in the treatment of MRONJ patients is widely accepted. An investigation of the MRONJ lesions' biofilms as potential pathogens seems logical. Materials and methods: We investigated the clinical data of our MRONJ patients who received surgery in advanced stage of the disease. Special attention was granted to the local colonizers harvested from osseous MRONJ specimens and submucosal putrid infections. Results: Eleven out of 71 patients presented a spontaneous onset of the disease and for 60 out of 71 patients a trigger was detected. Breast cancer (29.6%) and prostate cancer (22.5%) were the most frequent underlying disease for prescription of an antiresorptive therapy, mostly zoledronate. Submucosal soft tissue biofilms significantly differed from biofilms harvested from the MRONJ lesions bottom, yet the most frequent bacteria were equally present in both groups: Streptococcus species (spp.), Prevotella spp., Actinomyces spp., Veillonella spp., and Parvimonas micra. The cephalosporins, cefuroxime and cefotaxime, and ß-lactam antibiotics with ß-lactamase inhibitor revealed the greatest susceptibility for the detected bacteria. Conclusion: The bacteria from the submucosal areas and the bottom of the infected bone presented comparable susceptibility to the common antibiotics regimes. Streptococcus spp., Prevotella spp., and Veillonella spp. present a high abundance in MRONJ lesions beside Actinomyces spp. The MRONJ lesions bottom is in many cases not infected by Actinomyces spp. Clinical relevance: The removal of the necrotic bone reduces the variety of bacteria found in MRONJ lesions, in particular at the bottom of the lesion. [ABSTRACT FROM AUTHOR]

Objectives: Actually, there is no detailed guidance on how to deal with wound closure after surgical removal of medication-related osteonecrosis of the jaw (MRONJ) lesions. This study attempts to compare the difference in outcome between the mucosal and the mucoperiosteal flap closure after surgery.Patients and methods: In this retrospective monocentric cohort study, patients (n = 61; 35 female/26 male) suffering from MRONJ and requiring surgical therapy at the University of Aachen between 2013 and 2015 were included. Due to intra-institutional variances, one group was treated with the mucosal, the other group with the mucoperiosteal technique. The success rate, i.e., mucosal closure and no relapse at the point of follow-up, was evaluated and compared. All patients were clinically investigated for the postoperative follow-up during a special consultation appointment.Results: The success rates between the different techniques after 2 years follow-up were very similar. In the group of mucosal wound closure, 22 of 29 (75.86%) patients revealed mucosal integrity without signs of MRONJ. The rate in the mucoperiosteal wound closure group was almost identical (24 of 32 (75%)).Conclusion: No differences in the success rates between the two different techniques could be evaluated.Clinical relevance: The results of this study suggest that the complete removal of the necrotic bone might have a higher impact on the success rates than the technique of the wound closure. Due to the fact that the mucoperiosteal wound closure technique offers a better overview of the extent of the MRONJ lesion, the authors advise to use this technique. [ABSTRACT FROM AUTHOR]

Objective: The most debated topic about medication-related osteonecrosis of the jaws (MRONJ) is its therapy, as there are no definitive guidelines. The aims of this systematic review were (a) to outline the best therapeutic approach according to the stage at diagnosis and (b) to perform a meta-analysis to assess whether the drug-holiday protocol may be or not an effective method in the management of MRONJ patients.Materials and methods: The systematic review was performed following the PRISMA principles. Results were screened according to inclusion and exclusion criteria regarding staging before/after treatment, follow-up, and information provided by the authors. For statistical analysis, linear variables are reported as means and standard deviations, medians, and inter-quartile range (IQR); normality of data, according to the distribution of complete healing (primary outcome variable), was assessed with the Kolmogorov-Smirnov test. A p value < 0.05 was considered statistically significant for all tests.Results: Thirteen studies were selected out of 1480. None of them was case-controlled or randomized. Conservative approach showed good results at early stages, but heterogeneous result at advanced stages (100% stage 0, stage I range 81–97%, stage II range 63.6–100%, stage III 73%). Surgical approach showed heterogeneous results at all stages (stage I range 0–100%, stage II range 52–100%, stage III range 50–100%). Statistical analysis showed a significantly higher prevalence of completely healed sites in patients who followed the drug-holiday protocol.Conclusions: The results suggest that the current stage-specific approach for MRONJ therapy is based on a sound clinical rationale. Conservative treatment appears to yield better outcomes at early stages, while further investigations are needed to elucidate the best protocols for the management of advanced stages. The drug-holiday protocol statistically promotes complete healing after oral surgery procedures but the application should be dictated by the condition of each patient.Clinical relevance: At present, early MRONJ stages should be primarily treated by means of a conservative approach while more advanced stages must be carefully evaluated. Individual decisions should be made for every single case even with respect to the drug-holiday protocol. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present study was to evaluate the effectiveness of platelet-rich fibrin (PRF) as a wound-healing accelerator in patients undergoing oral bisphosphonate therapy and requiring tooth extractions. Materials and methods: A total of 102 patients were divided into a PRF group and control group. The patients received oral bisphosphonate therapy for osteoporosis for an average of 32 months. Blood was collected and PRF was introduced into the socket of the PRF group only. Monitoring of mucosal healing was conducted for 3 months in both groups, and radiographic evaluation in the sockets was performed in the PRF group. Delayed recovery was defined as exposed bone and vulnerable granulation tissue without epithelization after 4 weeks and resolving by 8 weeks. Results: There were no intraoperative complications, and none of the patients exhibited onset of medication-related osteonecrosis of the jaw (MRONJ). Delayed recovery was observed in 9 out of 73 control patients (12%), whereas 29 PRF patients exhibited complete epithelialization of the socket within 1 month. The prevalence of delayed recovery was significantly higher in the control group than the PRF group ( P < 0.05). Multivariate logistic regression analysis revealed that risk factors and use of PRF were independent significant factors to relate to delayed recovery ( P = 0.02). Conclusions: Early epithelization was confirmed in all PRF patients. Thus, PRF may reduce the risk of delayed recovery in patients undergoing oral bisphosphonate therapy. Clinical relevance: PRF may be useful in preventing MRONJ in patients receiving oral bisphosphonate (BP). [ABSTRACT FROM AUTHOR]

Objective: The objective of this study were to find the annual case trend of inflammatory jawbone diseases and to investigate the impact of medication-related osteonecrosis of the jaws (MRONJ). Material and methods: A retrospective study of 372 patients diagnosed with inflammatory jawbone condition except for alveolar osteitis from 2007 to 2015 was initiated. History taking and investigation of etiologic factors MRONJ, osteoradionecrosis (ORN), odontogenic infection, foreign body, and trauma were investigated. A separate analysis showed the number of MRONJ cases in two age groups (under 70 years; 70 years and over) and serum C-terminal peptide (s-CTX) values that were found. Results: The results showed that the number of MRONJ cases was significantly larger in the older age group ( p < 0.05). Regarding gender and sites of lesions, MRONJ was significantly frequent in the female and the mandible ( p < 0.05). The R values for the regression analysis for MRONJ ( R = 0.9234) and odontogenic etiology ( R = 0.0427) signified linear increase in the number of MRONJ cases, whereas bone lesions due to traditional odontogenic etiology stayed stationary. Conclusion: The number of MRONJ has escalated, and most of the patients are elderly people. The current trend of inflammatory conditions of the jaw may have changed since the advent of MRONJ. Clinical relevance: Long-term bisphosphonate therapy became a major risk factor for the osteomyelitis and osteonecrosis of the jaws. Thorough medical history, taking would be essential and communication with prescribing physicians should be emphasized during the dental treatment planning. [ABSTRACT FROM AUTHOR]

Objectives: Some recent reports have indicated that local infection causes osteonecrosis of the jaw and described that tooth extraction may not be a direct cause of developing medication-related osteonecrosis of the jaw (MRONJ) in patients receiving antiresorptive medications. Tooth extraction and elimination of the source of infection are expected to reduce the risk of developing MRONJ. However, there is no data regarding prevention for developing osteonecrosis of the jaw in patients receiving denosumab. Therefore, the aim of this study was to investigate the outcome of tooth extractions with proper wound closure in patients receiving denosumab. Patients and methods: Forty teeth in 19 patients treated with denosumab therapy were extracted under preoperative intravenous antibiotics. Patients who had already developed MRONJ in the extraction sites or who had a history of radiation therapy were excluded. During surgery, bone edges were smoothed and all wounds were closed using the double-layered technique. Results: Thirty-seven extraction sites (92.5 %) in 17 out of 19 patients (89.5 %) were healed. However, three extraction sites in two patients had complications; one patient had exposed bone and developed MRONJ (stage 1) and the other developed a mucosa fistula. Additional surgical procedures were performed and all wounds were completely healed. Conclusions: Tooth extractions in patients receiving denosumab can be performed in an appropriate manner and result in good outcomes. Clinical relevance: This study indicated that tooth extraction with proper wound closure to avoid secondary infection may be effective for the prevention of MRONJ even in high-risk patients. [ABSTRACT FROM AUTHOR]