Dental Implant Failure in Post-Menopausal Women on Oral Bisphosphonates: A Systematic Review and Meta-Analysis.

A systematic review was designed to investigate the effect of treatment with oral bisphosphonate (BP) on osseointegration of dental implants and the incidence of BP-related osteonecrosis of the jaw (BRONJ) in postmenopausal women. Multiple electronic databases, including MEDLINE (PubMed), EMBASE, and SCOPUS, were searched to find all eligible articles published since 1990. All titles and abstracts retrieved by searching information sources were evaluated independently by 2 authors against the eligibility criteria. The number of cases ranged from 11 to 235, and the number of controls ranged from 14 to 343. Alendronate was used in all other studies. Risedronate was used in 6 studies, while ibandronate was used in 4 studies. The number of implants in cases ranged from 25 to 1267, while in controls, the number of implants ranged from 28 to 1450. The time between the placement of implant and the follow-up visit ranged from 4-6 months to 8 years. The results show that out of 2582 placed implants, 50 (1.94%) failed in BP-treated patients. This is while out of 4050 placed implants, 188 (4.6%) failed in the non-BP group. The results from the meta-analysis demonstrated that BP therapy is significantly associated with increased implant failure rates (RR = 1.73 [95% CI, 1.03-2.83], P = .04). Overall, the qualitative assessment of this review suggests that oral treatment with BPs in postmenopausal women does not increase the rate of dental implant failure. Thus, further studies with larger sample sizes should compare BP and non-BP groups in regard to dental implants.

The effectiveness of autologous platelet concentrates in prevention and treatment of medication-related osteonecrosis of the jaws: A systematic review.

The systematic review aims to answer the PICOS question: "Are the autologous platelet concentrates (APCs) an effective strategy in prevention and/or treatment of patients at risk of/affected by medication-related osteonecrosis of the jaws (MRONJ)?". A literature search was conducted via PubMed, MEDLINE, EMBASE, and CINAHL (January 2006 - September 2023). 30 articles were included, evaluating preventive (n = 8*) and treatment strategies (n = 23*). The risk of bias and quality of studies were assessed utilising ROB-2, ROBIN-1 and GRADE criteria. Meta-analysis was undertaken for eligible studies. The application of APCs demonstrated a statistically significant effectiveness in prevention of MRONJ in 86.13% (p < 0.001) but failed to achieve the same level of certainty in treatment of established MRONJ in 83.4% (p = 0.08). High levels of bias were identified; thus, the results should be interpreted with caution. More high quality prospective randomised controlled trials are needed to further evaluate the effectiveness of APCs in management of MRONJ.

Photobiomodulation Can Prevent Medication-Related Osteonecrosis of the Jaw Formation in Tooth Extraction Site of Rat Model.

Objective: This study aims to explore the preventive potential of photobiomodulation (PBM) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) using a rat model. Methods: An experimental rat model was established, exposing rats to zoledronic acid (ZA), a primary risk factor for BRONJ. An 810 nm diode laser was applied with parameters of 0.33 W/cm2 power density and 10 J/cm2 energy density for 30 sec. PBM was initiated 1 day pre-extraction and continued for 2 weeks. The impact of PBM on wound healing in both soft and hard tissues was evaluated post tooth extraction. Results: ZA exposure hindered wound healing in both soft and hard tissues after tooth extraction. PBM intervention effectively mitigated the adverse effects of ZA, promoting healing processes in both tissue types. This suggests the potential of PBM as a preventive strategy for BRONJ in patients on long-term bisphosphonate treatment. Moreover, PBM exhibited enhanced wound healing in normal rats, indicating its broader applicability beyond BRONJ cases. Conclusions: PBM shows promise in preventing and improving wound healing in BRONJ and normal cases. These findings underscore the significance of optimizing PBM parameters and suggest its potential clinical relevance as a preventive intervention for BRONJ and a promoter of wound healing.

Ozone therapy effect in medication-related osteonecrosis of the jaw as prevention or treatment: microtomographic, confocal laser microscopy and histomorphometric analysis.

OBJECTIVE: This study aimed to evaluate the efficacy of ozone therapy in the preoperative (prevention) and/or postoperative (treatment) of MRONJ. MATERIAL AND METHODS: Forty male Wistar rats were caudally treated with zoledronic acid (ZOL) and to ozone therapy before extraction (prevention, POG), after extraction (treatment, TOG), or both (prevention and treatment, TPOG), and treated with saline (SAL). The animals received intramuscular fluorochrome (calcein and alizarin), and 28 days postoperatively, they were euthanized, and the tissues were subjected to microtomographic computed tomography (microCT), LASER confocal, and histomorphometric analyses. RESULTS: Micro-CT showed a higher bone volume fraction average in all groups than that in the ZOL group (P < 0.001), the ZOL group showed high porosity (P = 0.03), and trabecular separation was greater in the TOG group than in the POG group (P < 0.05). The mineral apposition rate of the POG group was high (20.46 ± 6.31) (P < 0.001), followed by the TOG group (20.32 ± 7.4). The TOG group presented the highest mean newly formed bone area (68.322 ± 25.296) compared with the ZOL group (P < 0.05), followed by the SAL group (66.039 ± 28.379) and ZOL groups (60.856 ± 28.425). CONCLUSIONS: Ozone therapy modulated alveolar bone repair in animals treated with ZOL, mainly after surgery trauma, leading to bone formation as healing tissue. CLINICAL RELEVANCE: Osteonecrosis has been a challenge in dentistry, and owing to the lack of a consensus regarding therapy, studies presenting new therapies are important, and ozone has been one of the therapies explored empirically.

Survey of the association between tooth extraction and development of medication-related osteonecrosis of the jaw in patients undergoing cancer treatment with bone-modifying agents.

OBJECTIVE: This study aimed to verify whether tooth extraction before the administration of bone-modifying agents (BMA) was effective in preventing the onset of medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: This retrospective study included patients with a history of receiving BMA for cancer treatment. The patients were classified into three groups based on the timing of tooth extraction: no tooth extraction before the onset of MRONJ, tooth extraction before the administration of BMA, and tooth extraction after the administration of BMA. The incidence of MRONJ was compared between the groups. Fisher's exact test and Bonferroni correction were used to test for differences in proportions between the three groups. RESULTS: The total number of subjects was 123. Twenty-four patients (19.5%) developed MRONJ. The incidence rates were 12.3% (10/81), 17.9% (5/28), and 64.3% (9/14) in the non-extraction group, the extraction before BMA administration group, and the extraction after BMA administration group, respectively, showing statistically significant differences between the extraction after BMA administration group and the non-extraction groups and between the extraction after BMA administration group and the extraction before BMA administration group (p < 0.001, p = 0.0049). On the other hand, there was no statistically significant difference in incidence between the non-extraction and the extraction before BMA administration group (p = 0.5274). CONCLUSIONS: Tooth extraction before the administration of BMA is effective in preventing the onset of MRONJ in patients receiving BMA for cancer treatment. Prevention of MRONJ development in patients receiving BMA for cancer treatment contributes to the maintenance of patients' quality of life.

The role of leukocyte and platelet-rich fibrin in the prevention of medication-related osteonecrosis of the jaw, in patients requiring dental extractions: an observational study.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is a significant complication which can present following a dental extraction in patients receiving anti-resorptive and anti-angiogenic medications. The purpose of this study was to investigate the possible beneficial effect of L-PRF in the prevention of MRONJ in patients receiving these medications and requiring dental extractions. METHODS: Thirty-nine patients were included and divided into two groups, depending on whether L-PRF was used after the required dental extraction or not. Subsequently, the patients were categorised into low and high-risk for developing MRONJ, as recommended by the SDCEP guidance. RESULTS: None of the patients in the L-PRF group returned with established MRONJ. Five high-risk patients in the control group presented with established MRONJ in the follow-up appointment. A significant statistical difference (p = 0.04) was observed following a comparison of the high-risk patients of the two groups. CONCLUSION: These encouraging results suggest that L-PRF may be useful in the prevention of MRONJ following a dental extraction especially in patients of the higher risk category. A protocol for the management of this type of patients is also introduced.

Dentists' Intention to Use Teleconsultation for the Treatment of Patients With Osteoporosis: An Online Survey Study.

Introduction: To properly combine osteoporosis treatment with dental treatment and to prevent medication-related osteonecrosis of the jaw (MRONJI), a system of communication between health providers can be smoothly made within a short time is required. With the recent increase in the possibility of telemedicine being introduced in Korea, it is expected that the introduction of teleconsultation between health providers treating osteoporosis will reduce the discomfort of patients and health providers and improve satisfaction. In this study, a survey was conducted on the knowledge and experience of MRONJ to find out the willingness of dentists treating osteoporosis patients for teleconsultation. Methods: An online questionnaire-based survey was conducted to investigate the intention for teleconsultation for MRONJ with a total of 516 dentists between September and October 2021. Results: Two-thirds of the respondents had experience of requesting consultation other dentists or doctors for the osteoporosis or MRONJ patients. They answered that the referral letter was the most used consultation request method and that it took a long time to get a reply. As for the intention of teleconsultation, 70% of the respondents answered that they were willing. The more experienced or the higher the educational level, the higher the intention for teleconsultation. Although the intention of dentists for teleconsultation was high, satisfaction with the cost of teleconsultation was low. Discussion: Although dentists' intention to use teleconsultation was high, satisfaction with the cost of medical care for teleconsultation was low, so it seems that this should be coordinated.

Navigating the complexities and controversies of medication-related osteonecrosis of the jaw (MRONJ): a critical update and consensus statement.

OBJECTIVES: To provide a critical update identifying the knowledge gaps and controversies in medication-related osteonecrosis of the jaw (MRONJ) within the Belgian healthcare context and outline opportunities for improvement and research in these areas. METHODS: A literature review was performed to identify guidelines from international clinical societies in oncology or oral and maxillofacial surgery on diagnosing, preventing, and treating MRONJ. The recommendations were critically assessed in light of recent developments in the field and confronted with the clinical experience of experts. RESULTS: Despite progress in the diagnostic criteria of MRONJ, the continued need for an 8-week timeout period should be reconsidered. Furthermore, 3D imaging techniques should be introduced to improve diagnosis and staging. The staging system remains ambiguous regarding Stage 0 MRONJ, and ongoing confusion exists regarding the term non-exposed MRONJ. The prevention of MRONJ should be tailored, considering the individual patient's risk of MRONJ, frailty, and life expectancy. More research seems needed into the efficacy and safety of drug holidays, considering the risks of rebound remodeling on fractures. With renewed interest in surgical and adjunct management techniques, adequately designed clinical studies are needed to help translate trial outcomes into universally applicable treatment guidelines taking into account individual patient characteristics. CONCLUSIONS: Important knowledge gaps remain and hamper the development of clinical guidelines. Several controversies were identified where consensus is lacking, and further harmonization between stakeholders is necessary. Finally, the need for randomized controlled comparative clinical trials in MRONJ resonates harder than ever to identify the best treatment for individual patients.

Medication-related osteonecrosis of the jaw (MRONJ): a review of pathogenesis hypothesis and therapy strategies.

Medication-related osteonecrosis of the jaw (MRONJ), a severe side effect caused by antiresorptive antiangiogenic medication, particularly bisphosphonates (BPs), has become a challenging disease with serious and profound effects on the physical and mental health of patients. Although it occurs with high frequency and is harmful, the exact mechanism of MRONJ remains unknown, and systematic and targeted approaches are still lacking. Maxillofacial surgeons focus on the etiology of osteonecrosis in the mandible and maxilla as well as the appropriate oral interventions for high-risk patients. Adequate nursing care and pharmacotherapy management are also crucial. This review provides a current overview of the clinicopathologic feature and research of MRONJ caused by BPs, with an emphasis on the potential mechanisms and current therapy and prevention strategies of the disease. We are of the opinion that an in-depth comprehension of the mechanisms underlying MRONJ will facilitate the development of more precise and efficacious therapeutic approaches, resulting in enhanced clinical outcomes for patients.

Oral health conditions in patients under antiresorptive therapy are comparable to unexposed during supportive periodontal care.

OBJECTIVES: To investigate oral health and oral health-related quality of life (OHRQoL) of patients under antiresorptive therapy (ART) during supportive periodontal care (SPC) considering history of medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: In this cross-sectional study, 100 patients (50 receiving ART (exposed) and 50 without ART (unexposed)) in regular SPC were enrolled for a clinical oral examination and the evaluation of OHRQoL using the OHIP-G14-questionnaire. History of MRONJ was assessed by anamnesis and reviewing patient records. RESULTS: There were no statistically significant group differences in age (exposed: 70.00 ± 9.07 versus unexposed: 71.02 ± 8.22 years), sex, distribution of systemic diseases and duration of SPC (on average 8.61 ± 5.73 years). Number of teeth (21.02 ± 5.84 versus 21.40 ± 5.42), DMFT (18.38 ± 3.85 versus 17.96 ± 4.08), probing pocket depth (2.31 ± 0.20 versus 2.38 ± 0.26), clinical attachment level (3.25 ± 0.76 versus 3.46 ± 0.58) and bleeding on probing (15.07 ± 11.53 versus 15.77 ± 13.08) were also not significantly different. The OHIP-G14 sum-score was significantly higher in exposed participants (6.10 ± 6.76 versus 3.62 ± 5.22, p = 0.043). History of MRONJ was prevalent in 8% of patients under ART. Periodontal/peri-implant-related MRONJ were reported in three participants with cancer (n = 1 before and n = 2 after active periodontal therapy). History of MRONJ due to endodontic/restorative reasons was reported in one patient with osteoporosis. CONCLUSIONS: Patients under ART in SPC demonstrated similar clinical periodontal and dental status but lower OHRQoL compared to unexposed (not statistically significant). Patient awareness of the MRONJ-risk and appropriate preventive measures should be ensured. CLINICAL RELEVANCE: SPC in osteoporotic patients under ART appeared safe regarding MRONJ, but further investigations on the MRONJ-risk in patients with different risk-profiles are necessary. STUDY REGISTRATION: clinicaltrials.gov (#NCT04192188).

Impact of beta-tricalcium phosphate on preventing tooth extraction-triggered bisphosphonate-related osteonecrosis of the jaw in rats.

Antiresorptive or antiangiogenic drugs can cause medication-related osteonecrosis of the jaw that is refractory. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) may be caused by procedures such as tooth extraction damage the alveolar bone, release bisphosphonates (BPs) and impede healing. This study investigated strategies for BRONJ prevention and molecular mechanisms of its onset. We assessed the effectiveness of filling extraction sockets with beta-tricalcium phosphate (ß-TCP). Rats were administered zoledronic acid (ZA) 1.2 mg/kg once per week for 2 weeks, and a molar was extracted. They were randomly assigned to the ß-TCP group (bone defects filled with 0.01 g of ß-TCP) or control group. Tissue content measurements indicated 2.2 ng of ZA per socket in the ß-TCP group and 4.9 ng in the control group, confirming BP distribution and BP adsorption by ß-TCP in vivo. At 4 weeks after extraction, the ß-TCP group had normal mucosal coverage without inflammation. Moreover, at 8 weeks after extraction, enhanced bone healing, socket coverage, and new bone formation were observed in the ß-TCP group. Connective tissue in the extraction sockets suggested that local increases in BP concentrations may suppress the local autophagy mechanisms involved in BRONJ. Filling extraction sockets with ß-TCP may prevent BRONJ.

Sex difference in the morbidity and pain response with stage 0 of medication-related osteonecrosis of the jaws.

OBJECTIVE: Medication-related osteonecrosis of the jaws (MRONJ) is a potentially severe complication associated with antiresorptive or antiangiogenic therapies. Prior studies, including our own clinical data, have indicated a higher incidence of MRONJ among women compare to men. However, robust evidence establishing a relationship between sex and the prevalence of MRONJ is lacking. METHODS: We conducted a meta-analysis and utilized murine models to investigate potential sex-based differences in the morbidity associated with MRONJ. RESULTS: Our results revealed no significant difference in the incidence of MRONJ between the sexes when using exposed necrotic bone as a diagnostic criterion. However, a histological examination of the murine models identified the presence of stage 0 MRONJ. Notably, pain assessments across all groups revealed that male mice with stage 0 MRONJ displayed less severe pain symptoms than their female counterparts. CONCLUSIONS: Our findings suggested that sex does not contribute to the risk of developing MRONJ. However, considering that approximately 50% of stage 0 MRONJ cases progress to more advanced stages, the less pronounced pain in male patients might delay medical consultation and potentially lead to disease progression. Clinicians should be particularly vigilant about the subdued pain response in male patients with stage 0 MRONJ to prevent disease advancement.

Prevention and management of drug-induced osteonecrosis of the jaws using platelet-rich fibrin: A clinical feasibility study.

OBJECTIVE: Although a standard treatment guideline has not been established to date, various treatment modalities have been described in the literature based on the staging of medication-related osteonecrosis of the jaw (MRONJ). The aim of this case series was to describe the outcomes of surgical intervention of MRONJ cases with the adjunctive use of platelet-rich fibrin (PRF). MATERIALS AND METHODS: Thirteen patients under therapy with zoledronic acid, seven of them underwent surgical removal of necrotic bone with debridement, followed by placement of three to four PRF membranes and achieving primary closure. In six patients, PRF was used preventively to avoid MRONJ. RESULTS: The surgical treatment outcomes were successful in all patients, with a follow-up range of 12-48 months. In the presented cases, the intraoral evaluation showed excellent soft tissue healing except for one patient secondary wound healing was reported. Additionally, there was no recurrence of bone exposure in all cases. PRF membranes were comparatively effective in postsurgical pain control. CONCLUSION: The use of PRF could represent a valuable adjunct in the surgical management for advanced stages of MRONJ cases. CLINICAL RELEVANCE: This clinical case series describes the use of PRF membranes as a valuable adjunct in the surgical management of MRONJ patients, especially when treating advanced MRONJ cases. Moreover, PRF demonstrates usefulness in preventing such difficult complications from occurring.

Pentoxifylline and tocopherol as prophylaxis for osteonecrosis of the jaw due to bone-modifying agents in patients with cancer submitted to tooth extraction: a case series.

PURPOSE: To assess the prophylaxis effect of pentoxifylline and tocopherol (PENTO) on the frequency and severity of medication-related osteonecrosis of the jaw (MRONJ) diagnosed at three months in patients with cancer submitted to tooth extractions during the treatment with bone-modifying agents. METHODS: This case series was conducted at the outpatient dental clinic of the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) between April 2021 and April 2022. Patients ≥ 18 years old were included; those with maxillary metastasis or who performed head or neck radiotherapy were excluded. The PENTO protocol was prescribed two weeks before and two weeks after the tooth extraction, and patients were reassessed one week, one month, and three months after the extraction. The main outcome was the development of MRONJ. RESULTS: Of the 114 screened patients, 17 were included; they were aged between 43 and 73 years and were mostly female (88.2%). Thirty-two tooth extractions were performed (22 in the maxilla and 10 in the mandible). Breast cancer was the most predominant neoplasm (70.6%), being metastatic in 35.3% of patients. Also, all patients used intravenous bisphosphonates. Stage 1 MRONJ was diagnosed in three patients (17.6%), representing three (9.4%) of all tooth extractions. The repair of MRONJ was achieved 30 days after the PENTO protocol. CONCLUSION: The prophylaxis use of PENTO reduced the severity of injuries, was well-tolerated, and showed patient compliance.

Revisiting best practice guidelines and patient care workflow for managing the risk of medication-related osteonecrosis of the jaw: comparative summary and case studies.

OBJECTIVE: Patients taking antiresorptive medications in dental clinics are at risk of medication-related osteonecrosis of the jaw (MRONJ), which poses daily challenges for their clinicians. This paper aimed to summarize and revisit the three most recognized practice guidelines for the management and prevention of MRONJ, which were proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), and presented by the Journal of Bone and Mineral Research (JBMR) and the Journal of Clinical Oncology (JCO). Results and case studies: The AAOMS position paper focused on risk stratification by different medications, management decision trees, risk factors, pathophysiology, and disease staging. The JBMR international consensus presented eight focused questions, which were addressed by systematic reviews. The JCO clinical practice guideline presented six clinical questions, and each concluded with practical recommendations. Practical information was summarized and converted into an adoptable patient care workflow for clinicians to follow and apply in daily practice. Three case studies presented were treated following these guidelines. Each patient underwent advanced surgeries including alveoloplasty, tooth extraction, implant placement, and particulate bone grafting. Some of the considerations not fully informed were discussed and illustrated in each step of the patient care workflow, which included specifics for risk communication, updates on the use of antibiotics, biomarkers, and drug holidays. CONCLUSION AND PRACTICAL IMPLICATIONS: Structured risk communication with official informed consent documentation should be considered before initiating invasive treatments. Disease control phase with home care therapy should be provided prior to staged reconstructive therapy. Drug holidays and antibiotics coverage can be customized based on individual conditions and related procedures with interprofessional coordination.

[Preserving the oral health of patients on antiresorptive drugs]. / Préserver la santé orale des patients sous antirésorbeurs osseux.

PRESERVING THE ORAL HEALTH OF PATIENTS ON ANTIRESORPTIVE DRUGS. For many years, antiresorptive medication have proven their effectiveness in reducing the risk of pathological fractures in osteoporotic or tumoral bone. However, bisphosphonates and denosumab may, in rare cases, induce osteonecrosis of the jaw, especially when prescribed for malignant disease (bone metastases or multiple myeloma). The presence of oral infections and the performance of invasive procedures, particularly dental avulsions, increase the risk of this complication. The management of osteonecrosis of the jaw is complex, and the prescribing physician and the dental surgeon must implement preventive measures. There are numerous recommendations published by national and international scientific societies that guide practitioners in the oral management of these patients. An oral check-up and oral cavity restoration are strongly recommended before treatment, as well as the implementation of rigorous oral hygiene and regular visits to the dental surgeon. During and after treatment with antiresorptive medication, oral care protocols are used to reduce the risk of osteonecrosis of the jaws and, when it occurs, to manage it.

PRÉSERVER LA SANTÉ ORALE DES PATIENTS SOUS ANTIRÉSORBEURS OSSEUX. Depuis de nombreuses années, les antirésorbeurs osseux ont prouvé leur efficacité dans la diminution du risque de fracture pathologique sur os ostéoporotique ou tumoral. Parmi eux, les bisphosphonates et le dénosumab sont cependant susceptibles d'induire, dans de rares cas, une ostéonécrose des maxillaires, notamment lorsqu'ils sont prescrits pour une pathologie maligne (métastases osseuses ou myélome multiple). La présence de foyers infectieux bucco- dentaires et la réalisation de gestes invasifs, notamment des avulsions dentaires, augmentent le risque de cette complication. La prise en charge de l'ostéonécrose des maxillaires étant complexe, le médecin prescripteur et le chirurgien-dentiste doivent mettre en place des mesures préventives. Il existe de nombreuses recommandations éditées par des sociétés scientifiques nationales et internationales qui guident les praticiens dans la prise en charge bucco- dentaire de ces patients. Un bilan bucco-dentaire et une remise en état de la cavité buccale sont fortement recommandés avant la mise en place du traitement, ainsi que l'instauration d'une hygiène orale rigoureuse et de consultations régulières chez le chirurgien-dentiste. Pendant et après le traitement par antirésorbeurs osseux, des protocoles de soins bucco-dentaires permettent de diminuer le risque d'ostéonécrose des maxillaires et, lorsqu'elle survient, de la prendre en charge.

Endodontic treatment of odontogenic infection in a patient at risk of medication-related osteonecrosis of the jaw: a case report and review of treatment criteria.

Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon and severe condition in patients who are receiving treatment with antiresorptive and/or antiangiogenic drugs, which are frequently used to treat or prevent cancer metastases. The treatment of MRONJ is challenging because the choice of a specific dental treatment depends on several factors, including the systemic condition of the patient, type and dosage of medications, and clinical and radiographic characteristics of the dental lesions. This case report describes the conservative endodontic treatment of an odontogenic infection in a patient at risk of developing MRONJ owing to bisphosphonate treatment. Endodontic retreatment was performed to control the odontogenic infection and avoid tooth extraction. Certain factors favor the use of a conservative approach, such as a localized and small infection, the absence of systemic factors (such as metabolic disorders or medications) that can impair bone healing, and good oral hygiene.

Alterations in macrophage polarization in the craniofacial and extracranial skeleton after zoledronate application and surgical interventions - an in vivo experiment.

Purpose: Medication-related osteonecrosis occurs exclusively in the jaw bones. However, the exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) and the unique predisposition of the jaw bones have not been elucidated, making its treatment a challenge. Recent evidence indicates that macrophages might play a pivotal role in MRONJ pathogenesis. The aim of the present study was to compare the macrophage populations between the craniofacial and extracranial skeleton and to investigate the changes induced by zoledronate (Zol) application and surgical interventions. Materials and methods: An in vivo experiment was performed. 120 wistar rats were randomized to 4 groups (G1, G2, G3, G4). G1 served as an untreated control group. G2 and G4 received Zol injections for 8 weeks. Afterwards, the right lower molar of the animals from G3 and G4 was extracted and the right tibia osteotomized followed by osteosynthesis. Tissue samples were taken from the extraction socket and the tibia fracture at fixed time points. Immunohistochemistry was conducted to determine the labeling indexes of CD68+ and CD163+ macrophages. Results: Comparing the mandible and the tibia, we observed a significantly higher number of macrophages and a heightened pro-inflammatory environment in the mandible compared to the tibia. Tooth extraction caused an increase of the overall number of macrophages and a shift toward a more pro-inflammatory microenvironment in the mandible. Zol application amplified this effect. Conclusion: Our results indicate fundamental immunological differences between the jaw bone and the tibia, which might be a reason for the unique predisposition for MRONJ in the jaw bones. The more pro-inflammatory environment after Zol application and tooth extraction might contribute to the pathogenesis of MRONJ. Targeting macrophages might represent an attractive strategy to prevent MRONJ and improve therapy. In addition, our results support the hypothesis of an anti-tumoral and anti-metastatic effect induced by BPs. However, further studies are needed to delineate the mechanisms and specify the contributions of the various macrophage phenotypes.

Laser Devices and Autologous Platelet Concentrates in Prevention and Treatment of Medication-Related Osteonecrosis of the Jaws: A Systematic Review.

Background and Objectives: Medication-related osteonecrosis of the jaws (MRONJ) is a disease that affects many patients taking anti-angiogenic and antiresorptive medicines. Since the pathogenetic mechanism is still partially unknown, preventive strategies, as well as treatment alternatives, are needed. Therefore, the aim of this research is to describe the main evidence from the last 10 years of clinical trials regarding the use of auxiliary devices such as autologous platelet concentrates (APCs) and laser, other than their effects against MRONJ disease onset or therapy. Advantages in the healing process and recurrence rates were also analyzed. Materials and Methods: A systematic search of the electronic databases of PubMed and Scopus was carried out. Data from the studies were analyzed, and the risk of bias was evaluated. Results: Nineteen studies between interventional studies, observational studies, and cohort studies have been considered in this review. Conclusions: Based on the studies included, the literature analysis shows that APCs could be a beneficial alternative in preventing and treating MRONJ. Laser technology, as a surgical tool or used on the antimicrobial photodynamic or photobiomodulation side, has been becoming increasingly popular in the last few years. The latest proposal concerning the combination of both auxiliary tools suggests interesting effects, but more studies should be conducted to evaluate eventual relapses and long-term consequences.