Prevention Of Medication-related Osteonecrosis Of The Jaw Research Articles

Management and maintenance of oral health: Personalized primary prevention strategies and protocols in patients at risk of developing medication-related osteonecrosis of the jaw

Skeletal complications arising from osteoporosis or bone metastases are associated with considerable pain, increased mortality, and diminished quality of life. Agents that prevent bone resorption, such as bisphosphonates, denosumab, and antiangiogenic agents, prove effective in reducing fracture risk and find extensive use in patients with osteoporosis or bone cancer metastases. Medication-related osteonecrosis of the jaw (MRONJ) is a potentially serious adverse event associated with high cumulative doses of antiresorptive drugs. Other risk factors for osteonecrosis of the jaw include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, inappropriate dentures, and other MRONJ-related medications. Preventive strategies encompass completing necessary oral surgery before initiating antiresorptive drug therapy, administering antibiotics before and/or after the procedure, rinsing the mouth with chlorhexidine, ensuring adequate wound healing post-tooth extraction, and maintaining good oral hygiene. The primary goal of treatment is to improve the patient’s quality of life by managing pain and infection, preventing the development of new lesions, and decelerating disease progression. Dentists and dental hygienists, operating within a multi-professional team, play a key role in the primary prevention of MRONJ. However, a standardized multidisciplinary approach, fostering sustained dialog between specialists involved in the management of patients at risk for MRONJ, remains essential. This review describes the preventive and individualized oral hygiene management in patients at risk for this condition.

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.

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. 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. 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. 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.

Awareness, perceptions and attitudes toward medication-related osteonecrosis of the jaw among physicians who treat osteoporosis

Osteoporosis is the most common indication for antiresorptive drugs (ARDs). Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of ARDs. Multiple risk factors can increase the risk of MRONJ, one of which is the duration of ARD intake, which is usually prolonged for osteoporosis cases. Prevention of MRONJ relies on collaborative care between treating physicians and dental practitioners. Therefore, knowledge about MRONJ and its prevention strategies is crucial for both teams. AimThis study aimed to assess the knowledge and attitudes of physicians toward MRONJ in osteoporosis patients. Another aim was to develop recommendations for the prevention of MRONJ. Materials and methodsThrough an online survey, basic information such as the practice location, training, knowledge, perceptions, and attitudes of physicians regarding ARDs and MRONJ in osteoporosis patients was collected. Statistical analysis was performed for all variables, and their correlations were explored. ResultsA total of 221 physicians participated in the survey: 34.8% were rheumatologists, 25.3% were endocrinologists, 8.6% were family medicine physicians, 5.9% were orthopedists, and 5.9% were internal medicine physicians. Of them, 58.0% reported more than 6 years of experience. Only 78.7% were aware of MRONJ and recognized that bisphosphonates (BPs) can contribute to MRONJ. In contrast, 56.0% recognized denosumab as a causative factor for MRONJ. Duration of ARD therapy and pre- and post-ARD dental care were known to influence the risk of MRONJ by 62% and 65.6% of the participants, respectively. Only 41.6% and 31.2% of participants informed patients about MRONJ prior to BP and denosumab therapy, respectively. Only 25.3% and 20.8% referred patients to dentists before BP and denosumab therapy, respectively. Overall, 65.6% of the participants had a negative attitude toward MRONJ, and 34.4% had a positive attitude. A positive attitude was mostly observed among rheumatologists (55.8%) compared to other specialists (p <0.001). More years of experience were associated with a higher level of knowledge and positive attitude. ConclusionThe findings of this study identified a notable gap in the awareness, knowledge and attitudes of physicians regarding MRONJ in osteoporosis patients. Continuing education programs about ARDs and MRONJ risk are highly recommended.

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

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. Types of practice guideline reviewed: This paper aimed to summarize and revisit 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), 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. 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.

Medication-Related Osteonecrosis: Why the Jawbone?

Medication-related osteonecrosis of the jaw (MRONJ) has emerged as a complication of anti-resorptive medications. Despite its low incidence rate, this problem has gained attention in recent years due to its devastating consequences and lack of preventive strategy. The fact that MRONJ incidence has been exclusive to the jawbones, despite the systemic effect of anti-resorptive medications, could be a starting point to unravel the multifactorial pathogenesis of this condition. This review aims to negotiate the question of why the jawbone is more susceptible to MRONJ than other skeletal sites. Approaching the problem from this perspective could provide new directions for the prevention of MRONJ and expand our understanding of the unique oral microenvironment.

Case series of medication-related osteonecrosis of the jaw (MRONJ) patients prescribed a drug holiday

The role of a drug holiday in the management of medication-related osteonecrosis of the jaw (MRONJ) remains controversial. Current UK guidance does not recommend this practice given the lack of conclusive evidence, and potential risk of skeletal-related events or cancer metastasis. This paper aims to describe a series of fifty patients with confirmed MRONJ who were prescribed a drug holiday as part of their management. Data were collected on exposures including: anti-resorptive and/or anti-angiogenic drug history, duration of drug, method of administration, concurrent therapy, MRONJ stage, management of MRONJ and duration of drug holiday. The primary outcome was complete healing as documented in the clinical notes. Multivariate Cox regression analysis was performed to evaluate the association between exposures and primary MRONJ outcome. Models were adjusted for age, sex, and index of multiple deprivation. Survival analysis was performed using a log-rank test, censoring any patients with no primary outcome recorded (p < 0.05). A total of 44% of patients stopped their medication for >36 months. Over half of all MRONJ cases presented in the posterior mandible and dental extraction was the most common precipitating factor (76%). Almost three-quarters (72%) of patients achieved complete healing. MRONJ recurrence (new site) was reported at 30%, mainly in those with incomplete healing of the initial area. There was a lack of evidence for an association between all recorded exposures and the primary MRONJ outcome using multivariate Cox regression. Similarly, we did not demonstrate evidence for an association between the duration of the drug holiday and MRONJ outcome. Our results support published guidelines, which do not recommend the discontinuation of bone modifying drugs for the prevention of MRONJ, or as part of treatment for established MRONJ.

The effect of drug holiday on preventing medication-related osteonecrosis of the jaw in osteoporotic rat model.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive medications managing osteoporosis, such as bisphosphonates (BPs). To date, there is very limited evidence from prospective, controlled studies to support or refute the controversial prevention regimen that if a discontinuation of BPs before dentoalveolar surgery, so called "drug holiday", is effective in reducing the risk of MRONJ development in patients with osteoporosis. We proposed an experimental animal study, aiming to investigate the prevention of MRONJ following tooth extractions in osteoporotic condition, with the implementation of a BP drug holiday. Twenty rats were subjected to bilateral ovariectomy. After establishing the osteoporotic condition, all rats were exposed to weekly injections of zoledronate acid (ZA) for 8 weeks. After ZA treatment, 10 rats were subjected to dental extraction and defined as control group, and the rest 10 rats assigned to the DH group had a drug holiday of 8 weeks prior to dental extraction. Eight weeks after the dentoalveolar surgery, bone turnover biomarker in serum, occurrence of MRONJ-like lesion and histomorphometric assessment of osteonecrosis in mandible, and bone microarchitecture indices in femur, were examined. Eight weeks after dental extraction, the DH group showed a recovered osteoclastic activity, indicated by significantly increased number of osteoclasts in the mandibles and serum level of C-terminal telopeptides of type I collagen, as compared to the control group. No significant differences were observed in the gross-view and histological occurrences of MRONJ-like lesions between the two groups.There was no significant difference in bone microarchitecture in the femur between the control and DH groups before ZA therapy and 8 weeks after dental extraction. Our data provided the first experimental evidence in the osteoporotic animal model that the implementation of a BP holiday in prior to dental extractions could partially recover osteoclastic activity, but could not alleviate the development of MRONJ-like lesion or exacerbate the osteoporotic condition in the femur. Longer-term drug holiday, or combination of drug holiday and other prophylaxes to prevent MRONJ in patients with osteoporosis could be worth exploring in future studies, to pave the way for clinical managements. This in vivo prospective study reported that a recovery of osteoclastic activity by a BP drug holiday for 8 weeks in osteoporosis rats did not alleviate the development of MRONJ-like lesion followed by dental extractions. It contributes to the understanding of regimens to prevent MRONJ.

Association Between Malignant Diseases and Medication-Related Osteonecrosis of the Jaw (MRONJ): A Systematic Review and Meta-Analysis.

The aim was to identify whether malignant diseases increase the risk of medication-related osteonecrosis of the jaw (MRONJ) occurrence when patients are exposed to bisphosphonate, antiresorptive or antiangiogenic drugs. To analyze related factors. A systematic literature searching was performed in PubMed, Embase, and Google Scholar for studies with information about whether patients have malignant diseases. Patients involved must be treated with MRONJ-related drugs and at high risk of developing MRONJ. A total of 6 cohort studies and 3 case-control studies were included. Analysis according 9 studies shows that malignant diseases have significant influence on MRONJ occurrence (risk ratio (RR): 2.62; 95% confidence interval (95% CI): 1.58-4.33; P =0.0002). Subgroup analysis according 6 cohort studies also shows that malignant diseases significantly affect MRONJ occurrence (RR: 3.50; 95% CI: 1.63-7.52; P =0.001). Chemotherapy have no obvious influence on MRONJ occurrence (RR: 1.64; 95% CI: 0.79-3.39; P =0.18). Intravenous drug administration significantly influences MRONJ occurrence (RR: 2.67; 95% CI: 1.27-5.58; P =0.009). Patients with malignant diseases have higher risk of MRONJ occurrence when exposed to bisphosphonate, antiresorptive, or antiangiogenic drugs. Cumulative dosages from intravenous drugs administration contribute to MRONJ developing. Prevention of MRONJ in patients with malignancy should be emphasized.

CLINICAL EFFECTIVENESS OF PHOTODYNAMIC ANTIMICROBIAL THERAPY IN MRONJ - SYSTEMATIC REVIEW

<h3>Objectives</h3> Medication-related osteonecrosis of the jaw (MRONJ) is a persistent avascular bone exposure related to antiresorptive and/or antiangiogenic drugs use. Photodynamic antimicrobial therapy (aPDT) is reported as a promising therapy for MRONJ. This study aimed to systematically review the literature about the use of aPDT in preventing and/or treating MRONJ. <h3>Study Design</h3> Prospective and retrospective cohorts, randomized and nonrandomized trials, and case series enrolling adult patients were considered for inclusion. Study selection and data extracted were analyzed independently by 2 researchers. A search was conducted according to PRISMA guideline on MEDLINE-PubMed, Scopus, Web of Science, and Cochrane Library, including studies up to August 2020, with a total of 904 articles, of which 2 were included in final review according to the inclusion criteria. <h3>Results</h3> Due to the high heterogeneity among the included studies, meta-analysis was not feasible. Diode laser was the light source reported in both studies, and 0.01% methylene blue and its derivative, 0.01% phenothiazine chloride, were the reported photosensitizers. <h3>Conclusions</h3> aPDT was effective for both prevention and treatment of MRONJ. Despite these promising results, further randomized controlled trials are necessary to ensure the effectiveness of isolated use of aPDT in the treatment and/or prevention of MRONJ.

Non-Invasive Physical Plasma Treatment after Tooth Extraction in a Patient on Antiresorptive Medication Promotes Tissue Regeneration

Postoperative tissue regeneration can be negatively affected by bisphosphonate administration, especially in patients with oncologic diseases. A serious complication of bisphosphonate therapy is the medication-related osteonecrosis of the jaw (MRONJ), which can be observed mainly after dental surgery. MRONJ is a progressive destruction of the bone that requires patients to stay in hospital for extended periods of time. For this reason, primary wound closure is particularly important in surgical procedures. In the case of wound dehiscence, there is a very high risk for MRONJ. In recent years, non-invasive physical plasma (NIPP) has become known for improving wound healing on the one hand, but also for its promising efficacy in cancer therapy on the other hand. We report on a 63-year-old patient with a history of multiple myeloma and receiving zoledronate, who developed wound dehiscence after tooth extraction. NIPP treatment resulted in complete epithelialization of the entire wound dehiscence. In conclusion, the use of NIPP in patients receiving antiresorptive drugs seems to support tissue regeneration and thus could be an important tool for the prevention of MRONJ.

The Role of Bone Grafts in Preventing Medication-Related Osteonecrosis of the Jaw: Histomorphometric, Immunohistochemical, and Clinical Evaluation in Animal Model.

To evaluate the effects of inorganic bovine bone graft (Lumina Bone, Criteria, Brazil) and beta-tricalcium phosphate (β-TCP) graft (ChronOS, Synthes, Brazil) in rats with the risk of developing post-extraction medication-related osteonecrosis of the jaw (MRONJ). Eighteen male Wistar rats weighing 350 to 450 g were induced to develop MRONJ using zoledronic acid for 5 weeks. In the sixth week, the right maxillary first molar was extracted. The animals in Group I (G1) did not receive bone grafts after tooth extraction, while Group II (G2) animals received inorganic bovine bone grafts, and Group III (G3) animals received beta-tricalcium phosphate (β-TCP) grafts. Clinical evaluation and histomorphometric and immunohistochemical analyses were performed. ANOVA and Tukey's statistical tests were used and a level of significance was considered to be 5%. In the clinical evaluation, animals from G2 and G3 did not present clinical manifestations of osteonecrosis, unlike the control group (G1) animals, which presented necrotic bone tissue exposure in all samples. In the histomorphometric evaluation, animals in G3 showed greater formation of bone tissue (66%) and less formation of bone lacuna (18%) than animals in G1 (58%/32%) and in G2 (59%/27%) (P < 0.05). Moderate (++) immunostaining was observed in G2 and G3 for RANKL, TRAP, and OC, while G1 showed moderate (++) labeling for OC and mild (+) immunostaining for TRAP and RANKL. Greater formation of bone tissue and fewer bone lacunae were found in animals treated with β-TCP. In clinical evaluation, bone graft groups presented with the clinical manifestation of MRONJ and showed higher intensity of immunostaining for TRAP and RANKL. Despite the limitations of experimental animal studies, the results of this work may assist in the development of future clinical research for the prevention of MRONJ.

Effects of the prevention of medication-related osteonecrosis of the jaw by local administration of a dental pulp stem cell-conditioned medium to the rat tooth extraction socket.

The onset of osteonecrosis of the jaw, which is a side effect of bisphosphonates, often develops after tooth extraction; measures for its prevention have not yet been established. While treatment with systemic administration of bone marrow stem cell-derived conditioned medium for medication-related osteonecrosis of the jaw (MRONJ) has been reported, its preventive effects have not been clarified yet, and the high degree of invasiveness of bone marrow fluid collection remains an issue. Therefore, we created a rat model of MRONJ using BP zoledronic acid, used a dental pulp stem cell-conditioned medium (DPSC-CM), which can be collected relatively easily, and locally applied it to the tooth extraction socket with atelocollagen and gelatin sponges. The preventive effect on the onset of MRONJ was subsequently examined. The results demonstrated that the bone exposure width of the extraction socket was reduced, and the mucosal covering was promoted in the atelocollagen + DPSC-CM group as compared with the other groups. Furthermore, histological results indicated a decrease in the number of empty bone lacunae, whereas immunohistochemical staining revealed the presence of many vascular endothelial growth factor (VEGF)-positive cells. Moreover, the results of the investigation of the sustained release of atelocollagen using VEGF indicated the release of VEGF over time. Our results suggest that local administration of DPSC-CM using atelocollagen may be a useful method for the prevention of MRONJ triggered by tooth extraction.

Differences in the Knowledge and Experience of Physicians and Dentists About Medication-Related Osteonecrosis of the Jaw in Osteoporotic Patients

Aim: Prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis requires the cooperation of physicians and dentists. We investigated the knowledge, experience, and behaviour related to medical and dental cooperation for MRONJ prevention in patients with osteoporosis between physicians and dentists practising in the Shiga prefecture. Materials and methods: We conducted a cross-sectional study to investigate the cooperation between practising physicians and dentists for preventing osteonecrosis of the jaw (ONJ) in patients with osteoporosis using 2 separate questionnaires from July 28, 2018, to February 3, 2019. Results: Of 461 dentists who were sent the questionnaires at their dental clinics, 307 (67%) responded via fax. Of 846 physicians who were sent the questionnaire at their clinics, 378 (45%) responded via fax. Of these, 268 (32%) were finally analysed because 110 (13%) physicians had never treated patients with osteoporosis; 50% dentists and 24% physicians were familiar with the MRONJ position paper in Japan, and 39% dentists and 9% physicians had encountered MRONJ in their clinical practice. A total of 30% physicians had requested oral health care by a dentist before administering bone-modifying agents (BMA) therapy. The knowledge and experience of MRONJ differed between physicians and dentists. Conclusion: The behaviour of physicians and dentists was insufficient to enable medical and dental cooperation for the prevention of MRONJ in patients with osteoporosis. The lack of cooperation between physicians and dentists during osteoporosis treatment in the Shiga prefecture in Japan is documented in this study.

Oral risk factors associated with medication-related osteonecrosis of the jaw in patients with cancer.

Bone-modifying agents (BMAs) are indispensable to cancer therapy. However, the number of patients with medication-related osteonecrosis of the jaw (MRONJ) is increasing according to the BMA administration. Oral factors predisposing to development of MRONJ are receiving attention, and oral management is recommended for prevention of MRONJ; however, the strategy and criteria have not yet been established. Therefore, we investigated the oral risk factors associated with MRONJ development in this study. Aretrospective study was carried outon 398 cancer patients who had received oncological-dose BMAs between 2007 and 2018; general health factors, demographic, and dental factorswere examined along with MRONJ development in all the patients. The cumulative occurrence rate of MRONJ was calculated using a Kaplan-Meier analysis. Clinical factors were analyzed using theCox regression analysis. MRONJ occurred in 42 of the 398 patients. The cumulative MRONJ incidence rates were 4.5, 12.9, 17.7, and 21.6% at 1, 2, 3, and 4years, respectively. Age (p = 0.038), male sex (p = 0.002), initiation of dental interventions before BMA administration (p = 0.020), alveolar bone loss involving more than half the root (p < 0.001), and torus mandibularis (p < 0.001) were significantly associated with MRONJ. Our findings suggest that patients with alveolar bone loss involving more than half the root on panoramic radiographs and torus mandibularis carry a high risk of MRONJ development. Early dental intervention before BMA administration and oral management during the treatment are important for preventing MRONJ.

Prevention and treatment of oral adverse effects of antiresorptive medications for osteoporosis - A position paper of the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Stomatology and Oral Pathology (Sobep), and Brazilian Association for Bone Evaluation and Osteometabolism (Abrasso).

Antiresorptive therapy is the main form of prevention of osteoporotic or fragility fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but severe adverse reaction to antiresorptive and antiangiogenic drugs. Physicians and dentists caring for patients taking these drugs and requiring invasive procedures face a difficult decision because of the potential risk of MRONJ. The aim of this study was to discuss the risk factors for the development of MRONJ and prevention of this complication in patients with osteoporosis taking antiresorptive drugs and requiring invasive dental treatment. For this goal, a task force with representatives from three professional associations was appointed to review the pertinent literature and discuss systemic and local risk factors, prevention of MRONJ in patients with osteoporosis, and management of established MRONJ. Although scarce evidence links the use of antiresorptive agents in the context of osteoporosis to the development of MRONJ, these agents are considered a risk factor for this complication. Despite the rare reports of MRONJ in patients with osteoporosis, the severity of symptoms and impact of MRONJ in the patients' quality of life make it imperative for health care professionals to consider this complication when planning invasive dental procedures.

Research progress in the treatment and prevention of medication-related osteonecrosis of the jaw

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of anti-resorption drugs and anti-angiogenesis drugs. Its mechanism is still unclear, which may be related to bone remodeling inhibition, angiogenesis inhibition, inflammation, etc. The main clinical symptoms are continuous infection, recurrent swelling and pain and impacting the patients' quality of life. Because of its serious symptoms and unclear treatment, MRONJ has attracted wide attention. Now there are many researches on the treatment and prevention of MRONJ. The treatment includes conservative treatment and surgical treatment. There is no clear evidence of the effectiveness of existing methods of prevention and treatment of MRONJ, and lacking the unified and accepted standard methods of prevention and treatment. In this article, current researches of the prevention and treatment of MRONJ are reviewed, including the mechanism of the methods.

Necrotizing periodontitis or medication-related osteonecrosis of the jaw (MRONJ) in a patient receiving Bemcentinib\u2014a case report

Bemcentinib is a newly developed AXL inhibitor that is currently under investigation in phase II trails for the treatment of acute myeloblastic leukemia (AML). Clinical and radiographic findings in this case were very similar to cases of MRONJ in patients receiving Sunitinib or other anti-angiogenetic substances, assuming that Bemcentinib may cause similar oral side effects. We present a male 81-year-old patient with a manifestation of alveolar bone necrosis at the central upper incisors following a 2-month regimen with the AXL-inhibitor Bemcentinib, administered for the treatment of secondary acute myeloblastic leukemia (sAML). Due to the duration of less than 8 weeks, the osteonecrosis was diagnosed as necrotizing periodontitis, but the intraoral clinical and radiographic findings were also compatible with the differential diagnosis of medication-related osteonecrosis of the jaw (MRONJ, stage II). Following to discontinuation of Bemcentinib, the affected bone was surgically revised including the removal of a demarcated bone sequester under preventive antibiotic treatment (metronidazole 400 mg t.i.d.). We hypothesize that Bemcentinib might increase the susceptibility for osteonecrosis of the jaw, probably related to its antiangiogenic effects and the resulting modulation of host immune response. Based on the current observations, it can be assumed that oro-dental health might be significant also prior and during treatment with Bemcentinib for the prevention of MRONJ.

RADIOGRAPHIC BONE CHANGES IN MULTIPLE MYELOMA PATIENTS WHO DEVELOPED MEDICATION-RELATED OSTEONECROSIS OF THE JAW: A CASE CONTROL STUDY

<h3>Background</h3> Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect caused by antiresorptive medications, which are used for multiple myeloma (MM) patients. Currently, new evidence suggests that there are early radiographic changes in the bone of patients that eventually will develop into clinical MRONJ. The detection of early bone changes may be important in early diagnosis and prevention of MRONJ by drug cessation. <h3>Objective(s)</h3> The aim of this study was to evaluate the radiographic changes in the jaws of patients with MM who developed MRONJ compared with those in whom MRONJ did not develop. <h3>Study Design</h3> A retrospective study was performed for MM patients who were referred to the oral medicine clinic at the University of Florida College of Dentistry from 2006 to 2018. The patient information and radiographs (panoramic and intraoral radiographs) were retrieved from their dental chart (axiUm). For evaluating the cortical border, the mental index (MI), panoramic mandibular index (PMI), and mandibular cortical index (MCI) were measured. The bone density ratio was measured by using Image J 1.51 j8 (NIH, Bethesda, MD) in 5 locations in the bone and 1 in the dentin. <h3>Results</h3> Of 87 patients with MM who were examined, 48 were females (56%), and 38 were males (44%). The mean age was 63.97 years. In total, 29 were diagnosed with MRONJ. Our study indicated that patients with MRONJ had denser bone compared with patients without MRONJ (<i>t</i> test <i>P</i> < .0001). In addition, classifying the cortical border with the MCI showed that the association between MRONJ and the thickness and the sharpness of the cortical border is considered to be statistically significant (Fisher's test, <i>P</i> = .0003). The MI and PMI differences between the 2 groups were not statically significant. <h3>Discussion/Conclusions</h3> The increase of radiographic bone density was significantly related to the development of MRONJ in patients with MM. The cortical border thickness and sharpness should be evaluated as prognostic factors for development of MRONJ in patients on antiresorptive medications.

Prevention of medication-related osteonecrosis of the jaw

Medication-related osteonecrosis of the jaw (MRONJ) is a rare adverse effect of several anti-resorptive and anti-angiogenic drugs that typically presents following a dental extraction. MRONJ is difficult to treat and can have a significant negative effect on quality of life; therefore, the implementation of preventative measures is recommended. The multidisciplinary healthcare team should work collectively to educate patients on the need for good oral hygiene and ensure that patients undergo remedial dental work prior to the initiation of implicated medicines. As medicine experts, a major aspect of the pharmacist’s role is to educate both patients and other healthcare professionals on the safe and effective use of medicines. Consequently, there is an opportunity for pharmacists working in all settings to contribute to the prevention of MRONJ. This article provides a summary of the most important background information in relation to the prevention of MRONJ, and outlines the potential opportunities for pharmacists working in community pharmacy, secondary care and general practice.

Medication-related osteonecrosis of the jaw: An update on the memorial sloan kettering cancer center experience and the role of premedication dental evaluation in prevention

The aim of this study was to investigate the relationship between type of antiresorptive medication and medication-related osteonecrosis of the jaw (MRONJ) onset and the role of premedication dental evaluation (PMDE) in the prevention of MRONJ. Our database of patients with MRONJ was reviewed. The Kruskal-Wallis test was used to analyze the onset dose of the 3 frequent medication types associated with MRONJ. To evaluate the role of PMDE in the prevention of MRONJ, all patients on antiresorptive and/or antiangiogenic medications seen in the Dental Service of Memorial Sloan Kettering Cancer Center during a 10-year period were subclassified into 2 groups. Group I comprised patients seen for PMDE before the commencement of A/A and group II patients seen after prior exposure to antiresorptive and/or antiangiogenic medications. Fischer's exact test was used to compare the incidence of MRONJ in both groups. Patients on denosumab developed MRONJ earlier compared with zoledronate and pamidronate (P = .003). Group I had a significantly reduced incidence of MRONJ (0.9%) compared with group II (10.5%) (P < .0001). Dentoalveolar trauma as a precipitating factor between groups I and II was not statistically significant. Denosumab was associated with an earlier occurrence of MRONJ compared with zoledronate and pamidronate. The role of PMDE may be an effective preventive strategy in reducing the incidence of MRONJ.