The Use of Human Amniotic Membrane (hAM) as a Treatment Strategy of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Systematic Review and Meta-Analysis of the Literature.

Background and objectives: Although it is very uncommon, medication-induced osteonecrosis of the jaw (also known as MRONJ) can have serious consequences. Traditionally, this adverse event has been recognised in patients who were treated with bisphosphonate (BP) drugs. Nevertheless, in recent years, it has been established that individuals having treatment with various types of medications, such as a receptor activator of nuclear factor kappa-Β ligand inhibitor (denosumab) and antiangiogenic agents, have had the same issue. The purpose of this research is to determine if the application of human amniotic membrane (hAM) may be used as a therapy for MRONJ. Material and Methods: A multi-source database (MEDLINE, EMBASE, AMED, and CENTRAL) systematic search was performed. The major objective of this study is to obtain an understanding of the efficacy of hAM when it is employed as a treatment modality for MRONJ. The protocol of this review was registered in the INPLASY register under the number NPLASY202330010. Results: The authors were able to include a total of five studies for the quality analysis, whereas for the quantity evaluation, only four studies were eligible. A total of 91 patients were considered for the investigation. After treatment with human amniotic membrane (hAM), a recurrence of osteonecrosis was observed in n = 6 cases (8.8%). The combined efficacy of surgical therapy and the use of hAM resulted in an overall success rate of 91.2%. Intraoperative complications were only documented in one article, and they were mostly caused by the positioning of the hAM, which led to wound breakdown at the surgical site. Conclusions: Based on the small amount of data and low-quality research included in this study, using human amniotic membranes to treat MRONJ might represent a feasible option. Nevertheless, further studies with a wider patient population are required to understand the long-term impacts.

The role of antiresorptive drugs and medication-related osteonecrosis of the jaw in nononcologic immunosuppressed patients: A systematic review.

Medication related osteonecrosis of the jaw (MRONJ) is a severe condition affecting the jaws of patients exposed to specific drugs, and is primarily described in patients receiving bisphosphonate (BP) therapy. However, more recently it has been observed in patients taking other medications, such as the RANK ligand inhibitor (denosumab) and antiangiogenic drugs. It has been proposed that the existence of other concomitant medical conditions may increase the incidence of MRONJ. The primary aim of this research was to analyze all available evidence and evaluate the reported outcomes of osteonecrosis of the jaws (ONJ) due to antiresorptive drugs in immunosuppressed patients. A multi-database (PubMed, MEDLINE, EMBASE and CINAHL) systematic search was performed. The search generated twenty-seven studies eligible for the analysis. The total number of patients included in the analysis was two hundred and six. All patients were deemed to have some form of immunosuppression, with some patients having more than one disorder contributing to their immunosuppression. Within this cohort the commonest trigger for MRONJ was a dental extraction (n=197). MRONJ complications and recurrence after treatment was sparsely reported in the literature, however a total of fourteen cases were observed. The data reviewed have confirmed that an invasive procedure is the commonest trigger of MRONJ with relatively high frequency of post-operative complications or recurrence following management. However, due to low-quality research available in the literature it is difficult to draw a definitive conclusion on the outcomes analysed in this systematic review.

A systematic review of metastatic cancer presenting in osteonecrosis of the jaws (MC-ONJ) in patients undergoing antiresorptive and/or antiangiogenic therapy for skeletal-related adverse events.

INTRODUCTION: Osteonecrosis of the jaw (ONJ) is reported to be primarily associated with patients receiving bisphosphonate therapies but has been found in patients taking a number of other medications. A number of recent reports have noted the presence of metastatic cancers in the histologic analysis of osteonecrotic lesions from the jaw. The aim of the present review is to estimate the frequency and the type of metastatic cancer most commonly found in ONJ specimens in patients undergoing antiresorptive and/or antiangiogenic drug therapy. MATERIAL AND METHODS: A multidatabase (PubMed, MEDLINE, EMBASE, and CINAHL) systematic search was performed. Any studies involving human participants treated with antiresorptive and antiangiogenic drugs were considered. Where study patients presented with malignant cells within osteonecrotic specimens, further data were collected. Data are presented using descriptive statistics. RESULTS: A total of 13 studies met the inclusion criteria for this systematic review. Thirty-seven study patients had histologic evidence of malignant cells within medication-related osteonecrosis of the jaw (MRONJ) specimens. The most frequent phenotype of malignant cells found within MRONJ specimens were breast cancer variants (n = 15). The frequency of malignant tumor cells found within the MRONJ specimens was calculated using 4 studies. Out of 604 patients, the frequency was 4.64% (n = 28). CONCLUSIONS: Based on the limited data available in the literature, it is plausible that not histologically analyzing all ONJ specimens could result in a small number of undiagnosed and untreated malignant diseases. Additional data based on a larger cohort of study patients is necessary to understand the role of MRONJ in metastatic spread and the influence of surgical treatment and reoccurrence.

The risk of osteonecrosis of the jaw and adverse outcomes in patients using antiresorptive drugs undergoing orthodontic treatment: A systematic review.

OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) is rare. It is a serious adverse effect of certain drugs, of which bisphosphonates (BPs) are the most widely known. The aim of this systematic review was to analyze all published evidence for the reported adverse outcomes as a result of orthodontic treatment in patients undergoing antiresorptive therapy. DATA: All types of studies involving patients undergoing orthodontic treatment and treated with antiresorptive drugs were considered. A meta-analysis was not conducted due to the high amount of variability and heterogeneity in the reporting and presentation of data among the studies meeting the inclusion criteria. SOURCES: A systematic search was performed using 4 databases (PubMed, MEDLINE, EMBASE and CINAHL). STUDY SELECTION: Seven studies matched the inclusion criteria for this review, reporting a total of 29 patients. MRONJ was only reported in 1 patient. The adverse outcomes following orthodontic treatment included difficulty achieving root parallelism (n = 4), difficulty achieving complete space closure (n = 3), exaggerated tooth mobility post-debond (n = 2), increased duration of orthodontic treatment beyond expected completion (n = 1), sclerotic alveolar bone changes seen on post-op radiographic images (n = 2), and an increased amount of root resorption (n = 1). CONCLUSIONS: The high amount of heterogeneity and limited evidence precluded a valid interpretation and analysis of the results through pooling of data. Additional data with sufficient quality, a reduction of bias, and a greater prospective cohort of patients is crucial to assess adverse effects, mechanisms of action, and associated risk factors in at-risk patients. CLINICAL SIGNIFICANCE: Based on the limited evidence available in the literature, it is unclear whether orthodontic treatment alone can precipitate MRONJ. However, antiresorptive drug therapy may be associated with a sub-optimal treatment outcome.