Recently, bisphosphonates (BPs) have been widely used in medical practice as anti-resorptive agents owing to their anti-osteoclatic action. In addition, these compounds are also used for their analgesic action and their potential anti-tumour effect. Patients treated with BPs may subsequently develop osteonecrosis of the jaw or maxillary bone after minor local trauma including dental work, recently labelled as bisphosphonate osteonecrosis of jaw (BRONJ). However, the etiopathogenic mechanisms of this pathological condition are poorly understood. Although, several pathways have been proposed for BRONJ occurrence, no single model can explain all morphological changes observed at the macro- and microscopic level. Recent research suggests that BPs may promote an anti-angiogenic effect which contributes directly to the clinical features associated with BRONJ. Remarkably, the anti-angiogenic effect promoting BRONJ might be in keeping with the anti-neoplastic action of BPs. The current review, presents clinical diagnostic criteria. In addition, based on our own experience we describe the histopathological criteria for diagnosis of BRONJ and the possible pathways which may lead to this frustrating pathological condition.

The present systematic review evaluates the safety of placing dental implants in patients with a history of antiresorptive or antiangiogenic drug therapy. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and OpenGrey databases were used to search for clinical studies (English only) to July 16, 2019. Study quality was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using a modified Newcastle-Ottawa scale and the Joanna Briggs Institute critical appraisal checklist for case series. A broad search strategy resulted in the identification of 7542 studies. There were 28 studies reporting on bisphosphonates (5 cohort, 6 case control, and 17 case series) and 1 study reporting on denosumab (case series) that met the inclusion criteria and were included in the qualitative synthesis. The quality assessment revealed an overall moderate quality of evidence among the studies. Results demonstrated that patients with a history of bisphosphonate treatment for osteoporosis are not at increased risk of implant failure in terms of osseointegration. However, all patients with a history of bisphosphonate treatment, whether taken orally for osteoporosis or intravenously for malignancy, appear to be at risk of “implant surgery-triggered” medication-related osteonecrosis of the jaw (MRONJ). In contrast, the risk of MRONJ in patients treated with denosumab for osteoporosis was found to be negligible. In conclusion, general and specialist dentists should exercise caution when planning dental implant therapy in patients with a history of bisphosphonate and denosumab drug therapy. Importantly, all patients with a history of bisphosphonates are at risk of MRONJ, necessitating this to be included in the informed consent obtained before implant placement.

This review sheds light on the recent published scientific evidence relating to the use of professionally delivered local antimicrobial agents (LA’s). The review also analyses drug delivery systems available to date and provides an update on the latest scientific evidence about the benefits, limitations, and clinical results obtained by use of local drugs in the treatment of periodontal disease. The search strategy revealed randomized controlled trials (RCTs) that compared the efficacy of adjunctive LA’s to mechanical therapy alone. Based on the available evidence gathered from this review, we can infer that the use of local antimicrobial agents in conjunction to scaling and root debridement (SRD) delivers significant benefits in periodontal therapy and it is a useful aid, avoiding many of the side effects that systemic antibiotic therapy may involve. Local drug delivery (LDD) is an efficient and effective means of delivering drugs based on the evidence presented in the review. The authors of this review would suggest the use of local antimicrobials in cases of localized periodontitis or individual areas that do not respond to the usual mechanical therapy alone. This review summarizes the current use of local drug delivery in periodontal management ensuring that the general practitioners are able to choose an appropriate local antimicrobial.

A promising approach to improve the poor antibacterial properties of dental composite resins has been the addition of metal oxide nanoparticles into the resin matrix. This systematic review aimed to determine whether the addition of zinc oxide nanoparticles (ZnO-NPs) improves the antibacterial properties of direct dental composite resins. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered with the PROSPERO database: CRD42019131383. A systematic literature search was conducted using the following databases: Medline (Ovid), the Cochrane Library, SCOPUS, CINAHL, Web of Science, Trove, Google Scholar, World Cat, and OpenGrey. The initial search retrieved 3178 results, which were then screened against inclusion and exclusion criteria, resulting in a total of four studies that were eligible for qualitative synthesis within this review. All the included studies were in vitro non-randomized post-test design experimental studies. A lack of congruity in the results obtained from these studies that used different tests to evaluate antibacterial activity was evident. Although some studies demonstrated a significant improvement of antibacterial properties in composites containing at least 1% ZnO-NPs (wt %), they are unlikely to present any clear clinical advantage due to the short lifetime of observed antibacterial properties.

The contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This in vitro study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities. pMSC multipotency was confirmed by successful differentiation into cells of both the osteogenic and endothelial lineages, as demonstrated by positive Alizarin Red S staining and Ac-LDL uptake. pMSC differentiation in the presence of non-cytotoxic BP concentrations showed that nitrogen containing BPs had a significant inhibitory effect on cell migration and endothelial marker gene expression, as well as compromised endothelial differentiation as demonstrated using von Willebrand factor immunofluorescence staining and tube formation assay. This in vitro study demonstrated that at non-cytotoxic levels, nitrogen-containing BPs inhibit differentiation of pMSCs into cells of an endothelial lineage and affect the downstream functional capability of these cells supporting a multi-modal effect of BPs on angiogenesis as pathogenic mechanism contributing to bone healing disorders such as bisphosphonate related osteonecrosis of the jaws (BRONJ).