## 5 Discussion
Furthermore, although potential associations between the development of MRONJ and several genes have been documented in the literature, they have all failed to clarify the responsibility of any genes as the sole risk factor for MRONJ development. With the goal of highlighting the current state of research quality, the current quality meta-review examined the highest quality evidence currently available that was published in the previous years on genetic and pharmacogenomics studies and MRONJ using the evidence scale developed by the Oxford Centre for Evidence-Based Medicine [61]. It is found that the authors of the reviews applied stringent inclusion criteria to those who were included in these investigations. The reviews' research counts, which ranged from 4 [40] to 15 articles, make this clear [41; 42; 43; 44]. On a very interesting note, the majority of the reviews included in this meta-review were released in 2019, with many of them appearing in the same editorial publication. All the SR and MA published reviews presented no registration in any public review registry. This indeed increased the chance of reporting bias. The majority of the articles included were low-ranked studies with a moderate to high risk of bias [40; 41; 42; 43; 44]. These deficiencies related to methodology have unquestionably contributed to an increase in the probability of inconsistency in general guidelines that have been issued. The authors have discovered that most of the reviews feature predominantly retrospective cohort studies with or without multiple arms (quite often without a sample size calculation) [22; 25; 26; 47; 48; 49; 50; 51; 52; 53; 54; 55; 56; 57; 58; 59]. That is why the results of these studies and reviews must be interpreted very carefully. Indeed, systematic reviews or meta-analyses will need to provide an outline of a clear and consistent protocol before they can be carried out. This will need to be conducted with the awareness that the results of these types of studies are frequently applied to medical practice in the form of guidance. Usually, different reviews have a rigorous and transparent protocol, which is strengthened by using the PRISMA checklist. Unfortunately, all of the included reviews did not follow what is currently considered the \"gold standard\" [40; 41; 42; 43; 44]. Indeed, this shortcoming has affected the adequacy of the evidence published results and conclusions. For better research, it is necessary to conduct analysis and research with excellent quality in the future. Quality research contained randomized control trials that are used to support evidence-based treatments and their protocols with efficiency. The authors suggest the following as some important rules for future studies related to pharmacogenomics and genetics associated with MRONJ:  
* It is recommended that a formula for calculating sample size be devised and used for each and every randomised controlled trial (RCT) and cohort study. * To the best of our ability, big RCTs should be conducted with sufficient depth to enable exact epidemiological and precise findings. * For every study, risk stratification should be used to reduce the impact of effect modification and confounding variables (e.g., length of drug taken, habits, periodontal status, etc. ).