## 5 Discussion  
According to the findings of our investigation, a large number of studies have been conducted to study the possible link between genetic variations and MRONJ; nevertheless, the conclusions drawn from these investigations have been contradictory thus far. Only one study included in the reviews analysed found that the CYP2C8 rs1934951 polymorphism was a risk factor for the development of MRONJ; however, other studies have evaluated the association between this polymorphism and susceptibility to MRONJ in cancer patients, but no predisposition was found [32]. Many other studies included in the reviews analysed revealed rs1152003 and the peroxisome proliferatorator-activated receptor-gamma (PPARG), but no correlation with the MRONJ group under investigation was found [50; 56]. Additionally, VEGF SNPs (rs3025039, rs699947, and rs2010963) were examined in other research; only for rs3025039 was a significant difference found, whilst differences for the other genotypes were minor (rs2010963 and rs699947) [49; 55]. The candidate genes and SNPs identified through these studies varied and rarely replicated in another. In recent years, rising evidence has been described to support the role of SNPs with MRONJ. However, these studies have shown either a weak or no connection between the genetic aspects measured and the possibility of MRONJ development [42]. Even though the pathophysiology of MRONJ is still a mystery to us, osteoclasts are thought to play an important part in its occurrence. To understand the mechanism, [PERSON] et al., analyzed the SNPs and revealed that osteoclastogenesis and differentiation, bone resorption, bone mineral density, and osteoporosis are all influenced by SNPs in seven genes [48]. MRONJ was shown to be more common in patients with genetic variation in genes encoding COL1A1 (rs1800012), RANK (rs12458117), MMP2 (rs243865), OPG (rs2073618), and OPN (rs11730582) [60]. Furthermore, [PERSON] et al. observed that MRONJ risk was strongly related to RBMS3 rs17024608 in the 53 patients who were using zoledronate for osteoporosis [46]. In fact, RBMS3 regulates collagen synthesis, contains a significant amount of bone matrix, and is critical for bone resorption. Bone remodelling may be affected and antiresorptive medicines made more potent by RBMS3 mutations, leading to MRONJ [47]. In addition, farnesyl pyrophosphate synthase is thought to be an additional important participant in the pathophysiology of MRONJ. This theory is based on speculation (FPPs). This is an important enzyme in the process known as the mevalonate pathway. It is responsible for the inhibition and disruption of particular proteins in the cytoskeleton of osteoclasts, which ultimately results in the prevention of bone resorption [51]. In order to investigate the prevalence of FDPS rs2297480 in a cohort of patients receiving zoledronate for multiple myeloma, breast cancer, and prostate cancer, [PERSON] et al. designed their study. The study found a strong association between MRONJ and FDPS rs2297480 polymorphism; however, its exact purpose is yet unknown [51]. The nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 (SIRT1) and E3 ubiquitin-protein ligase (HERC4) are crucial regulators of cell proliferation and differentiation processes in the skeletal system, according to [PERSON] et al. GWAS's study. This investigation verified that the HERC4 rs3758392 and SIRT1 rs7896005 polymorphisms were substantially linked with MRONJ in cancer patients [59]. Previous research highlighted that genetic polymorphism in numerous genes such as TGFb1, MMP2, CYP2C8, VEGF, COL1A1, RANK, OPG, OPN, and PPAR--which are responsible for the differentiation and activation of osteoclast--are considerably linked to MRONJ [43; 48; 49]. However, despite all the genetic studies (GWAS, WES, and CGS) that have been presented to establish the correct pathological mechanisms, they remain yet to be determined.