Surgery, radiation and chemotherapy are the common treatment modalities for most cancer patients. To reduce the frequency of skeletal-related events, parenteral administration of antiresorptive (AR) therapy e.g., zoledronate and denosumab have been commonly used .
Bisphosphonate (BP) is a commonly used AR drug. It inhibits the osteoclast-mediated bone resorption and changes the bone marrow microenvironment, to make it less favourable for cancer cells to survive, thus preventing cancer recurrence . In addition to its effect on osteoclasts, it also triggers the human T- cells in the immune pathway, which may be another potential mechanism in its anti-cancer activity . It was used to treat patients with malignant bone disease such as multiple myeloma and bone metastases of various solid tumors such as breast, lung, and prostate cancer . Recent data from clinical trials proved that adding nitrogen-containing bisphosphonate (N-BP) e.g., zoledronate to endocrine therapy or chemotherapy enhances disease-free survival rate of patients .
However, in 2003, Marx noted the complication of osteonecrosis of the jaw (ONJ) associated with the BP drug . He first reported 36 ONJ cases among patients who mainly received BP as an adjuvant cancer therapy. They were presented with exposed avascular bone in the maxillofacial region . Since then, bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been reported as an unusual, but consequential complication.
Denosumab, a new class of AR drug with a shorter half-life, was introduced as an alternative to BP. Denosumab is a human monoclonal antibody that inhibits the cytokine RANKL, which acts as a mediator within the formation and function of osteoclasts . Correspondingly, this non-bisphosphonate AR drug can also lead to ONJ, which was first reported in 2010 . The incidence of ONJ from denosumab and zoledronate fall in a range of 0.7-4% and 0.8-3%, respectively [7, 8].
Besides AR, in 2008, first ONJ associated with an anti-angiogenic agent (AA) drug was reported . Therefore, in 2014, the American Association of Oral and Maxillofacial Surgeons (AAOMSs) had updated the term ‘BRONJ’ to medication-related osteonecrosis of the jaw (MRONJ), in order to include all the medications that cause ONJ .
MRONJ is represented by painful necrotic exposed bone, or bone that can be probed through an intraoral or extraoral fistula, which occurred in the maxillofacial region that has lasted for more than 2 months, in which the patients had a history of AR/AA therapy but without history of radiation therapy and metastatic disease to the jaws . The pathogenesis of MRONJ has been studied for several years, but it has not yet been fully understood. It is hypothesized that MRONJ are related to either bone remodeling inhibition, inflammation and infection, angiogenesis inhibition, soft tissue toxicity, or immunity dysfunction [10, 11].
There are numerous risk factors leading to MRONJ. Among dental operative procedures, tooth extraction is the most frequently reported predisposing event . Other than extraction, periodontal disease, dental implant placement, endodontic treatment, oral surgery and maxillofacial trauma had also been reported to cause MRONJ [12, 13]. However, there were also cases of MRONJ which developed spontaneously .
When a patient is diagnosed with MRONJ, a multidisciplinary team approach is needed, including regular communication among oncologist, dentist, and oral and maxillofacial surgeon. According to AAOMSs, the treatment aims for patients with established MRONJ are to control pain, infection of soft and hard tissues, and the progression of bone necrosis, which may include surgical intervention, pain medication, antimicrobial mouthwashes, and antibiotic therapy . However, the treatment of this condition is generally challenging, and the optimal therapeutic option is yet to be established. Due to this fact, it highlights the importance of measures to prevent MRONJ.
Risk of developing MRONJ can be significantly reduced if preventive measures are taken. Premedication dental evaluation (PMDE) has been reported as an effective MRONJ prevention measure, in which it comprises a thorough oral assessment together with radiographic examination, detailed patient education, and completion of the dental treatment needs prior exposure to AR/AA drugs . The aim of PMDE is to achieve a good oral health condition by eliminating any possible oral pathology or risk factors [15, 16]. Treatment of dental caries and periodontal disease should be indicated at this point [14, 17]. Non-restorable tooth and tooth with hopeless prognosis need to be extracted [10, 17], as well as the partially erupted third molar [16, 17]. Furthermore, ill-fitting dentures should be examined and modified, particularly along the lingual flange region, in order to remove any pressure areas or sore spots [10, 16]. An appropriate oral hygiene instruction and the relevant information about MRONJ should be provided to the patients by the oral healthcare professionals [10, 14]. In a retrospective study, Owosho et al. reported a 10-year data in Memorial Sloan Kettering Cancer Center . It was found that there was a 12-fold reduction in the incidence of MRONJ when patients received PMDE . This was in accordance with several other studies which have proved that the implementation of PMDE had successfully reduced the development of MRONJ [18, 19].
Besides providing the dental treatments prior to the AR/AA therapy, creating dental awareness among these cancer patients is important to prevent and reduce the disease burden attributable to MRONJ. In a qualitative study, most of the patients demonstrated poor awareness and limited knowledge about the recommended preventive strategies of MRONJ  Patient education about prevention of MRONJ should be emphasized . It is necessary for healthcare professionals to inform their patients about the possible complications of AR/AA drugs and refer the patients to receive PMDE . Study has shown a remarkable reduction in the incidence of MRONJ when effective patient education and dental preventive measures were applied .
At present, the literature on patient awareness about the MRONJ and barrier to the PMDE are still scanty. Hence, the aims of this study are to assess the dental awareness in reducing the risk of MRONJ among non-head and neck cancer patients, and the barriers of them attending PMDE.