In this study, most dentists (65.0%) recorded both the name of the anti-osteoporotic drug and its duration of use. While the recommended period for a drug holiday differs for each drug, most (53.3%) dentists did not make such a distinction.
There were no statistically significant differences in whether bone-modifying medications were recorded or whether a referral from the attending physician was requested prior to dental surgery procedures between dentists with and those without experience with MRONJ. This result suggests what are necessary for the prevention of MRONJ. In a previous study, it was reported that the proportion of dentists who did not contact or ask for referral from an attending physician prior to dental procedures was low, and that it decreased slightly from 2014 (12.86%) to 2018 (11.67%) [11]. The authors of that study noted that such unsupervised procedures can reduce patients' quality of life.
We observed that more dentists advised patients to take drug holidays ≥6 months than ≤2 months for the prevention of MRONJ. This period is longer than that recommended in the literature [7, 10]. Hence, the optimal duration of a drug holiday cannot be determined from the results of our study alone, and further long-term studies are required for definitive conclusions to be drawn.
Due to the aging population, not only in Korea but also worldwide, an increasing number of elderly individuals with multiple co-morbidities are expected to undergo dental procedures, including implant placement. Thus, an awareness of the potential interactions in treatment regimens prescribed to the same patient by doctors in different fields of specialization will become increasingly important, necessitating optimal communication between healthcare professionals.
Poor patient compliance is one of the primary obstacles in the treatment of osteoporosis, commonly resulting from side effects of bone-modifying agents, or the fear thereof [12, 13]. On the other hand, excessive use of bone-modifying agents can increase the risk of MRONJ. MRONJ is a rare but serious complication following treatment with certain medications, and is defined as the presence of exposed bone in the oral and maxillofacial regions (or extra- or intra-oral fistulas) lasting more than 8 weeks. To be diagnosed with MRONJ, a patient should have no prior history of radiation, or of treatment with bone-resorption inhibitors or angiogenesis inhibitors, for tumor metastasis to the jawbones [7].
The exact mechanism of development of MRONJ is unclear, in spite of several proposed hypotheses. Additionally, varied opinions regarding the efficacy of surgical and non-surgical treatments have been presented [14, 15]. In addition to bisphosphonates, several drugs such as denosumab, steroids, and other angiogenesis inhibitors can cause MRONJ [7, 16]. Denosumab is an anti-human receptor activator of the nuclear factor kappa-Β ligand and inhibits the activity of osteoclasts. It is used to treat osteoporosis caused by bone absorption disorders [17], similar to bisphosphonates, and its cost-effectiveness [18] and convenience of administration has recently led to its increased use in Korea. Denosumab is also associated with a risk for MRONJ; however, the risk of fracture may increase either temporarily or permanently when its use is discontinued [7].
The determination of the type of bone-modifying medication and its duration of use, potential alternative medications, and a drug holiday of 2–3 months before performing dental procedures is essential for preventing MRONJ [7, 10]. The disadvantages of drug discontinuation should be weighed against its advantages. In a post-hoc analysis, Anagnostis et al. (2017) [19] concluded that drug holidays are advisable for patients who have not experienced recent fractures and for those at low risk of fracture, defined as follows: a femoral neck T-score ≥ -2.5; age <70 years; and no diseases or medications that could increase fracture risk. Drug holidays should be considered for patients with a 5-year history of alendronate use or a 3-year history of zoledronic acid (or risedronate) use [19, 20]. The duration of the drug holiday should also be based on bone mineral density [20]. The management of the osteoporotic condition with other bone-modifying medications is advisable if denosumab is discontinued [21, 22]. However, drug holidays are not recommended for bone-modifying medications such as denosumab, hormone replacement therapy, selective estrogen-receptor modulators, and teriparatide [21], or for patients with severe osteoporosis [10, 22]. Therefore, the determination of a drug discontinuation protocol may be beyond the scope of dentistry and it is important that dentists request a doctor's referral letter prior to any dental procedure in patients at risk for MRONJ. In addition, detailed records of bone-modifying agents must be requested and maintained. However, the results of our study showed that the proportion of dentists requesting referral letters was relatively low (59.1%). In addition, the proportion of dentists that encountered cases of MRONJ (29.3%) was higher than the general prevalence of MRONJ. This highlights the importance of dentists possessing adequate knowledge pertaining to this condition, and of proper dental management protocols.
Several prior studies have been conducted to examine the awareness of dentists regarding MRONJ in different countries. In a survey of 120 dentists in Romania, the majority were aware of bisphosphonate therapy and its complications, but were not familiar with the pathophysiology, diagnosis, and treatment of BRONJ [23]. In a survey of 204 Brazilian dentists and dental students, researchers discovered a lack of knowledge regarding bisphosphonates and BRONJ [24]. In a survey of 60 dentists and 60 dental students in Spain, 30 (50%) students and 41 (68.36%) dentists were determined to have up-to-date knowledge regarding BRONJ [25]. In a survey of 129 British dentists, more than 90% admitted a lack of awareness regarding drugs (other than bisphosphonates) that cause MRONJ. Furthermore, the lack of a standardized protocol was reported as the primary reason for reluctance in managing such patients [26]. In a survey of 222 Saudi physicians and dentists, only 31.5% were aware of BRONJ. The authors suggested that this could be improved through education [27]. In the present study, we found that the level of experience among dentists regarding MRONJ was high (29.3%); nevertheless, the documentation of patients’ history pertaining to the type of bone-modifying agent and the duration of its use was insufficient (65.0%). Hence, dentists should be made aware of the guidelines for treatment of such patients through regular educational programs.
Our study had some limitations. First, only 1000 dentists were surveyed; therefore, the results may not be generalizable to all dentists in Korea. Second, due to the limited scope of the questions in the survey, it was not possible to elucidate dentists’ knowledge of MRONJ pathogenesis. Third, due to the questionnaire survey system, the number of questions was limited, so detailed surveys were not possible. Nevertheless, the results of this survey can serve as a basis for larger, more detailed, long-term studies to investigate the dentist's perception.