The results of this study showed that most dentists only recorded the name of the osteoporotic drug, without documenting the duration of use. While the required period for a drug holiday is different for each drug, most dentists did not advise different drug holiday durations depending on drug type. Dentists recording both the name and duration of bone-modifying medications, as well as those requesting referral letters from doctors, more often had no prior experience with MRONJ cases. Therefore, the results of this study suggest that MRONJ can be prevented by maintaining a thorough medical record for patients on bone-modifying medications, and requesting a doctor’s referral letter prior to the performance of any dental procedures.
Furthermore, it was observed that drug holidays ≥6 months are more effective than 2–3-month drug holidays 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 demographic not only in Korea, but also worldwide, an increasing number of elderly individuals with multiple co-morbidities are expected to undergo various dental procedures, including implant placement. Thus, an awareness of the potential interactions in treatment regimens advised by multiple doctors in specialized fields, as well as optimal communication between healthcare professionals, will become increasingly important. Poor patient compliance and varied side effects of bone-modifying agents are the primary obstacles in the treatment of osteoporosis [11, 12]. On the other hand, excessive use of bone-modifying agents can also 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. Patients do not have any prior history of radiation or 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 [8, 9, 13, 14]. In addition to bisphosphonates, several drugs such as denosumab, steroids, and angiogenesis inhibitors can cause MRONJ [7, 15]. 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 [16], similar to bisphosphonates [8], and its efficacy and convenience of administration has recently led to its increased use in Korea [17]. Denosumab is also associated with a risk for MRONJ, but the risk of fracture may increase either temporarily or permanently when its use is discontinued [7].
Thus, the disadvantages of drug discontinuation should be weighed against its advantages; this requires that dentists request a doctor's referral letter prior to any dental procedure in patients at risk for MRONJ. In addition, detailed investigations and records of bone-modifying agents must be requested and maintained. Drug holidays are not recommended for certain drugs, as well as patients with severe osteoporosis [10, 18]. As the determination of a drug discontinuation protocol depends on both individual patient factors and the specific drug in question, this may be beyond the scope of dentistry; therefore, a doctor’s referral letter should always be obtained. However, the results of our study showed that the proportion of dentists requesting referral letters was relatively low. In addition, the proportion of dentists that encountered cases of MRONJ was higher than the general prevalence of MRONJ. This suggests that dentists are highly likely to encounter patients at risk for MRONJ, thus highlighting the importance of adequate knowledge pertaining to this condition, and proper dental management protocols.
The determination of bone-modifying medication type and its duration of use, potential alternative medications, and a drug holiday of 2–3 months before dental procedures is essential for preventing MRONJ [7, 10]. In our study, the optimal drug holiday duration reported by the respondents varied, and the percentage advising the guideline-recommended 2–3-month holiday was relatively low. A post-analysis study concluded that drug holidays should be advised for “patients at low risk of fracture,” who are defined by the following criteria: T-score > -2.5; no current fracture; age less than 70 years; and no diseases or medications that could increase fracture risk [19]. 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 drug holiday should be decided based on the results of bone mineral density assessment, fracture risk, and T-score [20]. The management of the osteoporotic condition with other bone-modifying medications is advised after discontinuation of denosumab during drug holidays or dental treatment [21, 22]. Drug holidays are not required with other bone-modifying medications such as hormone replacement therapy, selective estrogen-receptor modulators, and teriparatide [21]. Therefore, it is important that dentists obtain a doctor's referral letter before initiating treatment.
Several prior studies examining the awareness of dentists regarding BRONJ have been conducted in different countries. A survey of 120 dentists in Romania reported that the majority were aware of bisphosphonate therapy and its complications, but were not familiar with the pathophysiology, diagnosis, and treatment of BRONJ [23]. A survey of 204 Brazilian dentists and dental students reported a lack of knowledge regarding bisphosphonates and awareness pertaining to BRONJ [24]. In a survey of 120 dentists and 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 difficulties in managing such patients [26]. A recent study conducted in 2019 reported that only 31.5% of the surveyed physicians and dentists were aware of ONJ. The authors suggested that the level of knowledge and awareness regarding BRONJ could be increased through education [27]. In the present study, we found that the level of awareness of dentists regarding MRONJ was high; nevertheless, the documentation of patients’ history pertaining to bone-modifying agent type and duration of use was insufficient. Hence, dentists should be made aware of the standard guidelines for treatment of such patients through regular educational programming.
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, it was not possible to elucidate the dentists’ knowledge of MRONJ pathogenesis. Third, respondents in this survey were not aware of the available guidelines for implementing drug holidays. Fourth, the type of medication responsible for MRONJ could not be definitively ascertained. Nevertheless, the results of this survey can serve as a basis for further detailed, larger, long-term studies to reveal more causal relationships.