4 | DISCUSSION
Since the first report regarding BRONJ in 2003, several clinical and experimental studies have been conducted regarding its diagnosis, treatment and prognosis; however, many aspects related to this condition are still unclear.8 Due to the risk of recurrence of osteonecrosis of the jaw, there is no doubt that prevention is the best method of treatment. Thus, physicians should refer the patients for dental assessments and determination of risk factors prior to administration of bisphosphonates for them.9-11
In 2005, the Food and Drug Administration pointed to the risk of BRONJ to raise awareness about this condition among the health professionals. Kim et al, in 2016 reported that 9.21% of medical professionals had not heard about BRONJ while 9.9% correctly answered all five questions about it, indicating the poor knowledge of medical professionals about BRONJ.7
Treatment of periodontal disease and oral and dental care are highly important in patients requiring bisphosphonate therapy.11, 12 Thus, they need to be informed about the incidence and significance of BRONJ and should be provided with the necessary instructions in this respect.
The incidence of BRONJ following intravenous injection of bisphosphonates is 0.8% to 1.2%.13 This rate is 0.00038% to 0.06% in patients with oral intake of bisphosphonates.14 The diagnosis of BRONJ is not easy, and a diagnosis may not be reached due to conditions related to oral surgery.15 Thus, correct diagnosis of BRONJ is imperative in patients taking bisphosphonates. Mucosal ulceration and suppurative infection exposing the underlying bone is the most common clinical presentation of BRONJ. On the other hand, BRONJ does not well respond to different treatments. Thus, its prevention, and early and accurate diagnosis are highly important.13Osteonecrosis of the jaw often develops in patients with intravenous administration of bisphosphonates; however, patients with oral intake of bisphosphonates may also develop BRONJ in some cases. Risk of development of osteonecrosis is low in patients using oral bisphosphonates for less than 3 years; therefore, this time period is ideal for assessment of oral and dental status of patients.16, 17
Review of the literature on this topic revealed that most available studies have been conducted on the knowledge level of dental clinicians about BRONJ, and information regarding the knowledge level of physicians on this topic is limited. Hristamyan-Cilev et al, in 2019 evaluated the knowledge level of dentists practicing in Plovdiv, Bulgaria and reported that 17.03% of the participants had no knowledge about bisphosphonates and their side effects. Half of them reported that they had not visited any patient with complications of bisphosphonate treatment in their office, which could be related to their lack of knowledge in this respect.18 Kim et al. assessed the knowledge level of internal medicine specialists, family physicians, and orthopedists practicing in six medical centers in Seoul, and found that less than 30% of the patients had been referred to dental clinicians by physicians. Oncologists better detected the need for referral of patients to dental clinicians, followed by endocrinologists, rheumatologists, family physicians, and orthopedists.7Senturk et al, in 2016 evaluated the knowledge level of oncologists in Ankara city about the adverse side effects and positive effects of bisphosphonates; 66% of them reported that BRONJ was the most common complication of taking bisphosphonates, and 39.6% reported referral of patients to dental clinicians, which was almost similar to the rate in our study.19 Al-Mohaya et al. found that the knowledge level had a significant correlation with expertise, work experience (years), and having a specialty degree.20 It seems that aging and gaining work experience improve the knowledge of physicians about different diseases and their prevention and treatment. Since male and female physicians receive the same instructions in medical schools, the insignificant effect of gender on knowledge level is expected. On the other hand, younger graduates still have a fresh memory of what they have been taught in the university; this may explain the difference in the knowledge level of physicians with variable work experiences. When the physicians do not encounter such patients, they may forget the management of such cases over time unless they receive complementary education in this respect.
According to the suggested mechanism, bisphosphonates decrease the bone turnover, prevent the activity of osteoclasts, decrease bone remodeling, and exert their therapeutic effects as such.21 Thus, decreasing bone resorption and increasing the bone density can prevent angiogenesis and lead to necrosis of bone cells.22Since BRONJ is a possible side effect of bisphosphonate intake, physicians and other health professionals should be aware of the mechanism of action of bisphosphonates.
Dentoalveolar surgery is the main risk factor for BRONJ. Moreover, periodontal disease, denture use, and implant placement can serve as predisposing factors for BRONJ.9, 23 In addition to local factors, parameters such as the type of bisphosphonate, duration of treatment, and form of prescribed medication can affect the development of BRONJ. Also, bisphosphonates containing nitrogen that are administered intravenously for a long period of time are a major risk factor for development of BRONJ.9
In patients at high risk of BRONJ, dental procedures such as tooth extraction, endodontic surgery, and implant placement should be preferably avoided.24 Some dental procedures such as tooth extraction are a major risk factor for BRONJ. Evidence shows that tooth extraction is a common cause of BRONJ, causing this condition in 52% to 61% of the cases.9, 25-27 A cohort study reported that patients receiving bisphosphonate IV (zoledronate) who were candidates for dentoalveolar surgery (tooth extraction) had 33 times higher risk of development of BRONJ compared with those who were not candidates for this type of surgery. Some specialists discontinue the medication until its side effects vanish; this was particularly emphasized by Senturk et al.19 Temporary discontinuation of medication (drug holiday) has been beneficial for prevention of BRONJ in some cases, and seems to be the first treatment strategy for BRONJ.28, 29 Nonetheless, temporary discontinuation of drug seems to have no short-term benefit, but long-term discontinuation can help reach stability in areas of BRONJ, and decrease its signs and symptoms. However, risk of metastasis and aggravation of bone disorders increases in cancer patients upon discontinuation of bisphosphonates.30-32
As mentioned earlier, prevention is the best option for treatment of BRONJ. Accordingly, the risk of development of BRONJ decreases in case of referral of such patients by physicians to dentists. It is suggested to assess the oral health status of patients prior to the initiation of treatment with bisphosphonates and enhance the knowledge of patients regarding the risk of BRONJ.29 Also, the patients should be provided with necessary oral hygiene instructions and should be informed about the signs and symptoms of BRONJ.30Screening and routine dental examination should be repeated every 3 months for such patients because bisphosphonates have long-term effects on bone.23 Thus, dental clinicians should be involved in treatment of such patients.