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.