Knowledge of Iranian Dentists about Osteonecrosis of the Jaw due to the Use of Bisphosphonate DrugsABSTRACT
Objective: To evaluate the knowledge of Iranian dentists regarding bisphosphonate-related osteonecrosis of the jaw (BRONJ) etiology, risk assessment, and clinical management, aiming to identify gaps in knowledge and inform targeted educational interventions.
Material and Methods: This analytical cross-sectional study was performed on 2000 dentists whose list was obtained from the Medical Council Organization. A questionnaire, whose validity and reliability were ensured, containing demographic questions (age, sex, etc.), general questions, and questions about bisphosphonate use, was provided to individuals. The data were analyzed using the t-test, Mann-Whitney test, and Chi-Square test. The level of significance was p < 0.05.
Results: Of the participants, 56% were male, and the mean age was 32.5±5.6 and and 51.5% had less than 5 years of professional experience. Approximately 27.5% of dentists were familiar with the term MRONJ. The mean knowledge score was 10.4 ± 2.1, indicating poor dentists' knowledge. There was no significant difference between knowledge score, age, sex, working hours, and work experience.
Conclusion: Dentists' knowledge of BRONJ is inadequate. A patient with bisphosphonate-related osteonecrosis can be a significant challenge for the dentist, and sufficient understanding of the signs, treatments, and management of these patients is necessary for any dentist.
Keywords:
Diphosphonates; Osteonecrosis; Jaw; Bisphosphonate-Associated Osteonecrosis of the Jaw.
Introduction
Bisphosphonates are widely used in the management of osteoporosis, reduction of bone fragility in osteopenia (reduced bone density), reduction of osteolytic lesions (related to soft bone necrosis), multiple myeloma, and other bone disorders such as Paget's disease, incomplete bone formation, and bone metastasis in prostate, breast, and lung cancers [1,2]. Despite their positive effects on patients, a significant and vital adverse effect has emerged in a subset of patients receiving these drugs, which is called medication-related osteonecrosis of the jaw (MRONJ) [3,4].
MRONJ is diagnosed when a patient without a history of radiation therapy and under prescription with bisphosphonates has been exposed to bone necrosis in the upper or lower jaw for more than 8 weeks [5,6]. The incidence of MRONJ per year is 10 patients per million population, and with the increasing use of anti-angiogenic and anti-absorptive agents, its prevalence is expected to increase [7-9]. In the United States, the prevalence of BRONJ in patients receiving intravenous bisphosphonate therapy has been reported to be 0.8-12% [10]. In another study, the low prevalence of BRONJ (0.04/0%) was identified among patients receiving oral treatment compared to those receiving intravenous treatment [11]. On the other hand, Lo et al. [12] reported an increase in the prevalence of BRONJ from 0.04 to 0.21% after more than 4 years of bisphosphonate treatment [12].
Several risk factors for MRONJ include underlying disease, duration of anti-osteoporotic drug therapy, dental implant use, and oral and dental diseases [13,14]. MRONJ with uncertain clinical features and prevalence can negatively affect quality of life. Dentoalveolar surgery and periodontal diseases are major local risk factors, while the type of drug used, duration, and method of drug use are drug-related risk factors [8-10]. Therefore, removing all dental infection foci before starting treatment with anti-angiogenic and anti-absorptive agents is essential. Dentists should quickly identify this group of patients as susceptible individuals and manage the conditions effectively and efficiently [11-13].
With the increasing number of patients taking bisphosphonates and other anti-resorptive drugs, having sufficient knowledge about MRONJ is a crucial factor in preventing and managing the condition among dentists. This study aimed to investigate Iranian dentists' knowledge of bisphosphonate-related osteonecrosis of the jaw. Also, the Null Hypothesis (H0) was that there is no difference in Iranian dentists' knowledge of osteonecrosis of the jaw caused by bisphosphonate use across gender, age, academic degree, working hours per week, and years of professional experience.
Material and Methods
Study Design
The study was conducted as an analytical, cross-sectional study from Jun 2024 to July 2024. First, the list of Kerman dentists was obtained from the Medical Council Organization. The study method was a simple census, and all dentists in Kerman city were included if they were willing to participate. A researcher-designed questionnaire containing personal questions (e.g., age, gender), general questions, and questions related to bisphosphonate use was provided to participants, who were asked to complete and return it. The purpose of the study was explained to each participant, and they were assured that all their information would remain confidential and only be used for reporting purposes. As these studies require the cooperation of individuals, the study's purpose was thoroughly explained, and participants were assured that the research was harmless and that their information would remain confidential. There was no bias in this study.
Conducting Study
A final-year student visited clinics and distributed the questionnaire. Participants who agreed to enter the study had the right to withdraw at any time after the interview began. Since the questionnaire collected personal information, it was collected approximately 15 minutes after it was given to the participant.
Validity and Reliability of the Questionnaire
Two dental specialists and a statistician designed the questions in this questionnaire. To evaluate the questionnaire's validity and reliability, it was reviewed by five faculty specialists, who confirmed its scientific validity. The clarity and comprehensibility of the questions were discussed, and, based on their opinions and text analysis, the questionnaire's content validity was considered satisfactory. The initial questionnaire was given to a general dentist for feedback on its wording and was revised after ten days. The reliability of the questionnaire was determined to be acceptable using Cronbach's alpha coefficient (0.83). There were nine knowledge-related questions, with a score of 2 for each correct answer, 0 for each incorrect answer, and 1 for each "I don't know" response. Therefore, the knowledge score ranged from 0 to 18.
Static Analysis
Data were analyzed using the T-test, the Mann-Whitney U test, the Chi-square test, and SPSS 18 (IBM Corp., Armonk, NY, USA). The level of significance in data analysis was p<0.05.
Results
In this study, 2100 questionnaires were distributed, of which 2000 were returned (95.2%). Of the participants, 56% were male, and the mean age was 32.5±5.6 (male = 34.8±8.2; female 30.2±3.1). More than half of the participants (56.2%) were general dentists, and 51.5% had less than 5 years of professional experience (Table 1).
Only 12% of participants had undergone training on medication-related osteonecrosis of the jaw (MRONJ), while 64% expressed a need for further training in this area. A total of 100 dentists (5%) reported encountering cases of MRONJ in their practice. Additionally, 15 participants (7.5%) inquired about bone resorption medications, and merely 5% requested a referral letter from a physician prior to dental surgery. Notably, 92.5% did not document the name of the drug or the duration of its use, highlighting a significant gap in knowledge among dentists regarding MRONJ (see Table 2).
This study showed that 27.5% of the participants were familiar with the term MRONJ. Bisphosphonates were the most commonly reported drugs that caused MRONJ. A total of 56% stated that oral bisphosphonate use poses a greater risk of MRONJ than intravenous use, and 16.5% reported that patients should stop taking bone resorption drugs two months before tooth extraction or implant placement. Additionally, for 54.5%, bisphosphonate treatment is appropriate for osteoporosis.
Two hundred and ten participants (10.5%) knew that bisphosphonates are prescribed both orally and intravenously; 28% did not know how bisphosphonates are prescribed and 62.5% indicated the importance of oral and dental examination before starting bisphosphonate treatment.
In this study, 450 participants (22.5%) lacked knowledge of the clinical image of MRONJ, and 18% stated that the clinical image of MRONJ appears as necrosis, with or without exposure. Also, 81% were unaware of the management guidelines for patients at risk of MRONJ.
Only 15.5% stated that bisphosphonates remain in the body for six months after treatment, and 50.5% stated that bisphosphonates remain in the body for one year after treatment. Finally, 39% knew the method of bisphosphonate use, and 18.5% knew the treatment duration as a risk factor for MRONJ (Table 3).
The mean knowledge score was 10.4±2.1, indicating low knowledge among dentists. Table 4 shows the relationship between knowledge score and demographic variables. The results showed no significant differences in knowledge score, age, gender, working hours, or work experience (p>0.05).
Discussion
Bisphosphonates are a class of drugs known as diphosphonates. They prevent bone loss and are commonly used to treat osteoporosis (bone thinning). The effect of bisphosphonates is to inhibit the activity of a group of cells called osteoclasts, which are located within bones and have the function of absorbing mineral substances from bones. Alendronate and Etidronic acid are types of bisphosphonates. The use of bisphosphonates can reduce the risk of fractures in patients with osteoporosis. Bisphosphonates are drugs that slow down or prevent bone damage. They also reduce blood calcium levels. Although bisphosphonates have been widely used in metabolic bone disorders, few serious studies have examined their anti-inflammatory effects, immune-modulating properties, and mechanisms of action. Structurally and mechanistically, bisphosphonates are divided into two categories: amino-bisphosphonates and non-amino-bisphosphonates. The effects of bisphosphonates on cytokine diversity under laboratory conditions are complex and vary depending on the type of bisphosphonate tested, the concentration used, the cell type tested, and the method used to evaluate cultured cells [14,15].
Aminobisphosphonates exhibit a dual role in cytokine regulation: they transiently stimulate pro-inflammatory cytokines during initial exposure but suppress their production with chronic use [9,15,16]. This pharmacological nuance is particularly relevant in cancer care, where skeletal complications such as bone pain and structural instability frequently arise from metastatic spread (e.g., myeloma, breast, prostate, and lung cancers) or iatrogenic bone weakening caused by therapies like chemotherapy and hormone treatment. In these contexts, bisphosphonates serve a critical therapeutic role by inhibiting osteoclast-mediated bone resorption. Clinically, they mitigate bone loss (osteoporosis), lower fracture risk, stabilize serum calcium levels, and alleviate pain. Furthermore, emerging evidence suggests bisphosphonates may impede metastatic progression to bone in select patient populations [9,15,16].
Some studies have also shown that these drugs can increase lifespan in individuals with myeloma, breast cancer, and secondary prostate cancer. There are several different types of bisphosphonates, including: pamidronate disodium, ibandronic acid or ibandronate, sodium clodronate, and zoledronic acid [9].
Bisphosphonates increase bone volume. Bisphosphonate drugs slow down the activity of osteoclast cells and reduce the process of bone breakdown. As mentioned above, these drugs are available in different types, each with slightly different functions. Physicians are still learning more about how bisphosphonates work. However, their general functions include: interfering with osteoclast formation, correcting the destructive process of osteoclasts or preventing their premature death, altering signaling between osteoclasts and osteoblasts, and creating a barrier between bone and osteoclasts [9,15,16].
Researchers have found that bisphosphonates can reduce the rate of progression of multiple myeloma and secondary bone cancers in some individuals, or prevent their development. Researchers speculate that cancer cells are attracted to an environment where bones have broken down. They hope that by stopping this process, they can prevent cancer growth and help reduce bone damage [9,15,16].
This study investigated Iranian dentists' knowledge of osteonecrosis of the jaw associated with bisphosphonate use. Two hundred forty individuals (12%) participated in the osteonecrosis of the jaw training course caused by drug use, and 64% needed retraining in this area. Only 5% had encountered cases of MRONJ during their work; 7.5% asked about anti-osteoporosis drugs, and 5% requested a referral letter from their physician before undergoing dental surgery.
Since Marx's [8] seminal report of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in 2003, medical and dental communities have intensified research efforts to understand its pathophysiology and clinical management. Epidemiological data reveal stark contrasts in incidence rates: 0.001-0.1% for oral bisphosphonate users versus 1-12% for patients receiving intravenous formulations [17,18]. However, the escalating prevalence of medication-related osteonecrosis of the jaw (MRONJ), a broader classification encompassing BRONJ, is projected to rise significantly due to expanding clinical use of anti-resorptive and anti-angiogenic therapies. This trend underscores the imperative for dental professionals to adopt a multidisciplinary approach, prioritizing preventive protocols, early diagnostic strategies, and evidence-based therapeutic interventions to mitigate patient morbidity.
In the present study, 2100 questionnaires were distributed, of which 2000 questionnaires were returned (95.2%). The response rate in Patil's study and colleagues' was 46.8%, which was lower than in previous studies of physicians and dentists [18-20]. It was also revealed that 27.5% were familiar with MRONJ (drug-related jaw osteonecrosis). In the study by Patil et al. [19], 35% of dentists correctly defined MRONJ.
This study found that the dentists' knowledge scores were low. There was no significant difference in knowledge score, age, gender, working hours, or work experience. In Patil's study and colleagues' [19], a higher level of knowledge was observed among specialist dentists with more than 5 years of experience. This different response can be attributed to the fact that most of our participants were recent graduates with less than 5 years of work experience; therefore, their limited exposure, insufficient experience, and limited familiarity with relevant scientific articles may account for their limited knowledge.
In the Arnaud et al. [21] study, less than a third of the surveyed dental surgeons scored 70% or higher on the knowledge questions. In this study, younger physicians (less than 30 years old) and recent university graduates (less than 10 years) had better knowledge of bisphosphonates and the risk of MRONJ. A similar trend was observed in a study conducted in Spain. Other studies have shown that dental surgeons with less than 5 years of experience were better informed about this issue [22]. Since the association between osteonecrosis and BPs was first described by Marx in 2003, physicians who graduated before 2003 did not have the opportunity to study this topic during their initial training. As a result, our findings show that the university remains the primary source of information on this topic and that dentists lack additional training in this field [19]. Several other studies also reported higher levels of knowledge among oral and maxillofacial surgeons [19-22].
The most common drugs participants believed caused osteonecrosis of the jaw were bisphosphonates, consistent with the study by Patil et al. [19]. Familiarity with these drugs, their mechanisms of action, and their clinical signs for rapid identification of "at-risk" patients and necessary precautions during dental treatment is essential [23]. Bisphosphonates are primarily used to treat bone disorders and alter the rate of bone formation. Denosumab, a monoclonal antibody targeting RANK ligand, is a potent anti-resorptive agent prescribed to reduce fracture risk in osteoporosis and to prevent skeletal complications, such as bone metastases. By inhibiting osteoclast formation and activity, Denosumab suppresses bone resorption, thereby enhancing bone density. However, unlike bisphosphonates, which exhibit prolonged skeletal retention, the therapeutic effects of Denosumab diminish within six months of discontinuation due to its reversible mechanism of action [9].
One thousand one hundred and twenty individuals (56%) reported that oral bisphosphonate use carries a higher risk of MRONJ than intravenous administration, according to a study by Patil et al. [19]. Of the participants, 38.5% were aware of the higher risks associated with injection-administered anti-resorptive and anti-angiogenic agents compared to oral administration.
The type of drug, duration of treatment, and route of drug administration are drug-related risk factors that contribute to the development and progression of MRONJ. Patients taking nitrogen-containing bisphosphonates, intravenously administered bisphosphonates, or non-bisphosphonate drugs with prolonged exposure to the drug are at a higher risk of developing MRONJ [24].
Knowledge of risk factors prepares the dentist to address the patient better and to implement preventive measures before or during bisphosphonate or other anti-resorptive treatment. Three hundred and thirty individuals (16.5%) stated that patients should stop taking anti-osteoporosis drugs two months before tooth extraction or implant. In the study by Patil et al. [19], 31.6% of participants were familiar with this concept.
The concept of a "drug holiday," or a temporary pause in drug treatment, is recommended for preventing and managing MRONJ. The decision to approve a drug holiday for patients depends on factors such as cumulative drug dosage, route of administration, and related risk factors, including systemic diseases, concurrent use of corticosteroids, or anti-resorptive agents. No changes in medication are recommended for patients taking oral bisphosphonates for less than 4 years without clinical risk factors; drug discontinuation for 2 months before and after surgery is preferred for patients taking oral bisphosphonates with risk factors and those taking intravenous bisphosphonates [9].
It is necessary that, along with dentists, even specialist doctors who prescribe antiresorptive or anti-angiogenic drugs, and patients who take these drugs, be aware of their potential side effects. Previous studies have shown that fewer than 30% of physicians have referred these patients for dental visits before treatment [25]. General practitioners often prescribe bisphosphonates for postmenopausal women with osteoporosis, and patients are frequently unaware of their use during dental exams [26]. Obtaining a complete medical history, establishing communication between dentists and medical specialists, and providing patients with accurate information about MRONJ side effects are of utmost importance.
In this study, 54.5% were aware of the appropriate use of bisphosphonates for the treatment of osteoporosis. Patil et al. [19] reported unanimous agreement among surgeons on the correct clinical indications for bisphosphonate use, a finding consistent with that of Alhussein et al. [17]. In contrast, knowledge levels among dental practitioners vary significantly across studies. For instance, Gaballah and Hassan [27] found that 68.4% of participants correctly identified osteoporosis as the primary indication for bisphosphonate therapy, with most demonstrating familiarity with its modes of administration. However, Vinitzky-Brener et al. [28] observed a strikingly low knowledge rate of 1.64% in their cohort, underscoring disparities in clinician knowledge that may influence patient safety and treatment outcomes.
The most common disease for which bisphosphonates are prescribed is osteoporosis. This is not surprising, as evidence supports the use of oral bisphosphonates to increase bone density and reduce fracture-related mortality. In 2008, nearly 3 million prescriptions for bisphosphonates were written in Australia, a 27% increase from the previous year, with most for oral bisphosphonates. Similar patterns have been observed in other regions. Oral bisphosphonates are associated with side effects and non-compliance, so intravenous bisphosphonates are preferred. Currently, many individuals living with chronic diseases in the community can preserve more teeth than before due to advances in dentistry. Many of these individuals are seeking routine dental care to maintain their oral function, often requiring complex restorative techniques from cosmetic dentistry to implants [19,20].
We found that only 7.5% were asked about anti-osteoporotic drugs, and 81% did not know the guidelines for managing patients at risk of MRONJ. Various committees have published guidelines for clinical management of patients treated with bisphosphonates or those with drug-induced osteonecrosis of the jaw (MRONJ) [20-23]. Given the lack of effective, reproducible, and comprehensive treatment for MRONJ, it is recommended to prevent its occurrence. However, to implement these preventive measures, an acceptable level of knowledge about bisphosphonates and their risk factors is required [29]. One hundred twenty-five (62.5%) stated that dental examination and oral hygiene are essential before starting bisphosphonate treatment. According to Hristamyan-Cilev et al. [30], 50% of the dentists in Bulgaria lacked knowledge of the content of preventive examinations and evaluations for patients taking bisphosphonates. In the United Arab Emirates, almost two-thirds of the studied dentists were unaware of any recommendations for managing and treating patients at risk of bisphosphonate-related adverse effects [31]. Previous studies have shown that clinical guidelines and multiple recommendations can lead to fragmented and sometimes contradictory information [19,23]. The only official recommendations on managing patients at risk of bisphosphonate-related adverse events in France are those of the ANSM (Agence nationale de sécurité du médicament), published in 2007 [32]. These recommendations were complemented by two letters on MRONJ risk in patients treated with Denosumab in 2014 [18,26], and have not been updated since then.
Internationally, the AAOMS (American Association of Oral and Maxillofacial Surgeons) clinical guidelines have the highest referral and compliance rate [32]. In Han's [33] study, most dentists (65%) recorded the name of the anti-osteoporotic drug and its duration of use. However, most dentists (53.3%) did not know that the recommended duration for discontinuing the drug varies depending on the type of drug. In the study by Yazdani et al. [34], Tabriz dentists' knowledge of bisphosphonate-induced osteonecrosis was reported to be average. In Lopez-Jornet et al. [35] study, 68.3% of dentists were found to be aware of the latest updates. However, in Al-Mohaya et al. [20] study, this knowledge was observed in less than one-third of participants (31.5%).
The results of the Yazdani et al. [34] showed that women had significantly higher average knowledge scores than men, consistent with Alhussain [36]. No significant correlation between age and knowledge level was observed in our study, consistent with Yazdani et al. [34] but contradicting Alhussain [36], who reported that knowledge about BRONJ was higher in the under-34 age group. The lack of a significant correlation between knowledge and age in our study may be due to participants' inaccurate age responses.
The study faced limitations due to the non-cooperation of several participants and incomplete filling of many questionnaires.
Conclusion
Iranian dentists' knowledge of BRONJ is unsatisfactory. Patients with osteonecrosis caused by bisphosphonates can pose a significant challenge for dentists, and having sufficient knowledge of the symptoms is essential for proper management and treatment.
-
Financial Support
The authors would like to express their gratitude to the Vice Deputy of Research at Kerman University of Medical Sciences for their financial support (Reg. No. 401000592).
Data Availability
The data used to support the findings of this study can be made available upon request to the corresponding author.
References
-
[1] Fehm T, Felsenberg D, Krimmel M, Solomayer E, Wallwiener D, Hadjii P. Bisphosphonate-associated osteonecrosis of the jaw in breast cancer patients: Recommendations for prevention and treatment. Breast 2009; 18(4):213-217. https://doi.org/10.1016/j.breast.2009.07.001
» https://doi.org/10.1016/j.breast.2009.07.001 -
[2] Muthukrishnan A, Kumar LB, Ramalingam G. Medication-related osteonecrosis of the jaw: A dentist’s nightmare. BMJ Case Rep 2016; 2016:bcr2016214626. https://doi.org/10.1136/bcr-2016-214626
» https://doi.org/10.1136/bcr-2016-214626 -
[3] Papi P, Rosella D, Giardino R, Cicalini E, Piccoli L, Pompa G. Medication-related osteonecrosis of the jaw: Clinical and practical guidelines. J Int Soc Prev Community Dent 2016; 6(2):97-104. https://doi.org/10.4103/2231-0762.178742
» https://doi.org/10.4103/2231-0762.178742 -
[4] Jacobsen C, Zemann W, Obwegeser JA, Grätz KW, Metzler P. The phosphorous necrosis of the jaws and what can we learn from the past: A comparison of “phossy” and “bisphossy” jaw. Oral Maxillofac Surg 2012; 18:31-37. https://doi.org/10.1007/S10006-012-0376-Z
» https://doi.org/10.1007/S10006-012-0376-Z -
[5] Campisi G, Fedele S, Fusco V, Pizzo G, Di Fede O, Bedogni A. Epidemiology, clinical manifestations, risk reduction and treatment strategies of jaw osteonecrosis in cancer patients exposed to antiresorptive agents. Futur Oncol 2014; 10(2):257-275. https://doi.org/10.2217/fon.13.211
» https://doi.org/10.2217/fon.13.211 -
[6] Coleman R, Body JJ, Aapro M, Hadji P, Herrstedt J. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2014; 25(Suppl 3):iii124-iii137. https://doi.org/10.1093/annonc/mdu103
» https://doi.org/10.1093/annonc/mdu103 -
[7] Rosella D, Pap P, Pompa G, Capogreco M, De Angelis F, Di Carlo S. Dental students’ knowledge of medication-related osteonecrosis of the jaw. Eur J Dent 2017; 11(4):461-468. https://doi.org/10.4103/ejd.ejd_27_17
» https://doi.org/10.4103/ejd.ejd_27_17 -
[8] Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic. J Oral Maxillofac Surg 2003; 61(9):1115-1118. https://doi.org/10.1016/s0278-2391(03)00720-1
» https://doi.org/10.1016/s0278-2391(03)00720-1 -
[9] Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, et al. American association of oral and maxillofacial surgeons position paper onmedication-related osteonecrosis of the jaw-2014 update. J Oral Maxillofac Surg 2014; 72(10):1938-1956. https://doi.org/10.1016/j.joms.2014.04.031
» https://doi.org/10.1016/j.joms.2014.04.031 -
[10] Advisory Task Force on Bisphosphonate-Related Osteononecrosis of the Jaws. American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 2007; 65(3):369-376. https://doi.org/10.1016/j.joms.2006.11.003
» https://doi.org/10.1016/j.joms.2006.11.003 -
[11] Malden N, Lopes V. An epidemiological study of alendronate-related osteonecrosis of the jaws. A case series from the south-east of Scotland with attention given to case definition and prevalence. J Bone Miner Metab 2012; 30(2):171-182. https://doi.org/10.1007/s00774-011-0299-z
» https://doi.org/10.1007/s00774-011-0299-z -
[12] Lo JC, O’Ryan FS, Gordon NP, Yang J, Hui RL, Martin D, et al. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 2010; 68(2):243-253. https://doi.org/10.1016/j.joms.2009.03.050
» https://doi.org/10.1016/j.joms.2009.03.050 -
[13] Papapoulos S, Chapurlat R, Libanati C, Brandi ML, Brown JP, Czerwiński E, et al. Five years of denosumab exposure in women with postmenopausal osteoporosis: Results from the first two years of the FREEDOM extension. J Bone Miner Res 2012; 27(3):694-701. https://doi.org/10.1002/jbmr.1479
» https://doi.org/10.1002/jbmr.1479 -
[14] Yamazaki T, Yamori M, Ishizaki T, Asai K, Goto K, Takahashi K, et al. Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: A cohort study. Int J Oral Maxillofac Surg 2012; 41(11):1397-1403. https://doi.org/10.1016/j.ijom.2012.06.020
» https://doi.org/10.1016/j.ijom.2012.06.020 -
[15] Drake MT, Clarke BL, Khosla S. Bisphosphonates: Mechanism of action and role in clinical practice. Mayo Clin Proc 2008; 83(9):1032-1045. https://doi.org/10.4065/83.9.1032
» https://doi.org/10.4065/83.9.1032 -
[16] Russell RG. Bisphosphonates: Mode of action and pharmacology. Pediatrics 2007; 119(Suppl 2):S150-162. https://doi.org/10.1542/peds.2006-2023H
» https://doi.org/10.1542/peds.2006-2023H -
[17] Alhussain A, Peel S, Dempster L, Dh B, Clokie C. Knowledge, practices, and opinions of Ontario dentists when treating patients receiving bisphosphonates. J Oral Maxillofac Surg 2017; 73(6):1095-1105. https://doi.org/10.1016/j.joms.2014.12.040
» https://doi.org/10.1016/j.joms.2014.12.040 -
[18] Osta L, Osta B, Lakiss S, Hennequin M, Osta N. Bisphosphonate related osteonecrosis of the jaw: Awareness and level of knowledge of Lebanese physicians. Support Care Cancer 2015; 23(9):2825-2831. https://doi.org/10.1007/s00520-015-2649-1
» https://doi.org/10.1007/s00520-015-2649-1 -
[19] Patil V, Acharya S, Vineetha R, Nikhil K. Awareness about medication-related osteonecrosis of the jaw among dental professionals: A multicentre study. Oral Health Prev Dent 2020; 18(3):505-509. https://doi.org/10.3290/j.ohpd.a43361
» https://doi.org/10.3290/j.ohpd.a43361 - [20] Al-Mohaya MA, Al-Khashan HI, Mishriky AM, Al-Otaibi LM. Physicians’ awareness of bisphosphonates-related osteonecrosis of the jaw. Saudi Med J 2011; 32(8):830-835.
-
[21] Arnaud MP, Talibi S, Lejeune-Cairon S. Knowledge and attitudes of French dentists on bone resorption inhibitors (bisphosphonates and Denosumab): A cross-sectional study. J Stomatol Oral Maxillofac Surg 2022; 123(2):163-170. https://doi.org/10.1016/j.jormas.2021.04.010
» https://doi.org/10.1016/j.jormas.2021.04.010 -
[22] Limones A, Sáez-Alcaide LM, Díaz-Parreño SA, Helm A, Bornstein MM, Molinero-Mourelle P. Medication-related osteonecrosis of the jaws (MRONJ) in cancer patients treated with Denosumab VS. zoledronic acid: A systematic review and meta-analysis. Med Oral Patol Oral Cir Bucal 2020; 25(3):e326-e336. https://doi.org/10.4317/medoral.23324
» https://doi.org/10.4317/medoral.23324 -
[23] Kokane G, Sidana S, Galinde J. Awareness of bisphosphonate use and its dental complications among the awareness of bisphosphonate use and its dental complications among the dental practitioners. J Contemp Dent 2015; 5(1):1-6. https://doi.org/10.5005/jp-journals-10031-1095
» https://doi.org/10.5005/jp-journals-10031-1095 -
[24] Tanna N, Steel C, Stagnell S, Bailey E. Awareness of medication related osteonecrosis of the jaws (MRONJ) amongst general dental practitioners. Br Dent J 2017; 222(2):121-125. https://doi.org/10.1038/sj.bdj.2017.79
» https://doi.org/10.1038/sj.bdj.2017.79 -
[25] Kim J, Jeong S, Kim S, Kim Y. Perceptions of medical doctors on bisphosphonate-related osteonecrosis of the jaw. BMC Oral Health 2016; 16(1):92. https://doi.org/10.1186/s12903-016-0290-0
» https://doi.org/10.1186/s12903-016-0290-0 -
[26] Bauer JS, Beck N, Kiefer J, Stockmann P, Wichmann M, Eitner S. Awareness and education of patients receiving bisphosphonates. J Cranio-Maxillofacial Surg 2012; 40(3):277-282. https://doi.org/10.1016/j.jcms.2011.04.011
» https://doi.org/10.1016/j.jcms.2011.04.011 -
[27] Gaballah K, Hassan M. Knowledge and attitude of dentists on bisphosphonates use in the UAE: A descriptive cross-sectional study. Int Surg J 2017; 4(4):1398-1404. https://doi.org/10.18203/2349-2902.isj20171150
» https://doi.org/10.18203/2349-2902.isj20171150 -
[28] Vinitzky-Brener I, Ibáñez-Mancera NG, Aguilar-Rojas AM, ÁlvarezJardón AP. Knowledge of bisphosphonate-related osteonecrosis of the Jaws among Mexican dentists. Med Oral Patol Oral Cir Bucal 2016; 22(1):e84-87. https://doi.org/10.4317/medoral.21433
» https://doi.org/10.4317/medoral.21433 -
[29] Ciobanu GA, Camen A, Ionescu M, Vlad D, Munteanu CM, Gheorghiţă MI, et al. Risk factors for medication-related osteonecrosis of the jaw-A binomial analysis of data of cancer patients from Craiova and Constanta treated with zoledronic acid. J Clin Med 2023; 12(11):3747. https://doi.org/10.3390/jcm12113747
» https://doi.org/10.3390/jcm12113747 -
[30] Hristamyan-Cilev MA, Pechalova PP, Raycheva RD, Hristamyan VP, Kevorkyan AK, Stoilova YD. Bisphosphonate-associated osteonecrosis of the jaws: A survey of the level of knowledge of dentists about the risks of bisphosphonate therapy. Folia Med 2019; 61(1):303-311. https://doi.org/10.2478/folmed-2018-0075
» https://doi.org/10.2478/folmed-2018-0075 -
[31] Sadat-Ali M, AlAnii FM. Long-term use of bisphosphonates in osteoporosis. Saudi Med J 2017; 38(6):604-608. https://doi.org/10.15537/smj.2017.6.19793
» https://doi.org/10.15537/smj.2017.6.19793 -
[32] Mongiat-Artus P, Brenot-Rossi I, Beuzeboc P, Bruyère F, Karsenty G, Guy L, et al. The non-hormonal treatment of metastatic prostate cancer. Prog Urol 2013; 23(15):1258-1264. https://doi.org/10.1016/j.purol.2013.08.322 [In French].
» https://doi.org/10.1016/j.purol.2013.08.322 -
[33] Han AL. The awareness and practice of dentists regarding medication-related osteonecrosis of the jaw and its prevention: A cross-sectional survey. BMC Oral Health 2021; 21(1):155. https://doi.org/10.1186/s12903-021-01475-6
» https://doi.org/10.1186/s12903-021-01475-6 -
[34] Yazdani J, Mortazavi A, Abbasi E. Knowledge of Tabriz dentists about bisphosphonate-related osteonecrosis of the jaw in 2015. Med J Tabriz Uni Med Sciences Health Services 2019; 41(3):101-105. https://doi.org/10.34172/mj.2019.039
» https://doi.org/10.34172/mj.2019.039 -
[35] Lopez-Jornet P, Camacho-Alonso F, Molina-Minano F, Gomez-Garcia F. Bisphosphonate-associated osteonecrosis of the jaw. Knowledge and attitudes of dentists and dental students: A preliminary study. Jeval Clin Pract 2010; 16(5):878-882. https://doi.org/10.1111/j.1365-2753.2009.01203.x
» https://doi.org/10.1111/j.1365-2753.2009.01203.x - [36] Alhussain A. Knowledge, practice and opinions of Ontario dentists when treating patients receiving bisphosphonates, university of Toronto. PhD Thesis. Toronto: University of Toronto; 2013.
Edited by
-
Academic Editor:
Fátima Regina Nunes de Sousa
