PATHOLOGY
Knowledge, Practices, and Opinions of Ontario Dentists When Treating Patients Receiving Bisphosphonates Ahmed Alhussain, DDS, MSc,* Sean Peel, PhD,y Laura Dempster, DipDH, BScD(DH), MSc, PhD,z Cameron Clokie, PhD, DDS, DipABOMS,x and Amir Azarpazhooh, DDS, MSc, PhDk Purpose:
Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe but extremely rare complication of prolonged treatment with bisphosphonates (BPs). Improper treatment or misdiagnosis can have serious repercussions. In some cases, the treatment of BRONJ can require jaw resection, prolonged use of antibiotics, and long hospitalizations. This study aimed to measure the awareness of dentists in the Province of Ontario, Canada about BRONJ and to identify any gaps in their knowledge of the condition and its treatment. In particular, the study aimed to answer questions about the dentists’ knowledge of the current guidelines and their opinions and practices related to performing surgical dental procedures in patients taking BPs.
Materials and Methods:
The study involved sending a Web-based questionnaire to a random sample of dentists in Ontario, Canada (n = 1,579). Information about their awareness of BPs, their experiences treating patients presenting with ONJ, their experiences with different surgical procedures in patients taking intravenous or oral BPs, and their awareness of the BRONJ guidelines suggested by the American Association of Oral and Maxillofacial Surgeons was collected.
Results:
A response rate of 30% was achieved. Sixty percent of responding dentists had a good knowledge of BP and BRONJ; however, only 23% followed the guidelines for surgical treatment of a patient taking BPs, and 63% would refer patients if they were taking BPs. Approximately 50% of responding Ontario dentists were not comfortable treating patients with BRONJ at their current knowledge.
Conclusion:
The finding shows that although 60% of Ontario general dentists and specialists have a good knowledge about BRONJ, most are not comfortable performing oral surgery in patients taking BPs. Those who are comfortable have higher knowledge scores, suggesting greater educational efforts should be made to promote the knowledge of dentists regarding BP, ONJ, and BRONJ. Ó 2015 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg -:1-11, 2015
Osteoporosis is a skeletal disorder characterized by decreased bone density, a condition that predisposes individuals to an increased risk of fracture. This particular medical condition is most frequent in people older than 45 years, with a probable prevalence ratio of up to 1 in 4 women and 1 in 8 men in North America. There
are more than 5 million prescriptions written for osteoporosis per year in North America, and the overwhelming medication of choice for more than 95% of patients with osteoporosis is a bisphosphonate (BP).1 BPs also are used in oncologic patients to decrease bone metastasis, fractures, and pain.
Received from the Faculty of Dentistry, University of Toronto,
Address correspondence and reprint requests to Dr Azarpaz-
Toronto, ON, Canada.
hooh: Faculty of Dentistry, University of Toronto, Room 515-C,
*Former Resident.
124 Edward Street, Toronto, ON, Canada M5G 1G6; e-mail: amir.
yAssistant Professor.
[email protected]
zAssistant Professor.
Received September 9 2014 Accepted December 11 2014
xProfessor. kAssistant Professor.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
This study was supported in part by the Ronald E. Warren Award
0278-2391/15/00023-3 http://dx.doi.org/10.1016/j.joms.2014.12.040
from the Canadian Association of Oral and Maxillofacial Surgeons.
1
2 Despite the many benefits of BPs, in the early 2000s, several patients presented to dental offices with exposed necrotic bone in the maxilla or mandible of then-unknown etiology. Further investigations identified a common feature in these patients: they were taking BPs and most of them had recently undergone a surgical dental procedure.2 In 2003, Marx2 was the first to describe the relation of treatment with BPs to the occurrence of osteonecrosis of the jaw (ONJ). Subsequently, Ruggiero et al3 published a case series of ONJ related to the use of BPs. This realization led to numerous studies2,4,5 that examined the relation between BPs and exposed necrotic bone in the mouth, a clinical scenario that is now known as BP-related ONJ (BRONJ). BRONJ is defined as an area of exposed bone that persists longer than 8 weeks in a patient taking a BP.3 It is a severe but extremely rare complication of prolonged treatment with BPs.3,6 Studies have not yet conclusively established a mechanism by which BPs are responsible for causing BRONJ. However, one hypothesis is that BPs prevent osteoclastic activity by inhibiting farnesyl pyro-phosphonate synthase, a key amino acid in the mevalonate pathway.5,7 This action can lead to a decrease in bone absorption. It also has been suggested that BPs can prevent normal bone turnover remodeling. Microfractures of the bone are no longer repaired and angiogenesis might be inhibited, which leads to weakening of the bone structure.5,7 More recently, cases of ONJ have been reported in patients taking medications other than BPs, including the antiresorptive drug denosumab and the antiangiogenic drugs bevacizumab and sunitinib,8 suggesting that the mechanism of action is most likely related to antiresorptive and antiangiogenic effects rather than effects on a specific pathway. The incidence of oral BRONJ has been discussed in some studies, with important differences being reported.5,9 The incidence of BRONJ associated with oral BPs ranges from 0.001 to 0.1%, and that associated with intravenous (IV) BPs ranges from 1 to 12%. Longer duration of exposure results in increased risk.10 There has been no report of BRONJ associated with the less active BPs etidronate and clodronate, although they are used in oncologic studies.11 The American Association of Oral and Maxillofacial Surgeons (AAOMS) produced a guideline in 2009 that categorized patients into at-risk and stage 0, 1, 2, and 3 categories with specific treatment recommendations for each group.3 Contrary to the established guideline, there are anecdotal reports of some dentists refusing to treat patients who previously received or are currently receiving BPs. Barriers to a dentist’s adherence to practice guidelines include lack of awareness of the guideline and their attitudes and behaviors.12 This study aimed to evaluate the knowledge, practices,
DENTISTS TREATING PATIENTS ON BISPHOSPHONATES
and opinions of Ontario dentists about BRONJ when treating patients receiving BPs by measuring their knowledge of BPs and BRONJ and to identify how they manage patients on BP therapy.
Materials and Methods DESIGN
This study is a cross-sectional Web-based survey that was conducted over a period of 2 months and was approved by the research ethics board at the University of Toronto (Toronto, ON, Canada; protocol 27571). A list of the members of the Royal College of Dental Surgeons of Ontario (RCDSO) was obtained through the membership directory. Potential participants were defined as those who might perform dentoalveolar surgeries based on their professional RCDSO registration (general dentists, oral and maxillofacial surgeons, periodontists, prosthodontists, and endodontists). They were approached by e-mail and directed by link to an online interface (SurveyGizmo, Boulder, CO) displaying the survey instrument. Follow-up e-mail reminders were sent 4 times during a period of 2 months. No gift or remuneration was provided to the participants in the study. SURVEY INSTRUMENT
The survey tool included questions about participants’ knowledge of BPs, their experiences treating patients presenting with ONJ, any treatment modification in performing different surgical procedures (eg, tooth extraction, dental implant placement, periodontal surgery, or endodontic surgery) in patients taking IV or oral BPs, and their awareness of the BRONJ guidelines suggested by the AAOMS.3 For validation and adjustment, the survey instrument was pilot tested among 15 specialists and dentists at the Faculty of Dentistry, University of Toronto. Pilot testing aimed to evaluate the clarity of the survey questions, respondent burden (time needed to respond and level of understanding), face validity, and feasibility of the planned data analysis. Further, each respondent was asked follow-up questions to ensure that all sections were easy to understand. This field test resulted in revisions to the original questionnaire, from which a final questionnaire was drafted based on the following 4 principal domains. Domain 1—Perception and Current Practice Included in this domain were questions that measure participants’ general knowledge about BRONJ. They were asked 9 key knowledge questions about BP use, route of administration, incidence, and treatment for a patient with BRONJ based on the AAOMS 2009 position paper.3 They also were asked about
3
ALHUSSAIN ET AL
the volume of patients they see with BRONJ symptoms, at which stage of BRONJ they would refer the patient to a specialist, and their treatment. Domain 2—Scenario Cases In this domain, the participants were provided with a scenario of a patient who takes BPs and presents for a surgical procedure relevant to the field of specialty of the participant. Six scenarios were presented for simple, complicated, and impacted tooth extraction, placing dental implants, or performing periodontal or endodontic surgeries. The scenarios differed based on duration (#3 or >3 yr) and route of BPs given (oral or IV). The participants were asked about their management plan for these different scenarios: whether they would perform the surgical procedure; or would discontinue BPs for 3 months and then perform the procedure; or would not perform the procedure; or would refer to a specialist. Domain 3—Demographics Included in this domain were questions pertaining to participants’ age, gender, pattern of practice (currently practicing vs retired or not practicing), primary professional activity (eg, general dentist, specialist, military dentist, or academic instructor), location and years of practice, specialty field, and population of town or city where they practice. Domain 4—Knowledge Acquisition Included in this domain were questions that asked about the resources participants use to stay current in their knowledge (educational courses, scientific meetings, journal articles, or Internet), where they first learned about BRONJ, whether they feel comfortable treating patients with BRONJ, and their preferred method for continuing education related to BRONJ.
historically low response rates of dentists, the authors selected all 6,920 dentists with available e-mail addresses who would have direct surgical interventions (Fig 1). DATA ANALYSIS
Data from the online survey were downloaded from the SurveyGizmo Web site as an Excel file (Microsoft, Redmond, WA). After recoding the variables, the database was imported to SAS 9.2 (SAS Institute, Cary, NC) for management and analysis. Responses to the questions in this survey were summarized using descriptive statistics (percentages for categorical data and means and standard deviations for continuous variables). Descriptive analyses were conducted for the entire sample and for subgroups of participants (general dentists, periodontists, prosthodontists, oral surgeons, and endodontists). Responses were compared among these subgroups using the c2 test and the Fisher exact test for categorical variables and the Student t test for continuous variables. A score of 9 of 9 was given if the participant answered all knowledge questions correctly in the first domain. A series of bivariate and linear regression analyses were conducted to identify the characteristics of those with good knowledge of the guideline. Moreover, the results of the 6 scenario questions in domain 2 were divided into right or wrong treatment answers based on the AAOMS guideline3 or referral. The percentage of each category was
SAMPLE SIZE CALCULATION
The study sample (n) was calculated based on the size of the population (N = 11,151 RCDSO registered dentists and dental specialists): n = ([N][P][1P])/ ([N1][C/Z]2 + [P][1P]), where P is the proportion of the population expected to choose 1 of 2 responses (P = .5 to allow for maximum variance), C is the assumed sampling error (C = 0.05), and Z is the Zstatistic of the confidence interval (CI; Z = 1.96 for 95% confidence level).13 The sampling frame for the specialists was changed to their total population, because the difference between the calculated sample size using the method described earlier and the total population for each group of specialists was small. The sample size of the general dentists was calculated as 419. However, because of an anticipated inability to draw a truly random sample and considering the
FIGURE 1. Flow diagram of survey response. RCDSO, Royal College of Dental Surgeons of Ontario. Alhussain et al. Dentists Treating Patients on Bisphosphonates. J Oral Maxillofac Surg 2015.
4
DENTISTS TREATING PATIENTS ON BISPHOSPHONATES
derived for each practitioner. Multivariate regression analyses were applied to analyze the association of the frequency of scenario responses with the practitioner characteristics. All tests were conducted at a significance level of .05.
Results From a total of 6,920 RCDSO dentists with e-mail addresses who might perform dentoalveolar surgeries, the authors achieved a database of 5,255 members with valid e-mail addresses. From this pool, a total of 1,579 survey responses were collected, resulting in a response rate of 30%. The demographic characteristics of survey participants are listed in Table 1. Most participants were men (68%) and general practitioners (GPs; 86.2%) with more than 20 years of experience as a general dentist (56.1%) or as a specialist (50%). Almost half (45.7%) the participants were working in areas that have a population of more than 500,000 people. KNOWLEDGE QUESTIONS
Table 2 presents the results of the knowledge questions in the survey. Most participants (66.4%) correctly identified osteoporosis as the indication for BP use. Very few participants identified wrong indications for BP (2.3% for diabetes and 0.5% for hypertension). More than 80% of participants correctly selected the BP route to be oral or IV. Almost one fourth of participants did not know the answer to the question on the incidence of BRONJ in patients taking oral or IV BPs. The remaining knowledge questions (questions 5 to 9) pertained to the assessment of the knowledge of participants on treatment strategies of BRONJ in different stages of risk. The least aggressive strategies was selected for the lower degrees of risk, that is, patient education, treating symptoms, and mouth rinse were mostly selected for patients at risk, at stage 0, and at stage 1, respectively. Most participants selected antibiotics and in particular surgical debridement for the higher stages of risk, with 70.1% recommending antibiotics for stage 2 treatment and 68.3% recommending surgical debridement fort stage 3. Conversely, for the patient in stage 1, almost 12.3 and 66.4% of participants selected the wrong choices of no treatment and antibiotics, respectively, as their approach to treatment. This pattern of incorrect answers was similar for the scenario of a patient in stage 2. Table 3 presents the impact of participants’ characteristics on their knowledge score. Overall, the mean ( standard deviation) knowledge score for all participants was 5.6 1.9. No statistical difference was found between participants’ knowledge score and their gender or years in practice. However, there was a statistical difference in knowledge score with age, in which those 45 to 54 years old had a lower knowl-
Table 1. DESCRIPTION OF THE DENTISTS PARTICIPATING IN THE SURVEY
Demographics Men Oral surgeons Periodontists Prosthodontists Endodontists General practitioners Age (yr) 25-34 35-44 45-54 55-64 >65 Dental specialty Oral surgeons Periodontists Prosthodontists Endodontists GPs Other Working years As a GP 1-5 6-10 11-20 >20 As a specialist 1-5 6-10 11-20 >20 Local population 500,000
n (%) 678 (68.0) 48 (85.7) 30 (73.2) 13 (68.4) 18 (78.3) 555 (66.5) 131 (12.9) 233 (22.9) 297 (29.2) 271 (26.6) 86 (8.4) 57 (4.9) 42 (3.6) 20 (1.7) 26 (2.2) 1,003 (86.2) 16 (1.4)
125 (13.5) 89 (9.6) 193 (20.8) 521 (56.1) 24 (20.3) 12 (10.2) 23 (19.5) 59 (50.0) 45 (4.5) 161 (16.1) 338 (33.7) 458 (45.7)
Abbreviation: GP, general practitioner. Alhussain et al. Dentists Treating Patients on Bisphosphonates. J Oral Maxillofac Surg 2015.
edge score compared with other age groups. Being a specialist and in particular being an oral and maxillofacial surgeon, being comfortable treating patients with BRONJ, having some exposure to BRONJ cases in a given month, and practicing in large urban centers were associated with higher knowledge scores (P < .05). All these significant variables were analyzed in a linear regression model (Table 3). Only 2 factors remained important. 1) A pattern of a better knowledge score was found in those 25 to 34 years old compared with other groups. In particular, those 45 to 54 years old had a statistically lower knowledge score compared with younger practitioners 25 to 34 years old (b = 0.73; 95% CI, 1.07 to 0.30). 2)
5
ALHUSSAIN ET AL
Table 2. FREQUENCY OF RESPONSES TO THE QUESTIONS MEASURING PARTICIPANTS’ GENERAL KNOWLEDGE ABOUT BRONJ
Knowledge Q1: indication for BP use Knowledge Q2: BP route of administration Knowledge Q3, 4: incidence of BRONJ Oral IV Knowledge Q5-9: selected treatment for BRONJ stages At risk Stage 0 Stage 1 Stage 2 Stage 3
osteoporosis, 66.4%*
diabetes, 2.3%
Oral, 64.6%*
IV, 61.9%*
>11%
no treatment
46.1%* 20.6% 12.3% 12.8% 12.7%
3.6% 21.2% patient education
osteitis deformans, 26.7%* IM, 5.8%
bone metastases, 34.2%*
65 (58) Gender Men (536) Women (252) Practitioner type Specialists (127) GPs (660) Specialists Oral surgeons (54) Periodontists (37) Prosthodontists (18) Endodontists (18) Working years 1-5 (95) 6-10 (73) 11-20 (144) >20 (321) Patients per month 0 (563) $1 (209) Population 500,000 (80) Comfortable treating patients with BRONJ with current knowledge No or/unsure (442) Yes with minor supplementation (357)
Mean SD
P Value
Linear Regression Analysis Coefficient Estimate
95% CI
P Value
5.6 1.9 3 yr Scenario 3: impacted tooth extraction Oral BP #3 yr Oral BP >3 yr IV BP #3 yr IV BP >3 yr Scenario 4: implant placement Oral BP #3 yr Oral BP >3 yr IV BP #3 yr IV BP >3 yr Scenario 5: periodontal surgery Oral BP #3 yr Oral BP >3 yr IV BP #3 yr IV BP >3 yr Scenario 6: endodontic surgery Oral BP #3 yr Oral BP >3 yr IV BP #3 yr IV BP >3 yr Abbreviations: BP, bisphosphonate; IV, intravenous. * Correct answer to scenario question.
Alhussain et al. Dentists Treating Patients on Bisphosphonates. J Oral Maxillofac Surg 2015.
Ontario dentists when treating patients receiving BPs. The interest was in whether participants’ knowledge and approach to care of BRONJ was consistent with the established guidelines. The AAOMS 2009 guidelines were used to develop the knowledge and scenario questions and score the answers given by the participants.3 This position paper was prepared by clinicians based in multicenter hospitals and was approved by the AAOMS Board of Trustees in January 2009. The intent of the guidelines was to provide perspective on the risk of developing BRONJ and the risks and benefits of BPs to facilitate evidence-based decision making by the treating clinicians and the patient and provide guidelines for treating BRONJ.3 The recommendations of this multidisciplinary task force representing oral and maxillofacial surgery, oral medicine, endocrinology, and medical oncology in
the AAOMS 2009 position paper provide detailed guidance regarding the use of dental devices and selection of appropriate antibiotic therapy.3,13 This present study found that despite the existence of guidelines, Ontario dentists had a poor understanding of how or even whether to carry out surgical dental treatment in patients taking BPs. In total, only 23.8% of 1,579 responding dentists followed the AAOMS guideline, and 49.7% were not comfortable treating patients with BRONJ. The results show that in some scenarios almost 50% of participants, if they did not refer, would select the wrong treatment strategy. This approach can exacerbate or fail to resolve the main dental condition, can lead to serious complications for the patient, or might lead them to develop BRONJ. In particular, it has been shown that most patients taking BPs might be unfamiliar with the drug and its possible adverse
8
DENTISTS TREATING PATIENTS ON BISPHOSPHONATES
Table 5. FREQUENCY OF AGGREGATED RESPONSES TO SCENARIO QUESTIONS
Scenario Extraction Simple
Complicated
Impacted
Implant
Periodontal
Endodontic
Route and Duration of BP Administration
Right Answer, %
Wrong Answer, %
Referral, %
Total, n
oral 3 yr IV 3 yr oral 3 yr IV 3 yr oral 3 yr IV 3 yr oral 3 yr IV 3 yr oral 3 yr IV 3 yr oral 3 yr IV 3 yr
73.4 18.1 13.7 10 52 16.7 9.1 5.9 26.5 10.1 5.6 3.8 60.3 26.8 22.6 28.5 81 16.8 27 23.1 61.9 18.7 10.2 6.1
6.8 47.2 8.75 9.9 7.8 30 6.3 8.4 6.3 15.2 6.7 8.7 12.5 35.6 20.9 15.8 10.2 61.6 17.7 16.7 8.4 38.3 15.8 19.2
19.8 34.7 77.6 80.1 39.5 53.4 84.6 85 67.3 74.7 87.8 87.5 27.2 37.5 56.5 55.7 8.8 21.6 55.3 60.2 29.8 43 74 74.6
836 834 840 809 833 828 824 826 831 829 826 819 368 365 368 368 294 292 293 294 215 214 215 213
Abbreviations: BP, bisphosphonate; IV, intravenous. Alhussain et al. Dentists Treating Patients on Bisphosphonates. J Oral Maxillofac Surg 2015.
oral side effects. This would further highlight the responsibility of the treating dentists to be prepared to educate patients about the oral complications resulting from BP use and the need for appropriate dental care.14 Participants more frequently gave correct answers for the scenarios of patients on oral BP for less than 3 years, but more frequently gave wrong answers for the scenarios of patients on oral BP for more than
3 years or IV BP regardless of duration. This could be related to the participants not knowing the differences between oral and IV BPs, or the effect of extended duration of use, or the benefits and disadvantages of continuing or discontinuing BPs. When scenario patients were given IV BPs, participants were more likely to refer the patient. The authors also noted a decreased comfort level and increased referral when the complexity of the
Table 6. SUMMARY OF FINAL REGRESSION MODEL PRESENTING THE IMPACT OF SIGNIFICANT PRACTITIONERS’ CHARACTERISTICS ON DECISION MAKING OF REFERRAL VERSUS SELECTING A CORRECT TREATMENT STRATEGY
Parameter Gender (reference, women) Specialist (reference, GP) Population (reference, 5,000,000 yes
Estimate (95% CI)
P Value
3.53 (6.49 to 0.56) 17.17 (22.68 to 11.67) 4.54 (0.77 to 8.32) 1.29 (2.29 to 4.88) 8.36 (11.11 to 5.63)
.02
Knowledge, Practices, and Opinions of Ontario Dentists When Treating Patients Receiving Bisphosphonates Ahmed Alhussain, DDS, MSc,* Sean Peel, PhD,y Laura Dempster, DipDH, BScD(DH), MSc, PhD,z Cameron Clokie, PhD, DDS, DipABOMS,x and Amir Azarpazhooh, DDS, MSc, PhDk Purpose:
Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe but extremely rare complication of prolonged treatment with bisphosphonates (BPs). Improper treatment or misdiagnosis can have serious repercussions. In some cases, the treatment of BRONJ can require jaw resection, prolonged use of antibiotics, and long hospitalizations. This study aimed to measure the awareness of dentists in the Province of Ontario, Canada about BRONJ and to identify any gaps in their knowledge of the condition and its treatment. In particular, the study aimed to answer questions about the dentists’ knowledge of the current guidelines and their opinions and practices related to performing surgical dental procedures in patients taking BPs.
Materials and Methods:
The study involved sending a Web-based questionnaire to a random sample of dentists in Ontario, Canada (n = 1,579). Information about their awareness of BPs, their experiences treating patients presenting with ONJ, their experiences with different surgical procedures in patients taking intravenous or oral BPs, and their awareness of the BRONJ guidelines suggested by the American Association of Oral and Maxillofacial Surgeons was collected.
Results:
A response rate of 30% was achieved. Sixty percent of responding dentists had a good knowledge of BP and BRONJ; however, only 23% followed the guidelines for surgical treatment of a patient taking BPs, and 63% would refer patients if they were taking BPs. Approximately 50% of responding Ontario dentists were not comfortable treating patients with BRONJ at their current knowledge.
Conclusion:
The finding shows that although 60% of Ontario general dentists and specialists have a good knowledge about BRONJ, most are not comfortable performing oral surgery in patients taking BPs. Those who are comfortable have higher knowledge scores, suggesting greater educational efforts should be made to promote the knowledge of dentists regarding BP, ONJ, and BRONJ. Ó 2015 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg -:1-11, 2015
Osteoporosis is a skeletal disorder characterized by decreased bone density, a condition that predisposes individuals to an increased risk of fracture. This particular medical condition is most frequent in people older than 45 years, with a probable prevalence ratio of up to 1 in 4 women and 1 in 8 men in North America. There
are more than 5 million prescriptions written for osteoporosis per year in North America, and the overwhelming medication of choice for more than 95% of patients with osteoporosis is a bisphosphonate (BP).1 BPs also are used in oncologic patients to decrease bone metastasis, fractures, and pain.
Received from the Faculty of Dentistry, University of Toronto,
Address correspondence and reprint requests to Dr Azarpaz-
Toronto, ON, Canada.
hooh: Faculty of Dentistry, University of Toronto, Room 515-C,
*Former Resident.
124 Edward Street, Toronto, ON, Canada M5G 1G6; e-mail: amir.
yAssistant Professor.
[email protected]
zAssistant Professor.
Received September 9 2014 Accepted December 11 2014
xProfessor. kAssistant Professor.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
This study was supported in part by the Ronald E. Warren Award
0278-2391/15/00023-3 http://dx.doi.org/10.1016/j.joms.2014.12.040
from the Canadian Association of Oral and Maxillofacial Surgeons.
1
2 Despite the many benefits of BPs, in the early 2000s, several patients presented to dental offices with exposed necrotic bone in the maxilla or mandible of then-unknown etiology. Further investigations identified a common feature in these patients: they were taking BPs and most of them had recently undergone a surgical dental procedure.2 In 2003, Marx2 was the first to describe the relation of treatment with BPs to the occurrence of osteonecrosis of the jaw (ONJ). Subsequently, Ruggiero et al3 published a case series of ONJ related to the use of BPs. This realization led to numerous studies2,4,5 that examined the relation between BPs and exposed necrotic bone in the mouth, a clinical scenario that is now known as BP-related ONJ (BRONJ). BRONJ is defined as an area of exposed bone that persists longer than 8 weeks in a patient taking a BP.3 It is a severe but extremely rare complication of prolonged treatment with BPs.3,6 Studies have not yet conclusively established a mechanism by which BPs are responsible for causing BRONJ. However, one hypothesis is that BPs prevent osteoclastic activity by inhibiting farnesyl pyro-phosphonate synthase, a key amino acid in the mevalonate pathway.5,7 This action can lead to a decrease in bone absorption. It also has been suggested that BPs can prevent normal bone turnover remodeling. Microfractures of the bone are no longer repaired and angiogenesis might be inhibited, which leads to weakening of the bone structure.5,7 More recently, cases of ONJ have been reported in patients taking medications other than BPs, including the antiresorptive drug denosumab and the antiangiogenic drugs bevacizumab and sunitinib,8 suggesting that the mechanism of action is most likely related to antiresorptive and antiangiogenic effects rather than effects on a specific pathway. The incidence of oral BRONJ has been discussed in some studies, with important differences being reported.5,9 The incidence of BRONJ associated with oral BPs ranges from 0.001 to 0.1%, and that associated with intravenous (IV) BPs ranges from 1 to 12%. Longer duration of exposure results in increased risk.10 There has been no report of BRONJ associated with the less active BPs etidronate and clodronate, although they are used in oncologic studies.11 The American Association of Oral and Maxillofacial Surgeons (AAOMS) produced a guideline in 2009 that categorized patients into at-risk and stage 0, 1, 2, and 3 categories with specific treatment recommendations for each group.3 Contrary to the established guideline, there are anecdotal reports of some dentists refusing to treat patients who previously received or are currently receiving BPs. Barriers to a dentist’s adherence to practice guidelines include lack of awareness of the guideline and their attitudes and behaviors.12 This study aimed to evaluate the knowledge, practices,
DENTISTS TREATING PATIENTS ON BISPHOSPHONATES
and opinions of Ontario dentists about BRONJ when treating patients receiving BPs by measuring their knowledge of BPs and BRONJ and to identify how they manage patients on BP therapy.
Materials and Methods DESIGN
This study is a cross-sectional Web-based survey that was conducted over a period of 2 months and was approved by the research ethics board at the University of Toronto (Toronto, ON, Canada; protocol 27571). A list of the members of the Royal College of Dental Surgeons of Ontario (RCDSO) was obtained through the membership directory. Potential participants were defined as those who might perform dentoalveolar surgeries based on their professional RCDSO registration (general dentists, oral and maxillofacial surgeons, periodontists, prosthodontists, and endodontists). They were approached by e-mail and directed by link to an online interface (SurveyGizmo, Boulder, CO) displaying the survey instrument. Follow-up e-mail reminders were sent 4 times during a period of 2 months. No gift or remuneration was provided to the participants in the study. SURVEY INSTRUMENT
The survey tool included questions about participants’ knowledge of BPs, their experiences treating patients presenting with ONJ, any treatment modification in performing different surgical procedures (eg, tooth extraction, dental implant placement, periodontal surgery, or endodontic surgery) in patients taking IV or oral BPs, and their awareness of the BRONJ guidelines suggested by the AAOMS.3 For validation and adjustment, the survey instrument was pilot tested among 15 specialists and dentists at the Faculty of Dentistry, University of Toronto. Pilot testing aimed to evaluate the clarity of the survey questions, respondent burden (time needed to respond and level of understanding), face validity, and feasibility of the planned data analysis. Further, each respondent was asked follow-up questions to ensure that all sections were easy to understand. This field test resulted in revisions to the original questionnaire, from which a final questionnaire was drafted based on the following 4 principal domains. Domain 1—Perception and Current Practice Included in this domain were questions that measure participants’ general knowledge about BRONJ. They were asked 9 key knowledge questions about BP use, route of administration, incidence, and treatment for a patient with BRONJ based on the AAOMS 2009 position paper.3 They also were asked about
3
ALHUSSAIN ET AL
the volume of patients they see with BRONJ symptoms, at which stage of BRONJ they would refer the patient to a specialist, and their treatment. Domain 2—Scenario Cases In this domain, the participants were provided with a scenario of a patient who takes BPs and presents for a surgical procedure relevant to the field of specialty of the participant. Six scenarios were presented for simple, complicated, and impacted tooth extraction, placing dental implants, or performing periodontal or endodontic surgeries. The scenarios differed based on duration (#3 or >3 yr) and route of BPs given (oral or IV). The participants were asked about their management plan for these different scenarios: whether they would perform the surgical procedure; or would discontinue BPs for 3 months and then perform the procedure; or would not perform the procedure; or would refer to a specialist. Domain 3—Demographics Included in this domain were questions pertaining to participants’ age, gender, pattern of practice (currently practicing vs retired or not practicing), primary professional activity (eg, general dentist, specialist, military dentist, or academic instructor), location and years of practice, specialty field, and population of town or city where they practice. Domain 4—Knowledge Acquisition Included in this domain were questions that asked about the resources participants use to stay current in their knowledge (educational courses, scientific meetings, journal articles, or Internet), where they first learned about BRONJ, whether they feel comfortable treating patients with BRONJ, and their preferred method for continuing education related to BRONJ.
historically low response rates of dentists, the authors selected all 6,920 dentists with available e-mail addresses who would have direct surgical interventions (Fig 1). DATA ANALYSIS
Data from the online survey were downloaded from the SurveyGizmo Web site as an Excel file (Microsoft, Redmond, WA). After recoding the variables, the database was imported to SAS 9.2 (SAS Institute, Cary, NC) for management and analysis. Responses to the questions in this survey were summarized using descriptive statistics (percentages for categorical data and means and standard deviations for continuous variables). Descriptive analyses were conducted for the entire sample and for subgroups of participants (general dentists, periodontists, prosthodontists, oral surgeons, and endodontists). Responses were compared among these subgroups using the c2 test and the Fisher exact test for categorical variables and the Student t test for continuous variables. A score of 9 of 9 was given if the participant answered all knowledge questions correctly in the first domain. A series of bivariate and linear regression analyses were conducted to identify the characteristics of those with good knowledge of the guideline. Moreover, the results of the 6 scenario questions in domain 2 were divided into right or wrong treatment answers based on the AAOMS guideline3 or referral. The percentage of each category was
SAMPLE SIZE CALCULATION
The study sample (n) was calculated based on the size of the population (N = 11,151 RCDSO registered dentists and dental specialists): n = ([N][P][1P])/ ([N1][C/Z]2 + [P][1P]), where P is the proportion of the population expected to choose 1 of 2 responses (P = .5 to allow for maximum variance), C is the assumed sampling error (C = 0.05), and Z is the Zstatistic of the confidence interval (CI; Z = 1.96 for 95% confidence level).13 The sampling frame for the specialists was changed to their total population, because the difference between the calculated sample size using the method described earlier and the total population for each group of specialists was small. The sample size of the general dentists was calculated as 419. However, because of an anticipated inability to draw a truly random sample and considering the
FIGURE 1. Flow diagram of survey response. RCDSO, Royal College of Dental Surgeons of Ontario. Alhussain et al. Dentists Treating Patients on Bisphosphonates. J Oral Maxillofac Surg 2015.
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DENTISTS TREATING PATIENTS ON BISPHOSPHONATES
derived for each practitioner. Multivariate regression analyses were applied to analyze the association of the frequency of scenario responses with the practitioner characteristics. All tests were conducted at a significance level of .05.
Results From a total of 6,920 RCDSO dentists with e-mail addresses who might perform dentoalveolar surgeries, the authors achieved a database of 5,255 members with valid e-mail addresses. From this pool, a total of 1,579 survey responses were collected, resulting in a response rate of 30%. The demographic characteristics of survey participants are listed in Table 1. Most participants were men (68%) and general practitioners (GPs; 86.2%) with more than 20 years of experience as a general dentist (56.1%) or as a specialist (50%). Almost half (45.7%) the participants were working in areas that have a population of more than 500,000 people. KNOWLEDGE QUESTIONS
Table 2 presents the results of the knowledge questions in the survey. Most participants (66.4%) correctly identified osteoporosis as the indication for BP use. Very few participants identified wrong indications for BP (2.3% for diabetes and 0.5% for hypertension). More than 80% of participants correctly selected the BP route to be oral or IV. Almost one fourth of participants did not know the answer to the question on the incidence of BRONJ in patients taking oral or IV BPs. The remaining knowledge questions (questions 5 to 9) pertained to the assessment of the knowledge of participants on treatment strategies of BRONJ in different stages of risk. The least aggressive strategies was selected for the lower degrees of risk, that is, patient education, treating symptoms, and mouth rinse were mostly selected for patients at risk, at stage 0, and at stage 1, respectively. Most participants selected antibiotics and in particular surgical debridement for the higher stages of risk, with 70.1% recommending antibiotics for stage 2 treatment and 68.3% recommending surgical debridement fort stage 3. Conversely, for the patient in stage 1, almost 12.3 and 66.4% of participants selected the wrong choices of no treatment and antibiotics, respectively, as their approach to treatment. This pattern of incorrect answers was similar for the scenario of a patient in stage 2. Table 3 presents the impact of participants’ characteristics on their knowledge score. Overall, the mean ( standard deviation) knowledge score for all participants was 5.6 1.9. No statistical difference was found between participants’ knowledge score and their gender or years in practice. However, there was a statistical difference in knowledge score with age, in which those 45 to 54 years old had a lower knowl-
Table 1. DESCRIPTION OF THE DENTISTS PARTICIPATING IN THE SURVEY
Demographics Men Oral surgeons Periodontists Prosthodontists Endodontists General practitioners Age (yr) 25-34 35-44 45-54 55-64 >65 Dental specialty Oral surgeons Periodontists Prosthodontists Endodontists GPs Other Working years As a GP 1-5 6-10 11-20 >20 As a specialist 1-5 6-10 11-20 >20 Local population 500,000
n (%) 678 (68.0) 48 (85.7) 30 (73.2) 13 (68.4) 18 (78.3) 555 (66.5) 131 (12.9) 233 (22.9) 297 (29.2) 271 (26.6) 86 (8.4) 57 (4.9) 42 (3.6) 20 (1.7) 26 (2.2) 1,003 (86.2) 16 (1.4)
125 (13.5) 89 (9.6) 193 (20.8) 521 (56.1) 24 (20.3) 12 (10.2) 23 (19.5) 59 (50.0) 45 (4.5) 161 (16.1) 338 (33.7) 458 (45.7)
Abbreviation: GP, general practitioner. Alhussain et al. Dentists Treating Patients on Bisphosphonates. J Oral Maxillofac Surg 2015.
edge score compared with other age groups. Being a specialist and in particular being an oral and maxillofacial surgeon, being comfortable treating patients with BRONJ, having some exposure to BRONJ cases in a given month, and practicing in large urban centers were associated with higher knowledge scores (P < .05). All these significant variables were analyzed in a linear regression model (Table 3). Only 2 factors remained important. 1) A pattern of a better knowledge score was found in those 25 to 34 years old compared with other groups. In particular, those 45 to 54 years old had a statistically lower knowledge score compared with younger practitioners 25 to 34 years old (b = 0.73; 95% CI, 1.07 to 0.30). 2)
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Table 2. FREQUENCY OF RESPONSES TO THE QUESTIONS MEASURING PARTICIPANTS’ GENERAL KNOWLEDGE ABOUT BRONJ
Knowledge Q1: indication for BP use Knowledge Q2: BP route of administration Knowledge Q3, 4: incidence of BRONJ Oral IV Knowledge Q5-9: selected treatment for BRONJ stages At risk Stage 0 Stage 1 Stage 2 Stage 3
osteoporosis, 66.4%*
diabetes, 2.3%
Oral, 64.6%*
IV, 61.9%*
>11%
no treatment
46.1%* 20.6% 12.3% 12.8% 12.7%
3.6% 21.2% patient education
osteitis deformans, 26.7%* IM, 5.8%
bone metastases, 34.2%*
65 (58) Gender Men (536) Women (252) Practitioner type Specialists (127) GPs (660) Specialists Oral surgeons (54) Periodontists (37) Prosthodontists (18) Endodontists (18) Working years 1-5 (95) 6-10 (73) 11-20 (144) >20 (321) Patients per month 0 (563) $1 (209) Population 500,000 (80) Comfortable treating patients with BRONJ with current knowledge No or/unsure (442) Yes with minor supplementation (357)
Mean SD
P Value
Linear Regression Analysis Coefficient Estimate
95% CI
P Value
5.6 1.9 3 yr Scenario 3: impacted tooth extraction Oral BP #3 yr Oral BP >3 yr IV BP #3 yr IV BP >3 yr Scenario 4: implant placement Oral BP #3 yr Oral BP >3 yr IV BP #3 yr IV BP >3 yr Scenario 5: periodontal surgery Oral BP #3 yr Oral BP >3 yr IV BP #3 yr IV BP >3 yr Scenario 6: endodontic surgery Oral BP #3 yr Oral BP >3 yr IV BP #3 yr IV BP >3 yr Abbreviations: BP, bisphosphonate; IV, intravenous. * Correct answer to scenario question.
Alhussain et al. Dentists Treating Patients on Bisphosphonates. J Oral Maxillofac Surg 2015.
Ontario dentists when treating patients receiving BPs. The interest was in whether participants’ knowledge and approach to care of BRONJ was consistent with the established guidelines. The AAOMS 2009 guidelines were used to develop the knowledge and scenario questions and score the answers given by the participants.3 This position paper was prepared by clinicians based in multicenter hospitals and was approved by the AAOMS Board of Trustees in January 2009. The intent of the guidelines was to provide perspective on the risk of developing BRONJ and the risks and benefits of BPs to facilitate evidence-based decision making by the treating clinicians and the patient and provide guidelines for treating BRONJ.3 The recommendations of this multidisciplinary task force representing oral and maxillofacial surgery, oral medicine, endocrinology, and medical oncology in
the AAOMS 2009 position paper provide detailed guidance regarding the use of dental devices and selection of appropriate antibiotic therapy.3,13 This present study found that despite the existence of guidelines, Ontario dentists had a poor understanding of how or even whether to carry out surgical dental treatment in patients taking BPs. In total, only 23.8% of 1,579 responding dentists followed the AAOMS guideline, and 49.7% were not comfortable treating patients with BRONJ. The results show that in some scenarios almost 50% of participants, if they did not refer, would select the wrong treatment strategy. This approach can exacerbate or fail to resolve the main dental condition, can lead to serious complications for the patient, or might lead them to develop BRONJ. In particular, it has been shown that most patients taking BPs might be unfamiliar with the drug and its possible adverse
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DENTISTS TREATING PATIENTS ON BISPHOSPHONATES
Table 5. FREQUENCY OF AGGREGATED RESPONSES TO SCENARIO QUESTIONS
Scenario Extraction Simple
Complicated
Impacted
Implant
Periodontal
Endodontic
Route and Duration of BP Administration
Right Answer, %
Wrong Answer, %
Referral, %
Total, n
oral 3 yr IV 3 yr oral 3 yr IV 3 yr oral 3 yr IV 3 yr oral 3 yr IV 3 yr oral 3 yr IV 3 yr oral 3 yr IV 3 yr
73.4 18.1 13.7 10 52 16.7 9.1 5.9 26.5 10.1 5.6 3.8 60.3 26.8 22.6 28.5 81 16.8 27 23.1 61.9 18.7 10.2 6.1
6.8 47.2 8.75 9.9 7.8 30 6.3 8.4 6.3 15.2 6.7 8.7 12.5 35.6 20.9 15.8 10.2 61.6 17.7 16.7 8.4 38.3 15.8 19.2
19.8 34.7 77.6 80.1 39.5 53.4 84.6 85 67.3 74.7 87.8 87.5 27.2 37.5 56.5 55.7 8.8 21.6 55.3 60.2 29.8 43 74 74.6
836 834 840 809 833 828 824 826 831 829 826 819 368 365 368 368 294 292 293 294 215 214 215 213
Abbreviations: BP, bisphosphonate; IV, intravenous. Alhussain et al. Dentists Treating Patients on Bisphosphonates. J Oral Maxillofac Surg 2015.
oral side effects. This would further highlight the responsibility of the treating dentists to be prepared to educate patients about the oral complications resulting from BP use and the need for appropriate dental care.14 Participants more frequently gave correct answers for the scenarios of patients on oral BP for less than 3 years, but more frequently gave wrong answers for the scenarios of patients on oral BP for more than
3 years or IV BP regardless of duration. This could be related to the participants not knowing the differences between oral and IV BPs, or the effect of extended duration of use, or the benefits and disadvantages of continuing or discontinuing BPs. When scenario patients were given IV BPs, participants were more likely to refer the patient. The authors also noted a decreased comfort level and increased referral when the complexity of the
Table 6. SUMMARY OF FINAL REGRESSION MODEL PRESENTING THE IMPACT OF SIGNIFICANT PRACTITIONERS’ CHARACTERISTICS ON DECISION MAKING OF REFERRAL VERSUS SELECTING A CORRECT TREATMENT STRATEGY
Parameter Gender (reference, women) Specialist (reference, GP) Population (reference, 5,000,000 yes
Estimate (95% CI)
P Value
3.53 (6.49 to 0.56) 17.17 (22.68 to 11.67) 4.54 (0.77 to 8.32) 1.29 (2.29 to 4.88) 8.36 (11.11 to 5.63)
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