- Email: [email protected]
How Patients' Lack of Knowledge About Oral Bisphosphonates Can Interfere With Medical and Dental Care
R E S E A R C H
BRIEF
REPORT
How patients’ lack of knowledge about oral bisphosphonates can interfere with medical and dental care Cesar A. Migliorati, DDS, MS, PhD; Katia Mattos, BSc; Mitzi J. Palazzolo, DDS, MSc
isphosphonate-associated osteonecrosis (BON) is an oral complication of bisphosphonate therapy.1-3 In 2008, Edwards and colleagues’4 reviewed the pharmacovigilance process involved in the reporting of this oral complication. The results of the study demonstrated that although rapid, the recognition of BON and the dissemination of information resulted from an uncoordinated action of pharmaceutical manufacturers, dental and medical professionals, a nonprofit organization, patients and regulatory authorities. Therefore, a more coordinated action between the U.S. Food and Drug Administration, health care professions and the pharmaceutical industry could result in quicker recognition of new adverse reactions from medications, leading to improved patient care. Physicians who prescribe medications such as bisphosphonates should counsel patients about possible oral complications resulting from taking the medications. However, because BON is an adverse reaction that almost exclusively affects the oral cavity,5 physicians might be uncomfortable discussing it with their patients. Medications can cause a variety of side effects that can affect oral health, dental treatment and quality of life.6,7 Yet, communication between physicians and patients regarding these side effects might not be taking place as often as needed.8,9
B
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ABSTRACT Background. Oral bisphosphonate use has been associated with a small risk of developing oral osteonecrosis that occurs spontaneously or after the patient has undergone dental surgery. The authors conducted a study to determine whether patients taking bisphosphonates had knowledge about the medical indication for the therapy and the duration of treatment, as well as whether they had been educated by their physicians about possible adverse reactions. Methods. From June 2008 through April 2009, people seeking routine care in a dental clinic and who were being treated with bisphosphonates were invited to participate in the study. The participants were asked questions involving knowledge about the medical indications related to their taking bisphosphonates, the duration of their therapy and whether they had been educated about possible adverse reactions. Results. The authors interviewed 73 participants; 84 percent stated they knew why they were receiving bisphosphonate therapy. However, 80 percent said they were unsure about the duration of therapy, and 82 percent could not recall if they had been told about the risk of experiencing adverse reactions, including oral osteonecrosis, by their physicians. Conclusion. People taking bisphosphonates may be unfamiliar with the drug and its possible adverse oral side effects. Clinical Implications. Dentists should be prepared to educate patients about the risks of developing oral complications resulting from bisphosphonate use and the need for appropriate dental care. Questions regarding discontinuation of bisphosphonate therapy should be answered by the physician. Key Words. Patient knowledge; drugs; bisphosphonate; dental care; medical care; osteoporosis. JADA 2010;141(5):562-566.
Dr. Migliorati was a professor of Oral Medicine, Department of Diagnostic Sciences, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Fla., when this study was conducted. He now is a professor and the director of Oral Medicine, Department of Biologic and Diagnostic Sciences, University of Tennessee Health Science Center, College of Dentistry, 875 Union Ave., Suite N228, Memphis, Tenn. 38163, e-mail “[email protected]”. Address reprints to Dr. Migliorati. Ms. Mattos is a dental student, Harvard School of Dental Medicine, Boston. Dr. Palazzolo was an assistant professor of Oral Medicine, Department of Diagnostic Sciences, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Fla., when this study was conducted. She now lives in Wichita Falls, Texas.
May 2010
Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
R E S E A R C H
We conducted a study to determine whether patients taking bisphosphonates had knowledge about the medical indication for the therapy and the duration of treatment and whether they had been educated about possible adverse reactions. PARTICIPANTS, MATERIALS AND METHODS
We conducted a single-center observational study of consecutively seen patients who were seeking routine dental care at the dental school clinic at the College of Dental Medicine, Nova Southeastern University (NSU), Fort Lauderdale, Fla., during the period from June 2008 through April 2009. To be eligible for the study, patients had to be receiving either an oral or intravenous bisphosphonate drug, be fluent in English and provide written informed consent. The NSU Institutional Review Board reviewed the study to ensure protection of human participants and approved it. During their initial visits to the dental clinic, patients completed a health questionnaire. Dental students or faculty members who evaluated these health questionnaires informed us when they identified patients who were receiving bisphosphonate therapy. We invited these patients to enroll in the study and asked them to sign a written informed consent form. A single investigator (K.M.) conducted inperson interviews with participants to ensure uniformity. During the interview, she determined the interactions that took place between the participants and the physicians who prescribed the bisphosphonates for them via a series of standardized questions concerning the following: dthe bisphosphonate being taken; dthe specific medical condition being treated by the medication; dthe expected duration of the bisphosphonate therapy; dknowledge of potential adverse effects resulting from the use of the medication; dwhether bone mineral density (BMD) tests had been performed; dwhether the medical condition had improved after therapy was initiated. The interview process took 15 to 20 minutes. After the interview, we gave participants the opportunity to meet with an oral medicine specialist (C.A.M.) to discuss the interview and ask questions about bisphosphonate medications and any potential effect on their dental care. Two
BRIEF
REPORT
authors (C.A.M. and M.J.P.) conducted brief clinical examinations of participants to verify the integrity of the participants’ oral mucosa and the absence of osteonecrosis. RESULTS
We identified 73 consecutively seen patients as potential participants. They all agreed to enroll in the study, which suggests that people taking bisphosphonates are interested in learning about its possible side effects. Participants’ demographics and bisphosphonate histories are shown in Table 1. There were 71 women and two men, with a mean age of 66 years (range, 44-88 years). White participants accounted for 64 percent of the study sample and Hispanics 27 percent. Oral alendronate was the most commonly used bisphosphonate (60 percent), followed by oral risedronate (29 percent) and oral ibandronate (10 percent). One of the participants had breast cancer metastatic to the skeleton and was receiving a zoledronic acid intravenous infusion annually. The predominant diagnoses among participants were osteoporosis (74 percent) and osteopenia (22 percent). Participants underwent bisphosphonate therapy for an average of 23 weeks (range, two-240 weeks). When the interviewer asked participants specifically about bisphosphonate therapy, 84 percent participants said they recalled being informed why they were receiving bisphosphonate therapy (Table 2, page 565). However, 80 percent of the participants said they did not know or were uncertain about the duration of the treatment, and 82 percent said that they had not been told about the possible side effects of taking bisphosphonates. Participants reported having no knowledge of BON and reported that their physicians had not told them that they needed to inform their dentists that they were receiving bisphosphonate therapy. Most participants requested a consultation with the oral medicine specialist to discuss the risk of developing BON based on the type of dental treatment plan that they would be undergoing. The results of the brief clinical examination revealed that none of the participants had evidence of having BON. Forty-seven participants recalled that they had undergone BMD testing several times. Twenty-three partici-
ABBREVIATION KEY. BMD: Bone mineral density. BON: Bisphosphonate-associated osteonecrosis. NSU: Nova Southeastern University.
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Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
May 2010
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TABLE 1
Patients’ demographics and bisphosphonate history. VARIABLE
VALUE Demographics
Age (mean years)
66 (range, 44-88)
Sex (No. [%]) Female Male
71 (97) 2 (3)
Ethnicity (No. [%]) White Black Hispanic Other
47 2 20 4
Tobacco use (No. [%]) Yes No
32 (44) 41 (56)
Alcohol use (No. [%]) Yes No
11 (15) 62 (85)
(64) (3) (27) (6)
Bisphosphonate History Type (No. [%]) Oral alendronate Oral risedronate Oral ibandronate Intravenous zoledronate
44 (60) 21 (29) 7 (10) 1 (1)
Medical indication (No. [%]) Osteoporosis Osteopenia Breast cancer Unknown
54 16 1 2
Duration of therapy (weeks) Maximum Minimum
(74) (22) (1) (3)
240 2
pants did not recall if they had undergone BMD testing, and three were unsure if they had ever undergone BMD testing. Only 22 participants recalled being informed by their physicians about improvement of their BMD levels after receiving bisphosphonate therapy. DISCUSSION
The results of our interviews of participants who were taking bisphosphonates and came to a dental school in south Florida for routine dental care revealed that 82 percent of them did not recall or were unsure about having a discussion about the risk of developing BON with the physicians who prescribed the bisphosphonates. They expressed concern about undergoing dental treatment after being told by the oral medicine specialist about the possible complications. The results of our study are in agreement with 564
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those of two other studies.8,9 The results of an evaluation about what patients want to know when they are prescribed medications revealed that one of the most common concerns expressed by patients is not receiving enough information about side effects and risks.8 In the same study, investigators also found that patients also were concerned about not being informed adequately about the duration of therapy. In our study, 80 percent of participants could not recall being informed about the duration of their bisphosphonate therapy. We received this information directly from the participants and could not confirm its accuracy. Nonetheless, there is evidence that in general, the communication of drug risks and benefits to patients has been inadequate.9 The results of a study evaluating patients receiving lithium treatment revealed that they had poor knowledge about the medication.10 The study’s investigators speculated that physicians might be reluctant to inform patients about side effects of drugs because doing so could lead to poor compliance.10 The American Hospital Association lists several types of medication errors involving incomplete patient information (for example, not knowing about a patient’s allergies or medications) and unavailable drug information, such as lack of up-to-date warnings.11 Although participants in our study were being followed periodically by their physicians and twothirds of participants had been tested several times for BMD levels, about one-third of the participants recalled that they had not undergone BMD testing, and three participants were unsure if they had ever been tested. Almost another onethird recalled that their physicians had told them that their BMD levels had improved after they had undergone bisphosphonate therapy. Millions of people in the United States and around the world take prescription medications that may cause significant oral complications. Because populations are aging and patients are being treated for chronic diseases more frequently, it is not uncommon for patients to be taking multiple medications.12 Medications can cause oral complications that vary in severity and alter quality of life.6 Some medications can interfere with routine dental care. Thus, it is normal practice for dentists to have a complete knowledge of their patients’ medical problems and associated medications, as well as possible oral side effects of these drugs. Cases of BON have been associated with the use of bisphosphonates
May 2010
Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
R E S E A R C H
administered both intravenously and orally.13-15 The prevalence of BON is between 3 and 12 percent for patients who received bisphosphonates intravenously3-5,16,17 and less than 1 percent for patients who received bisphosphonates orally.5 Dentists should be prepared to discuss these risks with patients when reviewing medical histories and planning dental treatment. BON is a known adverse effect of bisphosphonate therapy1-3 and is discussed in the package inserts of all bisphosphonates. Therefore, dentists should inform patients who are taking bisphosphonates about BON before providing invasive dental care. When this information is provided, patients may indicate that they do not recall being told about this possible complication by their physicians who prescribed the bisphosphonates. Because of this possible miscommunication and the small risk of developing BON, it is recommended that the patient sign a written informed consent form before undergoing dental surgery or other invasive procedures.3,18,19 The informed consent form attests that the patient was informed about treatment alternatives and the risk of developing BON and agreed that the proposed treatment was the best option available. Serious consequences can occur when patients are misinformed. Patients who are concerned about the risk of developing BON might decline needed dental care. This decision could result in their experiencing complications or emergencies in the future or lead to the need for more invasive dental treatment. Furthermore, patients’ concerns about the risk of developing BON may result in their discontinuing bisphosphonate use without discussing their decisions with their physicians first. This action may place patients at risk of experiencing serious and potentially fatal adverse events such as hip fractures.20-22 Thus, dentists never should recommend that patients discontinue any form of medical therapy without first consulting with their physicians. In addition, physicians should tell their patients to inform their dentists that they are receiving bisphosphonate therapy and that use of the medication should not be discontinued without the agreement of the professional who prescribed the drug. A collaborative effort between physicians and dentists in educating patients about risks and adverse drug reactions could prevent serious misunderstandings and consequences. Furthermore, patients with poor oral health should consult with their dentists before commencing bisphosphonate
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REPORT
TABLE 2
Bisphosphonate information provided by the participants. QUESTION
PARTICIPANT’S RESPONSES (NO. [%]) Yes
No or Unsure
Reason for bisphosphonate therapy? *
61 (84)
12 (16)
How long are you going to be on therapy? †
15 (20)
58 (80)
Informed about risks or side effects? ‡
13 (18)
60 (82)
Informed about improvement? §
22 (30)
51 (70)
* Participant recalled being informed why a bisphosphonate was being prescribed. † Participant was informed about duration of therapy. ‡ Participant was warned about possible side effects of bisphosphonates. § Participant had been informed about better bone mineral density results associated with bisphosphonate therapy.
BOX
Points of discussion to use with patients when informing them of risks of bisphosphonate therapy. dAlthough the risk of developing bisphosphonate-
associated osteonecrosis (BON) is less than 1 percent, bisphosphonate use can reduce the risk of developing bone fractures 35 to 50 percent. dPeople with osteoporosis are at risk of developing bone fractures. Bisphosphonates can improve bone quality and reduce the risk of fractures. That is why your physician prescribed a bisphosphonate. dWe can work with your physician to reduce the risk of experiencing complications during dental care. dDo not discontinue the use of bisphosphonate on your own. dWe believe that good oral hygiene and routine dental care are the best way to prevent BON.
therapy.3,18,19 This recommendation is especially important for patients to whom intravenous formulations are prescribed. There are several strategies that could lead to improvement in this area,23,24 including those suggested in the box. We recognize that the results of our study are based solely on information provided by a small group of patients and that we did not interview the physicians who prescribed the bisphosphonates to confirm the accuracy of the information. Most participants were women (71 of 73), probably because postmenopausal women constitute the main group of people being prescribed bisphosphonates. Future studies should aim to include equal numbers of male and female patients who are receiving bisphosphonate therapy. The JADA, Vol. 141
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Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
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patient population that seeks dental care at NSU is heterogeneous and representative of not only south Florida, where we conducted our study, but also of different areas of the United States, as some people from these areas live in Florida during the winter. Therefore, not all of the participants we interviewed received their medical care in Florida, thus excluding the possibility that the results of our study represent a local reality. We also recognize that the questionnaire used in the study was derived from the routine medical history review used for new patients who seek dental treatment at NSU and, therefore, was not a validated instrument. The development of scientifically validated instruments for future studies is advisable. Information about medications provided to patients by health care providers can be overwhelming, and readers should consider this when interpreting the results of our study. Better patient-physician relationships could improve the quality of patient care.25 We postulate that an improvement in patient education about medication use and adverse effects that involves physicians, patients and dentists as a team could improve the quality of care and reduce complications of medical and dental treatment. CONCLUSIONS
The results of our small study show that patients who take bisphosphonates may not be aware that BON can develop after they undergo invasive dental care. We believe that a more effective communication process between prescribing physicians, dentists and patients using bisphosphonates is needed. ■ Disclosure. Dr. Migliorati is a consultant at Amgen, Thousand Oaks, Calif. The authors thank Dr. Adam Lloyd for his editorial assistance and Dr. Jessica Shireman for her help with the research. 1. Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007;22(10): 1479-1491. 2. Migliorati CA, Siegel MA, Elting LS. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment (published correction appears in Lancet Oncol 2006;7[7]:533). Lancet Oncol 2006;7(6):508-514. 3. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B; American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws: 2009 update. J Oral Maxillofac Surg 2009;67(5 suppl):2-12.
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4. Edwards BJ, Gounder M, McKoy JM, et al. Pharmacovigilance and reporting oversight in US FDA fast-track process: bisphosphonates and osteonecrosis of the jaw. Lancet Oncol 2008;9(12):1166-1172. 5. Woo SB, Hellstein JW, Kalmar JR. Narrative (corrected) review: bisphosphonates and osteonecrosis of the jaws (published correction appears in Ann Intern Med 2006;145[3]:235). Ann Intern Med 2006; 144(10):753-761. 6. Ciancio SG. Medications’ impact on oral health. JADA 2004; 135(10):1440-1448. 7. Gallagher L, Naidoo P. Prescription drugs and their effects on swallowing. Dysphagia 2009;24(2):159-166. 8. Nair K, Dolovich L, Cassels A, et al. What patients want to know about their medications; focus group study of patient and clinician perspectives. Can Fam Physician 2002;48(1):104-110. 9. Avorn J, Shrank WH. Communicating drug benefits and risks effectively: there must be a better way. Ann Intern Med 2009;150(8): 563-564. 10. Delany N. How much do patients on lithium know about their medication? Psychiatr Bull 1991;15(3):136-137. 11. Polinski JM, Cadarette SM, Arnold M, et al. High-risk patients’ readiness to undergo BMD testing for osteoporosis diagnosis in Pennsylvania. Int Q Community Health Educ 2008;29(3):223-240. 12. Gray CL, Gardner C. Adverse drug events in the elderly: an ongoing problem. J Manag Care Pharm 2009;15(7):568-571. 13. Migliorati CA, Schubert MM, Peterson DE, Seneda LM. Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an emerging oral complication of supportive cancer therapy. Cancer 2005; 104(1):83-93. 14. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61(9):1115-1117. 15. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004;62(5):527-534. 16. Jadu F, Lee L, Pharoah M, Reece D, Wang L. A retrospective study assessing the incidence, risk factors and comorbidities of pamidronate-related necrosis of the jaws in multiple myeloma patients. Ann Oncol 2007;18(12):2015-2019. 17. Wang EP, Kaban LB, Strewler GJ, Raje N, Troulis MJ. Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg 2007;65(7):1328-1331. 18. Migliorati CA, Casiglia J, Epstein J, Jacobsen PL, Siegel MA, Woo SB. Managing the care of patients with bisphosphonate-associated osteonecrosis: an American Academy of Oral Medicine position paper (published correction appears in JADA 2006;137[1]:26). JADA 2005; 136(12):1658-1668. 19. Edwards BJ, Hellstein JW, Jacobsen PL, Kaltman S, Mariotti A, Migliorati CA; American Dental Association Council on Scientific Affairs Expert Panel on Bisphosphonate-Associated Osteonecrosis of the Jaw. Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy: an advisory statement from the American Dental Association Council on Scientific Affairs (published correction appears in JADA 2009;140[5]:522). JADA 2008;139(12): 1674-1677. 20. Keene GS, Parker MJ, Pryor GA. Mortality and morbidity after hip fractures. BMJ 1993;307(6914):1248-1250. 21. Leibson CL, Tosteson AN, Gabriel SE, Ransom JE, Melton LJ. Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc 2002; 50(10):1644-1650. 22. Robbins JA, Biggs ML, Cauley J. Adjusted mortality after hip fracture: from the cardiovascular health study. J Am Geriatr Soc 2006; 54(12):1885-1891. 23. Nurit P, Bella BC, Gila E, Revital Z. Evaluation of a nursing intervention project to promote patient medication education. J Clin Nurs 2009;18(17):2530-2536. 24. Schwartz LM, Woloshin S, Welch HG. Using a drug facts box to communicate drug benefits and harms: two randomized trials. Ann Intern Med 2009;150(8):516-527. 25. Atlas SJ, Grant RW, Ferris TG, Chang Y, Barry MJ. Patientphysician connectedness and quality of primary care. Ann Intern Med 2009;150(5):325-335.
May 2010
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BRIEF
REPORT
How patients’ lack of knowledge about oral bisphosphonates can interfere with medical and dental care Cesar A. Migliorati, DDS, MS, PhD; Katia Mattos, BSc; Mitzi J. Palazzolo, DDS, MSc
isphosphonate-associated osteonecrosis (BON) is an oral complication of bisphosphonate therapy.1-3 In 2008, Edwards and colleagues’4 reviewed the pharmacovigilance process involved in the reporting of this oral complication. The results of the study demonstrated that although rapid, the recognition of BON and the dissemination of information resulted from an uncoordinated action of pharmaceutical manufacturers, dental and medical professionals, a nonprofit organization, patients and regulatory authorities. Therefore, a more coordinated action between the U.S. Food and Drug Administration, health care professions and the pharmaceutical industry could result in quicker recognition of new adverse reactions from medications, leading to improved patient care. Physicians who prescribe medications such as bisphosphonates should counsel patients about possible oral complications resulting from taking the medications. However, because BON is an adverse reaction that almost exclusively affects the oral cavity,5 physicians might be uncomfortable discussing it with their patients. Medications can cause a variety of side effects that can affect oral health, dental treatment and quality of life.6,7 Yet, communication between physicians and patients regarding these side effects might not be taking place as often as needed.8,9
B
562
JADA, Vol. 141
http://jada.ada.org
ABSTRACT Background. Oral bisphosphonate use has been associated with a small risk of developing oral osteonecrosis that occurs spontaneously or after the patient has undergone dental surgery. The authors conducted a study to determine whether patients taking bisphosphonates had knowledge about the medical indication for the therapy and the duration of treatment, as well as whether they had been educated by their physicians about possible adverse reactions. Methods. From June 2008 through April 2009, people seeking routine care in a dental clinic and who were being treated with bisphosphonates were invited to participate in the study. The participants were asked questions involving knowledge about the medical indications related to their taking bisphosphonates, the duration of their therapy and whether they had been educated about possible adverse reactions. Results. The authors interviewed 73 participants; 84 percent stated they knew why they were receiving bisphosphonate therapy. However, 80 percent said they were unsure about the duration of therapy, and 82 percent could not recall if they had been told about the risk of experiencing adverse reactions, including oral osteonecrosis, by their physicians. Conclusion. People taking bisphosphonates may be unfamiliar with the drug and its possible adverse oral side effects. Clinical Implications. Dentists should be prepared to educate patients about the risks of developing oral complications resulting from bisphosphonate use and the need for appropriate dental care. Questions regarding discontinuation of bisphosphonate therapy should be answered by the physician. Key Words. Patient knowledge; drugs; bisphosphonate; dental care; medical care; osteoporosis. JADA 2010;141(5):562-566.
Dr. Migliorati was a professor of Oral Medicine, Department of Diagnostic Sciences, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Fla., when this study was conducted. He now is a professor and the director of Oral Medicine, Department of Biologic and Diagnostic Sciences, University of Tennessee Health Science Center, College of Dentistry, 875 Union Ave., Suite N228, Memphis, Tenn. 38163, e-mail “[email protected]”. Address reprints to Dr. Migliorati. Ms. Mattos is a dental student, Harvard School of Dental Medicine, Boston. Dr. Palazzolo was an assistant professor of Oral Medicine, Department of Diagnostic Sciences, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Fla., when this study was conducted. She now lives in Wichita Falls, Texas.
May 2010
Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
R E S E A R C H
We conducted a study to determine whether patients taking bisphosphonates had knowledge about the medical indication for the therapy and the duration of treatment and whether they had been educated about possible adverse reactions. PARTICIPANTS, MATERIALS AND METHODS
We conducted a single-center observational study of consecutively seen patients who were seeking routine dental care at the dental school clinic at the College of Dental Medicine, Nova Southeastern University (NSU), Fort Lauderdale, Fla., during the period from June 2008 through April 2009. To be eligible for the study, patients had to be receiving either an oral or intravenous bisphosphonate drug, be fluent in English and provide written informed consent. The NSU Institutional Review Board reviewed the study to ensure protection of human participants and approved it. During their initial visits to the dental clinic, patients completed a health questionnaire. Dental students or faculty members who evaluated these health questionnaires informed us when they identified patients who were receiving bisphosphonate therapy. We invited these patients to enroll in the study and asked them to sign a written informed consent form. A single investigator (K.M.) conducted inperson interviews with participants to ensure uniformity. During the interview, she determined the interactions that took place between the participants and the physicians who prescribed the bisphosphonates for them via a series of standardized questions concerning the following: dthe bisphosphonate being taken; dthe specific medical condition being treated by the medication; dthe expected duration of the bisphosphonate therapy; dknowledge of potential adverse effects resulting from the use of the medication; dwhether bone mineral density (BMD) tests had been performed; dwhether the medical condition had improved after therapy was initiated. The interview process took 15 to 20 minutes. After the interview, we gave participants the opportunity to meet with an oral medicine specialist (C.A.M.) to discuss the interview and ask questions about bisphosphonate medications and any potential effect on their dental care. Two
BRIEF
REPORT
authors (C.A.M. and M.J.P.) conducted brief clinical examinations of participants to verify the integrity of the participants’ oral mucosa and the absence of osteonecrosis. RESULTS
We identified 73 consecutively seen patients as potential participants. They all agreed to enroll in the study, which suggests that people taking bisphosphonates are interested in learning about its possible side effects. Participants’ demographics and bisphosphonate histories are shown in Table 1. There were 71 women and two men, with a mean age of 66 years (range, 44-88 years). White participants accounted for 64 percent of the study sample and Hispanics 27 percent. Oral alendronate was the most commonly used bisphosphonate (60 percent), followed by oral risedronate (29 percent) and oral ibandronate (10 percent). One of the participants had breast cancer metastatic to the skeleton and was receiving a zoledronic acid intravenous infusion annually. The predominant diagnoses among participants were osteoporosis (74 percent) and osteopenia (22 percent). Participants underwent bisphosphonate therapy for an average of 23 weeks (range, two-240 weeks). When the interviewer asked participants specifically about bisphosphonate therapy, 84 percent participants said they recalled being informed why they were receiving bisphosphonate therapy (Table 2, page 565). However, 80 percent of the participants said they did not know or were uncertain about the duration of the treatment, and 82 percent said that they had not been told about the possible side effects of taking bisphosphonates. Participants reported having no knowledge of BON and reported that their physicians had not told them that they needed to inform their dentists that they were receiving bisphosphonate therapy. Most participants requested a consultation with the oral medicine specialist to discuss the risk of developing BON based on the type of dental treatment plan that they would be undergoing. The results of the brief clinical examination revealed that none of the participants had evidence of having BON. Forty-seven participants recalled that they had undergone BMD testing several times. Twenty-three partici-
ABBREVIATION KEY. BMD: Bone mineral density. BON: Bisphosphonate-associated osteonecrosis. NSU: Nova Southeastern University.
JADA, Vol. 141
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Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
May 2010
563
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BRIEF
REPORT
TABLE 1
Patients’ demographics and bisphosphonate history. VARIABLE
VALUE Demographics
Age (mean years)
66 (range, 44-88)
Sex (No. [%]) Female Male
71 (97) 2 (3)
Ethnicity (No. [%]) White Black Hispanic Other
47 2 20 4
Tobacco use (No. [%]) Yes No
32 (44) 41 (56)
Alcohol use (No. [%]) Yes No
11 (15) 62 (85)
(64) (3) (27) (6)
Bisphosphonate History Type (No. [%]) Oral alendronate Oral risedronate Oral ibandronate Intravenous zoledronate
44 (60) 21 (29) 7 (10) 1 (1)
Medical indication (No. [%]) Osteoporosis Osteopenia Breast cancer Unknown
54 16 1 2
Duration of therapy (weeks) Maximum Minimum
(74) (22) (1) (3)
240 2
pants did not recall if they had undergone BMD testing, and three were unsure if they had ever undergone BMD testing. Only 22 participants recalled being informed by their physicians about improvement of their BMD levels after receiving bisphosphonate therapy. DISCUSSION
The results of our interviews of participants who were taking bisphosphonates and came to a dental school in south Florida for routine dental care revealed that 82 percent of them did not recall or were unsure about having a discussion about the risk of developing BON with the physicians who prescribed the bisphosphonates. They expressed concern about undergoing dental treatment after being told by the oral medicine specialist about the possible complications. The results of our study are in agreement with 564
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http://jada.ada.org
those of two other studies.8,9 The results of an evaluation about what patients want to know when they are prescribed medications revealed that one of the most common concerns expressed by patients is not receiving enough information about side effects and risks.8 In the same study, investigators also found that patients also were concerned about not being informed adequately about the duration of therapy. In our study, 80 percent of participants could not recall being informed about the duration of their bisphosphonate therapy. We received this information directly from the participants and could not confirm its accuracy. Nonetheless, there is evidence that in general, the communication of drug risks and benefits to patients has been inadequate.9 The results of a study evaluating patients receiving lithium treatment revealed that they had poor knowledge about the medication.10 The study’s investigators speculated that physicians might be reluctant to inform patients about side effects of drugs because doing so could lead to poor compliance.10 The American Hospital Association lists several types of medication errors involving incomplete patient information (for example, not knowing about a patient’s allergies or medications) and unavailable drug information, such as lack of up-to-date warnings.11 Although participants in our study were being followed periodically by their physicians and twothirds of participants had been tested several times for BMD levels, about one-third of the participants recalled that they had not undergone BMD testing, and three participants were unsure if they had ever been tested. Almost another onethird recalled that their physicians had told them that their BMD levels had improved after they had undergone bisphosphonate therapy. Millions of people in the United States and around the world take prescription medications that may cause significant oral complications. Because populations are aging and patients are being treated for chronic diseases more frequently, it is not uncommon for patients to be taking multiple medications.12 Medications can cause oral complications that vary in severity and alter quality of life.6 Some medications can interfere with routine dental care. Thus, it is normal practice for dentists to have a complete knowledge of their patients’ medical problems and associated medications, as well as possible oral side effects of these drugs. Cases of BON have been associated with the use of bisphosphonates
May 2010
Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.
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administered both intravenously and orally.13-15 The prevalence of BON is between 3 and 12 percent for patients who received bisphosphonates intravenously3-5,16,17 and less than 1 percent for patients who received bisphosphonates orally.5 Dentists should be prepared to discuss these risks with patients when reviewing medical histories and planning dental treatment. BON is a known adverse effect of bisphosphonate therapy1-3 and is discussed in the package inserts of all bisphosphonates. Therefore, dentists should inform patients who are taking bisphosphonates about BON before providing invasive dental care. When this information is provided, patients may indicate that they do not recall being told about this possible complication by their physicians who prescribed the bisphosphonates. Because of this possible miscommunication and the small risk of developing BON, it is recommended that the patient sign a written informed consent form before undergoing dental surgery or other invasive procedures.3,18,19 The informed consent form attests that the patient was informed about treatment alternatives and the risk of developing BON and agreed that the proposed treatment was the best option available. Serious consequences can occur when patients are misinformed. Patients who are concerned about the risk of developing BON might decline needed dental care. This decision could result in their experiencing complications or emergencies in the future or lead to the need for more invasive dental treatment. Furthermore, patients’ concerns about the risk of developing BON may result in their discontinuing bisphosphonate use without discussing their decisions with their physicians first. This action may place patients at risk of experiencing serious and potentially fatal adverse events such as hip fractures.20-22 Thus, dentists never should recommend that patients discontinue any form of medical therapy without first consulting with their physicians. In addition, physicians should tell their patients to inform their dentists that they are receiving bisphosphonate therapy and that use of the medication should not be discontinued without the agreement of the professional who prescribed the drug. A collaborative effort between physicians and dentists in educating patients about risks and adverse drug reactions could prevent serious misunderstandings and consequences. Furthermore, patients with poor oral health should consult with their dentists before commencing bisphosphonate
BRIEF
REPORT
TABLE 2
Bisphosphonate information provided by the participants. QUESTION
PARTICIPANT’S RESPONSES (NO. [%]) Yes
No or Unsure
Reason for bisphosphonate therapy? *
61 (84)
12 (16)
How long are you going to be on therapy? †
15 (20)
58 (80)
Informed about risks or side effects? ‡
13 (18)
60 (82)
Informed about improvement? §
22 (30)
51 (70)
* Participant recalled being informed why a bisphosphonate was being prescribed. † Participant was informed about duration of therapy. ‡ Participant was warned about possible side effects of bisphosphonates. § Participant had been informed about better bone mineral density results associated with bisphosphonate therapy.
BOX
Points of discussion to use with patients when informing them of risks of bisphosphonate therapy. dAlthough the risk of developing bisphosphonate-
associated osteonecrosis (BON) is less than 1 percent, bisphosphonate use can reduce the risk of developing bone fractures 35 to 50 percent. dPeople with osteoporosis are at risk of developing bone fractures. Bisphosphonates can improve bone quality and reduce the risk of fractures. That is why your physician prescribed a bisphosphonate. dWe can work with your physician to reduce the risk of experiencing complications during dental care. dDo not discontinue the use of bisphosphonate on your own. dWe believe that good oral hygiene and routine dental care are the best way to prevent BON.
therapy.3,18,19 This recommendation is especially important for patients to whom intravenous formulations are prescribed. There are several strategies that could lead to improvement in this area,23,24 including those suggested in the box. We recognize that the results of our study are based solely on information provided by a small group of patients and that we did not interview the physicians who prescribed the bisphosphonates to confirm the accuracy of the information. Most participants were women (71 of 73), probably because postmenopausal women constitute the main group of people being prescribed bisphosphonates. Future studies should aim to include equal numbers of male and female patients who are receiving bisphosphonate therapy. The JADA, Vol. 141
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REPORT
patient population that seeks dental care at NSU is heterogeneous and representative of not only south Florida, where we conducted our study, but also of different areas of the United States, as some people from these areas live in Florida during the winter. Therefore, not all of the participants we interviewed received their medical care in Florida, thus excluding the possibility that the results of our study represent a local reality. We also recognize that the questionnaire used in the study was derived from the routine medical history review used for new patients who seek dental treatment at NSU and, therefore, was not a validated instrument. The development of scientifically validated instruments for future studies is advisable. Information about medications provided to patients by health care providers can be overwhelming, and readers should consider this when interpreting the results of our study. Better patient-physician relationships could improve the quality of patient care.25 We postulate that an improvement in patient education about medication use and adverse effects that involves physicians, patients and dentists as a team could improve the quality of care and reduce complications of medical and dental treatment. CONCLUSIONS
The results of our small study show that patients who take bisphosphonates may not be aware that BON can develop after they undergo invasive dental care. We believe that a more effective communication process between prescribing physicians, dentists and patients using bisphosphonates is needed. ■ Disclosure. Dr. Migliorati is a consultant at Amgen, Thousand Oaks, Calif. The authors thank Dr. Adam Lloyd for his editorial assistance and Dr. Jessica Shireman for her help with the research. 1. Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007;22(10): 1479-1491. 2. Migliorati CA, Siegel MA, Elting LS. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment (published correction appears in Lancet Oncol 2006;7[7]:533). Lancet Oncol 2006;7(6):508-514. 3. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B; American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws: 2009 update. J Oral Maxillofac Surg 2009;67(5 suppl):2-12.
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4. Edwards BJ, Gounder M, McKoy JM, et al. Pharmacovigilance and reporting oversight in US FDA fast-track process: bisphosphonates and osteonecrosis of the jaw. Lancet Oncol 2008;9(12):1166-1172. 5. Woo SB, Hellstein JW, Kalmar JR. Narrative (corrected) review: bisphosphonates and osteonecrosis of the jaws (published correction appears in Ann Intern Med 2006;145[3]:235). Ann Intern Med 2006; 144(10):753-761. 6. Ciancio SG. Medications’ impact on oral health. JADA 2004; 135(10):1440-1448. 7. Gallagher L, Naidoo P. Prescription drugs and their effects on swallowing. Dysphagia 2009;24(2):159-166. 8. Nair K, Dolovich L, Cassels A, et al. What patients want to know about their medications; focus group study of patient and clinician perspectives. Can Fam Physician 2002;48(1):104-110. 9. Avorn J, Shrank WH. Communicating drug benefits and risks effectively: there must be a better way. Ann Intern Med 2009;150(8): 563-564. 10. Delany N. How much do patients on lithium know about their medication? Psychiatr Bull 1991;15(3):136-137. 11. Polinski JM, Cadarette SM, Arnold M, et al. High-risk patients’ readiness to undergo BMD testing for osteoporosis diagnosis in Pennsylvania. Int Q Community Health Educ 2008;29(3):223-240. 12. Gray CL, Gardner C. Adverse drug events in the elderly: an ongoing problem. J Manag Care Pharm 2009;15(7):568-571. 13. Migliorati CA, Schubert MM, Peterson DE, Seneda LM. Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an emerging oral complication of supportive cancer therapy. Cancer 2005; 104(1):83-93. 14. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61(9):1115-1117. 15. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004;62(5):527-534. 16. Jadu F, Lee L, Pharoah M, Reece D, Wang L. A retrospective study assessing the incidence, risk factors and comorbidities of pamidronate-related necrosis of the jaws in multiple myeloma patients. Ann Oncol 2007;18(12):2015-2019. 17. Wang EP, Kaban LB, Strewler GJ, Raje N, Troulis MJ. Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg 2007;65(7):1328-1331. 18. Migliorati CA, Casiglia J, Epstein J, Jacobsen PL, Siegel MA, Woo SB. Managing the care of patients with bisphosphonate-associated osteonecrosis: an American Academy of Oral Medicine position paper (published correction appears in JADA 2006;137[1]:26). JADA 2005; 136(12):1658-1668. 19. Edwards BJ, Hellstein JW, Jacobsen PL, Kaltman S, Mariotti A, Migliorati CA; American Dental Association Council on Scientific Affairs Expert Panel on Bisphosphonate-Associated Osteonecrosis of the Jaw. Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy: an advisory statement from the American Dental Association Council on Scientific Affairs (published correction appears in JADA 2009;140[5]:522). JADA 2008;139(12): 1674-1677. 20. Keene GS, Parker MJ, Pryor GA. Mortality and morbidity after hip fractures. BMJ 1993;307(6914):1248-1250. 21. Leibson CL, Tosteson AN, Gabriel SE, Ransom JE, Melton LJ. Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc 2002; 50(10):1644-1650. 22. Robbins JA, Biggs ML, Cauley J. Adjusted mortality after hip fracture: from the cardiovascular health study. J Am Geriatr Soc 2006; 54(12):1885-1891. 23. Nurit P, Bella BC, Gila E, Revital Z. Evaluation of a nursing intervention project to promote patient medication education. J Clin Nurs 2009;18(17):2530-2536. 24. Schwartz LM, Woloshin S, Welch HG. Using a drug facts box to communicate drug benefits and harms: two randomized trials. Ann Intern Med 2009;150(8):516-527. 25. Atlas SJ, Grant RW, Ferris TG, Chang Y, Barry MJ. Patientphysician connectedness and quality of primary care. Ann Intern Med 2009;150(5):325-335.
May 2010
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