Title	Patients Being Treated with Oral Alendronate and in Need of a Dental Implant May Reduce the Risk of Osteonecrosis of the Jaw by Taking a Drug Holiday
Clinical Question	In patients being treated with oral alendronate and wanting a dental implant, does taking a drug holiday decrease the likelihood of developing osteonecrosis of the jaw?
Clinical Bottom Line	Patients being treated with oral alendronate and in need of a dental implant should have their dentist discuss the discontinuation of their oral bisphosphonate with their prescribing physician before continuing with dentoalveolar surgical treatment. The amount of risk reduction seems to necessitate further investigation and therefore, one cannot provide a definitive answer to the clinical question.
Best Evidence
PubMed ID Author / Year Patient Group Study type (level of evidence) 25234529 Ruggiero/2014 184 studies Practice Guideline Key results Ruggiero et. al and the AAOMS divides individuals from 184 studies into three categories. The first category consists of individuals who have taken oral bisphosphonates for less than 4 years with no other clinical risk factors. These people should not alter or delay surgical treatment, but the guidelines advise that the dentist contact the prescribing physician to consider a drug holiday. The second category consists of individuals who have taken oral bisphosphonates for less than 4 years in conjunction with corticosteroids. The physicians of these patients should definitely be contacted to discuss a drug holiday of at least 2 months prior to surgery. The third category consists of individuals who have taken oral bisphosphonates for more than 4 years with or without concomitant medical therapy. The physicians of these patients should also be contacted to discontinue anti-resportive medications for 2 months prior to oral surgery; the medication should not be restarted until osseous healing has occurred. 21163625 Manfredi/2010 25 patients Case series Key results Twenty-two of the 25 patients with bisphosphonates-related osteonecrosis of the jaws (BRONJ) were treated and observed in this study; 7 of these patients discontinued oral alendronate therapy for a period of at least 3 months. Each patient had one site with dentoalveolar surgical treatment (seven total sites). Two of these sites displayed healing improvement, and five sites had complete mucosal healing. However, no differences were observed between patients who suspended bisphosphonate therapy and those who did not.
Evidence Search	("dental implants"[MeSH Terms] OR ("dental"[All Fields] AND "implants"[All Fields]) OR "dental implants"[All Fields]) AND ("jaw diseases"[MeSH Terms] OR ("jaw"[All Fields] AND "diseases"[All Fields]) OR "jaw diseases"[All Fields] OR ("jaw"[All Fields] AND "disease"[All Fields]) OR "jaw disease"[All Fields]) AND ("diphosphonates"[MeSH Terms] OR "diphosphonates"[All Fields]) ("osteonecrosis"[MeSH Terms] OR "osteonecrosis"[All Fields]) AND ("jaw"[MeSH Terms] OR "jaw"[All Fields]) AND aaoms[All Fields]
Comments on The Evidence	Validity: The Ruggiero study is a practice guideline set by the American Association of Oral and Maxillofacial Surgery. It consists of the review and application of 184 studies. However, although the recommendations are based on many studies, they consist of low quality evidence. The Manfredi case series included 25 patients, but only 18 of those patients underwent oral surgery. Out of those 18, only 7 reported discontinuation of bisphosphonate therapy in the appropriate manner. Perspective: There are no apparent conflict of interests or bias within the evidence provided. The portion of the Ruggiero paper that addresses drug holidays and dentoalveolar surgery, including dental implants, advocates for drug holidays of at least 2 months prior to surgery, especially if one is in the second or third category of individuals (see Key Results). The second category’s recommended discontinuation is based on reports that corticosteroids combined with antiresorptive therapy may increase the risk for osteonecrosis of the jaw. The third category’s recommended discontinuation uses the theoretical benefit, based on studies of bone physiology and pharmacokinetics, to guide their advice. These recommendations seem valid due to support by a multitude of studies. Therefore, although the author admits to a lack of definitive evidence to recommend an absolute treatment option, these guidelines seem justified in order to potentially reduce development of osteonecrosis of the jaw. The Manfredi case series serves to demonstrate a common thread within this area of implantology and dentoalveolar surgery. The common thread is that there is no absolute causal link between not suspending anti-resorptive medication and developing osteonecrosis of the jaw. More long-term, randomized control studies would be needed in order to provide a clearer picture of what exactly is the best treatment option for these patients and what is the expected percent reduction of osteonecrosis if the drug holiday is utilized.
Applicability	The Ruggiero paper included the most current studies on bone physiology and pharmacokinetics as well as case studies and case series reports. Although the evidence is relatively weak, it does seem sound enough to support the current guidelines. In clinical practice, the demographic that will likely be in this position is older females diagnosed with osteoporosis. Although I agree with the current guideline, I believe there must be better evidence within these particular patients receiving dentoalveolar surgery. There also needs to be better evidence for what discontinuation of oral bisphosphonates does to the risk factor for developing pathologic fractures within this demographic. When those two areas have proper evidence, then we can have an absolute treatment option. As of now, the general dentist must discuss the risks of developing osteonecrosis of the jaw with the patient as well as the patient’s physician. However, whether or not suspension of medication ensues must be the prescribing physician’s decision.
Specialty	(General Dentistry) (Oral Surgery)
Keywords	Alendronate; Dental Implants; Osteonecrosis; Bisphopshonates; Drug Holiday
ID#	3257
Date of submission	06/13/2017
E-mail	velajj@livemail.uthscsa.edu
Author	Jeremy Vela
Co-author(s)
Co-author(s) e-mail
Faculty mentor	Edward Ellis, III, DDS
Faculty mentor e-mail	ellise3@uthscsa.edu
Basic Science Rationale (Mechanisms that may account for and/or explain the clinical question, i.e. is the answer to the clinical question consistent with basic biological, physical and/or behavioral science principles, laws and research?) None available
Comments and Evidence-Based Updates on the CAT (FOR PRACTICING DENTISTS', FACULTY, RESIDENTS and/or STUDENTS COMMENTS ON PUBLISHED CATs) None available