Title

For Patients Taking Nonbisphosphonate Medications such as Xgeva, Avastin, or Sutent, Medication Related Osteonecrosis of the Jaw (MRONJ) Following Dentoalveolar Surgery Occurs at a Rate Comparable to that of Patients Taking IV Bisphosphonates

Clinical Question

In a patient who needs emergency dental care that is taking nonbisphosphonate medications such as Xgeva, Avastin, or Sutent, does MRONJ occur as frequently postoperatively as a patient receiving IV bisphosphonates?

Clinical Bottom Line

For patients taking nonbisphosphonate medications such as Xgeva, Avastin, or Sutent, MRONJ following dentoalveolar surgery occurs at a rate comparable to that of patients taking IV bisphosphonates. These drugs, when used concurrently with bisphosphonates, have a synergistic effect, and the risk for MRONJ is even greater. Any patient receiving these medications and needing dentoalveolar surgery must be given special precautions.

Best Evidence

PubMed ID	Author / Year	Patient Group	Study type (level of evidence)
22985897	Troeltzsch/2012	Patients taking denosumab, bevacizumab, and sunitinib	Narrative Review
Key results	Denosumab (Xgeva) therapy causes MRONJ at a rate similar to IV bisphosphonates. Bevacizumab (Avastin) and sutinib (Sutent) related ONJ cases have been reported, but evidence of a causal relationship is still anecdotal.
25234529	Ruggiero/2014	Patients taking medications that can cause ONJ	Practice Guideline
Key results	Patients at risk of developing MRONJ can be treated conservatively for caries and periodontal disease and may benefit from pain medication and antibiotics. Patients at a higher ONJ-staging classification benefit from antimicrobial rinses and antibiotics. Patients currently receiving IV therapy with an antiresorptive/antiangiogenic medication are at a very high risk of developing MRONJ, and elective tooth extraction should be avoided. If MRONJ has been identified, debridement and resection may be necessary along with antimicrobial rinses and antibiotics. These patients may also require immediate reconstruction.
24120382	Lescaille/2013	42 oncologic patients with ONJ	Prospective Cohort Study
Key results	Patients receiving bevacizumab (Avastin) in conjunction with the bisphosphonate zoledronic acid had a 6.07 times greater risk of developing spontaneous MRONJ when compared to patients only receiving zoledronic acid therapy (95% CI: 1.3-28.2, p < 0.05).

Evidence Search

((("Osteonecrosis"[Mesh]) AND "denosumab" [Supplementary Concept]) AND "sunitinib" [Supplementary Concept]) AND "bevacizumab" [Supplementary Concept]; osteonecrosis of the jaw and bevacizumab

Comments on
The Evidence

Validity: The clinical review did not specify how many studies it included in the review, although multiple references are listed. The authors of the review did not have any bias based on competing interests regarding the medications or treatments mentioned in the review. The practice guideline was released by the American Association of Oral and Maxillofacial Surgeons. This certain issue is an addendum to the guidelines they had released previously. The cohort study contained patients being treated with the same medications for similar malignancies. Adequate follow-up was performed and recall bias was unlikely. There were no competing interests in this study. Perspective: Based upon these articles, MRONJ of the jaw can occur in any patient taking Xgeva, Avastin, or Sutent following invasive dental procedures. When these drugs are given in combination with bisphosphonates, the risk for MRONJ is even greater. These articles did not specify which dental surgical procedures created the greatest risk for MRONJ, and this should be considered before performing any procedure that could upset bone homeostasis.

Applicability

These studies followed patients receiving nonbisphosphonate antiresorptive/antiangiogenic medications for malignancies. Elective surgical procedures should be performed with extreme caution in these patients or postponed until the antiresorptive/antiangiogenic medications are discontinued. Patients should be managed based upon their individual signs and symptoms. Practitioners should follow the guidelines presented in the American Association of Oral and Maxillofacial Surgeons position paper.

Specialty

(Oral Medicine/Pathology/Radiology) (Endodontics) (General Dentistry) (Oral Surgery) (Orthodontics) (Periodontics)

Keywords

denosumab, bevacizumab, sunitinib, MRONJ, medication-related osteonecrosis of the jaw

ID#

2811

Date of submission

03/16/2015

E-mail

hamiltonta@livemail.uthscsa.edu

Author

Trevor Hamilton

Co-author(s)

Co-author(s) e-mail

Faculty mentor

Gregory K. Spackman, DDS, MBA

Faculty mentor e-mail

Spackman@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