PERSPECTIVES J Oral Maxillofac Surg 72:655-657, 2014
Management of Antiresorptive Osteonecrosis of the Jaws With Primary Surgical Resection Eric R. Carlson, DMD, MD* In 2003, medical and dental professionals began to encounter an increasing number of patients exhibiting exposed necrotic bone of the jaws with underlying diagnoses of metastatic cancer and osteoporosis that were classified as bisphosphonate-related osteonecrosis of the jaws (BRONJ). The authors of anecdotal reports and peer-reviewed publications around that time concluded that the management of patients with BRONJ was extremely difficult because their surgical debridements were not completely effective in eradicating the necrotic bone. Therefore, it was recommended that surgical treatment be performed only in those patients who were symptomatic, such as those with a pathologic fracture associated with their osteonecrosis, in which case a segmental resection was indicated. As such, conservative therapy became the accepted method of management of this disease process based primarily on the experience and opinions of 2 reputable and highly respected members of the specialty of oral and maxillofacial surgery. In fact, these recommendations set the stage for the recapitulation of non–evidencebased conservative treatment recommendations in subsequently published peer-reviewed articles on this subject. BRONJ has since been classified under the umbrella of antiresorptive osteonecrosis of the jaws (ARONJ) owing to the fact that osteonecrosis of the jaws also has been observed in patients exposed to human receptor activator for nuclear factor-kB ligand inhibitor medications. It is the purpose of this Perspective to proclaim resection as the optimum and definitive management of stage I, II,
and III osteonecrosis of the jaws in patients specifically exposed to antiresorptive therapy.
*Professor and Kelly L. Krahwinkel Chairman, Director of
Tennessee Medical Center, 1930 Alcoa Highway, Suite 335, Knox-
Rationale for Aggressive Surgical Therapy Despite the opinions of numerous oral and maxillofacial surgeons and other practitioners that conservative therapy is the preferential method of management of ARONJ, many surgeons have approached this diagnosis with resection based primarily on the tenet that dead tissue is a surgical problem (Table 1).1-4 First, the philosophical rationale for aggressive surgical therapy for ARONJ is based on a general understanding that surgical therapy is paramount in the treatment of complex wounds of the human body when necrotic tissue is present. The chronic presence of dead bone in the jaws from osteoradionecrosis, osteomyelitis, or an unspecified cause has always been approached with surgical removal as part of a treatment algorithm, because dead tissue cannot be resurrected, but rather will continue to exist as a complex chronic wound when left untreated. Second, clinical observation and evidence from the literature indicate that the burden of necrotic bone in foci of conservatively treated ARONJ commonly increases over time. Watters et al5 presented their review of 154 patients diagnosed with BRONJ, 109 of whom had been treated with intravenous bisphosphonates and 100 of whom were assessed with follow-up examinations. At variable and nonuniform final follow-up
Residency Program, Department of Oral and Maxillofacial Surgery,
ville, TN 37920; e-mail: [email protected]
University of Tennessee Medical Center; Director, Oral/Head and
Received October 29 2013
Neck Oncologic Surgery Fellowship Program, University of
Accepted December 5 2013
Tennessee Cancer Institute, Knoxville, TN. Dr Carlson provides expert witness testimony for Hollingsworth
Ó 2014 American Association of Oral and Maxillofacial Surgeons
LLP in re Aredia/Zometa litigation.
http://dx.doi.org/10.1016/j.joms.2013.12.007
0278-2391/13/01529-2$36.00/0
Address correspondence and reprint requests to Dr Carlson: Department of Oral and Maxillofacial Surgery, University of
655
656
ANTIRESORPTIVE OSTEONECROSIS OF THE JAWS
Table 1. SUCCESS RATES ASSOCIATED WITH RESECTION VERSUS DEBRIDEMENT OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAWS
Study
Year
Surgical Procedure
Carlson and Basile1 Graziani et al2 Graziani et al2 Williamson3 Wutzl et al4
2009 2012 2012 2010 2008
resection resection debridement resection debridement
Cases, n
Intravenous
Oral
Success Rate
95 120 227 40 58
68
27
24
16
92% 73% 54% 100% 48%
Eric R. Carlson. Antiresorptive Osteonecrosis of the Jaws. J Oral Maxillofac Surg 2014.
examinations, 26 patients were categorized as progressive, 42 patients were categorized as unchanged, 26 patients were categorized as partial resolution, and 6 patients were designated as resolved. In the final analysis, 94% of patients in their study subjected to conservative therapy showed unresolved areas of osteonecrosis. Third, evidence from the literature shows that resection is effective in the management of osteonecrosis of the jaws associated with antiresorptive medications (Table 1). That said, it is important to distinguish debridement from resection, with the former representing subtherapeutic surgical therapy for ARONJ.1,2 Resection of ARONJ represents a calculated removal of necrotic bone and a normal bone margin based on preoperative imaging with a panoramic radiograph and computed tomograms and the intraoperative use of surgical saws and rotary burs in a generally anesthetized patient. Resection of the mandible, in particular, may occur in the form of a marginal resection or a segmental resection.1 Resection of the maxilla involves a partial or total maxillectomy that intentionally enters the maxillary sinus or nasal cavities, depending on the location and magnitude of the necrosis of the maxilla.1 All resections should include a margin of normal surrounding bone to realize viable bleeding bone at the periphery of the bone defect. Debridement represents a somewhat haphazard and empirical application of bone curetting, saucerization, and other palliative measures to reduce, but not completely eliminate, necrotic bone.1,2 The more precisely executed resection in a patient with ARONJ whose comorbid medical conditions have been managed preoperatively is more likely to result in cure of the patient’s focus of necrotic bone (Table 1). In their head-to-head study of debridement versus resection of BRONJ sites, Graziani et al2 found that 49% of cases showed improvement after debridement, whereas no improvement and worsening were noted in 35% and 16% of cases, respectively. Resection of BRONJ sites resulted in a statistically significant difference (P = .002) as improvement was seen in 68% of cases, with no improvement and worsening
noted in 27% and 5% of cases, respectively. Overall, a positive outcome was noted in 73% of cases subjected to resection, whereas a positive outcome was noted in 54% of cases subjected to debridement. The primary outcome variable of a change in the BRONJ staging of the patients in this study was different from that of Carlson and Basile1 in which the primary outcome variable consisted of an assessment of cure of the BRONJ site after resection, as noted by postoperative maintenance of full mucosal coverage without pain or infection.
Assessment of Recommendations for Conservative Management Numerous investigators continue to recommend conservative management of ARONJ, and the rationale for these conservative and frequently palliative rather than curative recommendations can be summarized several-fold. The first explanation surrounds the recapitulation of previously published conservative recommendations consistent with the theme of minimizing patient symptoms and intermittently eliminating infection rather than definitively eliminating the osteonecrosis. Under the circumstances, many investigators correctly point out that ARONJ is a relapsing and remitting diagnosis. Contrary to many comments regarding ARONJ in the international literature, foci of osteonecrosis do not predictably sequester followed by their simple removal, thereby resulting in effective soft tissue healing without recurrence of the osteonecrosis. It is also noteworthy that many investigators recommending conservative management are non-surgeons who would not find themselves in a position to provide their patients the definitive surgical resection described in this Perspective. Another explanation for the continued recommendation of conservative therapy of ARONJ is one of semantics. The peer-reviewed literature related to ARONJ frequently uses the terms management and treatment in article titles, and the reader must delve into the article to determine the specific form of management and treatment and their outcomes. In so
657
ERIC R. CARLSON
doing, our specialty has realized that conservative management most commonly translates to palliation of ARONJ, whereas surgical resection most commonly translates to cure of the patient’s osteonecrosis. Therefore, to provide palliation of ARONJ is not to definitively manage or treat the patient’s disease. In other words, to conservatively manage ARONJ overstates the treatment and management of this disease. Neither is uniformly accomplished. To surgically resect ARONJ is to effectively manage or treat the disease, similar to ablative surgery performed for neoplastic disease. Therefore, it might be more appropriate to use the terms palliate or cure when defining management strategies of ARONJ.
References 1. Carlson ER, Basile JD: The role of surgical resection in the management of bisphosphonate related osteonecrosis of the jaws. J Oral Maxillofac Surg 67(suppl 1):85, 2009 2. Graziani F, Vescovi P, Campisi G, et al: Resective surgical approach shows a high performance in the management of advanced cases of bisphosphonate-related osteonecrosis of the jaws: A retrospective survey of 347 cases. J Oral Maxillofac Surg 70:2501, 2012 3. Williamson RA: Surgical management of bisphosphonate induced osteonecrosis of the jaws. Int J Oral Maxillofac Surg 39:251, 2010 4. Wutzl A, Biedermann E, Wanschitz F, et al: Treatment results of bisphosphonate-related osteonecrosis of the jaws. Head Neck 30:1224, 2008 5. Watters AL, Hansen HJ, Williams T, et al: Intravenous bisphosphonate-related osteonecrosis of the jaw: Long-term follow-up of 109 patients. Oral Surg Oral Med Oral Pathol Oral Radiol 115:192, 2013
Management of Antiresorptive Osteonecrosis of the Jaws With Primary Surgical Resection Eric R. Carlson, DMD, MD* In 2003, medical and dental professionals began to encounter an increasing number of patients exhibiting exposed necrotic bone of the jaws with underlying diagnoses of metastatic cancer and osteoporosis that were classified as bisphosphonate-related osteonecrosis of the jaws (BRONJ). The authors of anecdotal reports and peer-reviewed publications around that time concluded that the management of patients with BRONJ was extremely difficult because their surgical debridements were not completely effective in eradicating the necrotic bone. Therefore, it was recommended that surgical treatment be performed only in those patients who were symptomatic, such as those with a pathologic fracture associated with their osteonecrosis, in which case a segmental resection was indicated. As such, conservative therapy became the accepted method of management of this disease process based primarily on the experience and opinions of 2 reputable and highly respected members of the specialty of oral and maxillofacial surgery. In fact, these recommendations set the stage for the recapitulation of non–evidencebased conservative treatment recommendations in subsequently published peer-reviewed articles on this subject. BRONJ has since been classified under the umbrella of antiresorptive osteonecrosis of the jaws (ARONJ) owing to the fact that osteonecrosis of the jaws also has been observed in patients exposed to human receptor activator for nuclear factor-kB ligand inhibitor medications. It is the purpose of this Perspective to proclaim resection as the optimum and definitive management of stage I, II,
and III osteonecrosis of the jaws in patients specifically exposed to antiresorptive therapy.
*Professor and Kelly L. Krahwinkel Chairman, Director of
Tennessee Medical Center, 1930 Alcoa Highway, Suite 335, Knox-
Rationale for Aggressive Surgical Therapy Despite the opinions of numerous oral and maxillofacial surgeons and other practitioners that conservative therapy is the preferential method of management of ARONJ, many surgeons have approached this diagnosis with resection based primarily on the tenet that dead tissue is a surgical problem (Table 1).1-4 First, the philosophical rationale for aggressive surgical therapy for ARONJ is based on a general understanding that surgical therapy is paramount in the treatment of complex wounds of the human body when necrotic tissue is present. The chronic presence of dead bone in the jaws from osteoradionecrosis, osteomyelitis, or an unspecified cause has always been approached with surgical removal as part of a treatment algorithm, because dead tissue cannot be resurrected, but rather will continue to exist as a complex chronic wound when left untreated. Second, clinical observation and evidence from the literature indicate that the burden of necrotic bone in foci of conservatively treated ARONJ commonly increases over time. Watters et al5 presented their review of 154 patients diagnosed with BRONJ, 109 of whom had been treated with intravenous bisphosphonates and 100 of whom were assessed with follow-up examinations. At variable and nonuniform final follow-up
Residency Program, Department of Oral and Maxillofacial Surgery,
ville, TN 37920; e-mail: [email protected]
University of Tennessee Medical Center; Director, Oral/Head and
Received October 29 2013
Neck Oncologic Surgery Fellowship Program, University of
Accepted December 5 2013
Tennessee Cancer Institute, Knoxville, TN. Dr Carlson provides expert witness testimony for Hollingsworth
Ó 2014 American Association of Oral and Maxillofacial Surgeons
LLP in re Aredia/Zometa litigation.
http://dx.doi.org/10.1016/j.joms.2013.12.007
0278-2391/13/01529-2$36.00/0
Address correspondence and reprint requests to Dr Carlson: Department of Oral and Maxillofacial Surgery, University of
655
656
ANTIRESORPTIVE OSTEONECROSIS OF THE JAWS
Table 1. SUCCESS RATES ASSOCIATED WITH RESECTION VERSUS DEBRIDEMENT OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAWS
Study
Year
Surgical Procedure
Carlson and Basile1 Graziani et al2 Graziani et al2 Williamson3 Wutzl et al4
2009 2012 2012 2010 2008
resection resection debridement resection debridement
Cases, n
Intravenous
Oral
Success Rate
95 120 227 40 58
68
27
24
16
92% 73% 54% 100% 48%
Eric R. Carlson. Antiresorptive Osteonecrosis of the Jaws. J Oral Maxillofac Surg 2014.
examinations, 26 patients were categorized as progressive, 42 patients were categorized as unchanged, 26 patients were categorized as partial resolution, and 6 patients were designated as resolved. In the final analysis, 94% of patients in their study subjected to conservative therapy showed unresolved areas of osteonecrosis. Third, evidence from the literature shows that resection is effective in the management of osteonecrosis of the jaws associated with antiresorptive medications (Table 1). That said, it is important to distinguish debridement from resection, with the former representing subtherapeutic surgical therapy for ARONJ.1,2 Resection of ARONJ represents a calculated removal of necrotic bone and a normal bone margin based on preoperative imaging with a panoramic radiograph and computed tomograms and the intraoperative use of surgical saws and rotary burs in a generally anesthetized patient. Resection of the mandible, in particular, may occur in the form of a marginal resection or a segmental resection.1 Resection of the maxilla involves a partial or total maxillectomy that intentionally enters the maxillary sinus or nasal cavities, depending on the location and magnitude of the necrosis of the maxilla.1 All resections should include a margin of normal surrounding bone to realize viable bleeding bone at the periphery of the bone defect. Debridement represents a somewhat haphazard and empirical application of bone curetting, saucerization, and other palliative measures to reduce, but not completely eliminate, necrotic bone.1,2 The more precisely executed resection in a patient with ARONJ whose comorbid medical conditions have been managed preoperatively is more likely to result in cure of the patient’s focus of necrotic bone (Table 1). In their head-to-head study of debridement versus resection of BRONJ sites, Graziani et al2 found that 49% of cases showed improvement after debridement, whereas no improvement and worsening were noted in 35% and 16% of cases, respectively. Resection of BRONJ sites resulted in a statistically significant difference (P = .002) as improvement was seen in 68% of cases, with no improvement and worsening
noted in 27% and 5% of cases, respectively. Overall, a positive outcome was noted in 73% of cases subjected to resection, whereas a positive outcome was noted in 54% of cases subjected to debridement. The primary outcome variable of a change in the BRONJ staging of the patients in this study was different from that of Carlson and Basile1 in which the primary outcome variable consisted of an assessment of cure of the BRONJ site after resection, as noted by postoperative maintenance of full mucosal coverage without pain or infection.
Assessment of Recommendations for Conservative Management Numerous investigators continue to recommend conservative management of ARONJ, and the rationale for these conservative and frequently palliative rather than curative recommendations can be summarized several-fold. The first explanation surrounds the recapitulation of previously published conservative recommendations consistent with the theme of minimizing patient symptoms and intermittently eliminating infection rather than definitively eliminating the osteonecrosis. Under the circumstances, many investigators correctly point out that ARONJ is a relapsing and remitting diagnosis. Contrary to many comments regarding ARONJ in the international literature, foci of osteonecrosis do not predictably sequester followed by their simple removal, thereby resulting in effective soft tissue healing without recurrence of the osteonecrosis. It is also noteworthy that many investigators recommending conservative management are non-surgeons who would not find themselves in a position to provide their patients the definitive surgical resection described in this Perspective. Another explanation for the continued recommendation of conservative therapy of ARONJ is one of semantics. The peer-reviewed literature related to ARONJ frequently uses the terms management and treatment in article titles, and the reader must delve into the article to determine the specific form of management and treatment and their outcomes. In so
657
ERIC R. CARLSON
doing, our specialty has realized that conservative management most commonly translates to palliation of ARONJ, whereas surgical resection most commonly translates to cure of the patient’s osteonecrosis. Therefore, to provide palliation of ARONJ is not to definitively manage or treat the patient’s disease. In other words, to conservatively manage ARONJ overstates the treatment and management of this disease. Neither is uniformly accomplished. To surgically resect ARONJ is to effectively manage or treat the disease, similar to ablative surgery performed for neoplastic disease. Therefore, it might be more appropriate to use the terms palliate or cure when defining management strategies of ARONJ.
References 1. Carlson ER, Basile JD: The role of surgical resection in the management of bisphosphonate related osteonecrosis of the jaws. J Oral Maxillofac Surg 67(suppl 1):85, 2009 2. Graziani F, Vescovi P, Campisi G, et al: Resective surgical approach shows a high performance in the management of advanced cases of bisphosphonate-related osteonecrosis of the jaws: A retrospective survey of 347 cases. J Oral Maxillofac Surg 70:2501, 2012 3. Williamson RA: Surgical management of bisphosphonate induced osteonecrosis of the jaws. Int J Oral Maxillofac Surg 39:251, 2010 4. Wutzl A, Biedermann E, Wanschitz F, et al: Treatment results of bisphosphonate-related osteonecrosis of the jaws. Head Neck 30:1224, 2008 5. Watters AL, Hansen HJ, Williams T, et al: Intravenous bisphosphonate-related osteonecrosis of the jaw: Long-term follow-up of 109 patients. Oral Surg Oral Med Oral Pathol Oral Radiol 115:192, 2013
