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P1.42. Laser application in prevention and management of osteonecrosis related to bisphosphonates therapy: A preliminary study
Poster Abstracts Oral AbstractsPoster ListOrals ListPan. Disc. & Symp. Abs.Keynote Abs.Keynote Bios.ProgramIAOOWelcomeCommittee Listings
136
Poster session I / Oral Oncology Supplement 3 (2009) 123–161
showed positivity in 82.5% of the cases and of these, 40.7% with immunoreactivity between 51cells. doi:10.1016/j.oos.2009.06.325
P1.40. Concomittant oral bisphosphonate use as a risk factor for osteonecrotic phenomenon of the jaw in head and neck radiation patients: A case–control study W.G. Maxymiw a,*, A. Hope b, A. Bailey b, R. Wood b, L. Lee b, J.F. Rodrigues b,c a
Princess Margaret Hospital, Canada University of Toronto, Canada c San Paulo State University, Brazil b
Introduction: Osteoradionecrosis (ORN) of the jaws is a serious complication of head and neck radiation therapy. Osteonecrosis of the jaws (ONJ) is a more recently described complication of bisphosphonate therapy. Both are clinically similar. There has been an increased use of oral bisphosphonates for osteopenic diseases in the general population. Radiation therapy or combined chemotherapy-radiation therapy regimens in the treatment of head and neck malignancies in these patients may cause osteonecrotic phenomenon of the jaws. Methods and materials: Over the course of approximately two and one half years (August 2005–January 2008) six patients presented to the dental clinic at Princess Margaret Hospital with clinically-atypical bone exposure developing spontaneously or following dental extractions. All were taking oral bisphosphonates. All had prior radiation treatment. Using the Princess Margaret dental database which records pertinent demographic and clinical data, a case–control study was undertaken. For each of the six bisphosphonate/ORN cases, seven controls were identified. The controls were within 7 years of the index age; treated within the same 5-year period; were the same gender; had the same cancer diagnosis at the same anatomic site, and were treated the same. Results: All cases had bone exposure and none of 42 controls had bone exposure. Only one of 42 controls was an oral bisphosphonate user. Curiously the incidence of this appears to be increasing with 5 of the 6 cases bone-exposure cases appearing within a 15 month period. Discussion: Based on this case–control study concomitant oral bisphosphonate use with head and neck radiation patients should be considered as a risk factor for osteonecrotic phenomenon. Further, since osteonecrosis of the jaw induced by bisphosphonate is refractory to treatment the differentiation of the two is important. doi:10.1016/j.oos.2009.06.326
P1.41. The GEN-VA-BO study (GENetic VAriants in Bisphosphonate-related Ostenecrosis of the jaws): A cooperation proposal S. Fedele *, S. Porter, F. D’aiuto, N. Donos, H. Ireland, S. Humphries University College London, United Kingdom University of Palermo, Italy Osteonecrosis of the jawbones is recently-reported complication of the use of bisphosphonates (BP). Because only a minority of BP users develop jaw necrosis, it is likely that one or more pre-existent susceptibility factors exist. Current knowledge of osteonecrosis of the jaws and other skeletal sites suggests that individual genetic predisposition may be related to the presence of polymorphisms of (i)
coagulation pathways (inherited thrombophilia), (ii) osteoblast and osteoclast signaling cascades, and (iii) cytochrome P450. However, these data come from small studies, are relevant to osteonecrosis of skeletal sites other than the jaw bones and are not always related to the use of BP. Therefore, there is a need to conduct further analyses on larger cohorts of patients. The GEN-VA-BO (GENetic VAriants in Bisphosphonate-related Ostenecrosis of the jaws) multicentre study is a case–control genetic study of blood specimens belonging to 800 individuals categorized into three groups (A, B, C). Group A (n = 200) is the test group which encompasses individuals with of BP-related jaw osteonecrosis. Group B (n = 300) and C (n = 300) are control groups consisting of individuals on BP therapy without osteonecrosis and healthy subjects respectively. The GEN-VA-BO started in 2009 and is scheduled to complete patient enrolment and gene analysis in 24–30 months. At present, a network of 14 clinical centres in Europe and Israel has been identified. However, collaboration with further clinical centres is needed in order to reach the planned number of participants and to eventually perform replication studies. The Second World Congress of the IAOO offers a unique opportunity to present the GEN-VA-BO study to the scientific community and identify new potential collaborators. We are particularly interested in clinical centres with cohort of at least 20 patients affected by BP-related jaw osteonecrosis and with ability to enrol matched controls. doi:10.1016/j.oos.2009.06.327
P1.42. Laser application in prevention and management of osteonecrosis related to bisphosphonates therapy: A preliminary study S. Capodiferro, E. Maiorano, G.P. Pilolli, G. Favia * University of Bari, Italy Introduction: Prevention of jaws osteonecrosis (JON) in patients taking bisphosphonates (BP) and the surgical management of JON related to BP therapy is still much debated. Laser capabilities in the sterilization, decontamination and bio-stimulation of oral tissues are, instead, generally accepted. For such reasons, we experimentally used diode and erbium:YAG laser both in prevention of JON in patient taking BP and needing oral surgery and in the surgical management of JON. Methods: 4 patients were included in this study; totally, we performed 9 teeth extractions in patients taking oral BP (2 during oral BP therapy, 6 after suspension at least for 3 months, and 1 after occurrence of JON of the mandible and subsequent suspension) and two surgical treatment of JON (1 of the anterior mandible and 1 of the tuber maxillae); the latter were treated with the following protocol: preoperative antibiotic therapy and biostimulation with diode laser, intraoperative treatment of the residual cavity after piezoelectric curettage with erbium:YAG laser and finally with simultaneous iodiopovidone solution and diode laser; postoperative biostimulation with diode laser. The extractions were performed during antibiotic therapy with a final treatment by erbium:YAG laser deeply inside the residual alveolar sockets followed by direct suture. Results: No occurrence of JON was obtained in all cases of tooth extraction. In the cases of JON, a complete healing of the covering mucosa was obtained in no more than 15 days. No recurrence was obtained. Discussion: Considering the missing of a standardized protocol both for prevention and surgical treatment of JON related to BP therapy, above all due to the presence of several variable factors (type, dose of BP and period of use, dimension of the lesion in close rela-
tionship to the occurrence sites, etc.) and good capabilities of laser in the sterilization and biostimulation of oral hard and soft tissue, we suggest that studies on larger cases could confirm our preliminary data. doi:10.1016/j.oos.2009.06.328
P1.43. Osteonecrosis of the jaws associated with the use of bisphosphonates: Radiological presentation O. Florence a,*, B. Denis b, B. Gaelle a,c, B. Anne-Gaelle a, G. René a a
Centre Léon Bérard, Lyon, France Clinique de l’ Europe, Lyon, France c Hopital Edouard Herriot, Lyon, France b
Introduction: The aim of the study is (1) to recall existing knowledge about pathophysiological aspects of osteonecrosis of the jaws associated with bisphosphonate therapy; (2) to describe the radiological presentation of the disease; and (3) to determine if a pathognomonic radiological feature can be identified. Materials and methods: This is a retrospective review of 15 patients (10 women and 5 men) treated with bisphosphonates for bone metastatic disease. Median age was 68.2 years. Panoramic radiograph of the jaw, maxillary CT scan and radionuclide imaging were reviewed by 2 radiologists. Results: The most frequent manifestations were osteolytic lesions. Many heterogeneous areas of both sclerosis and demineralisation were seen. A double cortical aspect was identified in one patient. Complications including fracture, oroantral fistula, and bone sequestrum were diagnosed. Discussion: Radiological features of osteonecrosis of the jaws remain aspecific. Nonetheless, when consistent with the clinical presentation, osteosclerosis associated with osteocondensation should suggest the diagnosis. Imaging can be used to establish the severity of the disease, especially to identify complications, and is crucial for making relevant treatment decisions. doi:10.1016/j.oos.2009.06.329
P1.44. Effects of Nd:YAP laser biostimulation over jawbone necrosis in oncologic patients G.A.E. Lescaille a,b,*, V. Descroix a,b, B. Ruhin-Poncet a, C. Escande a, R. Toledo a, J. Azerad a,b a b
GHPS, France University Paris 7, France
Introduction: Bisphosphonate-associated osteonecrosis of the jaws are recently described by Marx in 2003. These oral lesions are defined by exposed necrotic bone after more than 6 weeks, often preceded by a dental surgery but can also occur spontaneously. Most of cases have been developed with intravenous bisphosphonates treatment used to stabilize metastatic cancer, despite several osteonecrosis of the jaws cases related to oral bisphosphonates. The pathophysiology remains unelucidated but may be related to poor bone and blood vessel remodeling coinciding with local trauma to the maxilla or mandible. The greatest risk is associated with duration of IV bisphosphonate use, though long-term oral alendronate has also been implicated. No one singularly effective treatment exists, though results of this study suggest that medical, surgical treatment in association with the use of laser may offer a better chance for cure (Vescovi et al., 2007).
137
Patients and methods: We describe our preliminary results on 15 patients affected by bisphosphonate-associated osteonecrosis of the jaws who were treated conventionally with surgical, medical treatment in combination with neodimium:yttrium–aluminum–Perovsyit (Nd:YAP) laser. Clinical variables such as pain (with visual analog scale), presence of pus, and diminution of mucosal flaps before and after treatment (with photo and measure of area) were evaluated to establish the effect of the laser irradiation. Results: All patients improved durably their symptomatology after first laser biostimulation. We observed 5 total closures of flap and 10 significant reductions of size of the lesion after a few weeks. Discussion: Because bisphosphonates are one of the most prescribed drug worldwide, these data may reflect the importance of the possibility of ONJ and the necessity to develop effective therapeutic strategies. YAP laser biostimulation appears to be an attractive adjuvant therapy devoiced of adverse effect. doi:10.1016/j.oos.2009.06.330
P1.45. Bisphosphonate-related osteonecrosis of the jaw: Clinical series (45 patients) S. Salino *, A.G. Bodard, R. Gourmet Centre Léon Bérard, Lyon, France Bisphosphonates are indicated in the treatment of several malignant pathologies (multiple myeloma, bone metastases of solid tumors, malignant hypercalcemia, etc.), and in certain benign pathologies as well (osteoporosis, etc.). These medications’ efficacy is well documented, but certain incapacitating side effects can appear. Among them, osteonecrosis of the jaw (ONJ) has been described from 2003 on.1–3 ONJ is defined as the presence of exposed jaw-bone over an 8 week period of time at least, in a patient with actual or previous bisphosphonate treatment, and no previous maxillo-facial radiotherapy.3 Most ONJ appear on patients treated with IV bisphosphonates, after dental procedures such as teeth extractions.4 The management of ONJ can either be conservative5 or surgical,6 but there is no really established treatment. This is probably why most authors tend to insist more and more on ONJ prevention. Our experience is based on a series of 45 patients presenting a total of 65 ONJ taken care of between 2004 and 2008. According to the general and local clinical contexts and to the radiological situations, the management was either conservative or surgical or both successively. The objective of the presentation is to try and define some clinical and radiological parameters which could influence the management of ONJ. doi:10.1016/j.oos.2009.06.331 References 1. Khosla S, Coll. 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;22:1479–91. 2. Marx RE. Pamidronate (Aredia) and Zoledronate (Zometa) Induced Avascular Necrosis of the Jaws: a Growing Epidemic. J Oral Maxillofac Surg 2003;61:1115–7. 3. Kyle RA, Coll. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 2007;25:2464–72. 4. Boonyapakorn T, Coll. Bisphosphonate-induced osteonecrosis of the jaws: prospective study of 80 patients with multiple myeloma and other malignancies. Oral Oncol; 2008.
Poster Abstracts Oral AbstractsPoster ListOrals ListPan. Disc. & Symp. Abs.Keynote Abs.Keynote Bios.ProgramIAOOWelcomeCommittee Listings
Poster session I / Oral Oncology Supplement 3 (2009) 123–161
136
Poster session I / Oral Oncology Supplement 3 (2009) 123–161
showed positivity in 82.5% of the cases and of these, 40.7% with immunoreactivity between 51cells. doi:10.1016/j.oos.2009.06.325
P1.40. Concomittant oral bisphosphonate use as a risk factor for osteonecrotic phenomenon of the jaw in head and neck radiation patients: A case–control study W.G. Maxymiw a,*, A. Hope b, A. Bailey b, R. Wood b, L. Lee b, J.F. Rodrigues b,c a
Princess Margaret Hospital, Canada University of Toronto, Canada c San Paulo State University, Brazil b
Introduction: Osteoradionecrosis (ORN) of the jaws is a serious complication of head and neck radiation therapy. Osteonecrosis of the jaws (ONJ) is a more recently described complication of bisphosphonate therapy. Both are clinically similar. There has been an increased use of oral bisphosphonates for osteopenic diseases in the general population. Radiation therapy or combined chemotherapy-radiation therapy regimens in the treatment of head and neck malignancies in these patients may cause osteonecrotic phenomenon of the jaws. Methods and materials: Over the course of approximately two and one half years (August 2005–January 2008) six patients presented to the dental clinic at Princess Margaret Hospital with clinically-atypical bone exposure developing spontaneously or following dental extractions. All were taking oral bisphosphonates. All had prior radiation treatment. Using the Princess Margaret dental database which records pertinent demographic and clinical data, a case–control study was undertaken. For each of the six bisphosphonate/ORN cases, seven controls were identified. The controls were within 7 years of the index age; treated within the same 5-year period; were the same gender; had the same cancer diagnosis at the same anatomic site, and were treated the same. Results: All cases had bone exposure and none of 42 controls had bone exposure. Only one of 42 controls was an oral bisphosphonate user. Curiously the incidence of this appears to be increasing with 5 of the 6 cases bone-exposure cases appearing within a 15 month period. Discussion: Based on this case–control study concomitant oral bisphosphonate use with head and neck radiation patients should be considered as a risk factor for osteonecrotic phenomenon. Further, since osteonecrosis of the jaw induced by bisphosphonate is refractory to treatment the differentiation of the two is important. doi:10.1016/j.oos.2009.06.326
P1.41. The GEN-VA-BO study (GENetic VAriants in Bisphosphonate-related Ostenecrosis of the jaws): A cooperation proposal S. Fedele *, S. Porter, F. D’aiuto, N. Donos, H. Ireland, S. Humphries University College London, United Kingdom University of Palermo, Italy Osteonecrosis of the jawbones is recently-reported complication of the use of bisphosphonates (BP). Because only a minority of BP users develop jaw necrosis, it is likely that one or more pre-existent susceptibility factors exist. Current knowledge of osteonecrosis of the jaws and other skeletal sites suggests that individual genetic predisposition may be related to the presence of polymorphisms of (i)
coagulation pathways (inherited thrombophilia), (ii) osteoblast and osteoclast signaling cascades, and (iii) cytochrome P450. However, these data come from small studies, are relevant to osteonecrosis of skeletal sites other than the jaw bones and are not always related to the use of BP. Therefore, there is a need to conduct further analyses on larger cohorts of patients. The GEN-VA-BO (GENetic VAriants in Bisphosphonate-related Ostenecrosis of the jaws) multicentre study is a case–control genetic study of blood specimens belonging to 800 individuals categorized into three groups (A, B, C). Group A (n = 200) is the test group which encompasses individuals with of BP-related jaw osteonecrosis. Group B (n = 300) and C (n = 300) are control groups consisting of individuals on BP therapy without osteonecrosis and healthy subjects respectively. The GEN-VA-BO started in 2009 and is scheduled to complete patient enrolment and gene analysis in 24–30 months. At present, a network of 14 clinical centres in Europe and Israel has been identified. However, collaboration with further clinical centres is needed in order to reach the planned number of participants and to eventually perform replication studies. The Second World Congress of the IAOO offers a unique opportunity to present the GEN-VA-BO study to the scientific community and identify new potential collaborators. We are particularly interested in clinical centres with cohort of at least 20 patients affected by BP-related jaw osteonecrosis and with ability to enrol matched controls. doi:10.1016/j.oos.2009.06.327
P1.42. Laser application in prevention and management of osteonecrosis related to bisphosphonates therapy: A preliminary study S. Capodiferro, E. Maiorano, G.P. Pilolli, G. Favia * University of Bari, Italy Introduction: Prevention of jaws osteonecrosis (JON) in patients taking bisphosphonates (BP) and the surgical management of JON related to BP therapy is still much debated. Laser capabilities in the sterilization, decontamination and bio-stimulation of oral tissues are, instead, generally accepted. For such reasons, we experimentally used diode and erbium:YAG laser both in prevention of JON in patient taking BP and needing oral surgery and in the surgical management of JON. Methods: 4 patients were included in this study; totally, we performed 9 teeth extractions in patients taking oral BP (2 during oral BP therapy, 6 after suspension at least for 3 months, and 1 after occurrence of JON of the mandible and subsequent suspension) and two surgical treatment of JON (1 of the anterior mandible and 1 of the tuber maxillae); the latter were treated with the following protocol: preoperative antibiotic therapy and biostimulation with diode laser, intraoperative treatment of the residual cavity after piezoelectric curettage with erbium:YAG laser and finally with simultaneous iodiopovidone solution and diode laser; postoperative biostimulation with diode laser. The extractions were performed during antibiotic therapy with a final treatment by erbium:YAG laser deeply inside the residual alveolar sockets followed by direct suture. Results: No occurrence of JON was obtained in all cases of tooth extraction. In the cases of JON, a complete healing of the covering mucosa was obtained in no more than 15 days. No recurrence was obtained. Discussion: Considering the missing of a standardized protocol both for prevention and surgical treatment of JON related to BP therapy, above all due to the presence of several variable factors (type, dose of BP and period of use, dimension of the lesion in close rela-
tionship to the occurrence sites, etc.) and good capabilities of laser in the sterilization and biostimulation of oral hard and soft tissue, we suggest that studies on larger cases could confirm our preliminary data. doi:10.1016/j.oos.2009.06.328
P1.43. Osteonecrosis of the jaws associated with the use of bisphosphonates: Radiological presentation O. Florence a,*, B. Denis b, B. Gaelle a,c, B. Anne-Gaelle a, G. René a a
Centre Léon Bérard, Lyon, France Clinique de l’ Europe, Lyon, France c Hopital Edouard Herriot, Lyon, France b
Introduction: The aim of the study is (1) to recall existing knowledge about pathophysiological aspects of osteonecrosis of the jaws associated with bisphosphonate therapy; (2) to describe the radiological presentation of the disease; and (3) to determine if a pathognomonic radiological feature can be identified. Materials and methods: This is a retrospective review of 15 patients (10 women and 5 men) treated with bisphosphonates for bone metastatic disease. Median age was 68.2 years. Panoramic radiograph of the jaw, maxillary CT scan and radionuclide imaging were reviewed by 2 radiologists. Results: The most frequent manifestations were osteolytic lesions. Many heterogeneous areas of both sclerosis and demineralisation were seen. A double cortical aspect was identified in one patient. Complications including fracture, oroantral fistula, and bone sequestrum were diagnosed. Discussion: Radiological features of osteonecrosis of the jaws remain aspecific. Nonetheless, when consistent with the clinical presentation, osteosclerosis associated with osteocondensation should suggest the diagnosis. Imaging can be used to establish the severity of the disease, especially to identify complications, and is crucial for making relevant treatment decisions. doi:10.1016/j.oos.2009.06.329
P1.44. Effects of Nd:YAP laser biostimulation over jawbone necrosis in oncologic patients G.A.E. Lescaille a,b,*, V. Descroix a,b, B. Ruhin-Poncet a, C. Escande a, R. Toledo a, J. Azerad a,b a b
GHPS, France University Paris 7, France
Introduction: Bisphosphonate-associated osteonecrosis of the jaws are recently described by Marx in 2003. These oral lesions are defined by exposed necrotic bone after more than 6 weeks, often preceded by a dental surgery but can also occur spontaneously. Most of cases have been developed with intravenous bisphosphonates treatment used to stabilize metastatic cancer, despite several osteonecrosis of the jaws cases related to oral bisphosphonates. The pathophysiology remains unelucidated but may be related to poor bone and blood vessel remodeling coinciding with local trauma to the maxilla or mandible. The greatest risk is associated with duration of IV bisphosphonate use, though long-term oral alendronate has also been implicated. No one singularly effective treatment exists, though results of this study suggest that medical, surgical treatment in association with the use of laser may offer a better chance for cure (Vescovi et al., 2007).
137
Patients and methods: We describe our preliminary results on 15 patients affected by bisphosphonate-associated osteonecrosis of the jaws who were treated conventionally with surgical, medical treatment in combination with neodimium:yttrium–aluminum–Perovsyit (Nd:YAP) laser. Clinical variables such as pain (with visual analog scale), presence of pus, and diminution of mucosal flaps before and after treatment (with photo and measure of area) were evaluated to establish the effect of the laser irradiation. Results: All patients improved durably their symptomatology after first laser biostimulation. We observed 5 total closures of flap and 10 significant reductions of size of the lesion after a few weeks. Discussion: Because bisphosphonates are one of the most prescribed drug worldwide, these data may reflect the importance of the possibility of ONJ and the necessity to develop effective therapeutic strategies. YAP laser biostimulation appears to be an attractive adjuvant therapy devoiced of adverse effect. doi:10.1016/j.oos.2009.06.330
P1.45. Bisphosphonate-related osteonecrosis of the jaw: Clinical series (45 patients) S. Salino *, A.G. Bodard, R. Gourmet Centre Léon Bérard, Lyon, France Bisphosphonates are indicated in the treatment of several malignant pathologies (multiple myeloma, bone metastases of solid tumors, malignant hypercalcemia, etc.), and in certain benign pathologies as well (osteoporosis, etc.). These medications’ efficacy is well documented, but certain incapacitating side effects can appear. Among them, osteonecrosis of the jaw (ONJ) has been described from 2003 on.1–3 ONJ is defined as the presence of exposed jaw-bone over an 8 week period of time at least, in a patient with actual or previous bisphosphonate treatment, and no previous maxillo-facial radiotherapy.3 Most ONJ appear on patients treated with IV bisphosphonates, after dental procedures such as teeth extractions.4 The management of ONJ can either be conservative5 or surgical,6 but there is no really established treatment. This is probably why most authors tend to insist more and more on ONJ prevention. Our experience is based on a series of 45 patients presenting a total of 65 ONJ taken care of between 2004 and 2008. According to the general and local clinical contexts and to the radiological situations, the management was either conservative or surgical or both successively. The objective of the presentation is to try and define some clinical and radiological parameters which could influence the management of ONJ. doi:10.1016/j.oos.2009.06.331 References 1. Khosla S, Coll. 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;22:1479–91. 2. Marx RE. Pamidronate (Aredia) and Zoledronate (Zometa) Induced Avascular Necrosis of the Jaws: a Growing Epidemic. J Oral Maxillofac Surg 2003;61:1115–7. 3. Kyle RA, Coll. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 2007;25:2464–72. 4. Boonyapakorn T, Coll. Bisphosphonate-induced osteonecrosis of the jaws: prospective study of 80 patients with multiple myeloma and other malignancies. Oral Oncol; 2008.
Poster Abstracts Oral AbstractsPoster ListOrals ListPan. Disc. & Symp. Abs.Keynote Abs.Keynote Bios.ProgramIAOOWelcomeCommittee Listings
Poster session I / Oral Oncology Supplement 3 (2009) 123–161