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Outcome evaluation of fluorescence-guided bone resection for the treatment of bisphosphonate-related osteonecrosis of the jaw
21st ICOMS 2013—Abstracts: Oral Papers sis. But concerning pre-operative planning of BRONJ-procedures, the determination of the exact size of a lesion might be more valuable. Future investigations may lead to safer pre-operative criteria on the necessary extend of resection. Key words: bisphosphonate; BRONJ; cone-beam; computedtomography; radiology http://dx.doi.org/10.1016/j.ijom.2013.07.072 T3.OR013 Monitoring of bone turnover markers and bone scintigraphy for teriparatide therapy in bisphosphonate related osteonecrosis of the jaw Y. Ohbayashi ∗ , M. Miyake, T. Miki, F. Sawai, A. Iwasaki, Y. Matsui Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan Treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains an intractable problem in many cases. Recent literatures have shown that the new treatment modality using teriparatide may be beneficial to BRONJ. However, the teriparatide therapy was not effective in all cases. It would be necessary to assess the therapeutic effectiveness of teriparatide with predictable procedures to treat BRONJ. We report here two cases of BRONJ treated by adjunctive teriparatide therapy for 6 months while simultaneously performing the monitoring of changes of bone turnover markers and the quantitative assessment of bone scintigraphy. Six months after the combination of teriparatide and conservative treatment, CT showed evidence of bone regeneration and the intraoral wound was completely healed. Biochemical bone formation markers were monitored at the time points of 0, 1, 3 and 6 months. Almost of all the markers related to the bone formation and resorption revealed an increase during the teriparatide treatment. The uptake area and quantitative value of technetium-99m-methylene diphosphonate showed a reduction after the administration of teriparatide. It was strongly suggested that teriparatide therapy is one of the useful treatments for BRONJ based on monitoring bone turnover results and employing bone scintigraphy. http://dx.doi.org/10.1016/j.ijom.2013.07.073 T3.OR014 The role of bisphosphonate type, local concentration and acidic milieu in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw S. Otto ∗ , J. Schwager, M. Schieker, M. Ehrenfeld, C. Pautke Ludwig-Maximilians-University of Munich, Germany Background: Osteonecrosis of the jaw occurs in patients receiving high doses of intravenous nitrogen-containing bisphosphonates in the course of their supportive cancer therapy. The exact pathomechanisms are elusive and questions of paramount importance remain unanswered. Recent studies indicate toxic effects of bisphosphonates on different cell types, apart from osteoclast inhibition. Since multipotent stem cells and osteoblasts play important roles in the processes of wound healing and bone regeneration, the aim of this study was to investigate the effects of different bisphosphonate derivatives and dose levels combined with varying pH-levels on mesenchymal stem cells and osteoblasts in vitro.
1189
Materials and methods: The effect of two nitrogen containing bisphosphonates (zoledronate and ibandronate) and one non-nitrogen containing bisphosphonate (clodronate) on mesenchymal stem cells (hMSC) and osteoblasts (HOB) was tested at different concentrations of the two N-BPs and equimolar concentrations of clodronate at different pH-values (7.4, 6.7). Cell viability and activity was analyzed by WST-assay. Cell motility was investigated by means of scratch wound assays and visualized using time-lapse microscopy. Results: Zoledronate and ibandronate showed a dose- and pH-dependent cellular toxicity. Increasing concentrations of both N-BPs and acidic milieus led to a significant decrease in cell viability and activity (p < 0.01), with more pronounced effects for zoledronate. In contrast, equimolar concentrations of clodronate did not affect the cell survival or activity significantly, apart from the effect of pH reduction itself, which was also detectable in controls without bisphosphonates. Conclusion: We conclude that high concentrations of nitrogencontaining bisphosphonates and local inflammation associated pH changes might play a key role in the pathogenesis of ONJ in patients receiving high doses of nitrogen containing bisphosphonates due to malignant diseases. Key words: bisphosphonate; bisphosphonate-related osteonecrosis of the jaw; acadic milieu; pH http://dx.doi.org/10.1016/j.ijom.2013.07.074 T3.OR015 Outcome evaluation of fluorescence-guided bone resection for the treatment of bisphosphonate-related osteonecrosis of the jaw S. Otto ∗ , C. Pache, G. Mast, M. Ehrenfeld, C. Pautke Ludwig-Maximilians-University of Munich, Germany Background: Bisphosphonate-related osteonecrosis of the jaw has become a well known problem of rising clinical importance. The treatment is exceptionally hard. Fluorescence guided bone resection is a promising technique for the treatment of BRONJ. Therefore the aim of this study was to evaluate the outcome of fluorescence guided bone resection in the treatment of BRONJ. Patients and methods: Between 2009 and 2012 34 patients with 41 BRONJ lesions as well as 2 patients suffering from osteonecrosis under treatment with denosumab were treated using fluorescence guided bone resection (mainly stages II and III according to AAOMS 2009). The mean age of the 22 female and 14 male patients was 68.8 years (SD 10.6 years). Doxycycline 100 mg 1-0-1 orally was administered for 7–10 days preoperatively. Intraoperatively vital and necrotic bone areas were visualized using the Velscope system. Plastic wound closure was performed in every case. The treatment outcome was evaluated at the last check up (at least 3 months postoperatively). Results: 31/34 patients (91.2%) were free of symptoms and 37/41 (90.2%) of the BRONJ lesions showed complete mucosal healing as well as 2/2 patients suffering from osteonecrosis under treatment with denosumab. In 3/34 (8.8%) patients and 4/41 lesions due to BRONJ developed dehiscence and or bone exposure. Discussion: Fluorescence guided bone resection offers the opportunity to visualize vital and necrotic bone intraoperatively which is of crucial importance in order to remove the necrotic bone parts completely and in order to avoid the resection of vital bone parts. The treatment outcome stresses the value of this innovative technique in the treatment of BRONJ.
1190
21st ICOMS 2013—Abstracts: Oral Papers
Key words: fluoresecence guided bone resection; bisphosphonate; bisphosphonate related osteonecrosis of the jaw http://dx.doi.org/10.1016/j.ijom.2013.07.075
Hyperbaric oxygen as an adjuntive therapy in the treatment of bisphosphonate related osteonecrosis of the jaws C.A. Salcedo Gil 1,∗ , J.I. Iriarte Ortabe 1 , M.J. Pastor Fortea 1 , V. Lasa Menendez 1 , J.M. Batle Vidal 2
T3.OR016 Improving diagnosis of early bisphosphonate-related osteonecrosis of the jaws: schneiderian membrane thickening in a case-control study A. Pelaz García 1,∗ , L. Gallego López 1 , L.M. Gutiérrez 2 , J. Megías Barrera 2 , S. Costilla García 2
T3.OR017
Junquera
1
Cabue˜nes Hospital, Spain 2 Central University Hospital of Asturias, Spain Background and objetives: Bisphosphonates are antiresorptive drug fully accepted for the treatment of metastatic bone disease, osteoporosis and other bone diseases. In 2003, Marx published 36 patients with exposed bone of the jaws induced by bisphosphonates. Although Bisphosphonate-related Osteonecrosis of he Jaws’s (BONJ) diagnostic criteria proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS) excludes the use of imaging studies, is plenty accepted that imaging tests play a key role not only for the diagnosis itself, but also to define the extention of the affected bone. Methods: An observational case-control study was designed including patients diagnosed and treated by BONJ in the University Central Hospitall during 96 months. All cases showed the diagnostic criteria of the AAOMS. Control subjects included were healthy people who had never received bisphosphonates and belonged to the same geographic area and hospital than cases. Results: Seventy cases were identified, but only 32 cases included studies with Computed Tomography (CT). By gender, 10 patients were men and 22 women, with a mean age of 69.2 years. In 20 patients (62.5%) intravenously zoledronic acid was administred. The average time of bisphosphonate administration was 17.9 months. Mandibulatr involvement was found in 19 patients and stage II was the most common degree of the disease (18 cases). Schneiderian membrane thickening was objectified in 20 maxillary sinuses of 18 patients (56.3%) by CT and thirteen of these patients (40.6%) presented the Schneiderian membrane thickening without underlying bone exposure. In control subjects, Schneiderian membrane thickening of the mucosa was recognizable only 6 different subjects (18.8%). Conclusions: In our study, the thickening of the Schneiderian membrane is significantly more frequent in cases. The presence of this sign may be an early sign of involvement of BONJ and should be taken into consideration in further studies. Key words: bisphosphonate; osteonecrosis; Scheiderian membrane
1 Department of Oral and Maxillofacial Surgery, Hospital Universitari Son Espases, Spain 2 Hyperbaric and Underwater Research Institute, MEDISUB, Spain
Background and objectives: Since the first description of bisphosphonates related osteonecrosis of the jaw (BRONJ) made in 2003 there has been an increased number of cases described in the literature and it remains a difficult condition to treat. In the last few years the challenge has been to improve healing in BRONJ, and different adjunctive treatments have been advocated; hyperbaric oxygen (HBO2) has generated good results and an improvement of the quality of life in different case reports and series. We aim to validate these results. The objective of this study is to evaluate the beneficial effects of HBO2, as an adjunctive therapy, in the treatment of BRONJ, comparing our results with a thorough literature review. Methods: We analyzed 15 patients with BRONJ treated with HBO2 as an adjunctive therapy between January 2006 and January 2013 and compared them with 15 patients with BRONJ that had not received HBO2. We retrospectively studied gender, age, and localization of osteonecrosis, bisphosphonates indication, the number of HBO2 treatment, and the clinical and radiological behaviour of osteonecrosis when adjunctive therapy with HBO2 was used. Results: We observed a clinical improvement in the group of patients who presented with BRONJ when treated with HBO2 as an adjunctive therapy. The clinical outcome was statistically significant in the group of patients treated with HBO2 when we compared lesion stage and osteonecrosis stabilization; 2 patients had complete remission and the rest had long term satisfactory outcome. Conclusions: HBO2 as an adjunctive therapy benefits patients with BRONJ and this supports the results of other studies where HBO2 has shown potential benefits and should be considered as part of the routine treatment of BRONJ. Key words: bisphosphonates; osteonecrosis; hyperbaric oxygen http://dx.doi.org/10.1016/j.ijom.2013.07.077 T3.OR018 Surgical treatment of bisphosphonate-induced osteonecrosis of the jaws significantly reduces pain M. Schiodt 1,∗ , J. Rostgaard 1 , P. Oturai 2 , S. Steno 1 , T. Kofod 1
http://dx.doi.org/10.1016/j.ijom.2013.07.076
1
Department of Oral and Maxillofacial Surgery, Rigshospitalet, University Hospital of Copenhagen, Denmark 2 Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University Hospital of Copenhagen, Denmark Background and objectives: Treatment of bisphosphonate (BP)-induced osteonecrosis of the jaws (ONJ) varies from conservative to surgical and there exist no global consensus. Since 2010 we have used a systematic surgical approach. The objectives are to present the effect of surgical treatment of consecutive patients with ONJ.
1189
Materials and methods: The effect of two nitrogen containing bisphosphonates (zoledronate and ibandronate) and one non-nitrogen containing bisphosphonate (clodronate) on mesenchymal stem cells (hMSC) and osteoblasts (HOB) was tested at different concentrations of the two N-BPs and equimolar concentrations of clodronate at different pH-values (7.4, 6.7). Cell viability and activity was analyzed by WST-assay. Cell motility was investigated by means of scratch wound assays and visualized using time-lapse microscopy. Results: Zoledronate and ibandronate showed a dose- and pH-dependent cellular toxicity. Increasing concentrations of both N-BPs and acidic milieus led to a significant decrease in cell viability and activity (p < 0.01), with more pronounced effects for zoledronate. In contrast, equimolar concentrations of clodronate did not affect the cell survival or activity significantly, apart from the effect of pH reduction itself, which was also detectable in controls without bisphosphonates. Conclusion: We conclude that high concentrations of nitrogencontaining bisphosphonates and local inflammation associated pH changes might play a key role in the pathogenesis of ONJ in patients receiving high doses of nitrogen containing bisphosphonates due to malignant diseases. Key words: bisphosphonate; bisphosphonate-related osteonecrosis of the jaw; acadic milieu; pH http://dx.doi.org/10.1016/j.ijom.2013.07.074 T3.OR015 Outcome evaluation of fluorescence-guided bone resection for the treatment of bisphosphonate-related osteonecrosis of the jaw S. Otto ∗ , C. Pache, G. Mast, M. Ehrenfeld, C. Pautke Ludwig-Maximilians-University of Munich, Germany Background: Bisphosphonate-related osteonecrosis of the jaw has become a well known problem of rising clinical importance. The treatment is exceptionally hard. Fluorescence guided bone resection is a promising technique for the treatment of BRONJ. Therefore the aim of this study was to evaluate the outcome of fluorescence guided bone resection in the treatment of BRONJ. Patients and methods: Between 2009 and 2012 34 patients with 41 BRONJ lesions as well as 2 patients suffering from osteonecrosis under treatment with denosumab were treated using fluorescence guided bone resection (mainly stages II and III according to AAOMS 2009). The mean age of the 22 female and 14 male patients was 68.8 years (SD 10.6 years). Doxycycline 100 mg 1-0-1 orally was administered for 7–10 days preoperatively. Intraoperatively vital and necrotic bone areas were visualized using the Velscope system. Plastic wound closure was performed in every case. The treatment outcome was evaluated at the last check up (at least 3 months postoperatively). Results: 31/34 patients (91.2%) were free of symptoms and 37/41 (90.2%) of the BRONJ lesions showed complete mucosal healing as well as 2/2 patients suffering from osteonecrosis under treatment with denosumab. In 3/34 (8.8%) patients and 4/41 lesions due to BRONJ developed dehiscence and or bone exposure. Discussion: Fluorescence guided bone resection offers the opportunity to visualize vital and necrotic bone intraoperatively which is of crucial importance in order to remove the necrotic bone parts completely and in order to avoid the resection of vital bone parts. The treatment outcome stresses the value of this innovative technique in the treatment of BRONJ.
1190
21st ICOMS 2013—Abstracts: Oral Papers
Key words: fluoresecence guided bone resection; bisphosphonate; bisphosphonate related osteonecrosis of the jaw http://dx.doi.org/10.1016/j.ijom.2013.07.075
Hyperbaric oxygen as an adjuntive therapy in the treatment of bisphosphonate related osteonecrosis of the jaws C.A. Salcedo Gil 1,∗ , J.I. Iriarte Ortabe 1 , M.J. Pastor Fortea 1 , V. Lasa Menendez 1 , J.M. Batle Vidal 2
T3.OR016 Improving diagnosis of early bisphosphonate-related osteonecrosis of the jaws: schneiderian membrane thickening in a case-control study A. Pelaz García 1,∗ , L. Gallego López 1 , L.M. Gutiérrez 2 , J. Megías Barrera 2 , S. Costilla García 2
T3.OR017
Junquera
1
Cabue˜nes Hospital, Spain 2 Central University Hospital of Asturias, Spain Background and objetives: Bisphosphonates are antiresorptive drug fully accepted for the treatment of metastatic bone disease, osteoporosis and other bone diseases. In 2003, Marx published 36 patients with exposed bone of the jaws induced by bisphosphonates. Although Bisphosphonate-related Osteonecrosis of he Jaws’s (BONJ) diagnostic criteria proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS) excludes the use of imaging studies, is plenty accepted that imaging tests play a key role not only for the diagnosis itself, but also to define the extention of the affected bone. Methods: An observational case-control study was designed including patients diagnosed and treated by BONJ in the University Central Hospitall during 96 months. All cases showed the diagnostic criteria of the AAOMS. Control subjects included were healthy people who had never received bisphosphonates and belonged to the same geographic area and hospital than cases. Results: Seventy cases were identified, but only 32 cases included studies with Computed Tomography (CT). By gender, 10 patients were men and 22 women, with a mean age of 69.2 years. In 20 patients (62.5%) intravenously zoledronic acid was administred. The average time of bisphosphonate administration was 17.9 months. Mandibulatr involvement was found in 19 patients and stage II was the most common degree of the disease (18 cases). Schneiderian membrane thickening was objectified in 20 maxillary sinuses of 18 patients (56.3%) by CT and thirteen of these patients (40.6%) presented the Schneiderian membrane thickening without underlying bone exposure. In control subjects, Schneiderian membrane thickening of the mucosa was recognizable only 6 different subjects (18.8%). Conclusions: In our study, the thickening of the Schneiderian membrane is significantly more frequent in cases. The presence of this sign may be an early sign of involvement of BONJ and should be taken into consideration in further studies. Key words: bisphosphonate; osteonecrosis; Scheiderian membrane
1 Department of Oral and Maxillofacial Surgery, Hospital Universitari Son Espases, Spain 2 Hyperbaric and Underwater Research Institute, MEDISUB, Spain
Background and objectives: Since the first description of bisphosphonates related osteonecrosis of the jaw (BRONJ) made in 2003 there has been an increased number of cases described in the literature and it remains a difficult condition to treat. In the last few years the challenge has been to improve healing in BRONJ, and different adjunctive treatments have been advocated; hyperbaric oxygen (HBO2) has generated good results and an improvement of the quality of life in different case reports and series. We aim to validate these results. The objective of this study is to evaluate the beneficial effects of HBO2, as an adjunctive therapy, in the treatment of BRONJ, comparing our results with a thorough literature review. Methods: We analyzed 15 patients with BRONJ treated with HBO2 as an adjunctive therapy between January 2006 and January 2013 and compared them with 15 patients with BRONJ that had not received HBO2. We retrospectively studied gender, age, and localization of osteonecrosis, bisphosphonates indication, the number of HBO2 treatment, and the clinical and radiological behaviour of osteonecrosis when adjunctive therapy with HBO2 was used. Results: We observed a clinical improvement in the group of patients who presented with BRONJ when treated with HBO2 as an adjunctive therapy. The clinical outcome was statistically significant in the group of patients treated with HBO2 when we compared lesion stage and osteonecrosis stabilization; 2 patients had complete remission and the rest had long term satisfactory outcome. Conclusions: HBO2 as an adjunctive therapy benefits patients with BRONJ and this supports the results of other studies where HBO2 has shown potential benefits and should be considered as part of the routine treatment of BRONJ. Key words: bisphosphonates; osteonecrosis; hyperbaric oxygen http://dx.doi.org/10.1016/j.ijom.2013.07.077 T3.OR018 Surgical treatment of bisphosphonate-induced osteonecrosis of the jaws significantly reduces pain M. Schiodt 1,∗ , J. Rostgaard 1 , P. Oturai 2 , S. Steno 1 , T. Kofod 1
http://dx.doi.org/10.1016/j.ijom.2013.07.076
1
Department of Oral and Maxillofacial Surgery, Rigshospitalet, University Hospital of Copenhagen, Denmark 2 Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University Hospital of Copenhagen, Denmark Background and objectives: Treatment of bisphosphonate (BP)-induced osteonecrosis of the jaws (ONJ) varies from conservative to surgical and there exist no global consensus. Since 2010 we have used a systematic surgical approach. The objectives are to present the effect of surgical treatment of consecutive patients with ONJ.