Ozonotherapy for Treatment of Radiation Therapy-induced Jaw Osteonecrosis and Bisphosphonates: Case Report / Ozonioterapia para o Tratamento de Osteonecrose em Mandíbula Induzida pela Radioterapia Associada com Bisfosfonato: Relato de Caso / Ozonoterapia para el Tratamiento de la Osteonecrosis de la Mordaza Inducida por Terapia de Radiación y Bisfosfonatos: Relato de Caso

Introduction: The inhibition of osteoclastic activity, associated with different treatment modalities in patients with head and neck cancer, make bones unable to respond to repair processes related to physiological traumas or infection and may result in bone necrosis. The present study aims to report a clinical case of osteoradionecrosis in mandible, and how its sequels were controlled by ozonotherapy. Case report: A 73-year-old female patient with infiltrative ductal breast carcinoma with mandibular metastasis was submitted to chemo and radiotherapy at head and neck region associated with bisphosphonate. Three years later, she was diagnosed with hemimandibular osteoradionecrosis that exhibited communication with oral cavity and with a chronic, suppurative and persistent associated infection. It was applied adjuvant therapy with ozone through the cutaneous fistula and the exposed and necrotic bone. Additionally, non-vital bone debridement was proceeded in two surgical steps. The patient is after a 1-year follow-up non-symptomatic. Conclusion: It is supposed that ozonotherapy, due to its antibacterial and immunoregulatory mechanism of action, was an important therapeutic agent for improving the patient's quality of life.

Introdução: A inibição da atividade osteoclástica, associada a diversas modalidades de tratamento utilizadas em pacientes com câncer de cabeça e pescoço, torna o osso incapaz de responder aos processos de reparo relacionados a traumas fisiológicos ou à infecção, e pode resultar em necrose óssea. O presente estudo tem como objetivo relatar um caso clínico de osteonecrose em mandíbula como consequência do uso de bisfosfonato associado à quimioterapia e à radioterapia para tratamento de câncer de mama com metástase para mandíbula, tendo suas sequelas controladas por meio do uso da ozonioterapia. Relato do caso: Paciente do sexo feminino, 73 anos, com história de carcinoma ductal infiltrante de mama com metástase óssea em mandíbula, a qual foi submetida ao tratamento de quimioterapia e radioterapia em região de cabeça e pescoço; três anos depois, foi diagnosticada com osteonecrose da hemimandíbula direita com exposição completa para a cavidade bucal e infecção crônica, supurativa e persistente. Foi realizada terapia adjuvante com aplicação de ozônio nas fístulas cutâneas e no remanescente ósseo exposto e necrosado, além do desbridamento dos sequestros ósseos em duas etapas cirúrgicas. Paciente encontra-se em acompanhamento há 1 ano, sem sintomatologia associada. Conclusão: Observou-se que a ozonioterapia, em razão da sua ação antibacteriana e cicatrizante, foi um importante agente terapêutico para a melhora da qualidade de vida da paciente.

Introducción: La inhibición de la actividad osteoclástica, asociada con las diversas modalidades de tratamiento utilizadas por los pacientes con cáncer de cabeza y cuello, hace que el hueso no pueda responder a los procesos de reparación relacionados con traumas o infecciones fisiológicas y puede provocar necrosis ósea. El presente estudio tiene como objetivo informar un caso clínico de osteonecrosis mandibular como consecuencia del uso de bisfosfonato asociado con quimioterapia y radioterapia para tartar el cáncer de mama con mandíbula metastásica, controlando sus secuelas mediante el uso de la terapia con ozono. Relato del caso: Paciente de 73 años con antecedentes de carcinoma ductal mamario infiltrante con metástasis en la mandíbula ósea fue sometida a quimioterapia y radioterapia en la región de la cabeza y el cuello. Tres años después, le diagnostica con osteonecrosis hemimandibular derecha con exposición completa a la cavidad oral e infección crónica, supurativa y persistente. La terapia adyuvante se realizó con la aplicación de ozono en las fístulas cutáneas y en el remanente óseo expuesto y necrótico, además del desbridamiento de los secuestros óseos en dos etapas quirúrgicas. El paciente ha estado bajo seguimiento durante 1 años in síntomas asociados. Conclusión: Debido a su acción antibacteriana y curativa, la ozonioterapia fue un importante agente terapéutico para mejorar la calidad de vida del paciente.

Medication-Related Osteonecrosis of the Jaw: An Autofluorescence-Guided Surgical Approach Performed with Er:YAG Laser.

OBJECTIVE: The aim of this study was to propose an autofluorescence (AF)-guided surgical approach performed with Er:YAG laser and Nd:YAG low-level laser therapy (LLLT). BACKGROUND DATA: Medication-related osteonecrosis of the jaw (MRONJ) therapy remains an unresolved problem. The proposed conservative and surgical treatment regimens are associated with contradictory success rates. However, the increased experience with MRONJ management suggests that surgical therapy can halt disease progression, and can allow a histology-based diagnosis of osteonecrosis. Surgical approach with Er:YAG laser is associated with significantly better results compared with medical treatment and traditional surgical approaches. One of the difficulties encountered during surgical removal of a MRONJ is the precise individuation of necrotic bone margins. PATIENT AND METHODS: A case of Stage III maxillary osteonecrosis treated with a new surgical approach is presented. RESULTS: After 7 months of follow-up, complete mucosal healing was evident, and the patient was free of symptoms. Such a technique allowed a highly accurate and minimally invasive approach through the selective ablation of the non-/hypofluorescent areas. CONCLUSIONS: Taking into account the advantages of laser therapy and the possible effectiveness of AF in highlighting surgical margins, this approach would probably achieve excellent outcomes.

Doxycycline fluorescence-guided Er:YAG laser ablation combined with Nd:YAG/diode laser biostimulation for treating bisphosphonate-related osteonecrosis of the jaw.

Laser therapy and fluorescence-guided surgery are highly reliable and predictable methods, but their combination has not been found to yield useful outcomes. We present a new therapeutic approach combining fluorescence-guided Er:YAG laser ablation with Nd:YAG/diode laser biostimulation for bisphosphonate-related osteonecrosis of the jaw (BRONJ). A woman was treated with zoledronic acid for bone metastasis from clear cell renal cell carcinoma and subsequently developed BRONJ in the left jaw. The management protocol included perioperative medical therapy (1% chlorhexidine gel, rifamycin, and doxycycline for 10 preoperative and 7 postoperative days), Er:YAG laser ablation guided by doxycycline fluorescence in vital bone under UV light, and Nd:YAG/diode laser biostimulation. The lesion regressed from stage 3 to stage 1 and showed nearly complete healing after laser therapy (3 and 23 cycles of ablation and biostimulation, respectively). These preliminary findings suggest the feasibility of the new approach, which is minimally invasive and biostimulative and causes very low morbidity.

Low-level laser therapy supported surgical treatment of bisphosphonate related osteonecrosis of jaws: a retrospective analysis of 11 cases.

OBJECTIVE: The aim of this study is to evaluate and report on low-level laser therapy (LLLT) supported medical-surgical treatment outcomes of 11 patients with bisphosphonate related osteonecrosis of the jaws (BRONJ) lesions. BACKGROUND DATA: BRONJ is a severe clinical condition, which adversely affects patients' lives. Even though various treatment modalities have been proposed, the ideal approach still remains to be debated. LLLT stands out among supportive approaches because of its favorable effects on tissue healing. MATERIALS AND METHODS: Eleven patients diagnosed with Stage II or III lesions (American Association of Oral and Maxillofacial Surgeons [AAOMS] classification) were included in the study. All patients received LLLT applications during the postoperative period in addition to medical and surgical treatment. Laser applications covering the entirety of the surgical site were performed with GaAlAs diode laser with the following parameters: 808 nm wavelength, 0.5 W power, continuous wave, noncontact mode at 0.5-1 cm distance from the oral mucosa, spot size 0.28 cm(2) (R=6 mm), for 3 sec per point (10 sec per cm(2)), and energy density of 5 J/cm(2) (energy per point,1.4 J). RESULTS: Elimination of previously recorded symptoms and a stable mucosal closure was achieved in all patients. Primary healing was achieved in seven patients and secondary healing course was observed in four patients. Permanence of obtained positive outcomes was noted in follow-up periods. CONCLUSIONS: Treatment of advanced BRONJ lesions with a combination of antibiotic therapy, surgical removal of the lesion, and consecutive low-level diode laser applications provided favorable results in all patients. In consideration of our findings, it can be assumed that LLLT may serve as a safe and effective adjunct to medical-surgical treatment of BRONJ lesions.

Laser GaAlAs (λ860 nm) photobiomodulation for the treatment of bisphosphonate-induced osteonecrosis of the jaw.

OBJECTIVE: The aim of this article is to report a case of bisphosphonate-induced osteonecrosis (ONJ-BP) of the jaw treated by curettage of the necrotic bone, low-level laser therapy (LLLT), and antibiotic therapy. BACKGROUND DATA: ONJ-BP is characterized by painful ulcerations of the oral mucosa, is prone to bone necrosis that does not heal within 8 weeks after diagnosis, and is often difficult to treat. No definitive standard of care has been established for ONJ-BP. LLLT improves wound healing, relieves pain, and appears to be a promising treatment modality for patients with ONJ-BP. MATERIALS AND METHODS: An 82-year-old man taking intravenous bisphosphonate presented with ONJ-BP after tooth extraction. The patient was treated by LLLT using a GaAlAs diode laser with the following settings: wavelength, 860 nm; 70 mW; continuous wave; and spot size 4 mm(2). An energy density of 4.2 J/cm(2) per point was applied in a punctual contact manner every 48 h for 10 days, in association with antibiotic therapy and curettage of the necrotic bone. Reduction in painful symptoms was reported after the second irradiation session, and tissue healing was complete at the end of the third week following oral curettage. The patient was followed up for 12 months and exhibited good oral healt and quality of life. CONCLUSIONS: The therapeutic protocol used in this study had a positive effect on tissue healing and remission of painful symptoms, resulting in better oral health and quality of life for the patient.

Association of laser phototherapy with PRP improves healing of bisphosphonate-related osteonecrosis of the jaws in cancer patients: a preliminary study.

The aim of this study was to compare retrospectively the effect of three different treatments on the healing outcome of bisphosphonate-related osteonecrosis of the jaws (BRONJ) in cancer patients. Twenty-two cancer patients were treated for BRONJ with one of the following protocols: clinical (pharmacological therapy), surgical (pharmacological plus surgical therapy), or PRP plus LPT (pharmacological plus surgical plus platelet rich plasma (PRP) plus laser phototherapy (LPT). The laser treatment was applied with a continuous diode laser (InGaAlP, 660 nm) using punctual and contact mode, 40 mW, spot size 0.042 cm(2), 6 J/cm(2) (6 s) and total energy of 0.24 J per point. The irradiations were performed on the exposed bone and surrounding soft tissue. The analysis of demographic data and risk factors was performed by gathering the following information: age, gender, primary tumor, bisphosphonate (BP) used, duration of BP intake, history of chemotherapy, use of steroids, and medical history of diabetes. The association between the current state of BRONJ (with or without bone exposure) and other qualitative variables was determined using the chi-square or Fisher's exact test. In all tests, the significance level adopted was 5%. Most BRONJ lesions occurred in the mandible (77%) after tooth extraction (55%) and in women (72%). A significantly higher percentage of patients reached the current state of BRONJ without bone exposure (86%) in the PPR plus LPT group than in the pharmacological (0%) and surgical (40%) groups after 1-month follow-up assessment. These results suggest that the association of pharmacological therapy and surgical therapy with PRP plus LPT significantly improves BRONJ healing in oncologic patients. Although prospective studies with larger sample sizes are still needed, this preliminary study may be used to inform a better-designed future study.

Bisphosphonate-related osteonecrosis: laser-assisted surgical treatment or conventional surgery?

Bisphosphonates (BSPs) are used for the treatment of multiple myeloma, metastatic breast and lung cancer, Paget's disease, osteoporosis, hypercalcemia due to malignancy, and many other skeletal diseases. BSPs reduce osteoclastic functions, which result in bone resorption. Bisphosphonates-related osteonecrosis of jaws (BRONJ) is a newly developed term that is used to describe the significant complication in patients receiving bisphosphonates. BSPs are known to exhibit an anti-angiogenetic effect that initiates tissue necrosis of the hard tissue. There is currently no consensus on the correct approach to this issue. The aim of this retrospective study is to compare the effects of laser surgery with biostimulation to conventional surgery in the treatment of BSP-induced avascular bone necrosis on 20 patients who have been treated in our clinic. BRONJ was evaluated in patients with lung, prostate, and breast cancer under intravenous BSP treatment. Twenty patients in this study developed mandibular or maxillary avascular necrosis after a minor tooth extraction surgery or spontaneously. Bone turnover rates were evaluated by serum terminal C-telopeptide levels (CTX) using the electrochemiluminescence immunoassay technique and patients were treated with laser or conventional surgical treatments and medical therapy. Ten patients were treated with laser surgery and biostimulation. An Er:YAG laser (Fotona Fidelis Plus II® Combine laser equipment, Slovenia) very long pulse (VLP) mode (200 mJ, 20 Hz) using a fiber tip 1.3 mm in diameter and 12 mm in length was used to remove the necrotic and granulation tissues from the area of avascular necrosis. Biostimulation was applied postoperatively using an Nd:YAG laser. Low-level laser therapy (LLLT) was applied to the tissues for 1 min from 4 cm distance using an Nd:YAG laser (Fotona-Slovenia) with a R24 950-µm fiber handpiece long-pulse (LP) mode, 0.25-W, 10 Hz power/cm(2) from the mentioned distance the spot size was 0.4 cm(2), and power output was 2.5 J. Energy density from the mentioned distance was calculated to be 6.25 J/cm(2). The other ten patients were treated with conventional surgery. Treatment outcomes were noted as either complete healing or incomplete healing. There were no statistically significant differences between laser surgery and conventional surgery (p > 0.05). CTX values also did not affect the prognosis of the patients. Treatment outcomes were significantly better in patients with stage II osteonecrosis than in patients with stage I osteonecrosis. Our findings suggest that dental evaluation of the patients prior to medication is an important factor in the prevention of BRONJ. Laser surgery is a beneficial alternative in the treatment of patients with this situation. Further randomized studies with larger patient numbers may also improve our understanding of treatment protocols for this situation.