Abstract

Background:

Osteoradionecrosis of the jaw (ORNJ) is the most severe and complex sequel of head and neck radiotherapy (RT) because of the bone involved, it may cause pain, paresthesia, foul odor, fistulae with suppuration, need for extra oral communication and pathological fracture. We treated twenty lesions of ORNJ using low-level laser therapy (LLLT) and antimicrobial photodynamic therapy (aPDT). The objective of this study was to stimulate the affected area to homeostasis and to promote the healing of the oral mucosa.

Methods:

We performed aPDT on the exposed bone, while LLLT was performed around the bone exposure (red spectrum) and on the affected jaw (infrared spectrum). Monitoring and clinical intervention occurred weekly or biweekly for 2 years.

Results:

100% of the sample presented clinical improvement, and 80% presented complete covering of the bone exposure by intact oral mucosa.

Conclusion:

LLLT and aPDT showed positive results as an adjuvant therapy to treat ORNJ.

Keywords:
Osteoradionecrosis; Oral cancer; Radiotherapy; Low-level laser therapy; Antimicrobial photodynamic therapy

Introduction

Cancer is as a major public health problem worldwide. In 2012 14.1 million new cases were diagnosed, with 8.2 million deaths and 32.6 million people living with cancer (considering the survival time of 5 years), and 22 million new cancer cases are estimated for 2030. Oral cancer is responsible for 300.000 new cases and 145.000 deaths⁹9- Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. IJC. 2015;136(5):E359-86.. Thus, this disease needs attention and research for the best practices in prevention and cure.

Treatments of oral cancer include surgery, radiotherapy (RT), chemotherapy or the combination of these methods, associated or not, all of them cause sequels to the patients. The chronic side effects on the oral cavity occur mainly because of impairments on cells and/or tissues, decreasing the capacity of bone repair, especially in the jaw. Infection or trauma may cause bone necrosis⁸8- Epstein JB, Thariat J, Bensadoun RJ, Barasch A, Murphy BA, Kolnick L, et al. Oral complications of cancer and cancer therapy: from cancer treatment to survivorship. CA Cancer J Clin. 2012;62(6):400-22.. The condition in which the irradiated bone is exposed to the oral cavity for at least three months is called osteoradionecrosis of the jaw (ORNJ). This condition occurs in the absence of tumor recurrence, tumor necrosis during RT or metastases in the bone²⁰20- O'Dell K, Sinha U. Osteoradionecrosis. Oral Maxillofac Surg Clin North Am. 2011;23(3):455-64.. Many risk factors may cause ORNJ¹⁸18- Niewald M, Fleckenstein J, Mang K, Holtrmann H, Spitzer WJ, Rübe C. Dental status, dental rehabilitation, procedures, demographic and oncological data as potential risk factors for infected osteoradionecrosis of the lower jaw after radiotherapy for oral neoplasms: a retrospective evaluation. Radiat Oncol. 2013;8:227.^,2121- Oh HK, Chambers MS, Martin JW, Lim HJ, Park HJ. Osteoradionecrosis of the mandible: treatment outcomes and factors influencing the progress of osteoradionecrosis. J Oral Maxillofac Surg. 2009;67(7):1378-86.^,2323- Raguse JD, Hossamo J, Tinhofer I, Hoffmeister B, Budach V, Jamil B, et al. Patient and treatment-related risk factors for osteoradionecrosis of the jaw in patients with head and neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;121(3):215-21.e1.

24- Rayatt SS, Mureau MA, Hofer SO. Osteoradionecrosis of the mandible: etiology, prevention, diagnosis and treatment. Indian J Plast Surg. 2007;40 Suppl:S65-71.^-2525- Ribeiro GH, Chrun ES, Dutra KL, Daniel FI, Grando LJ. Osteonecrosis of the jaws: a review and update in etiology and treatment. Braz J Otorhinolaryngol. Forthcoming 2017. doi: 10.1016/j.bjorl.2017.05.008.
https://doi.org/10.1016/j.bjorl.2017.05.... ^,2828- Schwartz HC, Kagan AR. Osteoradionecrosis of the mandible: scientific basis for clinical staging. Am J Clin Oncol. 2002;25(2):168-71., as shown in Figure 1.

ORNJ results from imbalance in the homeostasis of all tissues affected by head and neck RT²⁵25- Ribeiro GH, Chrun ES, Dutra KL, Daniel FI, Grando LJ. Osteonecrosis of the jaws: a review and update in etiology and treatment. Braz J Otorhinolaryngol. Forthcoming 2017. doi: 10.1016/j.bjorl.2017.05.008.
https://doi.org/10.1016/j.bjorl.2017.05.... . The pathophysiology is composed by three phases: (1) initial pre-fibrotic (injuries to endothelial cells due to reactive oxygen species caused by RT); (2) constitutive organized (continuous liberation of cytokines and reactive oxygen species causing abnormal fibroblastic activity); and (3) late fibro-atrophic process (start of a fragile tissue healing)⁵5- Delanian S, Porcher R, Rudant J, Lefaix JL. Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis. J Clin Oncol. 2005;23(34):8570-9.. There is no cure for established ORNJ, only clinical control, since the damage caused by head and neck RT is irreversible on the jaw²¹21- Oh HK, Chambers MS, Martin JW, Lim HJ, Park HJ. Osteoradionecrosis of the mandible: treatment outcomes and factors influencing the progress of osteoradionecrosis. J Oral Maxillofac Surg. 2009;67(7):1378-86..

Conventional treatments to ORNJ include non-surgical debridement²⁰20- O'Dell K, Sinha U. Osteoradionecrosis. Oral Maxillofac Surg Clin North Am. 2011;23(3):455-64., antibiotic therapy⁴4- Curi MM, Luciano LD. Osteoradionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases. J Oral Maxillofac Surg. 1997;55(6):540-4., hyperbaric oxygenation²⁸28- Schwartz HC, Kagan AR. Osteoradionecrosis of the mandible: scientific basis for clinical staging. Am J Clin Oncol. 2002;25(2):168-71., pentoxifylline-tocopherol-clodronate combination (PENTOCLO)²⁶26- Robard L, Louis MY, Blanchard D, Babin E, Delanian S. Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: preliminary results. Eur Ann Otorhinolaryngol Head Neck Dis. 2014;131(6):333-8., ultrasound¹⁰10- Harris M. The conservative management of osteoradionecrosis of the mandible with ultrasound therapy. Br J Oral Maxillofac Surg. 1992;30(5):313-8. and surgery²¹21- Oh HK, Chambers MS, Martin JW, Lim HJ, Park HJ. Osteoradionecrosis of the mandible: treatment outcomes and factors influencing the progress of osteoradionecrosis. J Oral Maxillofac Surg. 2009;67(7):1378-86.. Despite the numerous and well-reported therapeutic methods found in literature⁷7- El-Maghraby EMF, El-Rouby DH, Saafan AM. Assessment of the effect of low-energy diode laser irradiation on gamma irradiated rat's mandibles. Arch Oral Biol. 2013;58(7):796-805.^,1515- Martins MA, Martins MD, Lascala CA, Curi MM, Migliorati CA, Tenis CA, et al. Association of laser phototherapy with PRP improves healing of bisphosphonate-related osteonecrosis of the jaws in cancer patients: a preliminary study. Oral Oncol. 2012;48(1):79-84.^,1717- Minamisako MC, Ribeiro GH, Lisboa ML, Cordeiro MM, Grando LJ. Medication-related osteonecrosis of jaws: a low-level laser therapy and antimicrobial photodynamic therapy case approach. Case Rep Dent [Internet]. 2016[cited 2018 Jan 4];2016:6267406. Available from: http://dx.doi.org/10.1155/2016/6267406.
http://dx.doi.org/10.1155/2016/6267406... , there are no reports of the use of low-level laser therapy (LLLT) associated with antimicrobial photodynamic therapy (aPDT).

LLLT is associated with the increase of cellular metabolism through the activation of the mitochondrial respiratory chain, increasing the levels of ATP synthesis, cell proliferation, protein synthesis and angiogenesis, which are essential for wound healing¹²12- Kuffler DP. Photobiomodulation in promoting wound healing: a review. Regen Med. 2016;11(1):107-22.. LLLT also causes an analgesic effect, by inhibiting electrophysiological activity on the nerves, altering the release of neurotransmitters that are associated with pain relief, improving lymphatic flow, among others³3- Chow R. Low level laser therapy - mechanism of action: Analgesia. In: Lasers in Dentistry: Guide for clinical practice. Weinheim: Wiley-Blackwell; 2015. p. 34-9.. The aPDT acts on exogenous photoreceptors, promoting the interaction of the light with a photosensitizer, producing reactive oxygen species, which causes microbial reduction²2- Chavantes MC, Ribeiro MS, Pinto NC. Low power lasers: Introduction. In: Freitas PM, Simões A, editors. Lasers in Dentistry: Guide for clinical practice. Weinheim: Wiley-Blackwell; 2015. p. 19-22.. Moreover, its antimicrobial action does not cause bacterial resistance or microbial selection²⁷27- Rosa LP, Silva FC, Nader SA, Meira GA, Viana MS. Effectiveness of antimicrobial photodynamic therapy using a 660 nm laser and methyline blue dye for inactivating Staphylococcus aureus biofilms in compact and cancellous bones: an in vitro study. Photodiagnosis Photodyn Ther. 2015;12(2):276-81..

By reducing pain, improving the wound healing process and eliminating the opportunistic microorganisms, the use of both therapies allow the patient to continue the cancer treatment, while preserving his/her basic oral functions, such as eating, drinking, swallowing and talking. Thus, the patient is more likely to maintain a good general health status, better responding to the treatment for ORNJ. Additionally, these therapies are non-invasive, atraumatic and no significant adverse effects associated with them are reported in literature²⁹29- Simões A, Eduardo FP, Luiz AC, Campos L, Sá PH, Cristófaro M, et al. Laser phototherapy as topical prophylaxis agains head and neck cancer radiotherapy-induced oral mucositis: comparison between low and high/low power lasers. Lasers Surg Med. 2009;41(4):264-70..

Thus, the objective of this study was to assess the clinical effects of LLLT and aPDT to treat ORNJ in patients who underwent head and neck RT, as well as to propose an adjuvant treatment protocol to the pathology.

Materials and methods

This is a prospective analytic experimental study. All procedures were performed at the Dentistry Center of the University Hospital of the Federal University of Santa Catarina and were in accordance with the ethical standards of the Institutional Research Committee (no. 724.398, from July/2014) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Sample and classification of ORNJ

The inclusion criteria were patients aged over 18 years, of both sexes, who underwent head and neck RT and developed ORNJ, and who agreed with the informed consent form. The exclusion criteria were patients who developed osteonecrosis of the jaw, underage, who abandoned treatment or who did not sign the informed consent. We examined patients undergoing head and neck RT, with or without surgery and/or chemotherapy, due to cancer and primary tumor or metastasis in this area (oral cavity, oropharynx, nasopharynx and hypopharynx). The sample consisted of 20 ORNJ lesions (n=20), 6 in maxilla and 14 in mandible, which were evaluated weekly or biweekly for 2 years. The appointments depended on the availability of the patients. ORNJ lesions were graded using a clinical and imaging classification adapted from He, et al.¹¹11- He Y, Liu Z, Tian Z, Dai T, Qiu W, Zhang Z. Retrospective analysis of osteoradionecrosis of the mandible: Proposing a novel clinical classification and staging system. Int J Oral Maxillofac Surg. 2015;44(12):1547-57. (2015). The imaging parameters (B = bone necrosis) and the clinical parameters (S = soft tissue) are shown in Figure 2.

LLLT and aPDT protocol for ORNJ

We used a laser device (Therapy XT^® - Diode laser nm, DMC, São Carlos, SP, Brazil) at λ660 nm (red spectrum) and λ808 nm (infrared spectrum), with fixed power of 100 mW. We used the red LLLT first and the aPDT after, these therapies were performed only in cases of bone exposure and/or infection. Infrared LLLT was performed imperatively, even when there was no infection or exposed bone, this procedure was performed on the interval between red LLLT and aPDT (time pre-irradiation, in which methylene blue 0.01% was used to stain the area related to bone exposure) (Table 1). The number of LLLT sessions varied for each patient, depending on the severity of the ORNJ lesion, availability of the patient for treatment and when he/she started to be treated.

Statistical analysis

Data were analyzed using the software SPSS Statistics Version 24.0. We performed a descriptive analysis considering epidemiological features and clinical characteristics of ORNJ, and outcomes obtained through LLLT and aPDT. We performed the Chi-Square Test to verify the association between ORNJ stages and healing of the injured oral mucosa by treatment with LLLT and aPDT. The level of significance adopted was 5% (p<0.05).

Results

The sample consisted of patients from 40 to 71 years old, the mean age was of 59.1 years. Men presented a much higher prevalence of ORNJ lesions than women, with a ratio of 9:1 cases. Only one patient had melanoderma (5%), the other patients had leukoderma (95%). When asked about drugs, most patients (85%) mentioned smoking and drinking (Table 2). There were no reports of use of illicit drugs.

We could not establish a standardized RT protocol since all patients underwent head and neck RT under distinct protocols, due to being treated at different RT treatment centers.

The minimum radiation dose each patient received was 66Gy and the maximum was 92Gy, with mean total radiation dose of 72Gy. However, on five cases (25%) ORNJ was developed by receiving a total radiation dose above the mean, these patients did not reach stage III. All cases of ORNJ stage III occurred after 24 months. Half the patients presented the first ORNJ lesions within 24 months after the start of RT while the other half presented lesions after this period. Regarding where the ORNJ lesions occurred, we confirmed higher percentages on the mandible (70%). The lesions on the mandible were uniformly distributed for both the posterior (50%) and anterior (50%) regions, while the maxilla was predominantly affected on the posterior region (83.3%). The absence or presence of clinical findings such as extra oral communication, fistula with suppuration, pain and paresthesia were also assessed and are described on Table 2.

All ORNJ lesions were classified as stage I (Figure 3a), stage II (Figure 3b) or stage III (Figure 3c and 3d) to promote the most appropriate and efficient approach. No lesion was diagnosed as stage 0. Eight lesions were identified as stage I (40%), 7 as stage II (35%) and 5 as stage III (25%). After the classifying the lesions the treatment and monitoring began. Every patient was instructed on the need to maintain good oral health, hygiene of dental prostheses and regular flossing when indicated. Another standard measure was the prescription of chlorhexidine gluconate 0.12% to be used as mouth wash for 1 minute after regular oral hygiene, twice a day and continuously, regardless of the stage.

We chose some variables to analyze the therapy response to LLLT and aPDT. Stage I lesions received the most LLLT (both infrared and red spectra) sessions, while stage III received the most aPDT sessions. One of the cases of ORNJ stage I was submitted to 44 infrared spectrum LLLT sessions, 25 red spectrum LLLT sessions and 23 aPDT sessions while these numbers were 9, 11 and 21 for ORNJ stage II and 27, 16 and 38 for ORNJ stage III, respectively. The anterior mandible was the most irradiated region by LLLT and the posterior mandible was the region by aPDT. The posterior maxilla was the least irradiated region by both treatments.

Regarding the total radiation dose received during cancer treatment, the patients who underwent head and neck RT over 72Gy needed fewer sessions of LLLT and aPDT. Despite most patients receiving radiation doses lower than 72Gy, in some cases it was necessary to quadruple the infrared spectrum LLLT sessions and to triple both red spectrum LLLT and aPDT sessions to achieve better results. Similar findings were observed on the period between RT and the first record of ORNJ. Cases that presented ORNJ stages I and II within the first 24 months demanded almost twice as many LLLT sessions when compared to those who diagnosed after this period. However, a greater number of aPDT sessions were required to treat ORNJ stage III, after 24 months of the ending of RT.

LLLT and aPDT were applied multiple times during the 2 years of follow-up. In total, lesions stage I received 229 infrared spectrum LLLT, 137 red spectrum LLLT and 152 aPDT sessions. For stage II and stage III lesions we performed 83, 35 and 49 sessions and 83, 48 and 118 sessions, respectively. Considering only the cases in which there was complete remission of the ORNJ lesion, on average, it took 34.38 sessions and 17 weeks to treat ORNJ stage I, 16.17 sessions and 8 weeks to treat ORNJ stage II, and 39 sessions and 19 weeks to treat ORNJ stage III.

There was clinical improvement in 100% of the ORNJ lesions. The criteria for improvement of the clinical condition were the remission of fistulae, absence of necrosis on bone exposure, control of infections by the absence of pain, no suppuration or paresthesia, as well as the partial or total repair of the oral tissue. These effects were observed after both treatments. LLLT and aPDT were clinically effective in all cases, and in most of them (80%) the oral mucosa was fully coated (Table 3), reducing microbial contamination and avoiding the possibility of opportunistic infections through the oral cavity. The other lesions (20%) not completely healed (n=4) were classified mainly as ORNJ stage III (n=3).

Discussion

ORNJ is a severe and complex sequel of head and neck RT that may cause deep biological, sociological and psychological impacts on the quality of life of patients. Despite ORNJ being a controllable, but not curable disease, we note that even for the most severe lesions, the results obtained with the proposed treatments exceeded our expectations (Figure 4), since the beneficial effects (absence of pain, elimination of infection and suppuration, oral mucosa repair) were observed immediately after the initial sessions. Thus, the use of LLLT, with or without aPDT, can provide excellent results to control the disease, regardless of the stage.

The results of identification and characterization of the sample for this study were similar to those already established in global literature: oral cancer is more frequent starting at 50 years old; it affects more men than women and may even exceed the ratio of 5:1 cases; leukoderma patients are more affected when compared to other ethnic groups; smoking and drinking are extremely harmful habits, which may trigger or enhance the disease¹⁴14- Losi-Guembarovski R, Menezes RP, Poliseli F, Chaves VN, Kuasne H, Leichsenring A, et al. Oral carcinoma epidemiology in Paraná State, Southern Brazil. Cad Saude Publica. 2009;25(2):393-400.. According to literature, the radiation dose related to ORNJ is 70Gy¹⁶16- Marx R. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg. 1983;41(5):283-8.^,2424- Rayatt SS, Mureau MA, Hofer SO. Osteoradionecrosis of the mandible: etiology, prevention, diagnosis and treatment. Indian J Plast Surg. 2007;40 Suppl:S65-71.^,2828- Schwartz HC, Kagan AR. Osteoradionecrosis of the mandible: scientific basis for clinical staging. Am J Clin Oncol. 2002;25(2):168-71.. Therefore, the mean radiation dose of 72Gy observed in this study was capable of inducing ORNJ, however, some patients developed ORNJ with lower doses.

Regarding the time to develop ORNJ, He, et al.¹¹11- He Y, Liu Z, Tian Z, Dai T, Qiu W, Zhang Z. Retrospective analysis of osteoradionecrosis of the mandible: Proposing a novel clinical classification and staging system. Int J Oral Maxillofac Surg. 2015;44(12):1547-57. (2015) reported that 68% of the patients developed ORNJ within 24 months. In contrast, Notani, et al.¹⁹19- Notani K, Yamazaki Y, Kitada H, Sakakibara N, Fukuda H, Omori K. et al. Management of mandibular osteoradionecrosis corresponding to the severity of osteoradionecrosis and the method of radiotherapy. Head Neck. 2003;25(3):181-6. (2003) obtained a mean of 27.7 months, Oh, et al.²¹21- Oh HK, Chambers MS, Martin JW, Lim HJ, Park HJ. Osteoradionecrosis of the mandible: treatment outcomes and factors influencing the progress of osteoradionecrosis. J Oral Maxillofac Surg. 2009;67(7):1378-86. (2009) 30 months and D'Souza, et al.⁶6- D'Souza J, Goru J, Goru S, Brown J, Vaughan ED, Rogers SN. The influence of hyperbaric oxygen on the outcome of patients treated for osteoradionecrosis: 8 year study. Int J Oral Maxillofac Surg. 2007;36(9):783-7. (2007) 48 months. Despite some studies pointing means that exceed 24 months, we believe that this disease will become increasingly frequent in patients who underwent head and neck RT, which is what the most recent studies³3- Chow R. Low level laser therapy - mechanism of action: Analgesia. In: Lasers in Dentistry: Guide for clinical practice. Weinheim: Wiley-Blackwell; 2015. p. 34-9.^,1313- Lee IJ, Koom WS, Lee CG, Kim YB, Yoo SW, Keum KC, et al. Risk factors and dose-effect relationship for mandibular osteoradionecrosis in oral and oropharyngeal cancer patients. Int J Radiat Oncol Biol Phys. 2009;75(4):1084-91.^,2323- Raguse JD, Hossamo J, Tinhofer I, Hoffmeister B, Budach V, Jamil B, et al. Patient and treatment-related risk factors for osteoradionecrosis of the jaw in patients with head and neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;121(3):215-21.e1.^,2525- Ribeiro GH, Chrun ES, Dutra KL, Daniel FI, Grando LJ. Osteonecrosis of the jaws: a review and update in etiology and treatment. Braz J Otorhinolaryngol. Forthcoming 2017. doi: 10.1016/j.bjorl.2017.05.008.
https://doi.org/10.1016/j.bjorl.2017.05.... indicate. Several authors point the posterior mandible as the region most commonly affected by ORNJ, since the blood supplied to the mandible comes through the inferior alveolar artery, which is a facial artery and is significantly lower than the maxilla²³23- Raguse JD, Hossamo J, Tinhofer I, Hoffmeister B, Budach V, Jamil B, et al. Patient and treatment-related risk factors for osteoradionecrosis of the jaw in patients with head and neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;121(3):215-21.e1.^,2424- Rayatt SS, Mureau MA, Hofer SO. Osteoradionecrosis of the mandible: etiology, prevention, diagnosis and treatment. Indian J Plast Surg. 2007;40 Suppl:S65-71.. Furthermore, the cortical bone from the premolar to retromolar regions is considered the most vulnerable area to ORNJ. This region receives higher radiation doses during cancer treatment due to the greater bone density²⁰20- O'Dell K, Sinha U. Osteoradionecrosis. Oral Maxillofac Surg Clin North Am. 2011;23(3):455-64..

The treatment for ORNJ requires a broad spectrum of processes such as patient education regarding oral hygiene and harmful habits (smoking and drinking)²³23- Raguse JD, Hossamo J, Tinhofer I, Hoffmeister B, Budach V, Jamil B, et al. Patient and treatment-related risk factors for osteoradionecrosis of the jaw in patients with head and neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;121(3):215-21.e1., non-surgical debridement (sequestrectomy)²⁰20- O'Dell K, Sinha U. Osteoradionecrosis. Oral Maxillofac Surg Clin North Am. 2011;23(3):455-64., mouthwash with chlorhexidine gluconate 0.12%²¹21- Oh HK, Chambers MS, Martin JW, Lim HJ, Park HJ. Osteoradionecrosis of the mandible: treatment outcomes and factors influencing the progress of osteoradionecrosis. J Oral Maxillofac Surg. 2009;67(7):1378-86., long-term antibiotic therapy⁴4- Curi MM, Luciano LD. Osteoradionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases. J Oral Maxillofac Surg. 1997;55(6):540-4., hyperbaric oxygenation²⁸28- Schwartz HC, Kagan AR. Osteoradionecrosis of the mandible: scientific basis for clinical staging. Am J Clin Oncol. 2002;25(2):168-71., ultrasound¹⁰10- Harris M. The conservative management of osteoradionecrosis of the mandible with ultrasound therapy. Br J Oral Maxillofac Surg. 1992;30(5):313-8., PENTOCLO combination⁵5- Delanian S, Porcher R, Rudant J, Lefaix JL. Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis. J Clin Oncol. 2005;23(34):8570-9.^,2626- Robard L, Louis MY, Blanchard D, Babin E, Delanian S. Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: preliminary results. Eur Ann Otorhinolaryngol Head Neck Dis. 2014;131(6):333-8. and extensive surgery⁶6- D'Souza J, Goru J, Goru S, Brown J, Vaughan ED, Rogers SN. The influence of hyperbaric oxygen on the outcome of patients treated for osteoradionecrosis: 8 year study. Int J Oral Maxillofac Surg. 2007;36(9):783-7.^,2121- Oh HK, Chambers MS, Martin JW, Lim HJ, Park HJ. Osteoradionecrosis of the mandible: treatment outcomes and factors influencing the progress of osteoradionecrosis. J Oral Maxillofac Surg. 2009;67(7):1378-86.. The prescription of each therapeutic modality is individualized and some of them are controversial, however, all require long periods of intervention and none of them is definitive. For these reasons patients with ORNJ must be regularly monitored due to the high risk of disease progression. Proposing the use of LLLT and aPDT to treat ORNJ is grounded on the properties of these therapies and supported by metabolism-activating effects on bone, mucosa and tissues, both very well documented in literature²2- Chavantes MC, Ribeiro MS, Pinto NC. Low power lasers: Introduction. In: Freitas PM, Simões A, editors. Lasers in Dentistry: Guide for clinical practice. Weinheim: Wiley-Blackwell; 2015. p. 19-22.^,33- Chow R. Low level laser therapy - mechanism of action: Analgesia. In: Lasers in Dentistry: Guide for clinical practice. Weinheim: Wiley-Blackwell; 2015. p. 34-9.^,1212- Kuffler DP. Photobiomodulation in promoting wound healing: a review. Regen Med. 2016;11(1):107-22.^,2727- Rosa LP, Silva FC, Nader SA, Meira GA, Viana MS. Effectiveness of antimicrobial photodynamic therapy using a 660 nm laser and methyline blue dye for inactivating Staphylococcus aureus biofilms in compact and cancellous bones: an in vitro study. Photodiagnosis Photodyn Ther. 2015;12(2):276-81.^,2929- Simões A, Eduardo FP, Luiz AC, Campos L, Sá PH, Cristófaro M, et al. Laser phototherapy as topical prophylaxis agains head and neck cancer radiotherapy-induced oral mucositis: comparison between low and high/low power lasers. Lasers Surg Med. 2009;41(4):264-70..

The effectiveness of LLLT is supported by studies that point the effects of the therapy on the healing process of the oral mucosa by reducing the exudative phase, stimulating the healing process and by inducing the proliferation and transformation of fibroblasts and myofibroblasts¹1- Bayat M, Vasheghani MM, Razavi N. Effect of low-level helium-neon laser therapy on the healing of third-degree burns in rats. J Photochem Photobiol B. 2006;83(2):87-93.. The therapy also increases the blood flow by angiogenesis through revascularization and capillary growth²²22- Pessoa ES, Melhado RM, Theodoro LH, Garcia VG. A histologic assessment of the influence of low-intensity laser therapy on wound healing in steroid-treated animals. Photomed Laser Surg. 2004;22(3):199-204.. The acceleration of the tissue repair process occurs due to the release of growth factors (TGF, PDGF, FGF-β, IL6, IL8, IL1-α) that accelerate the formation and deposition of collagen type I and III³⁰30- Woodruff LD, Bounkeo JM, Brannon WM, Dawes KS, Barham CD, Waddell DL, et al. The efficacy of laser therapy in wound repair: a meta-analysis of the literature. Photomed Laser Surg. 2004;22(3):241-7. and by eliminating infections through antimicrobial aPDT action²⁹29- Simões A, Eduardo FP, Luiz AC, Campos L, Sá PH, Cristófaro M, et al. Laser phototherapy as topical prophylaxis agains head and neck cancer radiotherapy-induced oral mucositis: comparison between low and high/low power lasers. Lasers Surg Med. 2009;41(4):264-70..

According to the results of this study, we found that aPDT applied directly to an exposed bone with suppuration can be beneficial to control infected ORNJ lesions. Furthermore, we observed the remission of ORNJ and partial or total repair of the oral mucosa. Therefore, we can claim that LLLT and aPDT were essential to the success of disease control, reinforcing the importance of its applicability and indication.

Conclusion

The results of this study suggest that LLLT and aPDT as a new treatment of ORNJ brought important benefits to the patients, assisting on the clinical management of the disease.

The new therapeutic approach proposed led to a decrease on the stage of ORNJ lesions, acting as an adjuvant treatment within a set of clinical maneuvers, bringing beneficial effects to control the disease and improving the quality of life of the patients. All patients in the sample benefited from the new treatment performed.

Based on our results, we recommend the use LLLT, in both red and infrared spectra, and aPDT as an adjuvant treatment of ORNJ. We suggest further research to obtain more relevant data on the action of LLLT and aPDT to treat ORNJ lesions.

Ethics in Science

The manuscript has not been submitted to more than Journal of Applied Oral Science for simultaneous consideration. The material has not been published previously (partly or fully). This study is not split up into several parts to increase the quantity of submissions and submitted to various journals or to one journal over time. No data have been fabricated or manipulated (including images) to support our conclusions.

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (n.724.398, from July/2014) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed Consent

All participants of this study provided consent

Acknowledgements

The authors thank all patients who agreed to participate in this study and graduate Dentistry students who helped the researchers during the assistances.

References

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