Acta Scientific Dental Sciences

Case Report Volume 1 Issue 1

Oral Bisphosphonate Related Osteonecrosis of Jaws (BRONJ): A Case Report

Pravesh Kumar Jhingta1*, Deepak Sharma1, Vinay Kumar Bhardwaj2, Sanjeev Vaid3, Nishant Negi 3, and Divya Kashyap 1

1Department of Periodontology, HP Govt. Dental College and Hospital, Shimla, India
2Department of Public Health Dentistry, HP Govt. Dental College and Hospital, Shimla, India
3Department of Orthodontics and dentofacial orthopaedics, HP Govt. Dental College and Hospital, Shimla, India

*Corresponding Author:Dr. Pravesh Jhingta, Assistant Professor, Department of Periodontology, HP Govt. Dental College and Hospital, Shimla-171001, India.

Received: May 12, 2017; Published: June 26, 2017

Citation: Pravesh Jhingta., et al. “Oral Bisphosphonate Related Osteonecrosis of Jaws (BRONJ): A Case Report”. Acta Scientific Dental Sciences 1.1 (2017).

Abstract

Introduction:Bisphosphonates (BPs) are synthetic analogue of inorganic pyrophosphates, which exert an inhibitory effect on osteoclast activity. Intravenous (IV) BPs are primarily used and effective in the treatment and management of cancer-related conditions including hypercalcemia of malignancy. One of the serious adverse effects of bisphosphonate therapy is bisphosphonate-related osteonecrosis of the jaw (BRONJ). This is necrosis of the jaw bones persisting for more than 6 to 8 weeks, refractory to conservative treatment, observed in patients having no history of prior radiotherapy in the affected area, but treated with bisphosphonates - in - travenously for at least one year, or orally for a much longer period.

Case report:We present an uncommon case of oral bisphosphonate related osteonecrosis of jaw in maxilla and mandibular right posterior region in a female patient age 40 years and who had undergone treatment for breast carcinoma.

Discussion:Patients’ education in terms of the symptoms and initial signs of BRONJ is essential because if timely diagnosed, outcomes of treatments are favourable. Another important factor in prevention and treatment of BRONJ is the awareness among the physicians, regarding the potential risk of developing BRONJ in patients on BPs. Thus a better collaboration among the physicians and dentists would help immensely in decreasing the discomfort of the patient and thus in improving his quality of life.

Keywords: Bisphosphonate; BRONJ; Dentoalveolar; procedures; necrotic bone

Introduction

   Bisphosphonates (BPs) are synthetic analogue of inorganic pyrophosphates, which exert an inhibitory effect on osteoclast activity. Two classes of BPs are in clinical use today: a less potent group of non-nitrogen containing molecules (etidronate and clodronate) and a newer class of very potent agents that contain a nitrogen moiety (pamidronate, zoledronic acid, alendronate, risedronate, ibandronate and others) [1] .

   Intravenous (IV) BPs are primarily used and effective in the treatment and management of cancer-related conditions including hy - percalcemia of malignancy, skeletal-related events associated with bone metastases in the context of solid tumours and management of lytic lesions in the setting of multiple myeloma. Oral BPs are approved to treat osteoporosis and are frequently used to treat osteopenia as well. They are also used for Paget’s disease of bone, and osteogenesis imperfect of childhood [1] . Besides bone effects the nitrogen-BPs have anti tumoral and anti angiogenesis properties, which make them very important drugs in the treatment of primary and sec¬ondary bone oncologic disease [2] .

   One of the serious adverse effects of bisphosphonate therapy is bisphosphonate-related osteonecrosis of the jaw (BRONJ). This is necrosis of the jaw bones persisting for more than 6 to 8 weeks, refractory to conservative treatment, observed in patients having no his - tory of prior radiotherapy in the affected area, but treated with bisphosphonates - intravenously for at least one year, or orally for a much longer period, in relation to a general disease characterized by bone resorption [3] . The incidence of BRONJ remains undefined and it ranges from 0.8 to 12% for i.v. preparations [4-6] ; the incidence for oral preparations ranges from 0.01 to 0.04% [7] .

Case Report

   A female patient aged 40, was referred from the department of oncology, regional cancer centre, Indira Gandhi Medical College and Hospital Shimla to the department of periodontology, H.P. Government College and college and hospital Shimla, with the complaint of pain in the right upper and lower back regions of the mouth and discomfort while eating for the last 2 months. The patient had under - gone surgery, chemotherapy and radiotherapy 15 months ago for the treatment of carcinoma of left breast. Eight months after the com - pletion of treatment, the patient started complaining of skeletal pains in the left arm. A bone scan was carried out to rule out any bony metastasis and was found to be negative. Oral BPs (Tab Ibandronate 50 mg OD) was prescribed for the prevention of bone metastasis for past 6 months. On intra oral examination, scrapable curdy white lesions surrounded by erythamatous halo measuring 2 cm x 1 cm in right maxillary molars regions palatally w.r.t. 16,17,18 (Figure 1) and 1.5 cm x 1 cm in the right mandibular molar region lingually w.r.t. 46,47,48 (Figure 2) were present. On scraping the lesions, yellow denuded bone was visible with irregular and crusted margins (Figure 3). The teeth 18, 48, 16 and 17 were grade 3 mobile and tender on percussion.

Figure 1:

Figure 1:

Figure 2:

Figure 2:

Figure 3:

Figure 3:

   The patient diagnosed with BRONJ was managed conservatively. The curdy white lesions were gently scraped off, the histopathology examination of which showed it to be a candida growth. The differential diagnosis of BRONJ include, but are not limited to, avascular osteitis, osteomyelitis, osteoradionecrosis, sinusitis, gingivitis, periodontitis, caries, periapical pathology and temporomandibular disorders. Some of these conditions, such as periodontitis and periapical pathology could also contribute to the development of BRONJ in patients at risk. Osteoporosis may resemble BRONJ, presenting with an area of denuded avascular bone. However, osteoporosis can easily be differentiated from BRONJ by its classic radiographic appearance and by lack of history of BPs exposure.

   Oral prophylaxis was carried out and analgesics (Tab Diclofenac sodium 50 mg orally t.i.d), antimicrobial mouthwash (Chlorhexidine 0.2% b.d.), antibiotics (Amoxycillin-Clavulinic acid, 625 mg b.d. for 7 days) and topical antifungal ointment (Clotrimazole) 1% b.d. were prescribed. As patient’s condition did not improve, and extraction of symptomatic teeth 18 and 48 was done. At follow up visit incomplete healing of extraction site was observed (Figure 4).

Figure 4:

Figure 4:

   Teeth 16 and 17 were also extracted due to severe pain. IOPA and OPG Radiographic examination of the patient showed necrotic bone in the upper and lower posterior regions of the mouth (Figure 5, 6). As the patient had stage 2 BRONJ, conservative treatment was followed and the patient was symptomatically relieved at 3 and 6 months recall visits.

Figure 5:

Figure 5:

Figure 6:

Figure 6:

Discussion

   The risk factors related to the development of BRONJ involves administration of nitrogen-containing BPs predominantly when administered intravenously for long duration, patient undergoing dentoalveolar procedures, concomitant oral disease, age, systemic conditions such as renal dialysis etc and tobacco use [1] . It is more often found in the mandible than the maxilla (2:1 ratio) and more commonly in areas with thin mucosa overlying bony prominences such as tori, bony exostoses and the mylohyoid ridge [8] . In the pres - ent case, both maxilla and mandible were involved.

   Recent histological and microbiological data strongly support that actinomyces species play a critical role in the pathogenesis of this disorder [9-11] .

   Patients with oral BRONJ may be symptomatic or asymptomatic. Without any declared symptoms, they may present with exposed alveolar bone during routine dental evaluations. Patients may also present with symptoms such as pain and evidence of local or widespread infections. Most common radiographic finding of BRONJ is osseous sclerosis varying from subtle thickening of the lamina dura and alveolar crest to attenuated osteopetrosis like sclerosis. Histologically, BRONJ is characterised by presence of osteocyte depleted bone lacunae in the deeper layer of the bone and necrotic bone surrounded by many bacterial colonies [12] .

   American Association of Oral and Maxillofacial Surgeons (AAOMS) proposed the BRONJ staging system in 2007 [3] , which was later revised in 2009 [1] , to rationalise the treatment guidelines (Table 1). The major goals of the treatment for the patient at risk of developing or who have BRONJ are to prioritization and support of continued oncologic treatment and the preservation of the quality of life.

BRONJ Staging Treatment Strategies
At risk category No apparent necrotic bone in patients who have been treated with either oral or IV bisphosphonates. • No treatment indicated
• Patient education
Stage 0: No clinical evidence of necrotic bone, but non- specific clinical findings and symptoms. • Systemic management, including the use of pain medication and antibiotics
Stage 1: Exposed and necrotic bone in patients who are asymptomatic and have no evidence of infection. • Antibacterial mouth rinse
• Clinical follow-up on a quarterly basis
• Patient education and review of indications for continued bisphosphonate therapy
Stage 2: Exposed and necrotic bone associated with infec - tion as evidenced by pain and erythema in the region of the exposed bone with or without purulent drainage. • Symptomatic treatment with oral antibiotics
• Oral antibacterial mouth rinse
• Pain control
• Superficial debridement to relieve soft tissue irritation
Stage 3: Exposed and necrotic bone in patients with pain, infection, and one or more of the following: exposed and necrotic bone extending beyond the region of alveolar bone,(i.e., inferior border and ramus in the mandible, maxil - lary sinus and zygoma in the maxilla) resulting in patholog - ic fracture, extra-oral fistula, oral antral/oral nasal com - munication, or osteolysis extending to the inferior border of the mandible of sinus floor. • Antibacterial mouth rinse
• Antibiotic therapy and pain control
• Surgical debridement/resection for long term palliation of infection and pain

Table 1: Showing BRONJ staging and treatment strategies.


   Oncology patients can benefit greatly from the therapeutic effect of BPs by controlling bone pain and reducing the incidence of other skeletal complications. Thus BPs are the commonly prescribed drugs. In such a condition our first approach should be the prevention of the occurrence of BRONJ by a comprehensive intraoral examination and treatment prior to the initiation of BPs therapy [13] .

Bibliography

1.    Salvatore LR., et al. “American Association of Oral and Maxillofacial Surgeons Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaw- 2009 Update”. Journal of Oral and Maxillofacial Surgery 67.5Suppl (2009): 2-12.


2.    Wood J., et al. “Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid”. Journal of Pharmacology and Experimental Therapeutics 302.3 (2002): 1055-1061.

3.    American Association of Oral and Maxillofacial Surgeons Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaws. Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws. Journal of Oral and Maxillofacial Surgery 65.3 (2007):369-376.

4.    Bamias A., et al. “Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors”. Journal of Clinical Oncology 23.34 (2005): 85-89.

5.    Dimopoulos MA., et al. “Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid”. JHaematologica 91.7 (2006): 968-971.

6.    Pozzi S., et al. “Analysis of frequency and risk factors for developing bisphosphonate associated necrosis of the jaw”. American Society of Hematology Annual Meeting Abstracts 106 (2005): 50-57.

7.    Mavrokokki T., et al. “Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia”. Journal of Oral and Maxillofacial Surgery 65.3 (2007): 415-423.

8.    Ruggiero SL., et al. “Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases”. Journal of Oral and Maxillofacial Surgery 62.5 (2004): 527-529.

9.    Tubiana-Hulin M., et al. “Physiopathology and management of osteonecrosis of the jaws related to bisphosphonate therapy for malignant bone lesions. A French expert panel analysis”. Critical Reviews in Oncology/Hematology 71.1 (2009): 12-21.

10.    Helsloot RSJ., et al. “Bisphosphonate related osteonecrosis of the jaw; a literature review and a new hypothesis”. International Journal of Oral Research 2 (2011): 23-25.

11.    Naik NH and Russo TA. “Bisphosphonate-related osteonecrosis of the jaw: the role of actinomyces”. Clinical Infectious Diseases 49.11 (2009): 1729-1732.

12.    Kumar V and Sinha RK. “Bisphosphonate related osteonecrosis of the jaw: an update”. Journal of Maxillofacial and Oral Surgery 19 (2013): 22-27.

13.    Tong CK., et al. “Osteonecrosis of the jaw after oral bisphosphonate for osteoporosis”. Hong Kong Medical Journal 16.2 (2010):145-148.



Copyright: © 2017 Pravesh Jhingta., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



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