Bisphosphonates are drugs used in the treatment of various metabolic and malignant bone diseases. They inhibit bone resorption and thus bone renewal by suppressing the recruitment and activity of osteoclasts, thus shortening their life span. Intravenous bisphosphonates are used as part of the chemotherapeutic treatment of bone cancers such as multiple myeloma and metastatic disease from cancer of the breast, prostate and lungs; and have a significant impact on the quality of life for patients with advanced cancer that involves the skeletal system . Recently, oral bisphosphonates have been increasingly used to treat osteoporosis, Paget’s disease and paediatric osteogenesis imperfecta .

A possible association between bisphosphonate use and the appearance of osteonecrosis of the jaws (ONJ) was first reported in the literature in late 2003 by Wang et al. , who described three cases of osteonecrosis of the alveolar bone in female patients undergoing chemotherapy for metastatic breast cancer. Two of these patients developed ONJ following tooth extraction and the other developed ONJ spontaneously resulting in an oroantral fistula. Initially, the authors reported the osteonecrosis as resulting from the chemotherapy, but later reported that the most likely cause was the bisphosphonates . Also in 2003, M arx tracked 36 cases of painful bone exposures in the maxilla and mandible that were relatively refractory to conventional treatment. C arter & G oss also reported five cases of refractory osteonecrosis in late 2003. In 2004, R uggiero et al. reported 63 similar cases.

M arx defines bisphosphonate induced osteonecrosis of the jaws as a condition characterized by exposure of bone in the mandible or maxilla persisting for more than 8 weeks in a patient who has taken or currently is taking a bisphosphonate and who has no history of radiation therapy to the jaws. Most bodies recommend that the treatment of established cases of ONJ begins with palliation and infection control as the primary goals; with control of the progression of the disease using long-term courses of antibiotics, chlorhexidine mouthwash and periodic minor debridement of sequestra and wound irrigation. Extractions and all types of jaw surgery should be avoided . These measures do not always control the symptoms of ONJ and the progression of the disease process. This paper undertakes a prospective study designed to review the surgical management of cases of ONJ that did not respond to conservative management.

Methods

Forty patients, who were referred with ONJ that did not respond to conservative management, were treated surgically and followed up for periods of 6 months to 4 years. The surgical management of the ONJ involved antibiotic therapy, surgical debridement of all necrotic bone and primary closure without tension. Prior to being considered for surgical debridement, all patients with ONJ were managed conservatively for a minimum of 3 months. Conservative management followed the guidelines outlined by most authorities such as C arter and R uggiero . The treatment of established cases of ONJ began with palliation and infection control as the primary goals; with control of the progression of the disease using long-term courses of antibiotics, chlorhexidine mouthwash and periodic minor debridement of sequestra and wound irrigation. Following 3 months of conservative treatment, patients were examined clinically and radiographically and questioned on whether they were managing the ONJ. If it was considered that the patient had progressive disease with ongoing bone destruction or the patient was unable to manage the pain and infection, they were offered surgical debridement and primary closure of the ONJ wound site. Patients that elected to undergo surgical debridement were counselled as to the nature of this prospective study and signed consent forms to this effect. Following consultation with the patient’s oncologist, the patients continued bisphosphonate medication during the period of surgical treatment unless the oncologist felt the patient needed a break as part of their cancer drug management. For patients undergoing cancer treatment it was felt that bisphosphonate medication was an important part of the cancer management and necessary in prolonging their life.

All patients undergoing surgical debridement and tension-free primary closures were given amoxycillin, 1 g, preoperatively and then a 2 week postoperative course of amoxycillin (500 mg, t.d.s.). If patients were allergic to amoxycillin, they were given clindamycin (600 mg preoperative dose and 450 mg q.i.d. postoperatively). Depending on the extent of the debridement required, patients were treated under local or general anaesthesia. The surgical debridement involved removal of all necrotic bone, smoothing of any sharp bony edges and saucerization of any bony sockets. The latter was considered particularly important as these patients have a reduced ability to remodel bone and it was considered important that the soft tissue flaps lay on smooth bone with little indentation. At operation, it was not uncommonly found that the necrotic bone could be clearly delineated from surrounding bone and hence aided the margin for debridement. Dental extraction socket margins were reduced in height, particularly mandibular lingual plates and maxillary buccal plates, in order to reduce the depth of the bony defect so as to aid soft tissue drape over the surgical site. Buccal advancement flaps were raised with particular attention paid to the flaps sitting passively when sutured to achieve primary closure of the surgical site. Long-term synthetic resorbable suture material was used to hold surgical flaps in place and patients were given a 2-week course of antibiotics. Patients were examined at 1 week, 2 weeks and then at monthly intervals for 3 months postoperatively. Patients were then followed at 3 monthly intervals and asked to contact the clinic if they felt that they had any problems between these appointment times. Where patients had been followed up for more than 1 year postoperative X-rays were taken. Success for the surgical procedure was based on clinical and radiographic examination and patient experience. Success for clinical examination was based on there being an intact mucosa in the surgical area with no signs of infection or sinus formation. Success for radiographic examination was based on orthopantomogram (OPG) X-rays and/or CT where OPG did not provide sufficient view of the surgical area; they were taken when the patient was reviewed at 1 year following the surgical debridement. As follow-up times in this study vary from 6 months to 4 years, not all patients had had follow-up X-rays at the time of submission of this article. Radiographic success for the surgical procedures was determined by cessation of the bony destructive process or bony remodelling of the surgical area. The patients were interviewed as to the experience of the surgical site with regard to pain or any signs of infection during the follow-up period. A negative response was deemed successful. Figure 1 is a flow chart showing a summary of the treatment for patients in this study.

Flow chart showing a summary of the treatment for patients in this study.