This report presents the successful management of an advanced and refractory bisphosphonate-related osteonecrosis of the jaws (BRONJ) by hemimandibulectomy and an osteocutaneous fibula flap reconstruction in a patient with polycythaemia rubra vera, a rare haematological condition in which there is increased risk of thrombosis and haemorrhage. Union of the vascularized bone with the mandible depends on obtaining a BRONJ-free margin and rigid fixation of the bony ends. Magnetic resonance imaging can provide accurate delineation of necrotic bone and area of osteomyelitis. Placement of a 1 cm margin beyond this can envisage a BRONJ-free margin. Aggressive medical management of polycythaemia rubra vera by venesection, asprin and cytoreduction therapy along with anticoagulant prophylaxis against thromboembolic events in the first 2 weeks following major surgery can provide the basis of a good surgical and flap outcome. Nevertheless, the possibility of unpredictable haemorrhage must be considered throughout.
The use of vascularized reconstruction in the management of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is controversial. It is suggested that segmental resection and vascularized reconstruction are reserved for advanced cases of BRONJ and in those that are refractory to multiple debridement and conservative measures. This option is perceived as carrying an increased risk of postoperative complications, such as recurrence of BRONJ at the resection margins and nonunion. This could outweigh the potential advantages.
Polycythaemia rubra vera (PRV) is a rare, chronic myeloproliferative disorder characterized by increased red cell mass (erythrocytosis), leading to hyperviscosity with an increased risk of thrombosis. Haemorrhage can also occur with PRV in the presence of essential thrombocytosis, antithrombotic medication and von Willebrand’s disease. The increased risk of thrombosis and haemorrhage with PRV can make vascularized reconstruction challenging in this group of patients.
The authors present the case of a patient with an advanced and refractory case of BRONJ with PRV, who was successfully managed by hemimandibulectomy and vascularized fibula flap reconstruction.
An 82-year-old woman with long-standing PRV and significant osteoporosis, developed BRONJ after the extraction of a periodontally compromised lower right molar tooth. She had been treated with oral alendronate (70 mg weekly) following the diagnosis of osteoporosis-induced collapse of multiple spinal vertebral bodies 7 years earlier. With the diagnosis of BRONJ, alendronate was stopped and strontium ranelate (8 mg once per month) was prescribed as an alternative. The PRV was managed with hydroxycarbamide (500 mg 3 days/week and 1 g for the remaining 4 days/week), daily aspirin (75 mg) and the option of venesection to maintain a haematocrit level of less than 0.45. Other medical problems included multiple transient ischaemic attacks, gout, hypothyroidism and hypertension. There was no history of smoking.
At the initial stage, the BRONJ was unresponsive to conservative measures, including a course of pentoxyfylline and tocopherol. The sequestrum rapidly extended beyond the socket of the extracted tooth, causing inferior dental nerve paraesthesia. There was intractable jaw pain, odynophagia and chewing difficulties. Local debridement was repeated twice. The symptoms persisted and the patient became at high-risk of pathological fracture from a pencil-thin mandible ( Fig. 1 ). Resection of the affected bone was considered 11 months after the diagnosis of BRONJ due to the refractory response to repeated localized debridement and the persistence of BRONJ-related symptoms.
Imaging of the mandible was obtained using magnetic resonance imaging (MRI). Assessment of the necrotic bone was made by correlation of T1, STIR and post-gadolinium enhancement sequences. Bony destruction was seen affecting the right body and ramus of the mandible, extending from just distal of the right lower canine to the antegonial notch. There was also loss of continuity of the inferior dental canal with only a thin rim of the inferior border of the mandible remaining. In the light of this finding, a right hemimandibulectomy and vascularized fibula reconstruction was planned.
The presence of pathological fracture was found intra-operatively within the BRONJ-involved pencil-thin area of the mandible ( Fig. 2 ). The resection margin was sited 1 cm beyond the area of osteonecrosis as determined by MRI and this was placed at the mandibular angle posteriorly and in the socket of the lower right second incisor anteriorly. Harvesting of a fibula osteocutaneous flap with septocutaneous perforators was performed via the lateral approach under tourniquet control. The fibula bone was osteotomized at one site to reproduce normal facial contours and was internally fixed using a 2.0 Unilock rigid internal fixation system (Synthes Ltd -UK, Welwyn Garden City, Hertfordshire, UK) ( Fig. 3 ). End-to-end arterial anastomosis was performed between the peroneal artery to the facial artery while venous anastomosis was performed between the peroneal venae commitantae to the common facial vein using 3 mm vein coupler system (Synovis, St Paul, USA). The duration of surgery was 450 min.
The preoperative haemoglobin level was 14.8 g/dl and the haematocrit was 0.376. The patient remained on her usual PRV regime of hydroxycarbamide and aspirin, and received preoperative subcutaneous low-molecular weight heparin (4500 unit Tinzaparin) on the evening before the operation. During surgery, fluid rehydration was preferred over intraoperative blood transfusion as the estimated overall blood loss was approximately 400 ml. Intraoperative anticoagulation was not used. Immediate postoperative haemoglobin was 9.7 g/dl and the haematocrit was 0.306, which are ideal values for microvascular success. Histological examination of the resected specimen was consistent with drug-induced osteonecrosis. The specimen was composed of chronic active osteomyelitis, with bony sequestration, suppuration and periosteal bone formation. The sequestra were covered by heavy bacterial aggregates. There were areas of mucosal ulceration. Normal bone was found at both resection margins.
The patient developed transient sinus bradycardia secondary to vagal stimulation but apart from this, the postoperative recovery was unremarkable and her BRONJ symptoms had resolved completely. She received 7 days postoperative intravenous antibiotic prophylaxis (co-amoxiclav 1.5 g three times/day). The PRV regime was continued and daily subcutaneous low-molecular weight heparin (4500 units Tinzaparin nocte) was administered prophylactically against deep vein thrombosis/pulmonary embolism while she received in-patient hospital care for 2 weeks. Nutritional requirement was provided through nasogastric tube feeding for 7 days and oral intake was commenced thereafter. There was partial take of the skin graft at the donor site, which healed with regular dressings by 4 weeks post operation. The osteocutaneous fibula flap survived in its entirety following the operation (follow up period 24 months). The authors are unable to provide radiographic evidence for this due to the unit policy of not subjecting patients to radiation in the absence of on going clinical problems.