Journal of the Louisiana State Medical Society
Bisphosphonate-Related Osteonecrosis of the Jaw
Camille Robichaux; Menchu Ong, MD; Diana Veillon, MD; Stavan Patel, DDS, MD; James Cotelingam, MD
Although there has been a growing body of literature about bisphosphonates since 1969, it was not until 2003 that treatment with this medication was associated with osteonecrosis of the jaw. Presented herein is such a case.
CASE REPORT A 57-year-old female with history of diabetes mellitus and breast cancer with osteoporosis was treated with IV bisphosphonates for five years. She has a history of recurrent painful infections of the posterior right mandible. Infections intermittently resolved with antibiotic therapy and antimi- crobial mouthwash but continued to recur. Based on the clinical and radiological findings (Figure 1), a diagnosis of bisphosphonate related osteonecrosis of the jaw (BRONJ) was made and sequestrectomy performed. Histologic examination of the removed tissue showed osteonecrosis with chronic inflammatory changes in the periosteum, confirming the diagnosis of BRONJ. (Figure 2) DISCUSSION Bisphosphonates are used for treatment of hypercalce- mia and excessive bone resorption, including osteoporosis, postmenopausal status, metastatic carcinoma, multiple myeloma, Paget’s disease, and inheritable skeletal disor- ders, such as osteogenesis imperfecta. In 2003, Marx first identified osteonecrosis of the jaw associated with biphos- phonate therapy. Subsequently, the American Association of Oral andMaxillofacial Surgeons (AAOMS) 1 named three criteria for the diagnosis: current or previous treatment of the patient with a bisphosphonate (BP), exposed necrotic bone in the maxillofacial region that has persisted more than eight weeks, and absence of radiation therapy to the jaw. BRONJ is subdivided into four main stages. Stage 0 is diagnosed in patients with no clinical evidence of necrotic bone who complain of pain and altered neurosensory func- tion. Loosening of teeth in the absence of chronic periodontal disease may also be present. Stage 1 denotes a patient with exposed necrotic bone lacking signs of infection. Stage 2 indicates exposed necrotic bone with pain and clinical signs of infection. Stage 3 is reserved for those patients with signs
of infection, plus at least one severe complication, such as pathologic fracture or extra-oral fistula. 1 Bisphosphonates were first recognized as therapeutic agents in 1969, but it was not until 2003, when BRONJ was described. 2,3 BRONJ occurs in 1 in 10,000 patients who receive BP therapy. 4,5 However, a number of factors predis- pose to this condition. These include the type of BP used (amino vs. non-aminobisphosphonates), length of therapy, concomitant therapy with steroids, radiotherapy, chemo- therapy, dental procedures, and co-morbidities including diabetes mellitus, coagulation disorders, hypercalcemia, and obesity. 6-8 Although the exact mechanism is uncertain, a number of factors seem to play a role in the pathogenesis of BRONJ. Bisphosphonates act by suppressing bone turnover by inhi- bition of osteoclastic and osteoblastic activity and chelation of divalent cations, such as calcium. Cases of BRONJ in the maxilla are well reported in the literature, but the mandible is particularly predisposed to BRONJ due to its vascular- ity, affinity for trauma, local infection, and high turnover estimated at up to 20 times that of the normal iliac crest. 9 Unaffected areas of the jaw in patients with BRONJ have prominent trabecular structures and smaller and fewer Ha- versian Canals. 10 Aminobisphosphonates (alendronate and pamidronate) also have an antiangiogenic effect, 3,4 which, while preventing metastatic disease to the bone, may play a role in the pathogenesis. In short, the combination of de- creased bone turnover, decreased angiogenesis, prominent bacterial flora, and frequent mechanical activity lead to a predisposition to BRONJ. A number of therapeutic options are available to treat BRONJ. Per the 2009 update to the AAOMS guidelines, the goals of treatment for patients with BRONJ are preservation of quality of life while supporting the ongoing treatment. This includes controlling pain and secondary infection, while preventing extension of the current lesion and/or development of new lesions. 11 Prevention is key since the
200 J La State Med Soc VOL 166 September/October 2014
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