Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

An update on ONJ in oncology (#42)

Jacques Brown 1
  1. Centre de recherche du CHU de Québec - Université Laval, Quebec, QUéBEC, Canada

Cancer cells often alter bone remodelling resulting in high bone turnover, and consequently in skeletal-related events (SREs), causing severe morbidity in affected patients. The goals of bone targeted antiresorptive therapies, such as bisphosphonates (BPs) and denosumab (DMAb), are the reduction of incidence and the delay in occurrence of the SREs, to improve quality of life and pain control. While these medications are used in high-dose and at frequent intervals, the incidence of osteonecrosis of the jaw (ONJ) is greatest (1-15%) in the oncology patient population (1). Patients treated for osteoporosis with oral or intravenous BP regimes receive substantially less exposure to BP, and the risk in these patients is estimated at 0.001% to 0.01%, marginally higher than the incidence in the general population (<0.001%)(1). The International Task Force on Osteonecrosis of the Jaw defined ONJ as an area of exposed bone in the maxillofacial region that does not heal within eight weeks after identification by a health care provider, in a patient who was receiving or had been exposed to an antiresorptive agent and has not had radiation therapy to the craniofacial region (1). Anti-angiogenics such as bevacizumab, sunitinib and cabozantinib  have been associated with ONJ when used alone or in conjunction with BPs (2). The combination of BPs with bevacizumab roughly halves the time to ONJ from 23 months with BPs alone to 12.4 months (3). New insights into the pathophysiology include anti-resorptive effects of BPs and DMAb, effects of BPs on gamma delta T-cells and Dmab on monocyte and macrophage function, as well as the role of local bacterial infection, inflammation and necrosis (1, 4). Other risk factors for ONJ include glucocorticoid use, maxillary or mandibular bone surgery (especially tooth extraction), poor oral hygiene, chronic inflammation, diabetes mellitus and ill-fitting dentures. Prevention strategies for ONJ include elimination or stabilization of oral disease prior to initiation of antiresorptives, as well as maintenance of good oral hygiene. In cancer patients receiving high-dose BP or DMAb consideration should be given to withholding antiresorptive following extensive oral surgery until the surgical site heals with mature mucosal coverage. In a recent study from Australia, the incidence of ONJ in cancer patients was minimized from 4.6% to 0.8% through the implementation of prophylactic dental assessment and active dental intervention (5).