Anti-Resorptive Medications: Impact on Wound Healing and Oral Health

Osteonecrosis of the jaw (ONJ) is a recently described condition where systemic anti-resorptive therapeutics (bisphosphonates and anti-RANKL pharmacotherapies) are associated with necrotic osseous tissue in the oral cavity that is recalcitrant to normal healing.  ONJ lesions present as exposed bone in the oral cavity of >8 week duration in a patient on anti-resorptive medication.  ONJ represents the ‘perfect storm’ as it links the unique anatomical features of the oral cavity, with microbial colonization, physical trauma and underlying host immune responses.  That ONJ impacts the mandible and maxilla almost exclusively highlights the uniqueness of these skeletal sites and their response to therapeutics used for the treatment of systemic conditions.  Two ONJ at risk population groups include patients on anti-resorptives for the treatment of skeletal metastases (e.g. myeloma, breast, prostate cancer) and patients on anti-resorptives for the treatment of metabolic bone disease (e.g. osteoporosis, Paget’s disease).  The incidence of ONJ in cancer patients (typically on higher dose intravenous bisphosphonate therapy) is greater and with a shorter time-to-event than osteoporosis patients (typically on lower dose and oral administered bisphosphonates) where ONJ is considered rare.  Little is known regarding the impact of anti-resorptives on what is classified as ‘Stage 0’ lesions where there is no exposed bone and/or on the course of osseous healing that does not result in frank necrosis.

The relationship of oral and craniofacial bones with other skeletal sites, their response to metabolic bone disease as well as therapeutics used for the treatment of osteoporosis and skeletal metastasis will be discussed.   “Why the jaw?”, the multifactorial pathogenesis of ONJ, and evidence for the importance of osteoclasts and their role in wound healing will be highlighted.  Prevalence and recent findings will be combined with potential therapeutic strategies for the prevention and treatment of ONJ that optimize our understanding of the underlying biology with systemic and local strategies to facilitate osseous and mucosal healing.