Jaw Osteonecrosis

Aka: Jaw Osteonecrosis, Jaw Aseptic Necrosis, Mandibular Osteonecrosis, Mandible Aseptic Necrosis, Bisphosphonate-Associated Osteonecrosis of the Jaw, Medication Causes of Jaw Osteonecrosis

1. Pathophysiology
   1. Mandibular alveolar process undergoes constant bone remodeling
      1. Osteoclast-mediated bone resorption
      2. Osteoblast-mediated bone deposition
   2. Medications may disrupt bone remodeling
      1. Osteoclast apoptosis or inhibition
      2. Decreased localized Blood Flow
   3. Mandible is at increased risk of osteonecrosis due to increased bone turnover rate
2. Risk Factors
   1. Tooth Extraction (or dental implant)
      1. Precedes drug-induced Jaw Osteonecrosis in 45-61% of cases
   2. Head and Neck Radiation Therapy
      1. Increased risk at sites exposed to >60 Gy radiation
      2. Nabil (2011) Int J Oral Maxillofac Surg 40(3): 229-43 [PubMed]
3. Causes: Osteoporosis Agents
   1. Intravenous Bisphosphonates (occurs in 3-18% of patients)
      1. Zoledronic acid (Reclast)
      2. Ibandronate (Bonival)
   2. Oral Bisphosphonates (occurs in 0.1 to 0.2% of patients)
      1. Alendronate (Fosamax)
      2. Risedronate (Actonel)
   3. Denosumab (Prolia)
      1. RANK Ligand Inhibitor used in Osteoporosis, bone matastases, giant cell Bone Tumors
      2. Occurs in 0.7 to 1.9% of patients
   4. Romosozumab (Eventity)
      1. Sclerostin inhibitor used in Osteoporosis
4. Causes: Chemotherapeutic Agents
   1. Antiangiogenic Medications (monoclonal antibodies or nucleic acids)
      1. Chemotherapeutic agents that block solid tumor Angiogenesis (Vascular Endothelial Growth Factor)
      2. Bevacizumab (Avastin)
      3. Ramucirumab
      4. Ranibizumab
      5. Pegaptanib
   2. Tyrosine Kinase Inhibitors
      1. Axitinib (Inlyta)
      2. Bosutinib (Bosulif)
      3. Carbozantinib (Cabometyx)
      4. Dasatinib (Sprycel)
      5. Erlotinib (Tarceva)
      6. Imatinib (Gleevec)
      7. Nilotinib (Tasigna)
      8. Sorafenib (Nexavar)
      9. Sunitinib (Sutent)
   3. References
      1. Ruggiero (2014) J Oral Maxillofac Surg 72(10):1938-56 [PubMed]
      2. Vahtsevanos (2009) J Clin Oncol 27(32): 5356-62 [PubMed]
5. Signs
   1. Exposed, necrotic bone
   2. Tooth socket remains after Tooth Extraction
   3. Suppurative discharge from osteonecrosis site
   4. Mucosal sloughing
   5. Persistent jaw pain
   6. Fistula formation
   7. Gingival Hypertrophy or bone hypertrophy
6. Imaging
   1. Mandible XRay demonstrates radiolucency of bone in necrotic areas
7. Prevention
   1. Alert dentist to Radiation Therapy to head and neck
      1. Perioperative hyperbaric oxygen may be indicated prior to procedure
   2. Avoid dental surgery if patient is on intravenous Bisphosphonates, Antiangiogenic Medications, Denosumab
   3. Exercise caution in performing dental surgery on those on oral Bisphosphonates for >4 years
      1. Dentists typically will ask for medical clearance for dental surgery in these cases
   4. Oral bisphosphonate holiday
      1. Not evidence based (however standard of care in dental practice as of 2020)
         1. Stopping bisphosponates has not been shown to modify risk
      2. Protocol
         1. Stop oral Bisphosphonates for 2 months before dental procedure
         2. Wait at least 3 months after dental procedure to restart oral Bisphosphonates
8. References
   1. Glick (2020) Am Fam Physician 102(10):613-21 [PubMed]