II. 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

III. 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]

IV. 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

V. 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]

VI. 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

VII. Imaging

  1. Mandible XRay demonstrates radiolucency of bone in necrotic areas

VIII. 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

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Related Studies

Ontology: Aseptic necrosis of bone of jaw (C2711248)

Definition (NCI) An area of necrotic bone in the mandible or maxilla.
Definition (NCI_CTCAE) A disorder characterized by a necrotic process occurring in the bone of the mandible.
Concepts Disease or Syndrome (T047)
SnomedCT 441809006
English Jaw Osteonecrosis, ONJ, Osteonecrosis of Jaw, Aseptic necrosis of bone of jaw (disorder), Aseptic necrosis of bone of jaw, Osteonecrosis of jaw, jaw; osteonecrosis, osteonecrosis; jaw
Spanish necrosis aséptica de hueso de la mandíbula (trastorno), necrosis aséptica de hueso de la mandíbula, Osteonecrosis mandibular
Portuguese Osteonecrose da mandíbula
German Osteonekrose des Kiefers
Dutch osteonecrose van kaak, kaak; osteonecrose, osteonecrose; kaak
French Osteonécrose de la mâchoire
Czech Osteonekróza čelisti
Japanese 顎骨壊死, ガクコツエシ
Italian Osteonecrosi della mascella
Hungarian Állkapocs osteonecrosisa

Ontology: Bisphosphonate-Associated Osteonecrosis of the Jaw (C3178777)

Definition (MSH) Necrotic jaws or other maxillofacial skeleton necrosis associated with bisphosphonate use (see BISPHOSPHONATES). Injury, dental procedures, and trauma can trigger the necrotic process.
Concepts Pathologic Function (T046)
MSH D059266
SnomedCT 699687003
English Bisphosphonate-Related Osteonecrosis of the Jaw, Bisphosphonate Related Osteonecrosis of the Jaw, Osteonecrosis of the Jaws, Bisphosphonate Associated, Osteonecrosis of the Jaw, Bisphosphonate Related, Osteonecrosis of the Jaws, Bisphosphonate Related, Osteonecrosis of the Jaw, Bisphosphonate Induced, Osteonecrosis of the Jaws, Bisphosphonate-Associated, Bisphosphonate Induced Osteonecrosis of the Jaws, Osteonecrosis of the Jaw, Bisphosphonate-Related, Osteonecrosis of the Jaws, Bisphosphonate-Related, Bisphosphonate-Associated Osteonecrosis of the Jaw, Bisphosphonate-Induced Osteonecrosis of the Jaw, Bisphosphonate Induced Osteonecrosis of the Jaw, Osteonecrosis of the Jaws, Bisphosphonate-Induced, Bisphosphonate-Associated Osteonecrosis of the Jaws, Bisphosphonate Associated Osteonecrosis of the Jaws, Bisphosphonate Associated Osteonecrosis of the Jaw, Osteonecrosis of the Jaw, Bisphosphonate-Associated, Osteonecrosis of the Jaw, Bisphosphonate Associated, Osteonecrosis of the Jaw, Bisphosphonate-Induced, Bisphosphonate-Induced Osteonecrosis of the Jaws, Osteonecrosis of the Jaws, Bisphosphonate Induced, Bisphosphonate-Associated Osteonecrosis of the Jaw [Disease/Finding], Osteonecrosis of jaw due to bisphosphonate (disorder), Bisphosphonate related osteonecrosis of jaw, Osteonecrosis of jaw due to bisphosphonate
French Ostéonécrose de la mâchoire liée aux biphosphonates, Ostéonécrose de la mâchoire associée aux biphosphonates, Ostéonécrose de la mâchoire induite par les biphosphonates
Russian BISFOSFONAT-ASSOTSIIROVANNYI OSTEONEKROZ CHELIUSTI, BISFOSFONATNYI OSTEONEKROZ, БИСФОСФОНАТ-АССОЦИИРОВАННЫЙ ОСТЕОНЕКРОЗ ЧЕЛЮСТИ, БИСФОСФОНАТНЫЙ ОСТЕОНЕКРОЗ, BISFOSFONAT-SVIAZANNYI OSTEONEKROZ, БИСФОСФОНАТ-СВЯЗАННЫЙ ОСТЕОНЕКРОЗ
Spanish Osteonecrosis de los Maxilares Asociada a Bifosfonato, Osteonecrosis de los Maxilares Asociada a Bisfosfonato, osteonecrosis de mandíbula debida a bisfosfonato (trastorno), osteonecrosis de mandíbula debida a bisfosfonato
Czech osteonekróza čelistí indukovaná bisfosfonáty, osteonekróza čelisti způsobená bisfosfonáty
Polish Bifosfonianowa nekroza szczęk, Bifosfonianowa martwica kości szczęki i żuchwy, Martwica kości szczęk bifosfonianowa
Italian Osteonecrosi della mascella da bifosfonati, Osteonecrosi della mascella indotta da bifosfonati, Osteonecrosi della mascella da terapia con bifosfonati, Osteonecrosi dei mascellari da bifosfonati
German Bisphosphonat-assoziierte Osteonekrose, Kiefer, Bisphosphonat-assoziierte Kieferosteonekrose, Bisphosphonat-induzierte Osteonekrose, Kiefer, Kieferosteonekrose, Bisphosphonat-induzierte, Kieferosteonekrose, Bisphosphonat-assoziierte
Norwegian Bisfosfonatassosiert osteonekrose i kjeven, Bisfosfonatrelatert osteonekrose i kjeven, Kjeveosteonekrose grunnet bisfosfonat, Bisfosfonatassosiert kjeveosteonekrose, Bisfosfonatindusert osteonekrose i kjeven
Portuguese Osteonecrose da Arcada Osseodentária Associada a Bisfosfonatos, Osteonecrose Associada a Bisfosfonatos, Osteonecrose da Arcada Osseodentária Associada aos Bisfosfonatos, Osteonecrose da Arcada Osseodentária por Bisfosfonatos, Osteonecrose Associada aos Bifosfonatos, Osteonecrose da Arcada Osseodentária Associada a Bifosfonatos, Osteonecrose da Arcada Osseodentária Associada aos Bifosfonatos, Osteonecrose Associada aos Bisfosfonatos