Medication-related osteonecrosis of the jaw unrelated to bisphosphonates and denosumab—a review. King, Tanna and Patel. OOOO 2019;127:289299
1. Drug Class: Monoclonal antibodies. Suffix “-mab”
Examples:
Bevacizumab (Avastin)
Adalimumab (Humira)
Infliximab (Remicade)
Rituximab (Rituxan)
Commonly prescribed for: Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, osteoporosis
Comment: Increased risk when coupled with bone-modulating therapies.
In 2011, European Medicines Agency issued warning linking bevacizumab to ONJ and reported 55 cases in approximately 800,000 patients.
2. Drug Class:Tyrosine kinase inhibitors
30 TKIs have been approved for use, 8 are implicated in ONJ.
Suffix “-nib”
Examples: Suntinib (Sutent)
Imatinib (Gleevec)
Sorafenib (Nexavar)
Pazopanib (Votrient)
Axitinib (Inlyta)
Regorafenib (Stirvarga)
Cabozantanib (Cometriq)
Commonly prescribed for: Hematologic malignancies such as leukaemias, renal cell carcinomas, gastrointestinal stromal tumours , soft tissue sarcomas and neuroendocrine tumours.
Comment: Thought to be implicated via antiangiogenic effects
In review by Zhang et al of ONJ cases reported to FDA between 2010 and 2014, 418 cases were TKI- related.
Risk heightened with concurrent use of antiresoptives.
3. Drug Class: Mammalian target of rapamycin inhibitors
Suffix “-limus”
Examples: Everolimus (Afinitor)
Temsirolimus (Torisel)
Commonly prescribed for: Renal cell cancer, neuroendocrine cancer, breast cancer, lymphoma, organ transplantation
Comment: Implicated in ONJ with its sole use and when used in conjunction with bisphosphonates.
FDA FAERS study highlighted risk.
4: Drug Class: Variant fusion proteins
Suffix “-cept”
Examples: Afibercept (Zaltrap, Eylea)
Commonly prescribed for: Renal cell carcinoma, macular degeneration and macular edema.
Comment: Has antiangiogenics effects and also inhibits VEGF.
Case reports and clinical trial report risk and drug has a safety warning regarding ONJ risk.
5. Drug Class: Radiopharmaceuticals
Example: Radium 223 (Xofrigo)
Comment: Used to localize and manage bone metastases, sometimes in combination with chemotherapy.
Thought to have an additive effect when combined with other bone-modulating therapies in the development of MRONJ.
Most reports have patients with previous bisphosphonate exposure.
6. Drug Class: Disease modifying anti rheumatic drug
Example: Methotrexate
Commonly prescribed for: Rheumatoid arthritis, psoriatic arthritis, Crohn’s disease
Comment: The addition of MTX to bisphosphonate therapy is a well recognized risk factor. Sole use of MTX has also been implicated.
7. Drug Class: Corticosteroids
Example: Predisolone
Commonly prescribed for: Numerous reasons
Comment: 2 case reports in mandible
8. Drug Class: Selective estrogen receptor modulators
Example: Raloxifene (Evista)
Commonly prescribed for: Breast cancer, to maintain bone density in post menopausal women
Comment: Link not fully established however concerns raised.
1 case report