What hygienists need to know about jaw necrosis

November 21, 2018

Stable oral health can be a critical preventive measure against drug-induced osteonecrosis of the jaws.

The more complex a system, the more difficult it is to trace the root cause of a mistake. I woke up this morning to my lawn man calling me on my cell phone and wanting me to open the gate so that he could mow my lawn. I jumped out of bed, threw on my gym clothes and ran out the front door.

Fozzy, my standard poodle pup, ran alongside me and I quickly realized her electronic collar wasn’t working. She headed for the road just as fast as she does when I replenish her food bowl. A non-working collar meant one of two things: either her collar wasn’t charged properly or I’d have to replace the entire collar, which is a much more expensive option. I quickly read the operating manual for the electronic system and got lost in the maze of endless pages of instructions. I started to feel the tension rising, mainly because I have a cascade of home gadgets to maintain and I’m frequently pushed for time and sometimes panic when something goes wrong.

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Many of us feel the same concerns when our physician prescribes a new medication and we begin to worry about drug safety, effectiveness and interactions, especially if this new medication is one of many we need to manage. Some patients immediately Google the new drug and get lost in the maze of adverse side effects reported. Some common reasons expressed by patients for not taking a new medication are cost, misunderstanding of need, fear of unwanted side effects and mistrust of the prescribing doctor. Every pharma company has a group in its regulatory division dedicated to tracking adverse events and most companies are very diligent in reporting these side effects internally and to the FDA.7

Just like gadgets, medications can go horribly wrong, despite the best intentions of the providers who prescribe them or the companies who research, develop and market them. I remember the time period when Merck Pharmaceuticals took the blockbuster drug Vioxx off the market. Merck aggressively marketed this painkiller for arthritis pain and most people who took it didn’t need it.1 Those who took it were at greater risk of heart attack or stroke. When new drugs get approved by the FDA, there are often unresolved safety issues and the FDA has been reluctant to encourage post-marketing safety studies.1 Under the Donald Trump administration, the FDA is under pressure to approve drugs faster than before, even though one-third of new drugs have safety issues after FDA approval.2

Evolution of drugs that cause osteonecrosis of the jaws

I’ve been writing about drug-induced osteonecrosis of the jaws (DIONJ) for about 10 years. I’ve learned a lot about bone physiology and chemical injury by drugs approved by the FDA that cause this severe adverse drug reaction.3-5 When I first began learning about DIONJ, only bisphosphonates (oral and IV) were implicated in DIONJ pathogenesis. Besides bisphosphonates, the offending drugs have expanded to include:

  • Denosumab (Xgeva and Prolia) - It can treat osteoporosis and hypercalcemia. It can also treat bone cancer and bone problems in patients who have cancer.

  • Bevacizumab (Avastin) - It can treat colorectal, lung, glioblastoma, kidney, cervical and ovarian cancer.

  • Sunitinib (Sutent) - It can treat cancer, including kidney cancer, gastrointestinal stromal tumors and pancreatic neuroendocrine tumors.

  • Tocilizumab (Actemra) - It can treat moderate to severe rheumatoid arthritis. It can also treat polyarticular juvenile idiopathic arthritis and systemic juvenile idiopathic arthritis.  

When only bisphosphonates were implicated in the pathogenesis of DIONJ, some common names given to the DIONJ diagnosis were bisphosphonate-induced osteonecrosis, bisphosphonate-related osteonecrosis, bisphosphonate-associated osteonecrosis and anti-resorptive-related osteonecrosis. To further complicate matters, the American Association of Oral and Maxillofacial Surgeons favors the term Medication Related Osteonecrosis of the Jaw (MRONJ) while the American Medical Association prefers DIONJ and has adopted a site specific ICD-10 code of M87.10.8,9

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In reading the 2018 updated position paper on DIONJ by Marx and Tursun, University of Miami, division of oral and maxillofacial surgery, several important points were made:

  • Bisphosphonates aren’t the only known drugs to directly produce DIONJ, and these aforementioned drugs have different dosing schedules. Drugs administered can also be switched from one drug to another by a well-meaning physician, which can cause a more severe DIONJ.

  • Risk of developing DIONJ can’t be accurately predicted, mainly because dose over time needs to be considered. Early incidence reports of DIONJ caused by IV bisphosphonates in cancer patients was only 0.8 percent, which later expanded to 12-18 percent as researchers began to incorporate dental trained individuals in their reviews. Early incidence studies were drug company-sponsored, according to Marx and Tursun.9

  • According to Marx and Tursun, the only risk factor for DIONJ is the drug itself and risk depends on dose, route of administration, potency, frequency of administration and the length of time the drug has been administered. In addition, the drug’s half-life in the bone is important. According to Marx and Turbun, IV bisphosphonates load bone 140 times more and faster than the oral route.9

  • About 29 percent of cases of DIONJ develop exposed bone spontaneously without any initiating insult to the alveolar bone. Other initiating events in order of frequency include: dental extractions (61.6 percent), periodontal osseous surgery (5.6 percent), dental implant surgery (2.2 percent), bone biopsy (1.1 percent) and periapical surgery (0.5 percent). *Data derived from 478 patients in the University of Miami, division of oral and maxillofacial surgery database.

  • The most vulnerable anatomic site is the alveolar bone.

  • Co-morbidities that make DIONJ appear sooner or become more severe when combined with the offending drug include cancer, chemotherapeutic drugs, diabetes, immune-based diseases, anemia, age, smoking, obesity and renal dialysis. Although not considered a co-morbidity, it’s interesting to note that osteoporosis prevention and treatment with bisphosphonates and denosumab is more than 90 percent focused on females over the age of 50.9

  • Besides the offending drugs, stable oral health is a critical preventive measure. Reducing periodontal inflammation, caries intervention, removing unsalvageable teeth before an offending drug is prescribed and occlusion adjustment can reduce many of the initiating events that result in DIONJ.9

DIONJ isn’t a tsunami, but it isn’t an innocent trickle or a manufactured alarm either. Instead, it continues to cause very painful injuries to a small percentage of susceptible and innocent individuals. Prescribing physicians may not be well-versed on the pathogenesis of medications causing DIONJ and risk factors, especially the importance of stable oral health as an important preventive measure besides the drugs themselves. Dental hygienists are in a unique position to educate patients about DIONJ and how to reduce or prevent initiating events.

References

https://www.npr.org/series/5033105/vioxx-the-downfall-of-a-drug

https://www.npr.org/sections/health-shots/2017/05/09/527575055/one-third-of-new-drugs-had-safety-problems-after-fda-approval

https://www.rdhmag.com/articles/print/volume-29/issue-7/feature/the-return-of-the-dreaded-145phossy-jaw146.html

https://www.rdhmag.com/articles/print/volume-29/issue-6/columns/periodontal-therapy/the-matchgirls.html

https://www.rdhmag.com/articles/print/volume-34/issue-7/columns/drug-induced-osteonecrosis-of-the-jaws.html

https://www.rdhmag.com/articles/print/volume-34/issue-8/columns/dental-strategies-for-osteoporosis-drugs.html

https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/surveillance/adversedrugeffects/default.Htm

https://www.aaoms.org/docs/govt_affairs/advocacy_white_papers/mronj_position_paper.pdf

Marx, RE, Tursun R. University of Miami Division of Oral and Maxillofacial Surgery Position Paper on Drug Induced Osteonecrosis of the Jaws. April 23, 2018.