Imagine a cancer patient who has just undergone a tooth extraction. The wound does not heal after two weeks, nor after a month. Eight weeks pass, the jawbone becomes exposed, pain persists, and there are no signs of recovery. This condition is known as medication-related osteonecrosis of the jaw (MRONJ)—drug-related osteonecrosis of the jaw. The question that has remained incompletely answered is: who is most at risk of developing it?
drg. Isti Rahayu Suryani, M.Biotech., Sp.RKG, Subsp. RDP(K), PhD, a lecturer in the Department of Dental Radiology, Faculty of Dentistry, Universitas Gadjah Mada, spent five years addressing this question. In June 2024, she completed her doctoral dissertation at KU Leuven, Belgium, under the supervision of Prof. dr. Reinhilde Jacobs. Her work produced a series of findings that offer new insights into the relationship between polypharmacy, saliva, and jawbone destruction.
The More Medications, the Greater the Risk
Polypharmacy—the simultaneous use of multiple medications—is not merely an issue among older adults with multiple diseases. In cancer patients, combinations of antiresorptive drugs such as bisphosphonates and denosumab, together with chemotherapy, corticosteroids, and immunosuppressants, have become routine components of treatment. The problem is that the full impact of these combinations on post-extraction wound healing remains poorly understood.
Isti began by examining digital medical records from 3,977 patients treated at the Department of Oral and Maxillofacial Surgery, UZ Leuven, over six years, from September 2015 to April 2021. Of these, 353 patients met the inclusion criteria. All were male, with a mean age of 67.4 years.
The results were striking. Patients over 80 years of age who were taking combinations of antiresorptive and non-antiresorptive medications had 14.68 times higher odds of delayed healing than the control group. Those classified as having hyper-polypharmacy—taking 10 or more medications—had 58.86 times higher odds of developing MRONJ.
These figures are not merely statistics. They represent real patients whose jawbones can gradually become necrotic because their bodies are no longer able to heal effectively.
Interestingly, corticosteroids emerged as the strongest contributor to MRONJ, with an odds ratio of 2.18. Bisphosphonates, which have historically received the most attention, were more frequently associated with delayed healing rather than MRONJ itself. This finding raises new questions about how clinical protocols have traditionally been designed.
A Predictive Tool for Dentists on the Front Line
Identifying risk factors was not enough. Isti went one step further by validating a risk assessment tool known as the Adapted-University of Connecticut Osteonecrosis Numerical Scale (A-UCONNS). The tool combines underlying pathology, dental procedures, comorbidities, smoking habits, medication type and duration, and antiresorptive medication use into a single numerical score.
The results were promising. Each one-point increase in the A-UCONNS score increased the odds of MRONJ by 1.347 times. Patients classified as having “significant risk” (16 or higher) also demonstrated substantially poorer healing outcomes than those in the minimal-risk category.
“A-UCONNS could act as a valuable tool for enhancing care in medically compromised patients, where it can enable a clinician to identify high-risk patients who are more prone to develop MRONJ.” — Suryani IR et al., Health Science Reports, 2024
This means that before extracting a tooth from an oncology patient taking multiple medications, dentists may have an instrument to estimate what could happen and plan preventive measures from the outset.
Saliva and Socket Surface Area: Two Overlooked Local Factors
Half of Isti's dissertation focused on local rather than systemic factors. Two questions were examined: Do medication-induced changes in saliva contribute to MRONJ? And does the surface area of the alveolar socket following multiple tooth extractions affect the risk?
To address the first question, Isti and her team conducted a systematic review of 765 studies, ultimately identifying 10 eligible articles involving a total of 272 MRONJ cases. Their findings showed that reduced salivary flow and changes in salivary proteins—including interleukin-6, MMP9, and hypotaurine—were significantly associated with the development of MRONJ. Patients taking five or more medications had a prevalence of xerostomia as high as 71%, while the incidence of MRONJ in this group was nearly three times higher than in patients not taking medications.
For the second question, Isti and Rellyca Sola Gracea analyzed 40 patients undergoing multiple tooth extractions—20 patients with polypharmacy and 20 healthy controls. Using cone-beam computed tomography (CBCT) and digital 3D models, they calculated the surface area of the alveolar socket for each type of tooth.
The most striking finding was that 40% of all teeth extracted in patients with polypharmacy resulted in MRONJ. In the mandible, the figure reached 44%. Furthermore, a critical threshold was identified: extraction of four or more tooth roots in the mandible significantly increased the risk of MRONJ. The correlation between the number of extracted roots and sockets that subsequently developed MRONJ was very strong (r = +0.861, p < 0.001).
This was the first study to directly associate alveolar socket surface area with MRONJ risk in patients with polypharmacy.
From Leuven to Yogyakarta
Five years in Leuven was not an easy journey. Isti pursued her doctoral studies while simultaneously being a mother, wife, and researcher. Her dissertation, comprising five scientific articles published or accepted in indexed international journals, represents a meaningful contribution from Indonesia to global science—and, more concretely, to patients who have long been at risk without knowing it.
Now, after returning to the Faculty of Dentistry at Universitas Gadjah Mada, she has brought home more than research findings on MRONJ. She has brought a more comprehensive map of what happens inside the mouths of patients whose bodies are struggling against cancer, osteoporosis, and the burden of medications they must take every day.
For dentists who encounter older or oncology patients every day—patients whose medical records are filled with long medication lists—this research is a reminder that tooth extraction is not always a simple procedure. It is the gateway to a healing process that may proceed smoothly—or may fail altogether.
Source DOI: doi: 10.1007/s00784-021-04331-7
Authors: Anny Anggraini; drg. Achmad Zam Zam Aghasy, M.Kes.
Photo: Pexels