Timing of dental surgery in patients receiving bone-modifying agents: Medication related osteonecrosis of jaw (MRONJ) and implant outcomes in a cohort of 5,284 oncology patients within an integrated dental pathway.

Background: Medication-related osteonecrosis of the jaws (MRONJ) is an important toxicity of bone-modifying agents (BMAs). Guidelines recommend dental assessment and risk reduction before high-dose antiresorptive therapy, but real-world data on outcomes by timing of dental procedures relative to BMA therapy remain limited [1-4]. This study evaluated MRONJ and implant outcomes according to the timing of dentoalveolar surgery within an integrated oncology-dental pathway. Material and Methods: We retrospectively reviewed 5,284 consecutive patients referred for dental evaluation in the context of planned or ongoing BMA therapy from January 2019 to December 2023 at a tertiary centre. Primary diagnoses were breast cancer (n=3,611), multiple myeloma (n=1,305), lung cancer (n=300) and prostate cancer (n=68). BMAs included intravenous zoledronic acid (n=4,087), subcutaneous denosumab (n=1,187) and oral alendronate (n=10). Patients were categorised as pre-BMA (all invasive dental procedures completed before first BMA dose), intra-BMA (procedures during therapy within a coordinated 6-month "drug-holiday" window) or post-BMA (6 months after BMA completion). Outcomes were MRONJ (AAOMS criteria) and patient-level implant failure (1 failed implant per patient) with 18 months of follow-up. Chi-square tests and multivariable logistic regression were applied. Results: Overall, 4,025 patients (76.2%) were managed pre-BMA, 1,001 (18.9%) intra-BMA and 258 (4.9%) post-BMA. Extractions were performed in 1,448 patients (27.4%): 968 pre-BMA, 445 intra-BMA and 35 post-BMA. No MRONJ occurred after pre-BMA extractions (0/968), compared with 6/445 intra-BMA extraction patients (1.35%) and 2/35 post-BMA extraction patients (5.71%; ²=27.3, p1.2×10-6). Overall MRONJ incidence was 12/5,284 (0.23%), including 8 post-extraction cases, 1 case after implant placement intra-BMA and 3 spontaneous cases without preceding dentoalveolar surgery. A total of 366 patients received 915 implants. At the patient level, implant failure occurred in 45/366 implant patients (12.3%): 16/270 pre-BMA (5.9%), 20/71 intra-BMA (28.2%) and 9/25 post-BMA (36.0%; ²=39.8, p2.3×10-9). In multivariable models, pre-BMA implant placement was independently associated with substantially lower odds of any implant failure than intra-BMA placement (adjusted odds ratio [OR] 0.16; 95% confidence interval [CI] 0.08-0.33; p<0.0001), whereas post-BMA implants had similar odds of failure to intra-BMA implants (OR 1.43; 95% CI 0.55-3.77; p=0.46). Pre-BMA timing was also associated with lower odds of undergoing extractions than intra- or post-BMA management. Conclusions: Within an integrated oncology-dental pathway, completing necessary extractions and implants before BMA initiation, with adequate healing, was associated with no postsurgical MRONJ and the lowest patient-level implant failure rates. Dental surgery during or after BMA therapy, even with planned drug holidays, was associated with higher MRONJ and implant loss. Early dental referral and a cautious approach to elective implants after BMA initiation should be standard in oncology supportive care.