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. 2025 May 11;16(1):4367.
doi: 10.1038/s41467-025-59718-x.

Time since last intravenous bisphosphonate and risk of osteonecrosis of the jaw in osteoporotic patients

Jung-Hyun Park #  1   2 , Sung Hye Kong #  3   4 , Jungsil Lee  5 , Jongmin Oh  5   6   7 , Jae-Ryun Lee  8 , Hyo-Jung Lee  9 , Jin-Woo Kim  10   11
Affiliations

Time since last intravenous bisphosphonate and risk of osteonecrosis of the jaw in osteoporotic patients

Jung-Hyun Park et al. Nat Commun. .

Abstract

Medication-related osteonecrosis of the jaw is a rare but serious condition in which the jawbone fails to heal and becomes necrotic, typically after dental surgery in patients treated with bisphosphonates. However, clear evidence guiding how long bisphosphonate treatment should be paused before dental surgery remains limited. Here we show that a longer time since the last dose of intravenous bisphosphonate is associated with a reduced risk of jawbone necrosis. Using a nationwide retrospective cohort of 152,299 older adults diagnosed with osteoporosis, we analyze the relationship between the duration of bisphosphonate discontinuation prior to dental extraction and the occurrence of osteonecrosis of the jaw. We find that the risk is substantially lower when treatment is paused for more than 90 days, and lowest when the pause exceeds one year. The risk reduction appears more consistent with ibandronate, whereas with zoledronate, only pauses longer than one year show a meaningful association. These findings underscore the potential value of personalized prevention strategies based on bisphosphonate type.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. MRONJ-free survival according to the TSL between the last IV bisphosphonate and tooth extraction.
A Total participants, B Zoledronate users, C Ibandronate users. TSL time since the last dose of IV bisphosphonate before tooth extraction.
Fig. 2
Fig. 2. The nonlinear association of the TSL between the last IV bisphosphonate and tooth extraction with MRONJ risk.
A Unadjusted model of total participants, B adjusted model of total participants, C zoledronate users, and (D) ibandronate users. TSL time since the last dose of IV bisphosphonate before tooth extraction. Gray error bands represent 95% confidence intervals around the estimated risk curves. In (A), the black bars indicate the frequency of MRONJ cases observed within each corresponding time interval. Cox proportional hazard model was used to estimated hazard ratio and 95% confidence intervals. Adjustments were done in (B–D) for age, sex, economic status, Charlson comorbidity index, dose intensity of previous bisphosphonate use, and type of IV bisphosphonate.
Fig. 3
Fig. 3. Overview of participant selection and study design.
A Selection of participants, B graphical overview of the study design. TSL time since the last dose of IV bisphosphonate before tooth extraction.
Fig. 4
Fig. 4
Flowchart of participant selection to evaluate MRONJ occurrence among IV bisphosphonate users, regardless of dental extration.
See this image and copyright information in PMC

References

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