Table 2.
Risk of MRONJ according to the time since the last dose (TSL) of IV bisphosphonate before tooth extraction
| TSL of IV bisphosphonate before tooth extraction | MRONJ events/Total number of patients | Unadjusted HR (95% CI) | Model A HR (95% CI) | Model B HR (95% CI) | Model C HR (95% CI) |
|---|---|---|---|---|---|
| Total participants | |||||
| ≤90 days | 274/21,472 | Reference | Reference | Reference | Reference |
| 91–180 days | 138/19,486 | 0.56 (0.45, 0.68) | 0.56 (0.46, 0.69) | 0.56 (0.46, 0.69) | 0.57 (0.47, 0.70) |
| 181–365 days | 163/29,795 | 0.43 (0.35, 0.52) | 0.43 (0.36, 0.53) | 0.43 (0.36, 0.53) | 0.45 (0.37, 0.55) |
| >365 days | 341/81,546 | 0.33 (0.28, 0.39) | 0.36 (0.31, 0.43) | 0.37 (0.31, 0.43) | 0.43 (0.36, 0.50) |
| Zoledronate users | |||||
| ≤90 days | 33/2702 | Reference | Reference | Reference | Reference |
| 91–180 days | 39/2603 | 1.23 (0.77, 1.96) | 1.23 (0.77, 1.96) | 1.23 (0.77, 1.96) | 1.26 (0.79, 2.00) |
| 181–365 days | 34/4334 | 0.65 (0.40, 1.05) | 0.66 (0.41, 1.07) | 0.66 (0.41, 1.07) | 0.69 (0.43, 1.11) |
| >365 days | 51/10,159 | 0.44 (0.28, 0.68) | 0.46 (0.30, 0.72) | 0.46 (0.30, 0.72) | 0.51 (0.33, 0.79) |
| Ibandronate users | |||||
| ≤90 days | 241/18,770 | Reference | Reference | Reference | Reference |
| 91–180 days | 99/16,883 | 0.46 (0.36, 0.58) | 0.46 (0.37, 0.58) | 0.46 (0.37, 0.59) | 0.47 (0.38, 0.60) |
| 181–365 days | 129/25,461 | 0.39 (0.32, 0.49) | 0.40 (0.32, 0.49) | 0.40 (0.32, 0.49) | 0.42 (0.34, 0.52) |
| >365 days | 290/71,387 | 0.32 (0.27, 0.38) | 0.35 (0.29, 0.42) | 0.35 (0.30, 0.42) | 0.41 (0.35, 0.49) |
Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. The reference group comprises patients whose tooth extraction occurred within ≤90 days after the last IV bisphosphonate dose. All statistical tests were two-sided, and p values < 0.05 were considered statistically significant. Model A was adjusted for age and sex. Model B was adjusted for age, sex, economic status, and Charlson comorbidity index. Model C was adjusted for age, sex, economic status, Charlson comorbidity index, dose intensity of previous bisphosphonate use, and type of IV bisphosphonate.
MRONJ medication-related osteonecrosis of the jaw, IV intravenous, TSL time since the last dose, HR hazard ratio, CI confidence interval.