Few studies have explored the relationship between long-term exposure to particulate matter with an aerodynamic diameter of ≤2.5 μm (PM_2.5) and osteoporotic fracture, particularly in high PM_2.5 level areas. The aim of this study was to assess the association between long-term exposure to PM_2.5 and osteoporotic fracture. We performed a matched case–control study of 16,175 participants obtained from a hospital registry during 2005–2014 in Taiwan. A major osteoporotic fracture was defined as a fracture of the spine, hip, proximal humerus, and forearm. We applied satellite-based spatiotemporal models with 1-km resolution to individually calculate the 1-year average PM_2.5 concentration before the index date which was defined as the first visit date for the osteoporotic fracture. Logistic regression models with and without potential confounding factors were used to estimate odds ratios (OR) and 95% confidence intervals (CI) between PM_2.5 and osteoporotic fracture, whereas a restricted cubic spline model was used to estimate the dose–response relationship. The sample's median age was 44.7 years (interquartile range: 30.7, 63.1 years). We observed that long-term PM_2.5 exposure was associated with osteoporotic fracture, the OR was 1.12 (95% CI: 1.03, 1.22) per 10-μg/m³ increase in PM_2.5 in women. In the dose-response association, the OR of osteoporotic fracture was significantly increased for PM_2.5 exposures more than 41 μg/m³. We did not find a significant association between PM_2.5 (per 10-μg/m³ increase) and osteoporotic fracture among overall population (adjusted OR, 1.02 [95% CI, 0.97 to 1.08]) and men (adjusted OR, 0.94 [95% CI, 0.86 to 1.02]). The results of the stratified analysis showed that women were more sensitive to the adverse impact of PM2.5 that were men, and evidence was obtained of sex-based effect modification (P for interaction = 0.002). Our findings suggest that long-term exposure to PM_2.5 is associated with osteoporotic fracture, particularly among women.