Association between preoperative bisphosphonate therapy and postoperative neurocognitive-related outcomes in osteoporosis: a nationwide propensity score–matched cohort study

Postoperative neurocognitive complications are common in older surgical patients. These complications are associated with prolonged recovery and increased healthcare utilization, highlighting the importance of identifying modifiable perioperative factors. Although osteoporosis may coexist with cognitive vulnerability, evidence linking preoperative bisphosphonate therapy to postoperative neurocognitive outcomes remains limited. We conducted a nationwide propensity score–matched cohort study using TriNetX data from adults with osteoporosis undergoing surgery in the United States between 2005 and 2025. Bisphosphonate exposure was defined by prescriptions recorded within 90 days before surgery, with a 365-day ascertainment window for zoledronic acid. The primary outcome was delirium within 30 days after surgery. Secondary outcomes included antipsychotic initiation, delayed neurocognitive recovery, and psychotic or behavioral syndromes. Among 228,662 matched pairs, bisphosphonate therapy was associated with lower risks of delirium (relative risk [RR]: 0.38, 95% confidence interval [CI]: 0.30–0.48), antipsychotic initiation (RR: 0.40, 95% CI: 0.36–0.43), delayed neurocognitive recovery (RR: 0.76, 95% CI: 0.66–0.86; all p < 0.0001), and psychotic or behavioral syndromes (RR: 0.60, 95% CI: 0.45–0.81; p = 0.0006). Bisphosphonate use was also associated with lower risks of intensive care unit admission, emergency department visits, and hospital readmission. Preoperative bisphosphonate therapy was associated with lower risks of recorded postoperative neurocognitive outcomes and lower healthcare utilization in surgical patients with osteoporosis. Residual confounding and outcome under-ascertainment warrant cautious interpretation.