CONTEXT:Teriparatide and denosumab are effective treatments for osteoporosis and typically reserved as second-line options after patients have used bisphosphonates. However, limited head-to-head comparative effectiveness data exist between teriparatide and denosumab. OBJECTIVE:We compared changes in bone mineral density (BMD) between groups treated with teriparatide or denosumab after using bisphosphonates, focusing on the change in BMD while on either drug over 2 years. DESIGN:Observational cohort study using electronic medical records from two academic medical centers in the United States. PARTICIPANTS:The study population included osteoporotic patients >45 years who received bisphosphonates >1 year before switching to teriparatide or denosumab. OUTCOME MEASURES:Annualized BMD change from baseline at the lumbar spine, total hip, and femoral neck. RESULTS:Patients treated with teriparatide (n = 110) were compared with those treated with denosumab (n = 105); the mean (SD) age was 70 (10) years and median duration (interquartile range) of bisphosphonate use was 7.0 (5.6 to 9.7) years. Compared with denosumab users, teriparatide users had higher annualized BMD change at the spine by 1.3% (95% CI 0.02, 2.7%) but lower at the total hip by -2.2% (95% CI -2.9 to -1.5%) and the femoral neck by -1.1% (95% CI -2.1 to -0.1%). Those who switched to teriparatide had a transient loss of hip BMD for the first year, with no overall increase in the total hip BMD over 2 years. CONCLUSIONS:Among patients who use long-term bisphosphonates, the decision of switching to teriparatide should be made with caution, especially for patients at high risk of hip fracture.