Real-World Comparability of Antiresorptive Osteoporosis Treatment Groups Among Treatment-Naïve and Treatment-Experienced Women Ages 55 and Older in the United States.

Purpose: Selection of osteoporosis (OP) treatment is affected by patients' disease severity and fracture risk, potentially confounding real-world comparative effectiveness and safety studies of antiresorptive medications. To inform the choice of valid treatment contrasts for subsequent real-world comparative studies, we assessed comparability of antiresorptive OP treatment groups using negative control outcomes (NCOs). Patients and Methods: Women aged ≥55 years in Optum Results: Women in both treatment-naïve (n = 199,335) and treatment-experienced (n = 33,296) cohorts initiated treatment at a mean age of 71.8 years. Treatment-naïve women initiating denosumab had similar 1-year risks of most NCOs compared with initiators of ZA (maximum observed RD = 2.47% for colon cancer screening). However, significant risk differences were observed for seven NCOs when comparing ZA or denosumab with oral BPs. Among treatment-experienced women, all NCOs indicated similar risks when comparing denosumab to alendronate alone. Only one NCO (dementia: RD = 0.42%) was associated with treatment when comparing denosumab to oral BPs, and one (influenza vaccine: RD = 3.57%) was associated with treatment when comparing ZA to oral BPs. Results of the Bayesian analysis aligned with our qualitative interpretations. Conclusion: Comparative studies including denosumab or ZA versus oral BPs among treatment-experienced, commercially insured women aged ≥55 years in the United States are likely valid with respect to comparability of treatment groups. Our results do not support conducting observational studies examining these treatment contrasts in the overall treatment-naïve population. However, comparison of ZA and oral BPs among treatment-naïve women with a prior fracture may be undertaken with minimal expected residual bias.