Comparative Effectiveness and Safety Outcomes Between Denosumab and Bisphosphonate in South Korea.

Abstract

Both bisphosphonates and denosumab are the mainstays of treatment for osteoporosis to prevent fractures. However, there are still few trials directly comparing the prevention of fractures and the safety of two drugs in the treatment of osteoporosis. We aimed to compare the efficacy and safety between denosumab and bisphosphonates using a nationwide claims database. The database was covered with ten million, 20% of the whole Korean population sampled by age and sex stratification of the Health Insurance Review and Assessment Service in South Korea. Among 228,367 subjects who were over 50 years of age and taking denosumab or bisphosphonate from Jan 2018 to April 2022, the analysis was performed on 91,460 subjects after 1: 1 propensity score matching. The primary outcome was treatment effectiveness; total fracture, major osteoporotic fracture, femur fracture, pelvic fracture, vertebral fracture, adverse drug reactions; acute kidney injury, chronic kidney disease, and atypical femoral fracture. Total fracture and osteoporotic major fracture, as the main outcomes of efficacy, were comparable in the denosumab and bisphosphonate group (HR 1.06, 95% CI 0.98-1.15, p=0.14; HR 1.13, 95% CI 0.97-1.32, p=0.12, respectively). Safety for acute kidney injury, chronic kidney disease, and atypical femoral fracture also did not show any differences between the two groups. In subgroup analysis according to ages, the denosumab group under 70 years of age had a significantly lower risk for occurrences of acute kidney injury compared to the bisphosphonate group under 70 years of age (HR 0.53, 95% CI 0.29-0.93, p=0.03). In real-world data reflecting clinical practice, denosumab, and bisphosphonate showed comparable effectiveness for total fracture and osteoporosis major fracture and safety for acute kidney injury, chronic kidney disease, and atypical femoral fracture.