Real-World Safety and Effectiveness of Denosumab in Patients with Osteoporosis: A Prospective, Observational Study in South Korea

Abstract

Background: The efficacy and safety of denosumab have been established in a phase 3, randomized, placebo-controlled trial in Korean postmenopausal women with osteoporosis. This postmarketing surveillance study was aimed to investigate the safety and effectiveness of denosumab in Korean real-world clinical practice.Methods: Patients with osteoporosis who had received denosumab per the Korean approved indications in the postmarketing setting between September 2014 and September 2019 were enrolled. The primary endpoint was the incidence of adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was the percent change from baseline in bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck.Results: Of the 3,221 patients enrolled, 3,185 were included in the safety analysis set; 2,973 (93.3%) were female, and the mean± standard deviation (SD) age was 68.9±9.9 years. The mean±SD study period was 350.0±71.4 days. AEs, fatal AEs, and ADRs occurred in 19.3%, 0.8%, and 1.6%, respectively. The most frequent AEs, occurring in >0.5% of patients, were dizziness (0.7%), arthralgia (0.7%), back pain (0.6%), and myalgia (0.6%). Hypocalcemia occurred in 0.3% of patients. There were no cases of osteonecrosis of the jaw and atypical femoral fracture. Mean±SD percent change from baseline in BMD of the lumbar spine, total hip, and femoral neck was 7.3%±23.6%, 3.6%±31.4%, and 3.2%±10.7%, respectively.Conclusion: The safety and effectiveness of denosumab in Korean patients with osteoporosis in this study were comparable with those in the Korean randomized controlled trial, with no new safety findings.

Prevalence of denosumab-induced hypocalcemia: a retrospective observational study of patients routinely monitored with ionized calcium post-injection

“…The prevalence of hypocalcemia was higher in our study (6%) than in the original clinical trial (FREEDOM), which reported a prevalence of 0–0.1% [ 4 , 6 ]. A low prevalence of hypocalcemia (< 1% hypocalcemia) was also reported in the FREEDOM sub-analysis of patients with renal failure and in a post-marketing real-world prospective observational trial [ 12 , 17 ]. Our findings are in the same range as other large-scale studies on real-world cohorts, which reported the frequency of denosumab-induced hypocalcemia to range from 4 to 8% [ 7 , 8 , 10 ].…”

“…Using non-routine data, i.e., calcium analysis only if doctors ask for it [ 17 ], might include selection bias where only high-risk patients are followed up with calcium measurements. This might yield an overestimation of the prevalence of hypocalcemia, or it might risk missing cases of mild hypocalcemia.…”

Denosumab and the Risk of Diabetes in Patients Treated for Osteoporosis

“…32 Therefore, in choosing osteoporosis treatments, the potential for increased adverse event risks associated with denosumab may not be a primary concern. 33,34 Given the high osteoporosis prevalence, the extensive use of antiosteoporosis medications, and the negative effect of diabetes on both patient health and health care system burdens in the global aging population, our findings possess substantial clinical and public health significance.…”

Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study

“…Osteoporosis decreases bone strength, subsequently increasing the risk of fracture and leading to notable morbidity and diminished quality of life. Denosumab, the first-approved biologic agent for the treatment of osteoporosis, is a potent antiresorptive drug that can significantly reduce the risk of hip, vertebral, and non-vertebral fractures [ 2 , 3 ]. According to the most recent records of the Health Insurance Review and Assessment Service in South Korea, denosumab is the most frequently prescribed anti-osteoporosis drug, accounting for 30% of the entire market share of osteoporosis medications.…”