Background: Cardiovascular safety concerns for major cardiovascular events (MACE) were raised during the clinical trials of romosozumab. We aimed to evaluate the cardiovascular safety profile of romosozumab in a large pharmacovigilance database. Methods: All cases reported between January 2019 and December 2020 where romosozumab was reported were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS). The outcome of interest was MACE (myocardial infarction (MI), stroke, or cardiovascular death). A disproportionality analysis was conducted by estimating the reporting odds ratios (RORs) and 95% confidence intervals. Disproportionality analyses were stratified by sex and reporting region (US, Japan, other). Results: Of the 1995 eligible cases with romosozumab, the majority (N = 1188; 59.5%) originated from Japan. Overall, 206 suspected MACE reports were identified, of which the majority (n = 164; 13.8%) were from Japan, and 41 (5.2%) were from the United States (US). Among Japanese reports, patients were older and more frequently male than reports from the US. Similarly, cases with a reported MACE were older and had higher reports of cardioprotective drugs than those without cardiovascular events. Elevated reports for MACE (ROR 4.07, 95% CI: 2.39–6.93) was identified overall, which was primarily driven by the significant disproportionality measures in the Japanese reports. Conclusions: The current pharmacovigilance study identified a potential signal for elevated MACE, particularly in Japan. The results support the current safety warnings from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to avoid use in high-risk patients.

Purpose of Review In this narrative review, we have summarized the literature on fracture risk in T1DM and T2DM with a special focus on fracture site, time patterns, glucose-lowering drugs, and micro- and macrovascular complications. Recent Findings T1DM and T2DM were associated with an overall increased fracture risk, with preferent locations at the hip, vertebrae, humerus, and ankle in T1DM and at the hip, vertebrae, and likely humerus, distal forearm, and foot in T2DM. Fracture risk was higher with longer diabetes duration and the presence of micro- and macrovascular complications. In T2DM, fracture risk was higher with use of insulin, sulfonylurea, and thiazolidinediones and lower with metformin use. Summary The increased fracture risk in T1DM and T2DM concerns specific fracture sites, and is higher in subjects with longer diabetes duration, vascular complications, and in T2DM with the use of specific glucose-lowering medication.

OBJECTIVE To investigate trends in incidence rates (IRs) at various fracture sites for patients with type 1 diabetes and type 2 diabetes compared with patients without diabetes in Denmark in 1997–2017. RESEARCH DESIGN AND METHODS Patients aged ≥18 years with a vertebral, hip, humerus, forearm, foot, or ankle fracture between 1997 and 2017 were identified from Danish hospital discharge data. IRs per 10,000 person-years were calculated over the study period. Median IRs for the first (1997–2001) and the last (2013–2017) 5 years were compared. We used Poisson models to estimate age-adjusted IR ratios (IRRs) of fractures among patients with type 1 and type 2 diabetes versus patients without diabetes. RESULTS Except for foot fractures, fracture IRs were higher in patients with type 1 or type 2 diabetes compared with patients without diabetes. Hip fracture IRs declined between the first and last 5 years by 35.2%, 47.0%, and 23.4% among patients with type 1, type 2, and without diabetes, respectively. By contrast, vertebral fracture IRs increased 14.8%, 18.5%, 38.9%, respectively. While age-adjusted IRRs remained elevated in patients with type 1 diabetes compared with patients without diabetes, IRRs in patients with type 2 diabetes converged with those observed in patients without diabetes. CONCLUSIONS Unadjusted fracture rates are higher in patients with diabetes but have decreased between 1997 and 2017 except for vertebral fractures, which increased in all groups. Fracture rates change after age adjustment.