Definitions
Romosozumab, bisphosphonates, teriparatide, and denosumab, which widely used to treat osteoporosis, were investigated regardless of whether the data reporter suspected possible adverse events. Bisphosphonates were defined as alendronate, etidronate, ibandronate, minodronate, and risedronate: only oral bisphosphonate users were included based on earlier studies.4,6 The patient selection process is shown in Fig 1.
Cardiac and cerebrovascular events were evaluated. Cardiac events were defined by the Preferred Terms “myocardial infraction,” and/or “angina pectoris,” and cerebrovascular events by the Preferred Term “cerebral infarction,” in REAC. Data on sex, age, and presence of cardiac disease, cerebrovascular disease, hypertension, and diabetes were collected from DEMO. Cardiac disease was defined as identified comorbidities, including the reported Preferred Terms ”heart failure,” and/or ”angina pectoris,” and/or ”atrial fibrillation,” in HIST. These comorbidities have been reported to be associated with development of cardiac disease.7-9 Cerebrovascular disease was defined as identified comorbidities, including the reported Preferred Terms “cerebral infarction,” in HIST. Hypertension and diabetes were defined as identified comorbidities, including ”hypertension” and/or ”diabetes,” in HIST respectively. Duplicate reports from patients with non-oral bisphosphonate users and concomitant use of osteoporosis drugs and were excluded.