Abstract / Description
IntroductionRomosozumab is a dual antiresorptive/anabolic monoclonal antibody against sclerostin, approved for osteoporosis. Largely driven by the ARCH trial, unexpected concerns for cardiovascular safety arose, mandating a black-box warning. Despite numerous subsequent investigations, the true nature of this association is unelucidated.Materials and methodsReal-world data were analyzed through TriNetX network, further clarifying this association. Over 1 year, we analyzed patients aged > 50 with osteoporosis, exposed to romosozumab (Cohort A) or teriparatide/abaloparatide (Cohort B), with propensity score matching. We did not exclude patients with outcomes of interest prior to the index event.ResultsWe observed a significant association with lower hazard ratios among four- (HR 0.441, 95% CI 0.0.376-0.638, p < 0.0001) and three-point major adverse cardiovascular events (HR 0.624, 95% CI 0.567-0.688, p < 0.0001), with improved survival probabilities among Cohort A. Romosozumab participants continued to demonstrate a significantly lower hazard (and improved survival probabilities) of myocardial infarction, heart failure, and death, but no significant difference was observed with respect to cerebrovascular accidents. Subsequent E-value sensitivity analyses suggested moderate robustness to unmeasured confounding. Further subgroup analyses were performed over two and five years of follow-up, among patients aged 50-64 and > 65, along with male- and female-only cohorts.ConclusionThe true association between romosozumab and cardiovascular events remains unknown. Additional studies of a prospective nature are required to investigate this further. These findings do not demonstrate a clear increased cardiovascular risk signal in a real-world setting; however, they should be interpreted as associative rather than causal and are not sufficient to change current regulatory recommendations.