Related Experiment Video
Updated: Aug 5, 2026
A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis
Published on: May 14, 2013
Cardiovascular Outcomes Following Therapeutic Sclerostin Inhibition Compared With Alternative Anabolic Therapies: A
Maxim John Levy Barnett1, Justin Lam2, Catherine Anastasopoulou3
1Department of Endocrinology, Diabetes & Metabolism, Johns Hopkins Hospital, Baltimore, Maryland, USA, jhu.edu.
Introduction:
Romosozumab 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 Methods:
Real-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.
Results:
We 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.
Conclusion:
The 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.
Insights
This study found romosozumab was associated with lower cardiovascular event risk in osteoporosis patients compared to other treatments. However, the association is not causal and requires further investigation.
Area of Science:
- Endocrinology
- Cardiovascular Medicine
- Pharmacology
Background:
- Romosozumab, a sclerostin inhibitor, is approved for osteoporosis but carries a black-box warning for cardiovascular safety concerns.
- The ARCH trial raised concerns, leading to a black-box warning, yet the cardiovascular safety of romosozumab remains unclear.
- Previous investigations have not fully elucidated the cardiovascular safety profile of romosozumab.
Purpose of the Study:
- To investigate the real-world association between romosozumab use and major adverse cardiovascular events (MACE) in osteoporosis patients.
- To compare cardiovascular safety signals between romosozumab and teriparatide/abaloparatide in a real-world setting.
- To clarify the cardiovascular risk associated with romosozumab therapy.
Main Methods:
- Analysis of real-world data from the TriNetX network over one year.
- Inclusion of patients over 50 with osteoporosis, comparing romosozumab (Cohort A) to teriparatide/abaloparatide (Cohort B).
- Propensity score matching was employed to minimize confounding factors, with no exclusion of patients with prior outcomes of interest.
Main Results:
- Romosozumab use was associated with significantly lower hazard ratios for three- and four-point MACE (HR 0.624 and 0.441, respectively).
- Improved survival probabilities were observed in the romosozumab cohort, with lower hazards for myocardial infarction, heart failure, and death.
- No significant difference in cerebrovascular accidents was noted; E-value analyses suggested moderate robustness to unmeasured confounding.
Conclusions:
- The real-world data suggest romosozumab is not associated with increased cardiovascular risk, but findings are associative, not causal.
- Further prospective studies are necessary to definitively establish the cardiovascular safety of romosozumab.
- Current findings do not warrant changes to existing regulatory recommendations regarding romosozumab use.
Related Concept Videos
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...