Cardiovascular Outcomes Following Therapeutic Sclerostin Inhibition Compared With Alternative Anabolic Therapies: A Real-World Propensity Score-Matched Analysis.

Barnett MJL, Lam J, Anastasopoulou C

Journal of osteoporosis30 Jul 2026

PMID42535103PMCIDPMC13422644DOI10.1155/joos/2813928PepBankPUB-42535103

Summary

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 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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone6

In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Abaloparatide (Tymlos).

01HumanNot a test of Abaloparatide (Tymlos) aloneObservational studySafety outcome
In patients with osteoporosis, pooled teriparatide/abaloparatide was linked to higher four-point MACE hazard than romosozumab.
In plain wordsIn patients with osteoporosis, pooled teriparatide/abaloparatide was linked to higher four-point cardiovascular event risk than romosozumab.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseFour-point MACE
Study
n: not reported in source
Comparator
Romosozumab
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Hazard ratio
0.441 ratio
romosozumab versus teriparatide/abaloparatide
Upper confidence bound
0.638 ratio
95% CI
Source sentences
Summary
We observed a significant association with lower hazard ratios among four- (HR 0.441, 95% CI 0.0.376-0.638, p p < 0.0001), with improved survival probabilities among Cohort A.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Abaloparatide (Tymlos).
Show in the study text Report a problemFND-4253510301
02HumanNot a test of Abaloparatide (Tymlos) aloneObservational studySafety outcome
In patients with osteoporosis, pooled teriparatide/abaloparatide was linked to higher three-point MACE hazard than romosozumab.
In plain wordsIn patients with osteoporosis, pooled teriparatide/abaloparatide was linked to higher three-point cardiovascular event risk than romosozumab.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseThree-point MACE
Study
n: not reported in source
Comparator
Romosozumab
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Hazard ratio
0.624 ratio
romosozumab versus teriparatide/abaloparatide
Lower confidence bound
0.567 ratio
95% CI
Upper confidence bound
0.688 ratio
95% CI
Source sentences
Summary
We observed a significant association with lower hazard ratios among four- (HR 0.441, 95% CI 0.0.376-0.638, p p < 0.0001), with improved survival probabilities among Cohort A.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Abaloparatide (Tymlos).
Show in the study text Report a problemFND-4253510302
03HumanNot a test of Abaloparatide (Tymlos) aloneObservational studySafety outcome
In patients with osteoporosis, pooled teriparatide/abaloparatide was linked to higher myocardial infarction hazard than romosozumab.
In plain wordsIn patients with osteoporosis, pooled teriparatide/abaloparatide was linked to higher heart attack risk than romosozumab.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseMyocardial infarction
Study
n: not reported in source
Comparator
Romosozumab
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Abaloparatide (Tymlos).
Show in the study text Report a problemFND-4253510303
04HumanNot a test of Abaloparatide (Tymlos) aloneObservational studySafety outcome
In patients with osteoporosis, pooled teriparatide/abaloparatide was linked to higher heart failure hazard than romosozumab.
In plain wordsIn patients with osteoporosis, pooled teriparatide/abaloparatide was linked to higher heart failure risk than romosozumab.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseHeart failure
Study
n: not reported in source
Comparator
Romosozumab
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Abaloparatide (Tymlos).
Show in the study text Report a problemFND-4253510304
05HumanNot a test of Abaloparatide (Tymlos) aloneObservational studySafety outcome
In patients with osteoporosis, pooled teriparatide/abaloparatide was linked to higher death hazard than romosozumab.
In plain wordsIn patients with osteoporosis, pooled teriparatide/abaloparatide was linked to higher death risk than romosozumab.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseDeath
Study
n: not reported in source
Comparator
Romosozumab
Outcome group
Mortality · Whole body
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Abaloparatide (Tymlos).
Show in the study text Report a problemFND-4253510305
06HumanNot a test of Abaloparatide (Tymlos) aloneObservational studySafety outcome
In patients with osteoporosis, cerebrovascular accident risk did not differ significantly between pooled teriparatide/abaloparatide and romosozumab.
In plain wordsIn patients with osteoporosis, stroke risk did not differ significantly between pooled teriparatide/abaloparatide and romosozumab.
Peptide
Abaloparatide (Tymlos)
Outcome
No significant changeCerebrovascular accidents
Study
n: not reported in source
Comparator
Romosozumab
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Abaloparatide (Tymlos).
Show in the study text Report a problemFND-4253510306

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Version 2Current
22 Oct 2026, 02:25 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

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