Trial reportJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2014
RANKL inhibition with denosumab does not influence 3-year progression of aortic calcification or incidence of adverse cardiovascular events in postmenopausal women with osteoporosis and high cardiovascular risk.
Trial report in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00089791 (A Study to Evaluate Denosumab in the Treatment of Postmenopausal Osteoporosis FREEDOM), which is not on this map. Cited by 52 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Study to Evaluate Denosumab in the Treatment of Postmenopausal Osteoporosis FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis Every 6 Months)
Who cites it
52 citing papers in PubMed, 6 syntheses or guidelines pooled it, 122 citations in OpenAlex.
- Adynamic bone disorder in chronic kidney disease: meta-analysis and narrative review of potential biomarkers as diagnosis and therapeutic targets.Renal failure · 2025Pooled it
- Effect of osteoporosis medications on vascular and valvular calcification: a systematic review and meta-analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Pooled it
- Denosumab vs. bisphosphonates in primary osteoporosis: a meta-analysis of comparative safety in randomized controlled trials.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024Pooled it
- Osteoporosis in Patients with Chronic Kidney Diseases: A Systemic Review.International journal of molecular sciences · 2020Pooled it
- Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics.Science translational medicine · 2020Pooled it
- Bisphosphonates, atherosclerosis and vascular calcification: update and systematic review of clinical studies.Clinical interventions in aging · 2017Pooled it
- Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial.Journal of the American Heart Association · 2024Trial
- Intravenous Zoledronic Acid 5 mg on Bone Turnover Markers and Bone Mineral Density in East China Subjects with Newly Diagnosed Osteoporosis: A 24-month Clinical Study.Orthopaedic surgery · 2017Trial
- Targeting RANKL Prevents Bone Loss, Improves Muscle Function and Extends Lifespan in Progeroid Mice.Aging cell · 2026Article
- Osteoporosis therapies and coronary risk: insights from vascular calcification biology and sclerostin signaling.Frontiers in endocrinology · 2026Review
- Management of osteoporosis in chronic kidney disease.Clinical kidney journal · 2025Review
- Aortic valve stenosis and osteoporosis: insights from a mouse model.BMC cardiovascular disorders · 2025Article
- Considerations on the Development of Therapeutics in Vascular Calcification.Journal of cardiovascular development and disease · 2025Review
- RANKL, but Not R-Spondins, Is Involved in Vascular Smooth Muscle Cell Calcification through LGR4 Interaction.International journal of molecular sciences · 2024Article
- Novel Biomarkers of Bone Metabolism.Nutrients · 2024Review
- Efficacy and safety of denosumab treatment for Korean patients with Stage 3b-4 chronic kidney disease and osteoporosis.The Korean journal of internal medicine · 2024Article
- Drug adherence and treatment duration for denosumab and mortality risk among hip fracture patients.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023Article
- Cardiovascular Calcification Heterogeneity in Chronic Kidney Disease.Circulation research · 2023Review
- Review
- Denosumab Is Superior to Raloxifene in Lowering Risks of Mortality and Ischemic Stroke in Osteoporotic Women.Pharmaceuticals (Basel, Switzerland) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 8 institutions in 3 countries.
Funding
Abstract
Atherosclerosis and osteoporosis are chronic diseases that progress with age, and studies suggest aortic calcification, an indicator of atherosclerosis, is inversely associated with bone mineral density (BMD). The osteoprotegerin (OPG)/receptor activator of NF-κB (RANK)/RANK ligand (RANKL) system has been proposed as a shared regulatory system for bone and vasculature. Denosumab (DMAb), a monoclonal antibody against RANKL, improved BMD and reduced fracture risk in the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial. We evaluated whether or not treatment with DMAb influenced progression of aortic calcification (AC) and incidence of cardiovascular (CV) adverse events. We included 2363 postmenopausal women with osteoporosis (1142 placebo, 1221 DMAb), selected from 7808 participants in the FREEDOM trial (3906 placebo, 3902 DMAb), at high risk of CV events according to modified Raloxifene Use for the Heart (RUTH) criteria. CV adverse events were reported by participants. AC scores were assessed using a semiquantitative method from lateral spine X-rays. Change in AC score from baseline to 12 (n = 1377), 24 (n = 1231), and 36 months (n = 1045) was calculated as AC score at follow-up minus AC score at baseline. AC progression was defined as change in AC score >0. Baseline characteristics, CV risk factors, and AC scores were similar between treatment groups. Mean age of participants was 74 years (range, 60-90), 88% were white, and 77% had AC score >0 at baseline. Frequency of AC progression over 3 years did not differ between women in placebo (22%) and DMAb (22%) groups (p = 0.98). AC progression did not differ between treatment groups when analyzed by baseline estimated glomerular filtration rate or by baseline AC scores. Frequency of CV adverse events did not differ between placebo (40%) and DMAb (38%) groups (p = 0.26). In conclusion, DMAb treatment had no effect on progression of AC or incidence of CV adverse events compared to placebo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.