Evidence map›Paper›PMID 25884398›Full record

SynthesisPloS one2015

Bisphosphonates and risk of cardiovascular events: a meta-analysis.

Dae Hyun Kim, James R Rogers, Lisa A Fulchino, Caroline A Kim, Daniel H Solomon, Seoyoung C Kim

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 9 pooled it
3.6field-weighted citation impact, top 5% of its field
1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 9 syntheses or guidelines pooled it, 133 citations in OpenAlex.

  1. Pooled it
  2. Association between bisphosphonate use and stroke risk: a 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 · 2023
    Pooled it
  3. Comparative risk of acute myocardial infarction for anti-osteoporosis drugs in primary care: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022
    Pooled it
  4. Pooled it
  5. Pooled it
  6. Relationship Between Low Bone Mineral Density and Fractures With Incident Cardiovascular Disease: A Systematic Review and Meta-Analysis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017
    Pooled it
  7. European Heart Rhythm Association (EHRA)/European Association of Cardiovascular Prevention and Rehabilitation (EACPR) position paper on how to prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) and Asia Pacific Heart Rhythm Society (APHRS).Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2017
    Guideline
  8. Guideline
  9. Pooled it
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Role of Sclerostin in Cardiovascular System.International journal of molecular sciences · 2025
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Anti-sclerostin antibodies: a new frontier in fragility fractures treatment.Therapeutic advances in musculoskeletal disease · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Dae Hyun KimDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
James R RogersDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Lisa A FulchinoDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Caroline A KimDivision of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
Daniel H SolomonDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Seoyoung C KimDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Harvard University · USBrigham and Women's Hospital · USBeth Israel Deaconess Medical Center · US

Funding

Trial of risk mangement for prevention of accelerated atherosclerosis in SLEP60AR047782 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI SOLOMON, DANIEL HAL · 2001 to 2016
$18.8M
Harvard Clinical and Translational Science CenterKL2TR001100 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$8.5M
Training Program in Cardiovascular ResearchT32HL007374 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MITTLEMAN, MURRAY A · 1985 to 2019
$7.9M
Modifiable Disparities in Treatment for Rheumatoid ArthritisR01AR056215 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI SOLOMON, DANIEL HAL · 2009 to 2012
$1.9M
Patient Centered Outcomes Research in RheumatologyK24AR055989 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI SOLOMON, DANIEL HAL · 2008 to 2017
$1.5M
Cervical Dysplasia and Human Papillomavirus Infection in Rheumatoid Arthritis.K23AR059677 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI KIM, SEOYOUNG CATHERINE · 2010 to 2014
$680k
NCATS NIH HHS 1KL2 TR001100-01NCATS NIH HHS KL2 TR001100NHLBI NIH HHS T32 HL007374NHLBI NIH HHS T32 HL007374-35NIAMS NIH HHS K23 AR059677NIAMS NIH HHS K24-AR055989NIAMS NIH HHS P60-AR047782NIAMS NIH HHS R01-AR056215
6 · The paper itself

Abstract

BACKGROUND AND

objectivesSome evidence suggests that bisphosphonates may reduce atherosclerosis, while concerns have been raised about atrial fibrillation. We conducted a meta-analysis to determine the effects of bisphosphonates on total adverse cardiovascular (CV) events, atrial fibrillation, myocardial infarction (MI), stroke, and CV death in adults with or at risk for low bone mass.

methodsA systematic search of MEDLINE and EMBASE through July 2014 identified 58 randomized controlled trials with longer than 6 months in duration that reported CV events. Absolute risks and the Mantel-Haenszel fixed-effects odds ratios (ORs) and 95% confidence intervals (CIs) of total CV events, atrial fibrillation, MI, stroke, and CV death were estimated. Subgroup analyses by follow-up duration, population characteristics, bisphosphonate types, and route were performed.

resultsAbsolute risks over 25-36 months in bisphosphonate-treated versus control patients were 6.5% versus 6.2% for total CV events; 1.4% versus 1.5% for atrial fibrillation; 1.0% versus 1.2% for MI; 1.6% versus 1.9% for stroke; and 1.5% versus 1.4% for CV death. Bisphosphonate treatment up to 36 months did not have any significant effects on total CV events (14 trials; ORs [95% CI]: 0.98 [0.84-1.14]; I2 = 0.0%), atrial fibrillation (41 trials; 1.08 [0.92-1.25]; I2 = 0.0%), MI (10 trials; 0.96 [0.69-1.34]; I2 = 0.0%), stroke (10 trials; 0.99 [0.82-1.19]; I2 = 5.8%), and CV death (14 trials; 0.88 [0.72-1.07]; I2 = 0.0%) with little between-study heterogeneity. The risk of atrial fibrillation appears to be modestly elevated for zoledronic acid (6 trials; 1.24 [0.96-1.61]; I2 = 0.0%), not for oral bisphosphonates (26 trials; 1.02 [0.83-1.24]; I2 = 0.0%). The CV effects did not vary by subgroups or study quality.

conclusionsBisphosphonates do not have beneficial or harmful effects on atherosclerotic CV events, but zoledronic acid may modestly increase the risk of atrial fibrillation. Given the large reduction in fractures with bisphosphonates, changes in osteoporosis treatment decision due to CV risk are not justified.

Indexed as

Atrial FibrillationBone Density Conservation AgentsCardiovascular DiseasesDatabases, FactualDiphosphonatesFollow-Up StudiesHumansImidazolesMyocardial InfarctionOdds RatioOsteoporosisRiskStrokeZoledronic AcidBone Density Conservation AgentsDiphosphonatesImidazolesZoledronic Acid

Identifiers

PMID25884398
PMCPMC4401508
OpenAlexW2142372056

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.