Evidence map›Paper›PMID 24468719›Full record

ArticleBone2014

Bone cell-independent benefits of raloxifene on the skeleton: a novel mechanism for improving bone material properties.

Maxime A Gallant, Drew M Brown, Max Hammond, Joseph M Wallace, Jiang Du, Alix C Deymier-Black, Jonathan D Almer, Stuart R Stock, Matthew R Allen, David B Burr

Abstract read
In one paragraph

Article in Bone, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
9.5field-weighted citation impact, top 1% 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

48 citing papers in PubMed, 96 citations in OpenAlex.

  1. The comparison of alendronate and raloxifene after denosumab (CARD) study: A comparative efficacy trial.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024
    Trial
  2. Article
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  4. Bone Fragility: Time to Address the Matrix.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026
    Article
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  7. Review
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  10. Synthesis Studies and the Evaluation of CACS medicinal chemistry letters · 2024
    Article
  11. Article
  12. Article
  13. Elucidating the role of water in collagen self-assembly by isotopically modulating collagen hydration.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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  15. Article
  16. Review
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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

10 authors at 5 institutions in 1 country.

Maxime A GallantDepartment of Anatomy & Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr, MS-5035, Indianapolis, IN 46202, USA.
Drew M BrownDepartment of Anatomy & Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr, MS-5035, Indianapolis, IN 46202, USA.
Max HammondWeldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Drive, West Lafayette, IN 47907, USA.
Joseph M WallaceDepartment of Biomedical Engineering, Indiana University-Purdue University at Indianapolis, 723 West Michigan Street, SL 220, Indianapolis, IN 46202, USA.
Jiang DuDepartment of Radiology, University of California, 200 West Arbor Drive, MC 0834 San Diego, CA 92103, USA.
Alix C Deymier-BlackDepartment of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Cook Hall Room 2036, Evanston, IL 60208, USA.
Jonathan D AlmerAdvanced Photon Source, Argonne National Laboratory, Building 401, 9700 S. Cass Avenue, Argonne, IL 60439, USA.
Stuart R StockDepartment of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Abbott Hall Suite 810, 710 N Lake Shore Drive, Chicago, IL 60611, USA.
Matthew R AllenDepartment of Anatomy & Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr, MS-5035, Indianapolis, IN 46202, USA.
David B BurrDepartment of Anatomy & Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr, MS-5035, Indianapolis, IN 46202, USA; Department of Biomedical Engineering, Indiana University-Purdue University at Indianapolis, 723 West Michigan Street, SL 220, Indianapolis, IN 46202, USA. Electronic address: dburr@iupui.edu.
Indiana University – Purdue University Indianapolis · USNorthwestern University · USArgonne National Laboratory · USPurdue University West Lafayette · USUniversity of Indianapolis · US

Funding

Remodeling Suppression--Damage and bone toughnessR01AR047838 · NIAMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI BURR, DAVID B · 2002 to 2011
$3.6M
NIAMS NIH HHS R01 AR047838
6 · The paper itself

Abstract

Raloxifene is an FDA approved agent used to treat bone loss and decrease fracture risk. In clinical trials and animal studies, raloxifene reduces fracture risk and improves bone mechanical properties, but the mechanisms of action remain unclear because these benefits occur largely independent of changes to bone mass. Using a novel experimental approach, machined bone beams, both from mature male canine and human male donors, were depleted of living cells and then exposed to raloxifene ex vivo. Our data show that ex vivo exposure of non-viable bone to raloxifene improves intrinsic toughness, both in canine and human cortical bone beams tested by 4-point bending. These effects are cell-independent and appear to be mediated by an increase in matrix bound water, assessed using basic gravimetric weighing and sophisticated ultrashort echo time magnetic resonance imaging. The hydroxyl groups (OH) on raloxifene were shown to be important in both the water and toughness increases. Wide and small angle X-ray scattering patterns during 4-pt bending show that raloxifene alters the transfer of load between the collagen matrix and the mineral crystals, placing lower strains on the mineral, and allowing greater overall deformation prior to failure. Collectively, these findings provide a possible mechanistic explanation for the therapeutic effect of raloxifene and more importantly identify a cell-independent mechanism that can be utilized for novel pharmacological approaches for enhancing bone strength.

Indexed as

AnimalsBiomechanical PhenomenaBone and BonesBone Density Conservation AgentsDogsExtracellular MatrixHumansRaloxifene HydrochlorideSkeletonBone Density Conservation AgentsRaloxifene HydrochlorideMechanical testingRaloxifeneToughnessWater

Identifiers

PMID24468719
PMCPMC3955028
OpenAlexW1988443593

What OpenQuestion holds

Textmetadata
LicenceTDM
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.