Raloxifene Improves Bone Mechanical Properties in Mice Previously Treated with Zoledronate

Cory N. Meixner, Mohammad W. Aref, Aryaman Gupta, Erin M B McNerny, Drew Brown, Joseph M. Wallace, Matthew Allen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Bisphosphonates represent the gold-standard pharmaceutical agent for reducing fracture risk. Long-term treatment with bisphosphonates can result in tissue brittleness which in rare clinical cases manifests as atypical femoral fracture. Although this has led to an increasing call for bisphosphonate cessation, few studies have investigated therapeutic options for follow-up treatment. The goal of this study was to test the hypothesis that treatment with raloxifene, a drug that has cell-independent effects on bone mechanical material properties, could reverse the compromised mechanical properties that occur following zoledronate treatment. Skeletally mature male C57Bl/6J mice were treated with vehicle (VEH), zoledronate (ZOL), or ZOL followed by raloxifene (RAL; 2 different doses). At the conclusion of 8 weeks of treatment, femora were collected and assessed with microCT and mechanical testing. Trabecular BV/TV was significantly higher in all treated animals compared to VEH with both RAL groups having significantly higher BV/TV compared to ZOL (+21%). All three drug-treated groups had significantly more cortical bone area, higher cortical thickness, and greater moment of inertia at the femoral mid-diaphysis compared to VEH with no difference among the three treated groups. All three drug-treated groups had significantly higher ultimate load compared to VEH-treated animals (+14 to 18%). Both doses of RAL resulted in significantly higher displacement values compared to ZOL-treated animals (+25 to +50%). In conclusion, the current work shows beneficial effects of raloxifene in animals previously treated with zoledronate. The higher mechanical properties of raloxifene-treated animals, combined with similar cortical bone geometry compared to animals treated with zoledronate, suggest that the raloxifene treatment is enhancing mechanical material properties of the tissue.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalCalcified Tissue International
DOIs
StateAccepted/In press - Feb 28 2017

Fingerprint

zoledronic acid
Bone and Bones
Diphosphonates
Pharmaceutical Preparations
X-Ray Microtomography
Diaphyses
Femoral Fractures
Reducing Agents
Thigh
Raloxifene Hydrochloride
Gold
Femur

Keywords

  • Bisphosphonate
  • Bone quality
  • Mechanical properties
  • SERMs

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

Cite this

Raloxifene Improves Bone Mechanical Properties in Mice Previously Treated with Zoledronate. / Meixner, Cory N.; Aref, Mohammad W.; Gupta, Aryaman; McNerny, Erin M B; Brown, Drew; Wallace, Joseph M.; Allen, Matthew.

In: Calcified Tissue International, 28.02.2017, p. 1-7.

Research output: Contribution to journalArticle

Meixner, Cory N. ; Aref, Mohammad W. ; Gupta, Aryaman ; McNerny, Erin M B ; Brown, Drew ; Wallace, Joseph M. ; Allen, Matthew. / Raloxifene Improves Bone Mechanical Properties in Mice Previously Treated with Zoledronate. In: Calcified Tissue International. 2017 ; pp. 1-7.
@article{7e1895caf0724a61b98a72d3dfc4a283,
title = "Raloxifene Improves Bone Mechanical Properties in Mice Previously Treated with Zoledronate",
abstract = "Bisphosphonates represent the gold-standard pharmaceutical agent for reducing fracture risk. Long-term treatment with bisphosphonates can result in tissue brittleness which in rare clinical cases manifests as atypical femoral fracture. Although this has led to an increasing call for bisphosphonate cessation, few studies have investigated therapeutic options for follow-up treatment. The goal of this study was to test the hypothesis that treatment with raloxifene, a drug that has cell-independent effects on bone mechanical material properties, could reverse the compromised mechanical properties that occur following zoledronate treatment. Skeletally mature male C57Bl/6J mice were treated with vehicle (VEH), zoledronate (ZOL), or ZOL followed by raloxifene (RAL; 2 different doses). At the conclusion of 8 weeks of treatment, femora were collected and assessed with microCT and mechanical testing. Trabecular BV/TV was significantly higher in all treated animals compared to VEH with both RAL groups having significantly higher BV/TV compared to ZOL (+21{\%}). All three drug-treated groups had significantly more cortical bone area, higher cortical thickness, and greater moment of inertia at the femoral mid-diaphysis compared to VEH with no difference among the three treated groups. All three drug-treated groups had significantly higher ultimate load compared to VEH-treated animals (+14 to 18{\%}). Both doses of RAL resulted in significantly higher displacement values compared to ZOL-treated animals (+25 to +50{\%}). In conclusion, the current work shows beneficial effects of raloxifene in animals previously treated with zoledronate. The higher mechanical properties of raloxifene-treated animals, combined with similar cortical bone geometry compared to animals treated with zoledronate, suggest that the raloxifene treatment is enhancing mechanical material properties of the tissue.",
keywords = "Bisphosphonate, Bone quality, Mechanical properties, SERMs",
author = "Meixner, {Cory N.} and Aref, {Mohammad W.} and Aryaman Gupta and McNerny, {Erin M B} and Drew Brown and Wallace, {Joseph M.} and Matthew Allen",
year = "2017",
month = "2",
day = "28",
doi = "10.1007/s00223-017-0257-4",
language = "English (US)",
pages = "1--7",
journal = "Calcified Tissue International",
issn = "0171-967X",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Raloxifene Improves Bone Mechanical Properties in Mice Previously Treated with Zoledronate

AU - Meixner, Cory N.

AU - Aref, Mohammad W.

AU - Gupta, Aryaman

AU - McNerny, Erin M B

AU - Brown, Drew

AU - Wallace, Joseph M.

AU - Allen, Matthew

PY - 2017/2/28

Y1 - 2017/2/28

N2 - Bisphosphonates represent the gold-standard pharmaceutical agent for reducing fracture risk. Long-term treatment with bisphosphonates can result in tissue brittleness which in rare clinical cases manifests as atypical femoral fracture. Although this has led to an increasing call for bisphosphonate cessation, few studies have investigated therapeutic options for follow-up treatment. The goal of this study was to test the hypothesis that treatment with raloxifene, a drug that has cell-independent effects on bone mechanical material properties, could reverse the compromised mechanical properties that occur following zoledronate treatment. Skeletally mature male C57Bl/6J mice were treated with vehicle (VEH), zoledronate (ZOL), or ZOL followed by raloxifene (RAL; 2 different doses). At the conclusion of 8 weeks of treatment, femora were collected and assessed with microCT and mechanical testing. Trabecular BV/TV was significantly higher in all treated animals compared to VEH with both RAL groups having significantly higher BV/TV compared to ZOL (+21%). All three drug-treated groups had significantly more cortical bone area, higher cortical thickness, and greater moment of inertia at the femoral mid-diaphysis compared to VEH with no difference among the three treated groups. All three drug-treated groups had significantly higher ultimate load compared to VEH-treated animals (+14 to 18%). Both doses of RAL resulted in significantly higher displacement values compared to ZOL-treated animals (+25 to +50%). In conclusion, the current work shows beneficial effects of raloxifene in animals previously treated with zoledronate. The higher mechanical properties of raloxifene-treated animals, combined with similar cortical bone geometry compared to animals treated with zoledronate, suggest that the raloxifene treatment is enhancing mechanical material properties of the tissue.

AB - Bisphosphonates represent the gold-standard pharmaceutical agent for reducing fracture risk. Long-term treatment with bisphosphonates can result in tissue brittleness which in rare clinical cases manifests as atypical femoral fracture. Although this has led to an increasing call for bisphosphonate cessation, few studies have investigated therapeutic options for follow-up treatment. The goal of this study was to test the hypothesis that treatment with raloxifene, a drug that has cell-independent effects on bone mechanical material properties, could reverse the compromised mechanical properties that occur following zoledronate treatment. Skeletally mature male C57Bl/6J mice were treated with vehicle (VEH), zoledronate (ZOL), or ZOL followed by raloxifene (RAL; 2 different doses). At the conclusion of 8 weeks of treatment, femora were collected and assessed with microCT and mechanical testing. Trabecular BV/TV was significantly higher in all treated animals compared to VEH with both RAL groups having significantly higher BV/TV compared to ZOL (+21%). All three drug-treated groups had significantly more cortical bone area, higher cortical thickness, and greater moment of inertia at the femoral mid-diaphysis compared to VEH with no difference among the three treated groups. All three drug-treated groups had significantly higher ultimate load compared to VEH-treated animals (+14 to 18%). Both doses of RAL resulted in significantly higher displacement values compared to ZOL-treated animals (+25 to +50%). In conclusion, the current work shows beneficial effects of raloxifene in animals previously treated with zoledronate. The higher mechanical properties of raloxifene-treated animals, combined with similar cortical bone geometry compared to animals treated with zoledronate, suggest that the raloxifene treatment is enhancing mechanical material properties of the tissue.

KW - Bisphosphonate

KW - Bone quality

KW - Mechanical properties

KW - SERMs

UR - http://www.scopus.com/inward/record.url?scp=85013996027&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85013996027&partnerID=8YFLogxK

U2 - 10.1007/s00223-017-0257-4

DO - 10.1007/s00223-017-0257-4

M3 - Article

C2 - 28246928

AN - SCOPUS:85013996027

SP - 1

EP - 7

JO - Calcified Tissue International

JF - Calcified Tissue International

SN - 0171-967X

ER -