Zoledronate treatment has different effects in mouse strains with contrasting baseline bone mechanical phenotypes

M. W. Aref, E. M B McNerny, D. Brown, K. J. Jepsen, Matthew Allen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Summary: Two strains of mice with distinct bone morphologies and mechanical properties were treated with zoledronate. Our results show a different response to drug treatment in the two strains providing evidence that baseline properties of structure/material may influence response to zoledronate. Introduction: Bisphosphonates are highly effective in reducing fracture risk, yet some individuals treated with these agents still experience fracture. The goal of this study was to test the hypothesis that genotype influences the effect of zoledronate on bone mechanical properties. Methods: Skeletally mature male mice from genetic backgrounds known to have distinct baseline post-yield properties (C57/B6, high post-yield displacement; A/J, low post-yield displacement) were treated for 8 weeks with saline (VEH) or zoledronate (ZOL, 0.06 mg/kg subcutaneously once every 4 weeks) in a 2 × 2 study design. Ex vivo μCT and mechanical testing (4-pt bending) were conducted on the femur to assess morphological and mechanical differences. Results: Significant drug and/or genotype effects were found for several mechanical properties and significant drug × genotype interactions were found for measures of strength (ultimate force) and brittleness (total displacement, strain to failure). Treatment with ZOL affected bone biomechanical measures of brittleness (total displacement (−25 %) and strain to failure (−23 %)) in B6 mice significantly differently than in A/J mice. This was driven by unique drug × genotype effects on bone geometry in B6 animals yet likely also reflected changes to the tissue properties. Conclusion: These data may support the concept that properties of the bone geometry and/or tissue at the time of treatment initiation play a role in determining the bone’s mechanical response to zoledronate treatment.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalOsteoporosis International
DOIs
StateAccepted/In press - Jul 20 2016

Fingerprint

zoledronic acid
Phenotype
Bone and Bones
Genotype
Pharmaceutical Preparations
Diphosphonates
Drug Interactions
Femur

Keywords

  • Bisphosphonate
  • Mechanical properties
  • Remodeling suppression
  • Toughness

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Zoledronate treatment has different effects in mouse strains with contrasting baseline bone mechanical phenotypes. / Aref, M. W.; McNerny, E. M B; Brown, D.; Jepsen, K. J.; Allen, Matthew.

In: Osteoporosis International, 20.07.2016, p. 1-7.

Research output: Contribution to journalArticle

@article{55ecb2fe6a984db3b903f67e8abfac65,
title = "Zoledronate treatment has different effects in mouse strains with contrasting baseline bone mechanical phenotypes",
abstract = "Summary: Two strains of mice with distinct bone morphologies and mechanical properties were treated with zoledronate. Our results show a different response to drug treatment in the two strains providing evidence that baseline properties of structure/material may influence response to zoledronate. Introduction: Bisphosphonates are highly effective in reducing fracture risk, yet some individuals treated with these agents still experience fracture. The goal of this study was to test the hypothesis that genotype influences the effect of zoledronate on bone mechanical properties. Methods: Skeletally mature male mice from genetic backgrounds known to have distinct baseline post-yield properties (C57/B6, high post-yield displacement; A/J, low post-yield displacement) were treated for 8 weeks with saline (VEH) or zoledronate (ZOL, 0.06 mg/kg subcutaneously once every 4 weeks) in a 2 × 2 study design. Ex vivo μCT and mechanical testing (4-pt bending) were conducted on the femur to assess morphological and mechanical differences. Results: Significant drug and/or genotype effects were found for several mechanical properties and significant drug × genotype interactions were found for measures of strength (ultimate force) and brittleness (total displacement, strain to failure). Treatment with ZOL affected bone biomechanical measures of brittleness (total displacement (−25 {\%}) and strain to failure (−23 {\%})) in B6 mice significantly differently than in A/J mice. This was driven by unique drug × genotype effects on bone geometry in B6 animals yet likely also reflected changes to the tissue properties. Conclusion: These data may support the concept that properties of the bone geometry and/or tissue at the time of treatment initiation play a role in determining the bone’s mechanical response to zoledronate treatment.",
keywords = "Bisphosphonate, Mechanical properties, Remodeling suppression, Toughness",
author = "Aref, {M. W.} and McNerny, {E. M B} and D. Brown and Jepsen, {K. J.} and Matthew Allen",
year = "2016",
month = "7",
day = "20",
doi = "10.1007/s00198-016-3701-9",
language = "English (US)",
pages = "1--7",
journal = "Osteoporosis International",
issn = "0937-941X",
publisher = "Springer London",

}

TY - JOUR

T1 - Zoledronate treatment has different effects in mouse strains with contrasting baseline bone mechanical phenotypes

AU - Aref, M. W.

AU - McNerny, E. M B

AU - Brown, D.

AU - Jepsen, K. J.

AU - Allen, Matthew

PY - 2016/7/20

Y1 - 2016/7/20

N2 - Summary: Two strains of mice with distinct bone morphologies and mechanical properties were treated with zoledronate. Our results show a different response to drug treatment in the two strains providing evidence that baseline properties of structure/material may influence response to zoledronate. Introduction: Bisphosphonates are highly effective in reducing fracture risk, yet some individuals treated with these agents still experience fracture. The goal of this study was to test the hypothesis that genotype influences the effect of zoledronate on bone mechanical properties. Methods: Skeletally mature male mice from genetic backgrounds known to have distinct baseline post-yield properties (C57/B6, high post-yield displacement; A/J, low post-yield displacement) were treated for 8 weeks with saline (VEH) or zoledronate (ZOL, 0.06 mg/kg subcutaneously once every 4 weeks) in a 2 × 2 study design. Ex vivo μCT and mechanical testing (4-pt bending) were conducted on the femur to assess morphological and mechanical differences. Results: Significant drug and/or genotype effects were found for several mechanical properties and significant drug × genotype interactions were found for measures of strength (ultimate force) and brittleness (total displacement, strain to failure). Treatment with ZOL affected bone biomechanical measures of brittleness (total displacement (−25 %) and strain to failure (−23 %)) in B6 mice significantly differently than in A/J mice. This was driven by unique drug × genotype effects on bone geometry in B6 animals yet likely also reflected changes to the tissue properties. Conclusion: These data may support the concept that properties of the bone geometry and/or tissue at the time of treatment initiation play a role in determining the bone’s mechanical response to zoledronate treatment.

AB - Summary: Two strains of mice with distinct bone morphologies and mechanical properties were treated with zoledronate. Our results show a different response to drug treatment in the two strains providing evidence that baseline properties of structure/material may influence response to zoledronate. Introduction: Bisphosphonates are highly effective in reducing fracture risk, yet some individuals treated with these agents still experience fracture. The goal of this study was to test the hypothesis that genotype influences the effect of zoledronate on bone mechanical properties. Methods: Skeletally mature male mice from genetic backgrounds known to have distinct baseline post-yield properties (C57/B6, high post-yield displacement; A/J, low post-yield displacement) were treated for 8 weeks with saline (VEH) or zoledronate (ZOL, 0.06 mg/kg subcutaneously once every 4 weeks) in a 2 × 2 study design. Ex vivo μCT and mechanical testing (4-pt bending) were conducted on the femur to assess morphological and mechanical differences. Results: Significant drug and/or genotype effects were found for several mechanical properties and significant drug × genotype interactions were found for measures of strength (ultimate force) and brittleness (total displacement, strain to failure). Treatment with ZOL affected bone biomechanical measures of brittleness (total displacement (−25 %) and strain to failure (−23 %)) in B6 mice significantly differently than in A/J mice. This was driven by unique drug × genotype effects on bone geometry in B6 animals yet likely also reflected changes to the tissue properties. Conclusion: These data may support the concept that properties of the bone geometry and/or tissue at the time of treatment initiation play a role in determining the bone’s mechanical response to zoledronate treatment.

KW - Bisphosphonate

KW - Mechanical properties

KW - Remodeling suppression

KW - Toughness

UR - http://www.scopus.com/inward/record.url?scp=84979233713&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979233713&partnerID=8YFLogxK

U2 - 10.1007/s00198-016-3701-9

DO - 10.1007/s00198-016-3701-9

M3 - Article

C2 - 27439372

AN - SCOPUS:84979233713

SP - 1

EP - 7

JO - Osteoporosis International

JF - Osteoporosis International

SN - 0937-941X

ER -