One year of alendronate treatment lowers microstructural stresses associated with trabecular microdamage initiation

Jessica M. O'Neal, Tamim Diab, Matthew Allen, Brani Vidakovic, David Burr, Robert E. Guldberg

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Alendronate, an anti-remodeling agent, is commonly used to treat patients suffering from osteoporosis by increasing bone mineral density. Though fracture risk is lowered, an increase in microdamage accumulation has been documented in patients receiving alendronate, leading to questions about the potentially detrimental effects of remodeling suppression on the local tissue (material) properties. In this study, trabecular bone cores from the distal femur of beagle dogs treated for one year with alendronate, at doses scaled by weight to approximate osteoporotic and Paget's disease treatment doses in humans, were subjected to uniaxial compression to induce microdamage. Tissue level von Mises stresses were computed for alendronate-treated and non-treated controls using finite element analysis and correlated to microdamage morphology. Using a modified version of the Moore and Gibson classification for damage morphology, we determined that the von Mises stress for trabeculae exhibiting severe and linear microcrack patterns was decreased by approximately 25% in samples treated with alendronate compared with non-treated controls (p<0.01), whereas there was no reduction in the von Mises stress state for diffuse microdamage formation. Furthermore, an examination of the architectural and structural characteristics of damaged trabeculae demonstrated that severely damaged trabeculae were thinner, more aligned with the loading axis, and less mineralized than undamaged trabeculae in alendronate-treated samples (p<0.01). Similar relationships with damage morphology were found only with trabecular orientation in vehicle-treated control dogs. These results indicate that changes in bone's architecture and matrix properties associated with one year of alendronate administration reduce trabecular bone's ability to resist the formation of loading-induced severe and linear microcracks, both of which dissipate less energy prior to fracture than does diffuse damage.

Original languageEnglish
Pages (from-to)241-247
Number of pages7
JournalBone
Volume47
Issue number2
DOIs
StatePublished - Aug 2010

Fingerprint

Alendronate
Therapeutics
Dogs
Finite Element Analysis
Bone Matrix
Bone Density
Femur
Osteoporosis
Weights and Measures

Keywords

  • Bisphosphonate
  • Bone quality
  • Finite element modeling
  • Microcomputed tomography
  • Osteoporosis

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Medicine(all)

Cite this

One year of alendronate treatment lowers microstructural stresses associated with trabecular microdamage initiation. / O'Neal, Jessica M.; Diab, Tamim; Allen, Matthew; Vidakovic, Brani; Burr, David; Guldberg, Robert E.

In: Bone, Vol. 47, No. 2, 08.2010, p. 241-247.

Research output: Contribution to journalArticle

O'Neal, Jessica M. ; Diab, Tamim ; Allen, Matthew ; Vidakovic, Brani ; Burr, David ; Guldberg, Robert E. / One year of alendronate treatment lowers microstructural stresses associated with trabecular microdamage initiation. In: Bone. 2010 ; Vol. 47, No. 2. pp. 241-247.
@article{b87bf08d8de14805b364471061043a83,
title = "One year of alendronate treatment lowers microstructural stresses associated with trabecular microdamage initiation",
abstract = "Alendronate, an anti-remodeling agent, is commonly used to treat patients suffering from osteoporosis by increasing bone mineral density. Though fracture risk is lowered, an increase in microdamage accumulation has been documented in patients receiving alendronate, leading to questions about the potentially detrimental effects of remodeling suppression on the local tissue (material) properties. In this study, trabecular bone cores from the distal femur of beagle dogs treated for one year with alendronate, at doses scaled by weight to approximate osteoporotic and Paget's disease treatment doses in humans, were subjected to uniaxial compression to induce microdamage. Tissue level von Mises stresses were computed for alendronate-treated and non-treated controls using finite element analysis and correlated to microdamage morphology. Using a modified version of the Moore and Gibson classification for damage morphology, we determined that the von Mises stress for trabeculae exhibiting severe and linear microcrack patterns was decreased by approximately 25{\%} in samples treated with alendronate compared with non-treated controls (p<0.01), whereas there was no reduction in the von Mises stress state for diffuse microdamage formation. Furthermore, an examination of the architectural and structural characteristics of damaged trabeculae demonstrated that severely damaged trabeculae were thinner, more aligned with the loading axis, and less mineralized than undamaged trabeculae in alendronate-treated samples (p<0.01). Similar relationships with damage morphology were found only with trabecular orientation in vehicle-treated control dogs. These results indicate that changes in bone's architecture and matrix properties associated with one year of alendronate administration reduce trabecular bone's ability to resist the formation of loading-induced severe and linear microcracks, both of which dissipate less energy prior to fracture than does diffuse damage.",
keywords = "Bisphosphonate, Bone quality, Finite element modeling, Microcomputed tomography, Osteoporosis",
author = "O'Neal, {Jessica M.} and Tamim Diab and Matthew Allen and Brani Vidakovic and David Burr and Guldberg, {Robert E.}",
year = "2010",
month = "8",
doi = "10.1016/j.bone.2010.05.016",
language = "English",
volume = "47",
pages = "241--247",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - One year of alendronate treatment lowers microstructural stresses associated with trabecular microdamage initiation

AU - O'Neal, Jessica M.

AU - Diab, Tamim

AU - Allen, Matthew

AU - Vidakovic, Brani

AU - Burr, David

AU - Guldberg, Robert E.

PY - 2010/8

Y1 - 2010/8

N2 - Alendronate, an anti-remodeling agent, is commonly used to treat patients suffering from osteoporosis by increasing bone mineral density. Though fracture risk is lowered, an increase in microdamage accumulation has been documented in patients receiving alendronate, leading to questions about the potentially detrimental effects of remodeling suppression on the local tissue (material) properties. In this study, trabecular bone cores from the distal femur of beagle dogs treated for one year with alendronate, at doses scaled by weight to approximate osteoporotic and Paget's disease treatment doses in humans, were subjected to uniaxial compression to induce microdamage. Tissue level von Mises stresses were computed for alendronate-treated and non-treated controls using finite element analysis and correlated to microdamage morphology. Using a modified version of the Moore and Gibson classification for damage morphology, we determined that the von Mises stress for trabeculae exhibiting severe and linear microcrack patterns was decreased by approximately 25% in samples treated with alendronate compared with non-treated controls (p<0.01), whereas there was no reduction in the von Mises stress state for diffuse microdamage formation. Furthermore, an examination of the architectural and structural characteristics of damaged trabeculae demonstrated that severely damaged trabeculae were thinner, more aligned with the loading axis, and less mineralized than undamaged trabeculae in alendronate-treated samples (p<0.01). Similar relationships with damage morphology were found only with trabecular orientation in vehicle-treated control dogs. These results indicate that changes in bone's architecture and matrix properties associated with one year of alendronate administration reduce trabecular bone's ability to resist the formation of loading-induced severe and linear microcracks, both of which dissipate less energy prior to fracture than does diffuse damage.

AB - Alendronate, an anti-remodeling agent, is commonly used to treat patients suffering from osteoporosis by increasing bone mineral density. Though fracture risk is lowered, an increase in microdamage accumulation has been documented in patients receiving alendronate, leading to questions about the potentially detrimental effects of remodeling suppression on the local tissue (material) properties. In this study, trabecular bone cores from the distal femur of beagle dogs treated for one year with alendronate, at doses scaled by weight to approximate osteoporotic and Paget's disease treatment doses in humans, were subjected to uniaxial compression to induce microdamage. Tissue level von Mises stresses were computed for alendronate-treated and non-treated controls using finite element analysis and correlated to microdamage morphology. Using a modified version of the Moore and Gibson classification for damage morphology, we determined that the von Mises stress for trabeculae exhibiting severe and linear microcrack patterns was decreased by approximately 25% in samples treated with alendronate compared with non-treated controls (p<0.01), whereas there was no reduction in the von Mises stress state for diffuse microdamage formation. Furthermore, an examination of the architectural and structural characteristics of damaged trabeculae demonstrated that severely damaged trabeculae were thinner, more aligned with the loading axis, and less mineralized than undamaged trabeculae in alendronate-treated samples (p<0.01). Similar relationships with damage morphology were found only with trabecular orientation in vehicle-treated control dogs. These results indicate that changes in bone's architecture and matrix properties associated with one year of alendronate administration reduce trabecular bone's ability to resist the formation of loading-induced severe and linear microcracks, both of which dissipate less energy prior to fracture than does diffuse damage.

KW - Bisphosphonate

KW - Bone quality

KW - Finite element modeling

KW - Microcomputed tomography

KW - Osteoporosis

UR - http://www.scopus.com/inward/record.url?scp=77955984773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955984773&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2010.05.016

DO - 10.1016/j.bone.2010.05.016

M3 - Article

VL - 47

SP - 241

EP - 247

JO - Bone

JF - Bone

SN - 8756-3282

IS - 2

ER -