Theoretical analysis of alendronate and risedronate effects on canine vertebral remodeling and microdamage

Xiang Wang, Antonia M. Erickson, Matthew Allen, David Burr, R. Bruce Martin, Scott J. Hazelwood

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Bisphosphonates suppress bone remodeling activity, increase bone volume, and significantly reduce fracture risk in individuals with osteoporosis and other metabolic bone diseases. The objectives of the current study were to develop a mathematical model that simulates control and 1 year experimental results following bisphosphonate treatment (alendronate or risedronate) in the canine fourth lumbar vertebral body, validate the model by comparing simulation predictions to 3 year experimental results, and then use the model to predict potential long term effects of bisphosphonates on remodeling and microdamage accumulation. To investigate the effects of bisphosphonates on bone volume and microdamage, a mechanistic biological model was modified from previous versions to simulate remodeling in a representative volume of vertebral trabecular bone in dogs treated with various doses of alendronate or risedronate, including doses equivalent to those used for treatment of post-menopausal osteoporosis in humans. Bisphosphonates were assumed to affect remodeling by suppressing basic multicellular unit activation and reducing resorption area. Model simulation results for trabecular bone volume fraction, microdamage, and activation frequency following 1 year of bisphosphonate treatment are consistent with experimental measurements. The model predicts that trabecular bone volume initially increases rapidly with 1 year of bisphosphonate treatment, and continues to slowly rise between 1 and 3 years of treatment. The model also predicts that microdamage initially increases rapidly, 0.5-1.5-fold for alendronate or risedronate during the first year of treatment, and reaches its maximum value by 2.5 years before trending downward for all dosages. The model developed in this study suggests that increasing bone volume fraction with long term bisphosphonate treatment may sufficiently reduce strain and damage formation rate so that microdamage does not accumulate above that which is initiated in the first two years of treatment.

Original languageEnglish
Pages (from-to)938-944
Number of pages7
JournalJournal of Biomechanics
Volume42
Issue number7
DOIs
StatePublished - May 11 2009

Fingerprint

Alendronate
Diphosphonates
Canidae
Bone
Bone and Bones
Volume fraction
Chemical activation
Biological Models
Postmenopausal Osteoporosis
Risedronate Sodium
Bone Remodeling
Metabolic Bone Diseases
Osteoporosis
Theoretical Models
Dogs
Mathematical models

Keywords

  • Alendronate
  • Bisphosphonate
  • BMU
  • Bone remodeling
  • Canine
  • Microdamage
  • Risedronate
  • Simulation

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Rehabilitation
  • Biophysics
  • Biomedical Engineering

Cite this

Theoretical analysis of alendronate and risedronate effects on canine vertebral remodeling and microdamage. / Wang, Xiang; Erickson, Antonia M.; Allen, Matthew; Burr, David; Martin, R. Bruce; Hazelwood, Scott J.

In: Journal of Biomechanics, Vol. 42, No. 7, 11.05.2009, p. 938-944.

Research output: Contribution to journalArticle

Wang, Xiang ; Erickson, Antonia M. ; Allen, Matthew ; Burr, David ; Martin, R. Bruce ; Hazelwood, Scott J. / Theoretical analysis of alendronate and risedronate effects on canine vertebral remodeling and microdamage. In: Journal of Biomechanics. 2009 ; Vol. 42, No. 7. pp. 938-944.
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