title: Stiffness and strength of bone in osteoporotic patients treated with varying durations of oral bisphosphonates.
abstract: Apparent modulus and failure stress of trabecular bone structure from 45 women with osteoporosis treated with bisphosphonates for varying durations were studied using finite element analyses and statistical modeling. Following adjustments for patient age and bone volume, increasing bisphosphonate treatment duration for up to 7.3 years was associated with treatment-time-dependent increases in bone apparent modulus and failure stress. Treatment durations exceeding 7.3 years were associated with time-dependent decreases in apparent modulus and failure stress from the peak values observed.
  
  
  
  The purpose of this study was to clarify the relationship between bisphosphonate (BP) treatment duration and human bone quality. This study quantified changes in the apparent modulus and failure stress of trabecular bone biopsied from patients with osteoporosis who were treated with BPs for widely varying durations.
  
  
  
  Forty-five iliac crest bone samples were obtained from women with osteoporosis who were continuously treated with oral BPs for varying periods of up to 16 years. Micro-CT imaging was used to develop three-dimensional virtual models of the trabecular bone from these samples. Apparent modulus and failure stress of these virtual models were determined using finite element analyses (FEA). Polynomial regression and cubic splines, adjusted for relevant (age and BV/TV) covariates, were used to statistically model the data and quantify the relationships between BP treatment duration and apparent modulus or failure stress.
  
  
  
  Second-order polynomial models were needed to relate apparent modulus or failure stress to BP treatment duration. These models showed that these bone quality parameters (a) increased with increasing BP treatment duration up to approximately 7.3 years, (b) reached a maximum at this (~7.3 years) time, and then (c) declined with BP treatment durations exceeding ~7.3 years. A similar result was obtained by modeling with cubic splines.
  
  
  
  Changes in FEA-derived apparent stiffness and failure stress are attributable to changes in trabecular bone structure, which in turn are related to the duration of BP treatment. These relationships are evident even after adjustments are made in the statistical models for changes in age and BV/TV. According to these models, increases in trabecular bone apparent stiffness and failure stress linked to BPs cease and appear to reverse after approximately 7.3 years of treatment. Conclusions regarding optimal BP therapy duration await study of additional bone quality parameters.
authors.affiliation: Department of Biomedical Engineering, University of Kentucky, Lexington, KY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ward
authors.affiliation: Department of Statistics, University of Kentucky, Lexington, KY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wood
authors.affiliation: Department of Mechanical Engineering, University of Kentucky, Lexington, KY, USA.
authors.forename: K
authors.initials: K
authors.lastname: Rouch
authors.affiliation: Department of Biomedical Engineering, University of Kentucky, Lexington, KY, USA.
authors.forename: D
authors.initials: D
authors.lastname: Pienkowski
authors.affiliation: Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, KY, USA. hhmall@uky.edu.|Division of Nephrology, Bone & Mineral Metabolism, University of Kentucky Chandler Medical Center, 800 Rose Street, MN-564, Lexington, KY, 40536-0298, USA. hhmall@uky.edu.
authors.forename: H H
authors.initials: HH
authors.lastname: Malluche
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D003430:Cross-Sectional Studies; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D020342:Finite Element Analysis; D006801:Humans; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D004164:Diphosphonates
keywords: Antiresorptives; Biomechanics; Bone quality; Finite element analyses; Osteoporosis