Abstract
Summary
We aimed to determine the effects of bisphosphonates on mechanical properties independent of changes in bone density. Our results show that at equivalent bone densities, vertebrae from beagles treated with bisphosphonate have equivalent bone strength and reduced bone energy absorption compared to those from untreated animals.
Introduction
Assessing the relationship between mechanical properties and bone density allows a biomechanical evaluation of bone quality, with differences at a given density indicative of altered quality. The purpose of this study was to evaluate the strength-density and energy absorption-density relationships in vertebral bone following a one-year treatment with clinical doses of two different bisphosphonates in beagle dogs.
Methods
Areal bone mineral density (aBMD) and compressive mechanical properties (ultimate load and energy absorption) were assessed on lumbar vertebrae from skeletally mature beagle dogs treated with vehicle (VEH), alendronate (ALN), or risedronate (RIS). Relationships among properties were assessed using analyses of covariance.
Results
Neither treatment altered the strength-density relationship compared to VEH, suggesting increases in vertebral strength with bisphosphonate-treatment are explained by increased density. The energy absorption-density relationship was altered by ALN, resulting in significantly lower energy absorption capacity at a given aBMD compared to both VEH (−22%) and RIS (−14%).
Conclusions
These data document that after adjusting for increased aBMD, vertebrae from animals treated with bisphosphonates have similar strength as those from untreated animals. Conversely, when adjusted for increased aBMD, alendronate treatment, but not risedronate treatment, significantly reduces the energy required for vertebral fracture, indicative of an alteration in bone quality.
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Acknowledgements
The authors thank Dr. Tony Keaveny for insightful discussion regarding the topics addressed in this paper. This work was supported by NIH Grants AR047838 and AR007581 and a research grant from The Alliance for Better Bone Health (Procter & Gamble Pharmaceuticals and sanofi-aventis). Merck and Co. kindly provided the alendronate. This investigation utilized an animal facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR10601-01 from the National Center for Research Resources, National Institutes of Health.
Disclosures
Dr. Allen has research contracts with Eli Lilly and The Alliance for Better Bone Health. Dr. Burr has research contracts from Eli Lilly, Amgen and The Alliance for Better Bone Health. Furthermore, he serves on the Advisory Board for Eli Lilly and Company, and he has received lecture fees from Eli Lilly, The Alliance for Better Bone Health, Amgen, and Roche.
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Allen, M.R., Burr, D.B. Changes in vertebral strength-density and energy absorption-density relationships following bisphosphonate treatment in beagle dogs. Osteoporos Int 19, 95–99 (2008). https://doi.org/10.1007/s00198-007-0451-8
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DOI: https://doi.org/10.1007/s00198-007-0451-8