Three years of alendronate treatment does not continue to decrease microstructural stresses and strains associated with trabecular microdamage initiation beyond those at 1 year
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The effects of a 3-year alendronate treatment on trabecular stresses/strains associated with microdamage initiation were investigated using finite element modeling (FEM). Severely damaged trabeculae in the low-dose treatment group were associated with increased stresses compared with the high-dose treatment group (p = 0.006) and approached significance in the control group (p = 0.02).
Alendronate, a commonly prescribed anti-remodeling agent, decreases fracture risk in the vertebrae, hip, and wrist of osteoporotic individuals. However, evaluation of microdamage accumulation in animal and human studies shows increased microdamage density relative to controls. Microstructural von Mises stresses associated with severe and linear damage have been found to decrease after 1 year of alendronate treatment. In the present study, stresses/strains associated with damage were assessed after 3 years of treatment to determine whether they continued to decrease with increased treatment duration.
Microdamaged trabeculae visualized with fluorescent microscopy were associated with stresses and strains obtained using image-based FEM. Stresses/strains associated with severe, diffuse, and linearly damaged and undamaged trabeculae were compared among groups treated for 3 years with an osteoporotic treatment dose of alendronate, a Paget’s disease treatment dose of alendronate, or saline control. Architectural characteristics and mineralization were also analyzed from three-dimensional microcomputed tomography reconstructed images.
Severely damaged trabeculae in the osteoporotic treatment dose group were associated with increased stress compared with the Paget’s disease treatment dose group (p = 0.006) and approached significance compared to the control group (p = 0.02). Trabecular mineralization in severely damaged trabeculae of the low-dose treatment group was significantly greater compared to severely damaged trabeculae in the high-dose treatment and control group, suggesting that changes at the tissue level may play a role in these findings.
Trabecular level stresses associated with microdamage do not continue to decrease with prolonged alendronate treatment. Changes in mineralization may account for these findings.
KeywordsBisphosphonate Finite element modeling Microcomputed tomography Microdamage Osteoporosis
This study was supported by NIH grants 5R01AG027249, 5R01AR047838, and 5T32AR007581. Merck kindly provided the alendronate. The micro-CT system was provided by an NSF Major Research Instrumentation Award (9977551).
Conflicts of interest
Dr. Burr receives grant/research support from Eli Lilly, Procter and Gamble Pharmaceuticals, The Alliance for Better Bone Health, Pfizer, and NephroGenex. He is a consultant/scientific advisor for Eli Lilly, Procter and Gamble Pharmaceuticals, Amgen, and PharmaLegacy. He is a speaker for Amgen and Eli Lilly. The other authors have no conflicts of interest.
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