Duration-dependent effects of clinically relevant oral alendronate doses on cortical bone toughness in beagle dogs |
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| Affiliation: | 1. Department of Anatomy and Cell Biology, Indiana University School of Medicine, USA;2. Department of Biostatistics, Indiana University School of Medicine, USA;1. Department of Environmental Toxicology, University of California, Davis, Davis, CA 95616, USA;2. California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA;3. Division of Morphological Sciences and Biostatistics, Boonshoft School of Medicine, Wright State University, Dayton, OH 45434, USA;1. Department of Health Industry Management, Kainan University, Taoyuan, Taiwan;2. Department of Clinical Pharmacy, Taipei Medical University, Taipei, Taiwan;3. Department of Pharmacy, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;4. Department of Obstetrics and Gynecology, Branch of Hsinchu, Taipei Veterans General Hospital, Taiwan;5. Department Human Resource, Far Eastern Memorial Hospital, New Taipei City, Taiwan;6. Department of Healthcare Management, Yuanpei University of Medical Technology, Hsinchu, Taiwan;7. Department of Neurosurgery, Clinical Research Center, Graduate Institute of Injury Prevention and Control, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;1. Department of Human Biosciences, La Trobe University, Bundoora 3086, Australia;2. Department of Physiology, The University of Melbourne, Parkville 3010, Australia;3. Department of Medicine, The University of Melbourne, Parkville 3050, Australia;4. Bone and Mineral Medicine, Royal Melbourne Hospital, Parkville 3050, Australia;1. University of Exeter Medical School, UK;2. School of Psychology, University of Exeter, UK;1. Center for Musculoskeletal Research, Department of Orthopaedics & Rehabilitation, University of Rochester Medical Center, Rochester, NY 14642, United States;2. Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627, United States;3. Department of Orthopaedic Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States |
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| Abstract: | Bisphosphonates (BPs) have been shown to significantly reduce bone toughness in vertebrae within one year when given at clinical doses to dogs. Although BPs also reduce toughness in the cortical bone when given at high doses, their effect on cortical bone material properties when given at clinical doses is less clear. In part, this may be due to the use of small sample sizes that were powered to demonstrate differences in bone mineral density rather than the bone's material properties. Our lab has conducted several studies in which dogs were treated with alendronate at a clinically relevant dose. The goal of this study was to examine these published and unpublished data collectively to determine whether there is a significant time-dependent effect of alendronate on toughness of the cortical bone. This analysis seemed particularly relevant given the recent occurrence of atypical femoral fractures in humans. Differences in the toughness of ribs taken from dogs derived from five separate experiments were measured. The dogs were orally administered saline (CON, 1 ml/kg/day) or alendronate (ALN) at a clinical dose (0.2 mg/kg/day). Treatment duration ranged from 3 months to 3 years. Groups were compared using ANOVA, and time trends analyzed with linear regression analysis. Linear regressions of the percent difference in toughness between CON and ALN at each time point revealed a significant reduction in toughness with longer exposure to ALN. The downward trend was primarily driven by a downward trend in post-yield toughness, whereas toughness in the pre-yield region was not changed relative to CON. These data suggest that a longer duration of treatment with clinical doses of ALN results in deterioration of cortical bone toughness in a time-dependent manner. As the duration of treatment is lengthened, the cortical bone exhibits increasingly brittle behavior. This may be important in assessing the role that long-term BP treatments play in the risk of atypical fractures of the femoral cortical bone in humans. |
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