Theoretical analysis of alendronate and risedronate effects on canine vertebral remodeling and microdamage |
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| Authors: | Xiang Wang Antonia M Erickson Matthew R Allen David B Burr R Bruce Martin Scott J Hazelwood |
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| Institution: | 1. Lawrence J. Ellison Musculoskeletal Research Center, University of California Davis Medical Center, Sacramento, CA 95817, United States;2. Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, United States;3. Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, United States;4. Biomedical and General Engineering Department, California Polytechnic State University, San Luis Obispo, CA 93407, United States;1. Service de rhumatologie, CHRU de Besançon, Besançon, France;2. Servie des maladies infectieuses et tropicales, CHRU de Besançon, Besançon, France;3. Service de neurochirurgie, CHRU de Besançon, Besançon, France;1. LIOMM, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Calle 47 y 115, CP (1900) La Plata, Argentina;2. Facultad de Ingeniería, Universidad Nacional de La Plata, Calle 116 y 48, B1900TAG La Plata, Argentina;1. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Ankara, Ankara, Turkey;2. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Kirikkale, Kirikkale, Turkey;3. Department of Biochemistry, Faculty of Veterinary Medicine, University of Ankara, Ankara, Turkey;1. Faculty of Medicine, University of Helsinki, Finland;2. Department of Anaesthesia, Intensive Care Medicine, Emergency Medicine and Pain Medicine, Helsinki University Central Hospital, PO Box 140, 00029 HUS, Finland |
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| 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. |
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