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Local bone formation due to combined mechanical loading and intermittent hPTH-(1-34) treatment and its correlation to mechanical signal distributions
Authors:MD Roberts  TJ Santner  RT Hart
Institution:1. Department of Biomedical Engineering, Tulane University, New Orleans, LA, USA;2. Department of Statistics, The Ohio State University, Columbus, OH, USA;1. Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA;2. Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark;3. National Institute for Occupational Safety and Health (NIOSH), National Personal Protective Technology Laboratory, Pittsburgh, PA;4. VA Pittsburgh HCS and Department of Neurology, University of Pittsburgh, Pittsburgh, PA;5. Research Service, Department of Veterans Affairs Medical Center, Portland, OR;6. Sanford Burnham Medical Research Institute, Orlando, FL;7. California Pacific Medical Center Research Institute, San Francisco, CA;1. Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Largo Brambilla 3, 50134 Florence, Italy;2. Department of Surgery and Translational Medicine, University of Florence, Largo Palagi 1, 50139 Florence, Italy;3. Department of Biosciences and Territory, University of Molise, Contrada Fonte Lappone, Pesche 86090 Isernia, Italy;1. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China;2. Wenzhou Medical University, Wenzhou 325027, China;1. Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland;2. Department of Paediatrics and Adolescent Medicine, University of Turku, Turku, Finland;3. City of Turku Welfare Division, Primary Healthcare Services, Turku, Finland;4. Department of Clinical Microbiology, Turku University Hospital, Turku, Finland;5. Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland;1. Dental Research Division, School of Dentistry, Paulista University, São Paulo, SP, Brazil;2. School of Dentistry, Federal University of Maranhão, São Luís, MA, Brazil
Abstract:We evaluated the local response of cortical bone in the rat tibia due to combined treatment with synthetic parathyroid hormone, hPTH-(1-34), and mechanical stimulation by four-point bending. Forty-eight female retired breeder Sprague-Dawley rats were divided into six groups. Mechanically stimulated animals included the following groups: (1) Bend+PTH, (2) Sham+PTH, (3) Bend+Vehicle, (4) Sham+Vehicle. Non-mechanically stimulated animals included a (5) Control group that received neither loading nor injections, and a (6) PTH group that received only hPTH-(1-34) injections. The right limbs of mechanically loaded animals were exposed to a peak force of 50 N for 36 cycles at 2 Hz, three days per week for four weeks, and PTH-treated animals received injections equivalent to 50 μg/kg BW. Fluorochrome labeling was used to measure local formation at 12 sectors about the endocortical periphery. The distributions of endocortical bone formation were compared to the local formation differences between treatment groups and to a variety of potential mechanical stimuli signals. Results indicated that hPTH-(1-34) exerted a potent anabolic effect with near-uniform formation about the endocortical surface, and that localized formation peaks due to bending were further augmented in the presence of hPTH-(1-34) treatment. Correlation of formation patterns to mechanical signal distributions highlighted several candidate signals including the mid-principal stress, the dilatational strain, and the radial gradient of the local radial strain.
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