Effects of parathyroid hormone on cortical porosity,non-enzymatic glycation and bone tissue mechanics in rats with type 2 diabetes mellitus |
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| Institution: | 1. Institute of Biomechanics, TUHH Hamburg University of Technology, Hamburg, Germany;2. Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany;3. Department of Orthopedics, Technische Universität Dresden Medical Center, Dresden, Germany;4. Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany;5. Center for Regenerative Therapies Dresden, Germany;1. Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, St Vincent''s Hospital, Sydney, NSW, Australia;2. Department of Biology and Biochemistry, Bath University, Bath, UK;3. Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia;4. School of Medicine, The University of Notre Dame Australia, Sydney, NSW, Australia;1. Dept. of Orthopaedic Surgery, Center for Diabetes and Endocrine Research, University of Toledo Health Sciences Campus, Toledo, OH 43614, United States;2. Dept. of Physiology and Pharmacology, Center for Diabetes and Endocrine Research, University of Toledo Health Sciences Campus, Toledo, OH 43614, United States;3. Tufts University School of Medicine, and Maine Medical Center Research Institute, Scarborough, ME 04074, United States;1. Adrenal Steroid Group, ANZAC Research Institute, Concord Repatriation General Hospital, Hospital Road, Concord Hospital, NSW 2139, Australia;2. Bone Research Program, ANZAC Research Institute, Concord Repatriation General Hospital, Hospital Road, Concord Hospital, NSW 2139, Australia;1. INSERM UMR 1033, University of Lyon, Lyon, France;2. California Pacific Medical Center Research Institute, San Francisco, CA, USA;3. Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA;4. Park Nicollet Institute, Minneapolis, MN, USA;5. Division of Health Policy and Management, University of Minnesota, Minneapolis, MN, USA;6. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA;7. Center for Health Research, Kaiser Permanente Hawaii, Honolulu, HI, USA;8. Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA;9. Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA;10. Department Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA;11. Department of General Internal Medicine, University Hospital of Bern, Bern, Switzerland;12. Department of Medicine and Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA;13. Center for Chronic Disease Outcomes Research, VA Health Care System, Minneapolis, MN, USA;14. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA;1. Department of Internal Medicine III, Jena University-Hospital, Jena, Germany;2. Institute of Clinical Chemistry and Laboratory Diagnostics, Jena University-Hospital, Jena, Germany;3. Institute of Medical Statistics, Computer Sciences and Documentation, Jena University-Hospital, Jena, Germany |
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| Abstract: | Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and the efficacy of bone-forming agents are unclear. We studied diabetes and parathyroid hormone (PTH) treatment effects on cortical porosity (Ct.Po), non-enzymatic glycation (NEG) and bone mechanics in Zucker diabetic fatty (ZDF) rats.Eleven-week old ZDF diabetic (DB) and non-diabetic (ND) rats were given 75 μg/kg PTH (1–84) or vehicle 5 days per week over 12 weeks. The right femora and L4 vertebrae were excised, micro-CT scanned, and tested in 3-point bending and uniaxial compression, respectively. NEG of the samples was determined using fluorescence.Diabetes increased Ct.Po (vertebra (vert): + 40.6%, femur (fem): + 15.5% vs. ND group, p < 0.05) but had no effect on NEG. PTH therapy reduced vertebral NEG in the ND animals only (− 73% vs untreated group, p < 0.05), and increased femoral NEG in the DB vs. ND groups (+ 63%, p < 0.05). PTH therapy had no effect on Ct.Po. Diabetes negatively affected bone tissue mechanics where reductions in vertebral maximum strain (− 22%) and toughness (− 42%) were observed in the DB vs. ND group (p < 0.05). PTH improved maximum strain in the vertebra of the ND animals (+ 21%, p < 0.05) but did not have an effect in the DB group. PTH increased femoral maximum strain (+ 21%) and toughness (+ 28%) in ND and decreased femoral maximum stress (− 13%) and toughness (− 27%) in the DB animals (treated vs. untreated, p < 0.05). Ct.Po correlated negatively with maximum stress (fem: R = − 0.35, p < 0.05, vert: R = − 0.57, p < 0.01), maximum strain (fem: R = − 0.35, p < 0.05, vert: R = − 0.43, p < 0.05) and toughness (fem: R = − 0.34, p < 0.05, vert: R = − 0.55, p < 0.01), and NEG correlated negatively with toughness at the femur (R = − 0.34, p < 0.05) and maximum strain at the vertebra (R = − 0.49, p < 0.05).Diabetes increased cortical porosity and reduced bone mechanics, which were not improved with PTH treatment. PTH therapy alone may worsen diabetic bone mechanics through formation of new bone with high AGEs cross-linking. Optimal treatment regimens must address both improvements of bone mass and glycemic control in order to successfully reduce diabetic bone fragility.This article is part of a Special Issue entitled “Bone and diabetes”. |
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