title: Effects of parathyroid hormone on cortical porosity, non-enzymatic glycation and bone tissue mechanics in rats with type 2 diabetes mellitus.
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 75μg/kg PTH (1-84) or vehicle 5days per week over 12weeks. 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".
authors.affiliation: Institute of Biomechanics, TUHH Hamburg University of Technology, Hamburg, Germany; Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany. Electronic address: graeme.campbell@tuhh.de.
authors.forename: G M
authors.initials: GM
authors.lastname: Campbell
authors.affiliation: Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Tiwari
authors.affiliation: Department of Orthopedics, Technische Universität Dresden Medical Center, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Hofbauer
authors.affiliation: Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany.
authors.forename: A-K
authors.initials: AK
authors.lastname: Picke
authors.affiliation: Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rauner
authors.affiliation: Institute of Biomechanics, TUHH Hamburg University of Technology, Hamburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Huber
authors.affiliation: Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: J A
authors.initials: JA
authors.lastname: Peña
authors.affiliation: Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Damm
authors.affiliation: Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Barkmann
authors.affiliation: Institute of Biomechanics, TUHH Hamburg University of Technology, Hamburg, Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Morlock
authors.affiliation: Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany; Center for Regenerative Therapies Dresden, Germany.
authors.forename: L C
authors.initials: LC
authors.lastname: Hofbauer
authors.affiliation: Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: C-C
authors.initials: CC
authors.lastname: Glüer
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D016062:Porosity / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker; D016896:Treatment Outcome
chemical_list: D017127:Glycation End Products, Advanced; D010281:Parathyroid Hormone
keywords: Biomechanics; Bone-anabolics; Collagen; Diabetes; Non-enzymatic glycation; Preclinical studies