title: The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide-mediated vasorelaxation in BALB/c mice.
abstract: There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L-NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1-34] (80 µg/kg/day) or L-NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro-CT, histomorphometry and three-point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co-treatment with L-NAME blocked the action of PTH on blood flow, whereas L-NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co-treatment with L-NAME restricted the PTH-stimulated increase in cortical bone formation but had no clear-cut effects in trabecular bone. Co-treatment with L-NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO-mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone.
authors.affiliation: Department of Bioengineering, Imperial College London, London, UK.|Department of Cell and Developmental Biology, University College London, London, UK.|Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Gohin
authors.affiliation: Department of Biomedical Engineering, Florida Institute of Technology, Florida, USA.
authors.forename: A
authors.initials: A
authors.lastname: Carriero
authors.affiliation: Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Chenu
authors.affiliation: Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK.
authors.forename: A A
authors.initials: AA
authors.lastname: Pitsillides
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, UK.
authors.forename: T R
authors.initials: TR
authors.lastname: Arnett
authors.affiliation: Department of Bioengineering, Imperial College London, London, UK.|Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Marenzana
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D010281:Parathyroid Hormone; D009569:Nitric Oxide
keywords: bone blood flow; cortical bone; nitric oxide; parathyroid hormone; vasodilation
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