title: The effect of dipeptidyl peptidase-IV inhibition on bone in a mouse model of type 2 diabetes.
abstract: BACKGROUND
  Individuals with type 2 diabetes (T2D) are at greater risk of bone fractures than those without diabetes. Certain oral diabetic medications may further increase the risk of fracture. Dipeptidyl peptidase-IV (DPP-IV) inhibitors are incretin-based therapies that are being increasingly used for the management of T2D. It has been hypothesized that these agents may reduce fracture risk in those with T2D. In this study, we used a mouse model of T2D to examine the effects of the DPP-IV inhibitor, MK-0626, on bone.
  
  
  METHODS
  Male wild type (WT) and diabetic muscle-lysine-arginine (MKR) mice were treated with MK-0626, pioglitazone, alendronate or vehicle. The effects of treatment with MK-0626 on bone microarchitecture and turnover were compared with treatment with pioglitazone, alendronate and vehicle. Osteoblast differentiation was determined by alkaline phosphatase staining of bone marrow cells from WT and MKR mice after treatment with pioglitazone, MK-0626 or phosphate buffered saline.
  
  
  RESULTS
  We found that MK-0626 had neutral effects on cortical and trabecular bone in diabetic mice. Pioglitazone had detrimental effects on the trabecular bone of WT but not of diabetic mice. Alendronate caused improvements in cortical and trabecular bone architecture in diabetic and WT mice. MK-0626 did not alter osteoblast differentiation, but pioglitazone impaired osteoblast differentiation in vitro.
  
  
  CONCLUSIONS
  Overall, the DPP-IV inhibitor, MK-0626, had no adverse effects on bone in an animal model of T2D or directly on osteoblasts in culture. These findings are reassuring as DPP-IV inhibitors are being widely used to treat patients with T2D who are already at an increased risk of fractures.
authors.affiliation: Division of Endocrinology, Diabetes and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Emily Jane
authors.initials: EJ
authors.lastname: Gallagher
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Caroline
authors.initials: C
authors.lastname: Kornhauser
authors.forename: Aviva
authors.initials: A
authors.lastname: Tobin-Hess
authors.forename: Sol
authors.initials: S
authors.lastname: Epstein
authors.forename: Shoshana
authors.initials: S
authors.lastname: Yakar
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012313:RNA / Q000737:chemistry / Q000235:genetics; D014230:Triazoles / Q000494:pharmacology*; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; C570834:MK0626; D014230:Triazoles; D012313:RNA
keywords: DPPIV inhibitors; bone; diabetes; fractures
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