The effect of dipeptidyl peptidase-IV inhibition on bone in a mouse model of type 2 diabetes

Emily Jane Gallagher, Hui Sun, Caroline Kornhauser, Aviva Tobin-Hess, Sol Epstein, Shoshana Yakar, Derek Leroith

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)191-200
Number of pages10
JournalDiabetes/Metabolism Research and Reviews
Volume30
Issue number3
DOIs
StatePublished - 2014

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pioglitazone
Dipeptidyl Peptidase 4
Type 2 Diabetes Mellitus
Dipeptidyl-Peptidase IV Inhibitors
Bone and Bones
Osteoblasts
Alendronate
Incretins
Bone Remodeling
Bone Fractures
Therapeutics
MK0626
Bone Marrow Cells
Lysine
Alkaline Phosphatase
Arginine
Animal Models
Phosphates
Staining and Labeling
Muscles

Keywords

  • Bone
  • Diabetes
  • DPPIV inhibitors
  • Fractures

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

The effect of dipeptidyl peptidase-IV inhibition on bone in a mouse model of type 2 diabetes. / Gallagher, Emily Jane; Sun, Hui; Kornhauser, Caroline; Tobin-Hess, Aviva; Epstein, Sol; Yakar, Shoshana; Leroith, Derek.

In: Diabetes/Metabolism Research and Reviews, Vol. 30, No. 3, 2014, p. 191-200.

Research output: Contribution to journalArticle

Gallagher, EJ, Sun, H, Kornhauser, C, Tobin-Hess, A, Epstein, S, Yakar, S & Leroith, D 2014, 'The effect of dipeptidyl peptidase-IV inhibition on bone in a mouse model of type 2 diabetes', Diabetes/Metabolism Research and Reviews, vol. 30, no. 3, pp. 191-200. https://doi.org/10.1002/dmrr.2466
Gallagher, Emily Jane ; Sun, Hui ; Kornhauser, Caroline ; Tobin-Hess, Aviva ; Epstein, Sol ; Yakar, Shoshana ; Leroith, Derek. / The effect of dipeptidyl peptidase-IV inhibition on bone in a mouse model of type 2 diabetes. In: Diabetes/Metabolism Research and Reviews. 2014 ; Vol. 30, No. 3. pp. 191-200.
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AB - 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.

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