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The effect of dipeptidyl peptidase‐IV inhibition on bone in a mouse model of type 2 diabetes
Author(s) -
Gallagher Emily Jane,
Sun Hui,
Kornhauser Caroline,
TobinHess Aviva,
Epstein Sol,
Yakar Shoshana,
LeRoith Derek
Publication year - 2014
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2466
Subject(s) - pioglitazone , dipeptidyl peptidase 4 inhibitor , endocrinology , medicine , type 2 diabetes , osteoblast , incretin , diabetes mellitus , dipeptidyl peptidase 4 , bone remodeling , cortical bone , alkaline phosphatase , chemistry , enzyme , in vitro , biochemistry , pathology
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. Copyright © 2013 John Wiley & Sons, Ltd.