Safety of Antidiabetic Therapies on Bone

Original Paper

Abstract

Osteoporosis and diabetic disease have reached epidemic proportion and create significant public health concerns. The prevalence of these diseases is alarming and indicates that in the United States, 50% of elderly individuals are osteoporotic and almost 20% of population has either diabetic or prediabetic conditions (Centers for Disease Control and Prevention; http://www.cdc.gov). Osteoporosis and diabetes share many features including genetic predispositions and molecular mechanisms. The linkage between these two chronic diseases, which stems from overlapping molecular controls involved in bone homeostasis and energy metabolism, creates a possibility that certain antidiabetic therapies may affect bone. This concurs with recent findings, indicating that bone status is closely linked to regulation of energy metabolism and insulin sensitivity. Indeed, bone and energy homeostasis is under the control of the same regulatory factors, including insulin, peroxisome proliferator-activated receptor gamma, gastrointestinal hormones such as glucose inhibitory protein and glucagon inhibitory peptide, and bone-derived hormone osteocalcin. These factors and related mechanisms control glucose homeostasis and fatty acid metabolism in fat tissue, pancreas, and intestine, which are pharmacological targets for antidiabetic therapies. The same factors contribute to the bone quality by their effect on bone cell differentiation and bone remodeling process. This implies that bone should be considered as a vital target for therapies that modulate energy metabolism. This review is summarizing available data on the skeletal effects of clinically approved antidiabetic therapies.

Keywords

Bone BMD Fractures Antidiabetic therapy TZDs Metformin Insulin Glyburide Incretins DPP-4 inhibitors PPARγ 

Notes

Acknowledgments

This work was supported by grants from NIH/NIA AG028935 and American Diabetes Association’s Amaranth Diabetes Fund 1-09-RA-95.

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Orthopaedic Surgery, Department of Physiology and Pharmacology, Center for Diabetes and Endocrine ResearchUniversity of Toledo College of MedicineToledoUSA

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