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 US, 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 anti-diabetic 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 are under the control of the same regulatory factors, including insulin, peroxisome proliferator activated receptor gamma (PPARγ), gastrointestinal hormones such as glucose inhibitory protein (GIP) and glucagon inhibitory peptide (GLP), and bone derived hormone osteocalcin. These factors and related mechanisms control glucose homeostasis and fatty acids 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 which modulate energy metabolism. This review is summarizing available data on the skeletal effects of clinically approved anti-diabetic therapies. Keywords bone; BMD; fractures; anti-diabetic therapy; TZDs; metformin; insulin; glyburide; incretins; DPP-4 inhibitors; PPAR
Bone remodelingMaintenance of bone homeostasis throughout life relies on the bone remodeling process, which continually replaces old and damaged bone with new bone in order to maintain strength and elasticity (1). In a healthy state, bone resorption is balanced with bone formation. Changes in the milieu of local and systemic factors may alter this balance leading to changes in the bone mass and/or bone biomechanical properties. Aging, estrogen deficiency, and metabolic diseases negatively affect bone mass and/or bone quality leading to the development of osteoporosis and increased fracture rate.Two types of cells are involved in bone remodeling: osteoclasts resorb damaged bone, and osteoblasts form new bone at the site of the resorpted cavity. Osteoclasts and osteoblasts Address to correspondence: Beata Lecka-Czernik, PhD; Dept. Orthopaedic Surgery, University of Toledo Health Sciences Campus, 3000 Arlington Ave, Mail Stop 1008, Toledo OH 43614; Phone: 419-383-4041; Fax: 419-383-2871; beata.leckaczernik@utoledo
Bone as an integral part of energy metabolism systemIntegration of bone metabolism with energy metabolism has been presented recently as a model which links anabolic effect of insulin signaling in osteoblasts wi...