title: Energy Excess, Glucose Utilization, and Skeletal Remodeling: New Insights.
abstract: Skeletal complications have recently been recognized as another of the several comorbidities associated with diabetes. Clinical studies suggest that disordered glucose and lipid metabolism have a profound effect on bone. Diabetes-related changes in skeletal homeostasis result in a significant increased risk of fractures, although the pathophysiology may differ from postmenopausal osteoporosis. Efforts to understand the underlying mechanisms of diabetic bone disease have focused on the direct interaction of adipose tissue with skeletal remodeling and the potential influence of glucose utilization and energy uptake on these processes. One aspect that has emerged recently is the major role of the central nervous system in whole-body metabolism, bone turnover, adipose tissue remodeling, and beta cell secretion of insulin. Importantly, the skeleton contributes to the metabolic balance inherent in physiologic states. New animal models have provided the insights necessary to begin to dissect the effects of obesity and insulin resistance on the acquisition and maintenance of bone mass. In this Perspective, we focus on potential mechanisms that underlie the complex interactions between adipose tissue and skeletal turnover by focusing on the clinical evidence and on preclinical studies indicating that glucose intolerance may have a significant impact on the skeleton. In addition, we raise fundamental questions that need to be addressed in future studies to resolve the conundrum associated with glucose intolerance, obesity, and osteoporosis.
authors.affiliation: Department of Orthopaedic Surgery, University of Toledo Health Sciences Campus, Toledo, OH, USA.|Department of Physiology and Pharmacology, Center for Diabetes and Endocrine Research, University of Toledo Health Sciences Campus, Toledo, OH, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Lecka-Czernik
authors.affiliation: Center for Clinical & Translational Research, Maine Medical Center Research Institute, Scarborough, ME, USA.|Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Rosen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000378:metabolism* / Q000473:pathology; D016723:Bone Remodeling; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000378:metabolism / Q000473:pathology
chemical_list: D007328:Insulin; D005947:Glucose
keywords: BONE INTERACTORS; BONE-FAT INTERACTIONS; CELL/TISSUE SIGNALING; DISEASES AND DISORDERS OF/RELATED TO BONE; SYSTEMS BIOLOGY; TRANSCRIPTION FACTORS