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New evidence has recently emerged defining a close relationship between fat and bone metabolism. Adipose tissue is one of the largest organs in the body but its functions vary by location and origin. Adipocytes can act in an autocrine manner to regulate energy balance by sequestering triglycerides and then, depending on demand, releasing fatty acids through lipolysis for energy utilization, and in...
Type 2 diabetes affects an increasing proportion of older adults, the population that is also at elevated risk of fracture. Type 2 diabetes itself increases the risk of fracture, particularly in African–American and Latino populations. In Western countries, overweight and obesity, associated with reduced fracture risk, are highly prevalent in diabetic patients. Studies in East Asian countries that...
Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and the efficacy of bone-forming agents are unclear. We studied diabetes and parathyroid hormone (PTH) treatment effects on cortical porosity (Ct.Po), non-enzymatic glycation (NEG) and bone mechanics in Zucker diabetic fatty (ZDF) rats.Eleven-week old ZDF diabetic (DB) and non-diabetic (ND) rats were given...
Zucker Diabetic Fatty (ZDF) rats represent an established model of type 2 diabetes mellitus (T2DM) and display several features of human diabetic bone disease, including impaired osteoblast function, decreased bone strength, and delayed bone healing. Here, we determined whether glycemic control by insulin treatment prevents skeletal complications associated with diabetes. Subcritical femur defects...
Osteocalcin is among the most abundant proteins in bone and is produced exclusively by osteoblasts. Initially believed to be an inhibitor of bone mineralization, recent studies suggest a broader role for osteocalcin that extends to the regulation of whole body metabolism, reproduction, and cognition. Circulating undercarboxylated osteocalcin, which is regulated by insulin, acts in a feed-forward loop...
To determine osteocalcin (OC) and adipokines in type 1 diabetes (T1D) and healthy controls, and to explore possible associations between glucose and bone metabolism, body composition and adipokines.Serum levels of total OC, undercarboxylated (UC-OC), leptin, adiponectin, and other parameters of glucose and bone metabolism were measured in 128 patients with T1D (mean duration 21.2years) and in 77 healthy...
There is clear evidence that patients with type 2 diabetes mellitus (T2D) have increased fracture risk, despite having high bone mineral density (BMD) and body mass index (BMI). Thus, poor bone quality has been implicated as a mechanism contributing to diabetic skeletal fragility. Poor bone quality in T2D may result from the accumulation of advanced glycation end-products (AGEs), which are post-translational...
Prolonged exposure to excessive levels of endogenous or exogenous glucocorticoids is associated with serious clinical features including altered body composition and the development of insulin resistance, impaired glucose tolerance and diabetes. It had been assumed that these adverse effects were mediated by direct effects of glucocorticoids on tissues such as adipose or liver. Recent studies have...
Persons with type 1 and type 2 diabetes have increased fracture risk, attributed to deficits in the microarchitecture and strength of diabetic bone, thought to be mediated, in part, by the consequences of chronic hyperglycemia. Therefore, to examine the effects of a glucose-lowering SGLT2 inhibitor on blood glucose (BG) and bone homeostasis in a model of diabetic bone disease, male DBA/2J mice with...
We examined the diabetes–fracture relationship by race/ethnicity, including the link between pre-diabetes and fracture.We used Medicare- and mortality-linked data for respondents aged 65years and older from the third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999–2004 for three race/ethnic groups: non-Hispanic whites (NHW), non-Hispanic blacks (NHB), and Mexican Americans...
Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture healing due to decreased osteoblast activity. Further, no adequate treatments are currently available that can restore impaired healing in T1DM; hence a significant need exists to investigate new therapeutics for treatment of orthopedic complications. Sclerostin (SOST), a WNT antagonist, negatively regulates bone formation,...
Type 2 diabetes is associated with increased fracture risk and the mechanisms underlying the detrimental effects of diabetes on skeletal health are only partially understood. Antidiabetic drugs are indispensable for glycemic control in most type 2 diabetics, however, they may, at least in part, modulate fracture risk in exposed patients.Preclinical and clinical data clearly demonstrate an unfavorable...
There is growing evidence that the higher fracture rate observed in patients with type 2 diabetes mellitus (T2DM) is associated with normal, or even increased, areal bone mineral density (aBMD) by DXA. This has led to the hypothesis that patients with T2DM may have abnormalities in bone microarchitecture and/or material composition – i.e., key determinants of bone “quality.” Consistent with this hypothesis,...
Diabetes is associated with a number of lower extremity orthopedic conditions and complications including fractures, Charcot neuroarthropathy, plantar ulcers, and infection. These complications are of significant clinical concern in terms of morbidity, mortality, and socioeconomic costs. A review of each condition is discussed, with particular emphasis on the clinical importance, diagnostic considerations,...
Diabetes mellitus is associated with an increased risk of fractures, which is not explained by bone mineral density. Other markers as bone turnover markers (BTMs) may be useful.To assess the relationship between BTMs, diabetes, and fractures.A systematic literature search was conducted in August 2014. The databases searched were Medline at Pubmed and Embase. Medline at Pubmed was searched by “Diabetes...
Obesity and osteoporosis have become major public health challenges worldwide. The brain is well established as a pivotal regulator of energy homeostasis, appetite and fuel metabolism. However, there is now clear evidence for regulation between the brain and bone. Similarly, evidence also indicates that the involvement of the brain in bone and adipose regulation is both related and interdependent...
Low bone mineral density has been reported in children and adolescents with type 1 diabetes (T1DM). The aims of this cross-sectional study were to study growth, serum IGF1 concentrations and bone health parameters assessed by Dual Energy X-ray Absorptiometry (DXA).Height was measured and converted to Z scores (HAZ). Serum IGF1 concentrations were measured (ELISA) in a subset. Bone mineral content...
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