Osteocalcin: An Endocrine Link Between Bone and Glucose Metabolism

Bu B Yeap


Expert Rev Endocrinol Metab. 2011;6(2):177-185. 

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Expert Commentary

The experimental findings that demonstrate regulation of glucose metabolism by ucOC are important as they relate to the modern epidemics of obesity, diabetes and CVD. Obesity predisposes one to insulin resistance, which is a risk factor for diabetes and CVD.[2–6] Therefore, novel pathways by which insulin resistance can be ameliorated might reduce the incidence of diabetes, which in turn could prevent CVD-related morbidity and mortality.

Experimental data from knockout mice and cells indicate that ucOC stimulates insulin secretion and enhances insulin sensitivity.[17,21] Human data are primarily from observational studies in which lower TOC levels are associated with insulin resistance, hyperglycemia, Type 2 diabetes or worsened glycemic control.[23–28] More recently, lower TOC levels have been associated with an increased prevalence of metabolic syndrome.[29,30] The association with metabolic syndrome was mediated via waist circumference, hyperglycemia and triglyceride levels, and remained significant after adjusting for glucose level.[30] However, studies in which ucOC as well as TOC have been assayed are smaller in size and offer only qualified evidence of a role for ucOC specifically.[31–34] Therefore, more robust data are needed to extend the assessment of ucOC across larger observational studies.[20,36] Most of the reported studies were cross-sectional and it is difficult to assess causality in cross-sectional studies that only show associations at one point in time. Therefore, longitudinal studies examining the role of TOC and ucOC as independent predictors of incident diabetes and cardiovascular events would be highly important. When the role of ucOC in human metabolism has been more clearly defined, further studies will be needed to identify ways of modulating ucOC levels to influence clinical outcomes.

The role of osteoclasts in bone resorption and provision of an acidic resorption lacuna in which osteocalcin is decarboxylated offers an intriguing perspective on the interaction between fracture risk and diabetes.[48–51] More work is required to better understand how mechanisms modulating fracture risk in bones might impact on the regulation of glucose metabolism. The effects of antiresorptive therapy for osteoporosis on ucOC and glucose metabolism need to be clarified. Depending on the outcome of such studies, a plausible hypothesis explaining how optimization of bone health might minimize diabetes and cardiovascular risk could be proprosed. If this were proven to be the case, new therapeutic and public health measures might be conceived that would aim to maximize bone strength and subsequently prevent insulin resistance and diabetes.


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