Osteocalcin favoring glucose control is associated with decreased total hip bone mineral density-evidence from a cross-sectional study in T2DM male patients

Osteocalcin (OC), an osteoblast-derived protein, can regulate glucose metabolism. The release and activation of OC depend on bone resorption. It is possible that the process of OC favoring glucose control is associated with reduced bone mineral density (BMD). Our study aimed to test this speculation in males with type 2 diabetes mellitus (T2DM). A total of 196 adult males with T2DM were recruited, their hypoglycemic treatments were recorded. Serum Glycosylated hemoglobin A1c (HbA1c), OC, and BMDs at lumbar-spine1-4 (L1-4 BMD), total hip (TH BMD), and femoral neck (FN BMD) were measured. OC was inversely correlated to HbA1c (r=-0.225, P=0.002) and TH BMD (r=-0.222, P=0.002) in T2DM males. HbA1c had a positive correlation with TH BMD (r=0.282, P=0.026) in T2DM males with less than 10 years of diabetes, after controlling for age, BMI, insulin resistance, hypoglycemic treatment groups, and other potential confounders, but did not in those with more than 10 years of diabetes (r=0.093, P=0.382). In newly diagnosed T2DM patients without a medication history of hypoglycemic agents, HbA1c and TH BMD also had a positive correlation (r=0.856, P=0.001). However, the positive associations between HbA1c and TH BMD both disappeared after adjustments for OC in these T2DM patients. In conclusion, better glucose control is associated with decreased TH BMD in T2DM males with relative short diabetic duration, which is driven by the effect of OC. This supports the speculation, but additional human and animal studies are required to vigorously test this hypothesis.