Positive association between serum levels of bone resorption marker CTX and HbA1c in women with normal glucose tolerance

Abstract

Context: The bone formation marker osteocalcin (OCN) has a beneficial effect on glucose metabolism. In mice, the OCN bioactivity is induced by bone resorption. But in humans, the role of bone resorption in modulating glucose homeostasis is not clear. Objective: Our study aimed to examine the relationship between bone resorption and glucose homeostasis in humans. Design and Setting: This was a cross-sectional study conducted in a university teaching hospital. Subjects: A total of 195 women with normal glucose tolerance (NGT) were analyzed. Main Outcome Measures: Serum OCN, cross-linked C-telopeptide of type I collagen (CTX), fasting plasma glucose, and 2h post-challenge glucose levels during oral glucose tolerance test, fasting insulin, glycated hemoglobin A1c (HbA1c), hepatic and renal functions, electrolytes, and bone mineral densities (BMDs) at lumbar-spine and proximal femur, and anthropometric parameters were measured. Results: CTX was positively associated with HbA1c after adjustments for multiple confounding factors (r = 0.269, P = .006). OCN (β= 0.015, P = .000), lumbar-spine 2-4 (L2- 4) BMD (β=-0.128, P = .003) and HbA1c (β= 0.051, P = .01) were the major determinants of the variations of CTX (adjusted R2 for the model = 0.608, P = .01) based on multivariate regression analysis. Compared with those in the lowest HbA1c tertile, individuals in the highest tertile had significantly higher CTX concentrations (0.37±0.15 ng/ml vs 0.26±0.11 ng/ml, P=.000), even when multiple confounders were adjusted (P for trend = .015). Conclusions: Bone resorption marker serum CTX was independently associated HbA1c in NGT women. Whether the increased CTX level in NGT subjects is an early marker predicting the subtle impairment of glucose homeostasis and the risk of occurrence of diabetes requires additional study.