Low serum levels of undercarboxylated osteocalcin in postmenopausal osteoporotic women receiving an inhibitor of bone resorption

Abstract

Osteocalcin, a bone-specific protein synthesized by osteoblasts, undergoes vitamin K-dependent gamma-carboxylation. Undercarboxylated osteocalcin (ucOC) represents inadequately carboxylated osteocalcin, and this fraction increases with vitamin K insufficiency. Alendronate is a bisphosphonate that inhibits bone resorption, thereby increasing bone mineral density (BMD), while also reducing bone formation closely coupled with bone resorption. The aim of this cross-sectional study was to evaluate the influence of alendronate on serum levels of ucOC, cross-linked N-telopeptide of type 1 collagen (NTx), a marker of bone resorption, and bone alkaline phosphatase (BAP), a marker of bone formation. Forty-six postmenopausal osteoporotic women were divided into three groups: patients receiving alendronate (5 mg/day or 35 mg/week) for >or= 6 months (n = 29) or < 6 months (n = 7), and patients receiving no medication related to bone metabolism (n = 10). Serum ucOC levels were significantly lower in patients with long-term treatment (p < 0.0001) or short-term treatment (p = 0.0223) than in untreated patients. Serum ucOC levels correlated positively with both BAP (r = 0.695, p < 0.0001) and NTx (r = 0.494, p = 0.0004) in all participants. Since low serum levels of BAP and NTx are associated with decreased levels of bone formation and bone resorption, respectively, these findings suggest that low serum ucOC levels may reflect the suppression of bone turnover. In conclusion, low serum ucOC levels reflect suppressed bone turnover and/or adequate levels of vitamin K in patients receiving an inhibitor of bone resorption.