Higher carboxylated osteocalcin is an independent predictor of improved femoral bone strength: A cross-sectional study

Abstract

Carboxylated osteocalcin (cOC), produced during post-translational modification of osteocalcin (OC) in a vitamin K-dependent pathway, has a high affinity for calcium and hydroxyapatite. Despite the observed link between vitamin K deficiency and fracture risk, supplementation studies have not consistently demonstrated improvements in bone mineral density (BMD) or bone microarchitecture, though studies have reported improvement in cOC status. We hypothesise that these inconsistent findings are due to the lack of knowledge on the mechanisms by which cOC affects bone health. Hence, the aim of this study was to investigate the relationship between cOC and bone turnover markers, cortical and trabecular bone microarchitecture and strength. Forty-five patients who underwent hip arthroplasty for hip osteoarthritis were prospectively recruited. Patients with conditions or medications that could affect bone outcomes were excluded and intra-operative bloods and bone biopsies were collected. Cortical thickness and hip strength was measured with dual-energy X-ray absorptiometry and micro-computed tomography was used to determine trabecular bone microarchitecture. Cortical thickness, cross-sectional area, cross-sectional moment of inertia, femoral neck width and section modulus correlated positively with cOC (p < 0.05, all). There was no association between partially or fully un-carboxylated fractions and hip strength variables. Further, cOC was found to be an independent predictor of bone alkaline phosphastase while the partially or fully un-carboxylated OC predicted c-terminal telopeptide of type 1 collagen. In conclusion, higher cOC concentrations were associated with improved femoral bone strength, and the effect is possibly mediated through higher bone mineralisation, independent of age, parathyroid hormone, kidney function, BMD and physical activity.