Differential associations for menopause and age in measures of vitamin K, osteocalcin, and bone density: a cross-sectional exploratory study in healthy volunteers

Objective: To distinguish the effects of midlife aging from early postmenopause on vitamin K measures, bone formation biomarkers, and bone density. Design: Cycling older volunteers (CO; 40-52 years, n = 19) were compared to cycling young (CY; 20-30 years, n = 21) and untreated, age-matched women in the early postmenopause years (EPM; 40-52 years, mean years PM = 2.8 +/- 0.5, n = 19). We assessed sex steroids, vitamin status (phylloquinone, 25-hydroxyvitamin D, retinol), osteocalcin (OC), percentage of undercarboxylated osteocalcin (%ucOC), and bone mineral density (BMD) at the spine and hip with dual-energy x-ray absorptiometry. Results: CO women had similar estradiol and vitamin status as CY women, but lower OC (0.64 +/- 0.04 vs 0.97 +/- 0.08 nmot/L, P = 0.01) and BMD at the total hip (1.0038 +/- 0.032 vs 1.1126 +/- 0.030 g/cm(2), P = 0.02). In the two older groups, BMD was similar at all sites, but OC was elevated in the EPM women (1.10 +/- 0.10 vs 0.64 +/- 0.04 nmol/L, EPM vs CO, P = 0.001). Although phylloquinone was highest in the EPM women, %ucOC was also higher when compared with all cycling women (21.9 +/- 1.7% vs 17.4 +/- 0.9%, n = 40; P = 0.02). Conclusions: Premenopausal women show reduced BMD despite normal estrogen profiles. %ucOC may be a specific bone marker of the early postmenopause in healthy women.