ARS | Publication request: Differential Associations for Menopause and Age in Measures of Vitamin K, Osteocalcin, and Bone Density: a Cross-Sectional Exploratory Study in Healthy Volunteers

Submitted to: The Journal of the North American Menopause Society
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 1, 2006
Publication Date: September 1, 2006
Citation: Lukacs, J.L., Booth, S.L., Kleerekoper, M., Ansbacher, R., Rock, C.L., Reame, N.E. 2006. Differential associations for menopause and age in measures of vitamin k, osteocalcin, and bone density: a cross-sectional exploratory study in healthy volunteers. The Journal of the North American Menopause Society. 13(5):799-808.

Interpretive Summary: The purpose of this study is to determine if there are effects of mid-life aging that are different from the effects of early postmenopause on bone health. Fifty-nine women participated in this study, and were categorized into 3 groups: 21 premenopausal young women between 21 and 30 years old (CY), 19 premenopausal older women between 40 and 52 years old (CO) and 19 older postmenopausal women who were the same age as the older premenopausal group (EPM). We assessed sex steroids, vitamins A, D and K, measure of bone turnover, and bone mineral density (BMD) at spine and hip .The CO women had similar sex steroid levels and vitamin status as CY women, but had lower BMD at the total hip. In EPM women, bone formation markers were elevated compared to the CO women but their BMD was similar. Although vitamin K levels in blood were highest in the EPM women, a measure of vitamin K status was lower in the EPM women, as was measures of bone formation. Estrogen status was inversely related to vitamin K status. In conclusion, menopause and premenopausal aging have differential effects on bone health.

Technical Abstract: The purpose of this study is to distinguish the effects of mid-life aging from the early postmenopause on bone biomarkers and bone density. Fifty-nine community volunteers categorized into 3 groups participated: cycling young (CY; 20-30 yrs, n = 21), cycling older (CO; 40-52 yrs, n = 19) and untreated age-matched women in the early postmenopause years (EPM; 40-52 yrs, mean years PM = 2.8 +/- 0.5 yrs, n = 19). We assessed sex steroids, vitamin status (phylloquinone, 25-hydroxy vitamin D, retinol), bone-specific alkaline phosphatase isoenzyme (BAP), osteocalcin (OC), percent undercarboxylated osteocalcin [%ucOC]) and bone mineral density (BMD) at spine and hip with DXA.The CO women had similar estradiol (124 +/- 29 vs 87 +/- 9 pmol/L) and vitamin status as CY women, but lower OC (0.64 +/- 0.03 vs 0.97 +/- 0.08 nmol/L, p = 0.01) and BMD at the total hip (1.0038 +/- 0.032 vs 1.1126 +/- 0.030 gm/cm2, p = 0.02). In EPM women bone formation markers (BAP: 128.6 +/- 6.6 vs 86.7 +/- 5.5 U/L; OC: 1.10 +/- 0.10 vs 0.64 +/- 0.03 nmol/L) were elevated vs CO women (p # 0.05), but BMD was similar. Although phylloquinone was highest in the EPM women, %ucOC was higher vs both cycle groups combined (21.9 +/- 1.7% vs 17.4 +/- 0.9%, n = 40; p < 0.05). Estradiol was inversely related to %ucOC (r = -0.32, p = 0.05). In conclusion, menopause and premenopausal aging have differential effects on bone turnover and bone loss. Estradiol decline at menopause may influence osteocalcin and it's carboxylation prior to BMD effects.