Concentrations of Follicle-Stimulating Hormone Correlate with Alkaline Phosphatase and a Marker for Vitamin K Status in the Perimenopause

Abstract

Serum alkaline phosphatase (ALP), a gross marker of bone turnover, has been reported to be elevated after menopause, a period characterized by hallmark increases in follicle-stimulating hormone (FSH). Whether the ALP rise coincides with the perimenopausal transition when changes in FSH, estrogen levels, and menstrual cycles are first apparent is not known. The purpose of this cross-sectional study was twofold: (1) to characterize the influence of the perimenopausal transition on ALP activity and (2) to correlate ALP activity with more precise markers for bone, osteocalcin (OC), and vitamin K status assessed with undercarboxylated osteocalcin (ucOC). Thirty-eight studies of hourly FSH were conducted on cycle day 6 of the follicular phase in perimenopausal women volunteers, aged 40-54 years (mean body mass index [BMI] = 24.2 ± 0.5). Mean FSH was used to define the perimenopausal stage (early perimenopausal, mean FSH 15 IU/L, n = 27; late perimenopausal, mean FSH > 15 IU/L, n = 11). As expected, late perimenopausal women had irregular and longer menstrual cycles, lower estradiol (E2) and estrone (E1) levels, and a lower frequency of ovulations vs. the early group. ALP was higher (76.5 ± 8.3 vs. 58.3 ± 2.7 IU/L, p = 0.045) compared with the early perimenopausal group. In a subsample (n = 10), OC was associated with ALP (r = 0.69, p < 0.03), FSH was positively related to ucOC concentrations (r = 0.7, p < 0.03), and women with E1 concentrations <40 pg/ml had double the percentage of ucOC compared with those where E1 was >40 pg/ml (46.3% ± 6.6% vs. 22.0% ± 3.1%, p < 0.006). Clinical markers of the perimenopause are associated with a nonspecific but inexpensive marker of enhanced bone turnover (i.e., higher ALP) and correlate well with more precise markers of bone activity. These findings suggest that health-promotion strategies for preserving bone should be instituted well before the last menstrual period.