Changes in Biochemical Markers of Osteoblastic Activity during the Menstrual Cycle*

Abstract

Serum levels of osteocalcin [OC; bone Gla protein (BGP)] and bone alkaline phosphatase (B-AP) are both correlated to osteoblastic activity, which may be regulated by several hormones, including estrogen, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and PTH. Estrogen shows reproducible variations during the menstrual cycle, while available data on variations in serum 1,25-(OH)2D3 and serum immunoreactive PTH show midcyclic increases or no changes. In the present study we evaluated osteoblastic activity by measuring serum OC and B-AP during the menstrual cycle in eight healthy women, aged 20-47 yr. The cycles were synchronized by LH peaks, and follicular and luteal periods were normalized by lengths. Repeated measures analysis of variance showed that serum OC varied significantly (P less than 0.05), with highest levels during the luteal period. Although the same pattern was seen for serum B-AP, the variation just failed to reach significance (P less than 0.10), but the mean level was significantly higher during the luteal than during the follicular period (P less than 0.05). Gonadotropins and ovarian sex hormones showed significant variations. There were no significant changes in serum vitamin D-binding protein, serum total and free 1,25-(OH)2D3 index, or serum immunoreactive PTH-(1-84), but serum levels of somatomedin-C showed a significant variation, with the highest level during the luteal period (P less than 0.05). Blood levels and urinary excretion of minerals exhibited no significant variations. Cross-correlation studies between OC and estradiol showed the highest correlation coefficient, when OC was lagged about 7 days after estradiol (r = 0.69; P less than 0.05). Moreover, a high correlation was found between OC and somatomedin-C when matched at concurrent time points (r = 0.76; P less than 0.01). No significant correlations were found between the other calcium-regulating hormones and OC when matched at concurrent time points. In conclusion, we found a significant effect of the menstrual cycle on the serum levels of two osteoblastic bone markers, OC and B-AP. The changes indicated that osteoblastic activity is higher during the luteal period. However, whether the changes are caused by direct or indirect effects of the fluctuations in calciotropic hormones is still unresolved.

Changes in Bone Resorption During the Menstrual Cycle

“…This is in agreement with the findings of Schlemmer et al (6) and Tjellesen et al (5) but different from those of Nielsen et al (4) who reported an increase in serum OC and BAP during the LP in eight premenopausal women. Gorai et al (8) found differences in serum BAP between subphases of the menstrual cycle, but these did not show an overall FP-LP difference and did not seem to form a consistent pattern because values were generally higher nearer to day 0 but low at day 0 itself.…”

“…Our results are in agreement with two published studies (33,34) but do not agree with four others. (35)(36)(37)(38) The reasons our correlations of bone markers with E 2 and P differ from those reported in other studies (4,8) are not entirely clear. Those studies did not report whether calculated correlations were from multiple data points per woman or whether they were within woman or between women.…”

“…For purposes of graphing or examining summary values by day, the visits were assigned to 2-day bins, so that a visit on day −14 or −13 was counted as day −14, a visit on day −12 or −11 was counted as day −12, etc. Cycles were divided into FP (day −14 to day −1) and LP (days [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Subphases were defined following Gorai et al (7,8) as early (the first 4 days), mid-(the middle 6 days), or late (the last 4 days).…”

“…(2,3) However, the influence of the naturally occurring cyclic changes of estrogen and P levels on bone turnover in premenopausal women has received limited attention and the results of the few available studies are variable and inconclusive. (4)(5)(6)(7)(8) One study of eight women reported that the circulating osteocalcin (OC) concentration is increased during the luteal phase (LP) of the menstrual cycle in normal premenopausal women. (4) Gorai et al (7) reported that bone resorption markers such as urinary hydroxylysylpyridinoline, lysylpyridinoline, and type I collagen cross-linked N-telopeptide varied during the menstrual cycle in nine women.…”

“…(4)(5)(6)(7)(8) One study of eight women reported that the circulating osteocalcin (OC) concentration is increased during the luteal phase (LP) of the menstrual cycle in normal premenopausal women. (4) Gorai et al (7) reported that bone resorption markers such as urinary hydroxylysylpyridinoline, lysylpyridinoline, and type I collagen cross-linked N-telopeptide varied during the menstrual cycle in nine women. They reported a rise in those markers during the follicular phase (FP) and a fall during the LP.…”