Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women.
BACKGROUND
Sclerostin is a negative regulator of bone formation.


OBJECTIVE
The aim of the study was to compare serum sclerostin levels in premenopausal and postmenopausal women and evaluate its relationship to estrogen, TH, bone turnover, and bone mass.


METHODS
We conducted a cross-sectional observational study of healthy community-dwelling pre- and postmenopausal women.


METHODS
There were no interventions.


METHODS
We compared serum sclerostin levels in pre- and postmenopausal women and correlated sclerostin levels with female sex hormones, calciotropic hormones, bone turnover markers, and bone mineral density.


RESULTS
Premenopausal women were 26.8 yr old, and postmenopausal women were 56.8 yr old. Postmenopausal women had lower values for estradiol (30 +/- 23 vs. 10 +/- 4 pg/ml; P < 0.001), estrone (61 +/- 24 vs. 29 +/- 10 pg/ml; P <0.001), and free estrogen index (FEI) (6 +/- 4 vs. 3 +/- 2 pmol/nmol; P = 0.008) and significantly lower bone mineral density at all sites compared to premenopausal women, with no significant differences in levels of PTH, 25-hydroxy or 1,25-dihydroxy vitamin D levels. Postmenopausal women had significantly higher serum sclerostin levels (1.16 +/- 0.38 ng/ml vs. 0.48 +/- 0.15 ng/ml; P < 0.001). Because most of the premenopausal women were on oral contraceptives, subsequent analyses were limited to postmenopausal women. There were significant negative correlations between sclerostin and FEI and sclerostin and PTH in this group. Using multiple regression analysis, both FEI (beta = -0.629; P = 0.002) and PTH (beta = -0.554; P = 0.004) were found to be independent predictors of sclerostin levels in postmenopausal women.


CONCLUSIONS
Our findings suggest that serum sclerostin levels are regulated by both estrogens and PTH in postmenopausal women. These findings need to be explored further in larger prospective studies.
University of Connecticut Health Center, Farmington, Connecticut 06030, USA. fmirza@uchc.edu
Faryal S
FS
Mirza
I Desmond
ID
Padhi
Lawrence G
LG
Raisz
Joseph A
JA
Lorenzo
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D015415:Biomarkers; D015519:Bone Density / Q000502:physiology; D001846:Bone Development / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D003430:Cross-Sectional Studies; D004967:Estrogens / Q000097:blood*; D005260:Female; D005819:Genetic Markers; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D017698:Postmenopause / Q000097:blood*; D017697:Premenopause / Q000097:blood; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D004967:Estrogens; D005819:Genetic Markers; D012739:Gonadal Steroid Hormones; D010281:Parathyroid Hormone; C422903:SOST protein, human