Changes of serum sclerostin and Dickkopf-1 levels during the menstrual cycle. A pilot study.
Studies in postmenopausal women have identified sclerostin as a strong candidate for mediating estrogen effects on the skeleton. The effects of estradiol on sclerostin and Dickkopf-1 in younger women remain unclear. The main purpose of this study is to investigate the impact of estradiol and gonadotrophins fluctuations during the menstrual cycle on circulating sclerostin and Dickkopf-1 levels and the possible relationship of sclerostin and Dickkopf-1 with changes in N-terminal propeptide of type 1 collagen and C-telopeptide of collagen cross-links. Fourteen healthy premenopausal Caucasian women, with regular menses, aged 33.6 ± 4.5 years participated. After the first day of menstruation and every-other-day up to the next menses, fasting serum estradiol, luteinizing hormone, follicle-stimulating hormone, sclerostin, Dickkopf-1, N-terminal propeptide of type 1 collagen, and C-telopeptide of collagen cross-links levels were measured in peripheral blood. Participants completed dietary questionnaires and the International physical activity questionnaire during the cycle. Neither sclerostin nor Dickkopf-1 levels changed significantly across the menstrual cycle (p = 0.18 and p = 0.39, respectively), while N-terminal propeptide of type 1 collagen and C-telopeptide of collagen cross-links levels presented cyclic variation (p < 0.001 and p = 0.004, respectively). Baseline sclerostin (29.23 ± 10.62 pmol/L) positively correlated with N-terminal propeptide of type 1 collagen (r = 0.71, p < 0.01) and C-telopeptide of collagen cross-links (r = 0.63, p < 0.05), while Dickkopf-1 (4.82 ± 2.23 pmol/L) correlated positively with N-terminal propeptide of type 1 collagen (r = 0.56, p < 0.05). Mid-cycle E2 levels presented significant negative association with the percent decrease of C-telopeptide of collagen cross-links at all-time points during the luteal period (r = -0.60 to -0.68, p < 0.05-0.01). Circulating sclerostin and Dickkopf-1 levels do not change across the menstrual cycle and do not demonstrate any relationship with estradiol in premenopausal women. Further investigation is needed concerning the role of sclerostin and Dickkopf-1 on bone turnover in young estrogen-sufficient women.
Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", Medical School, Athens University, KAT Hospital, 10 Athinas Str., Kifissia, 14561, Athens, Greece. c_liakou@yahoo.com.
Chrysoula G
CG
Liakou
Unit of Endocrinology, Diabetes and Metabolism, Aretaieion Hospital, Athens Medical School, Athens University, 76 Vas. Sofias Av., 11528, Athens, Greece.
George
G
Mastorakos
Department of Biochemistry, KAT Hospital, 10 Athinas Str., Kifissia, 14561, Athens, Greece.
Konstantinos
K
Makris
School of Physical Education and Sports Sciences, University of Thessaly, 42100, Karies, Trikala, Greece.
Ioannis G
IG
Fatouros
School of Physical Education and Sports Sciences, Democritus University of Thrace, 69100, Komotini, Greece.
Alexandra
A
Avloniti
Department of Biochemistry, KAT Hospital, 10 Athinas Str., Kifissia, 14561, Athens, Greece.
Helen
H
Marketos
Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", Medical School, Athens University, KAT Hospital, 10 Athinas Str., Kifissia, 14561, Athens, Greece.
Julia D
JD
Antoniou
Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", Medical School, Athens University, KAT Hospital, 10 Athinas Str., Kifissia, 14561, Athens, Greece.
Antonios
A
Galanos
Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", Medical School, Athens University, KAT Hospital, 10 Athinas Str., Kifissia, 14561, Athens, Greece.
Ismene
I
Dontas
Hormone Laboratory, Aretaieion Hospital, Medical School, Athens University, 76 Vas. Sofias Av., 11528, Athens, Greece.
Demetrios
D
Rizos
Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", Medical School, Athens University, KAT Hospital, 10 Athinas Str., Kifissia, 14561, Athens, Greece.
Symeon
S
Tournis
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D024042:Collagen Type I / Q000097:blood; D005260:Female; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008597:Menstrual Cycle / Q000097:blood*; D010455:Peptides / Q000097:blood; D010865:Pilot Projects; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C422903:SOST protein, human
Bone turnover markers; Dkk-1; Estradiol; Sclerostin