, Volume 54, Issue 2, pp 543–551 | Cite as

Changes of serum sclerostin and Dickkopf-1 levels during the menstrual cycle. A pilot study

  • Chrysoula G. LiakouEmail author
  • George Mastorakos
  • Konstantinos Makris
  • Ioannis G. Fatouros
  • Alexandra Avloniti
  • Helen Marketos
  • Julia D. Antoniou
  • Antonios Galanos
  • Ismene Dontas
  • Demetrios Rizos
  • Symeon Tournis
Original Article


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.


Sclerostin Dkk-1 Estradiol Bone turnover markers 



bone mineral density


C-telopeptide of collagen cross-links


percent change of CTX






estrogen receptor-alpha


free estrogen index


follicular phase


follicle-stimulating hormone


international physical activity questionnaire


luteinizing hormone


luteal phase


low density lipoprotein receptor-related protein


metabolic equivalent of task


N-terminal propeptide of type 1 collagen


parathyroid hormone


receptor activator for nuclear factor-κB ligand


sex hormone-binding globulin


thyroid-stimulating hormone


Author contribution

Design and conduct of the study: Chrysoula G. Liakou, Julia D. Antoniou, George Mastorakos, Symeon Tournis. Biochemical analysis of the samples: Konstantinos Makris, Helen Marketos, Chrysoula G. Liakou, Dimitrios Rizos. Physical activity and dietary assessment: Ioannis G. Fatouros, Alexandra Avloniti. Data collection and analysis: Antonios Galanos, Chrysoula G. Liakou, George Mastorakos, Ioannis G. Fatouros, Alexandra Avloniti, Symeon, Tournis. Data interpretation: Chrysoula G. Liakou, George Mastorakos, Ioannis G. Fatouros, Konstantinos Makris, Symeon Tournis. Manuscript writing: Chrysoula G. Liakou, George Mastorakos, Ioannis G. Fatouros, Konstantinos Makris, Ismene Dontas, Symeon Tournis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Chrysoula G. Liakou
    • 1
    Email author
  • George Mastorakos
    • 2
  • Konstantinos Makris
    • 3
  • Ioannis G. Fatouros
    • 4
  • Alexandra Avloniti
    • 5
  • Helen Marketos
    • 3
  • Julia D. Antoniou
    • 1
  • Antonios Galanos
    • 1
  • Ismene Dontas
    • 1
  • Demetrios Rizos
    • 6
  • Symeon Tournis
    • 1
  1. 1.Laboratory for Research of the Musculoskeletal System “Th. Garofalidis”, Medical SchoolAthens UniversityKifissiaGreece
  2. 2.Unit of Endocrinology, Diabetes and Metabolism, Aretaieion Hospital, Athens Medical SchoolAthens UniversityAthensGreece
  3. 3.Department of BiochemistryKifissiaGreece
  4. 4.School of Physical Education and Sports SciencesUniversity of ThessalyTrikalaGreece
  5. 5.School of Physical Education and Sports SciencesDemocritus University of ThraceKomotiniGreece
  6. 6.Hormone Laboratory, Aretaieion Hospital, Medical SchoolAthens UniversityAthensGreece

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