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

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Abstract

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.

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Abbreviations

BMD:

bone mineral density

CTX:

C-telopeptide of collagen cross-links

DeltaCTX:

percent change of CTX

Dkk-1:

Dickkopf-1

E2:

estradiol

ERα:

estrogen receptor-alpha

FEI:

free estrogen index

FP:

follicular phase

FSH:

follicle-stimulating hormone

IPAQ:

international physical activity questionnaire

LH:

luteinizing hormone

LP:

luteal phase

LRP:

low density lipoprotein receptor-related protein

MET:

metabolic equivalent of task

P1NP:

N-terminal propeptide of type 1 collagen

PTH:

parathyroid hormone

RANKL:

receptor activator for nuclear factor-κB ligand

SHBG:

sex hormone-binding globulin

TSH:

thyroid-stimulating hormone

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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.

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Authors and Affiliations

  1. Laboratory for Research of the Musculoskeletal System “Th. Garofalidis”, Medical School, Athens University, KAT Hospital, 10 Athinas Str., Kifissia, 14561, Athens, Greece

    Chrysoula G. Liakou, Julia D. Antoniou, Antonios Galanos, Ismene Dontas & Symeon Tournis

  2. Unit of Endocrinology, Diabetes and Metabolism, Aretaieion Hospital, Athens Medical School, Athens University, 76 Vas. Sofias Av., 11528, Athens, Greece

    George Mastorakos

  3. Department of Biochemistry, KAT Hospital, 10 Athinas Str., Kifissia, 14561, Athens, Greece

    Konstantinos Makris & Helen Marketos

  4. School of Physical Education and Sports Sciences, University of Thessaly, 42100, Karies, Trikala, Greece

    Ioannis G. Fatouros

  5. School of Physical Education and Sports Sciences, Democritus University of Thrace, 69100, Komotini, Greece

    Alexandra Avloniti

  6. Hormone Laboratory, Aretaieion Hospital, Medical School, Athens University, 76 Vas. Sofias Av., 11528, Athens, Greece

    Demetrios Rizos

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  1. Chrysoula G. Liakou
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  2. George Mastorakos
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  3. Konstantinos Makris
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  4. Ioannis G. Fatouros
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  7. Julia D. Antoniou
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Correspondence to Chrysoula G. Liakou.

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Liakou, C.G., Mastorakos, G., Makris, K. et al. Changes of serum sclerostin and Dickkopf-1 levels during the menstrual cycle. A pilot study. Endocrine 54, 543–551 (2016). https://doi.org/10.1007/s12020-016-1056-9

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  • DOI: https://doi.org/10.1007/s12020-016-1056-9

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