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Association of activins, follistatins and inhibins with incident hip fracture in women with postmenopausal osteoporosis: a proof of concept, case–control study

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Abstract

Purpose

The activins-follistatins-inhibins (AFI) hormonal system is considered to regulate muscle and bone mass. We aimed to evaluate AFI in postmenopausal women with an incident hip fracture.

Methods

In this post-hoc analysis of a hospital based case-control study, we evaluated circulating levels of the AFI system in postmenopausal women with a low-energy hip fracture admitted for fixation compared with postmenopausal women with osteoarthritis scheduled for arthroplasty.

Results

Circulating levels of follistatin (p = 0.008), FSTL3 (p = 0.013), activin B and AB (both p < 0.001), as well as activin AB/follistatin and activin AB/FSTL3 ratios (p = 0.008 and p = 0.029, respectively) were higher in patients than controls in unadjusted models. Differences for activins B and AB remained after adjustment for age and BMI (p = 0.006 and p = 0.009, respectively) and for FRAX-based risk for hip fracture (p = 0.008 and p = 0.012, respectively) but were lost when 25OHD was added to the regression models.

Conclusions

Our data indicate no major changes in the AFI system in postmenopausal women at the time of hip fracture compared to postmenopausal women with osteoarthritis except for higher activin B and AB levels, whose significance, however, was lost when 25OHD was added to the adjustment models.

Clinical Trials

Clinical Trials identifier: NCT04206618.

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Data availability

Data will be available upon reasonable request.

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Authors and Affiliations

  1. Department of Endocrinology, 424 Military General Hospital, Thessaloniki, Greece

    Athanasios D. Anastasilakis

  2. First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Stergios A. Polyzos & Dimitrios A. Anastasilakis

  3. 2nd Orthopedic Department, 424 General Military Hospital, Thessaloniki, Greece

    Matthaios Savvidis & Athanasios Sarridimitriou

  4. Ansh Labs, Webster, TX, USA

    Ajay Kumar & Bhanu Kalra

  5. Department of Endocrinology and Diabetes and Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, Greece

    Polyzois Makras

  6. Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Boston, VA, USA

    Christos S. Mantzoros

  7. Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Christos S. Mantzoros

Authors
  1. Athanasios D. Anastasilakis
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  2. Stergios A. Polyzos
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  3. Matthaios Savvidis
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  4. Dimitrios A. Anastasilakis
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Contributions

Conception and design of the work: A.D.A., M.S., C.S.M. Acquisition, analysis, or interpretation of data: A.D.A., S.A.P., M.S., D.A.A., A.S., A.K., B.K., C.S.M. Drafting the work: A.D.A. Revising the work critically for important intellectual content: S.A.P., C.S.M. Final approval of the submitted version: A.D.A., S.A.P., M.S., D.A.A., A.S., A.K., B.K., C.S.M. Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: A.D.A., S.A.P., M.S., D.A.A., A.S., A.K., B.K., C.S.M.

Corresponding author

Correspondence to Athanasios D. Anastasilakis.

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Conflict of interest

C.S.M. is a consultant of Ansh Laboratories. A.K. and B.K. are Ansh Laboratories employees. A.D.A., S.A.P, M.S., D.A.A., A.S. and P.M. have no conflict of interest in relation to the present study.

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All procedures performed in the study were in accordance with the ethical standards of the institutional research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Anastasilakis, A.D., Polyzos, S.A., Savvidis, M. et al. Association of activins, follistatins and inhibins with incident hip fracture in women with postmenopausal osteoporosis: a proof of concept, case–control study. Endocrine 81, 573–578 (2023). https://doi.org/10.1007/s12020-023-03402-x

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  • DOI: https://doi.org/10.1007/s12020-023-03402-x

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