Activins, follistatins and inhibins in postmenopausal osteoporosis: A proof of concept, case-control study.


Journal

Metabolism: clinical and experimental
ISSN: 1532-8600
Titre abrégé: Metabolism
Pays: United States
ID NLM: 0375267

Informations de publication

Date de publication:
04 2023
Historique:
received: 06 10 2022
revised: 24 12 2022
accepted: 26 12 2022
pubmed: 2 1 2023
medline: 3 3 2023
entrez: 1 1 2023
Statut: ppublish

Résumé

Bone metabolism has been proposed to be affected by the activins-follistatins-inhibins (AFI) hormonal system. We aimed to evaluate AFI in patients with osteoporosis and osteopenia compared with postmenopausal and premenopausal controls. In this case-control study, circulating levels of the AFI system were evaluated, individually and jointly, between postmenopausal women with osteoporosis (BMD T-score ≤-2.5; n = 25) or osteopenia (BMD T-score >-2.5 and ≤-1; n = 25) and postmenopausal women with normal BMD (T-score >-1.0; n = 25) or premenopausal women with normal BMD (Z-score >-1.0; n = 25), with and without adjustment for potential confounders. In the sum of participants, AFI molecules and their ratios followed an opposite pattern of correlations for age and BMI vs. BMD. In unadjusted models, FSTL3 concentrations were higher, whereas activin B, inhibin A and inhibin B and the ratios of activin B/follistatin and activin B/FSTL3 were lower in the three postmenopausal groups compared with the premenopausal group. Activin A/follistatin and activin AB/follistatin ratios were lower in the osteoporosis group than the other three groups. After adjustment for BMI and age, inhibin B (p = 0.005), and the ratios of activin A/follistatin (p = 0.009), activin B/follistatin (p = 0.040) and activin AB/follistatin (p = 0.003) were lower in the osteoporotic group compared with the other groups. In fully adjusted logistic regression analysis log(inhibin B) (p = 0.041), log(activinA/follistatin) (p = 0.014), log(activinB/follistatin) (p = 0.025) and log(activinAB/follistatin) (p = 0.021), but not FSTL3, remained independently associated with the presence of osteoporosis. Lower inhibin B and higher ratios of activins A, B, and AB to follistatin are associated with lumbar spine BMD and the presence of osteoporosis independently from age or BMI.

Sections du résumé

BACKGROUND
Bone metabolism has been proposed to be affected by the activins-follistatins-inhibins (AFI) hormonal system. We aimed to evaluate AFI in patients with osteoporosis and osteopenia compared with postmenopausal and premenopausal controls.
METHODS
In this case-control study, circulating levels of the AFI system were evaluated, individually and jointly, between postmenopausal women with osteoporosis (BMD T-score ≤-2.5; n = 25) or osteopenia (BMD T-score >-2.5 and ≤-1; n = 25) and postmenopausal women with normal BMD (T-score >-1.0; n = 25) or premenopausal women with normal BMD (Z-score >-1.0; n = 25), with and without adjustment for potential confounders.
RESULTS
In the sum of participants, AFI molecules and their ratios followed an opposite pattern of correlations for age and BMI vs. BMD. In unadjusted models, FSTL3 concentrations were higher, whereas activin B, inhibin A and inhibin B and the ratios of activin B/follistatin and activin B/FSTL3 were lower in the three postmenopausal groups compared with the premenopausal group. Activin A/follistatin and activin AB/follistatin ratios were lower in the osteoporosis group than the other three groups. After adjustment for BMI and age, inhibin B (p = 0.005), and the ratios of activin A/follistatin (p = 0.009), activin B/follistatin (p = 0.040) and activin AB/follistatin (p = 0.003) were lower in the osteoporotic group compared with the other groups. In fully adjusted logistic regression analysis log(inhibin B) (p = 0.041), log(activinA/follistatin) (p = 0.014), log(activinB/follistatin) (p = 0.025) and log(activinAB/follistatin) (p = 0.021), but not FSTL3, remained independently associated with the presence of osteoporosis.
CONCLUSIONS
Lower inhibin B and higher ratios of activins A, B, and AB to follistatin are associated with lumbar spine BMD and the presence of osteoporosis independently from age or BMI.

Identifiants

pubmed: 36587801
pii: S0026-0495(22)00275-X
doi: 10.1016/j.metabol.2022.155397
pii:
doi:

Substances chimiques

Follistatin 0
Glycoproteins 0
Inhibins 57285-09-3
Activins 104625-48-1
Fstl3 protein, human 0
Follistatin-Related Proteins 0

Banques de données

ClinicalTrials.gov
['NCT04206618']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

155397

Informations de copyright

Copyright © 2022 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest CSM is a consultant of Ansh Laboratories. BK and AK are Ansh Laboratories employees. The rest of the authors have no conflict of interest in relation to the present study.

Auteurs

Athanasios D Anastasilakis (AD)

Department of Endocrinology, 424 Military General Hospital, Thessaloniki, Greece. Electronic address: a.anastasilakis@gmail.com.

Stergios A Polyzos (SA)

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

Nikolaos E Rodopaios (NE)

Department of Social Medicine, Preventive Medicine and Nutrition Clinic, School of Medicine, University of Crete, Voutes, 71003 Iraklion, Greece.

Polyzois Makras (P)

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

Ajay Kumar (A)

Ansh Labs, Webster, TX, USA.

Bhanu Kalra (B)

Ansh Labs, Webster, TX, USA.

Christos S Mantzoros (CS)

Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Boston VA Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

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Classifications MeSH