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

Published:December 29, 2022DOI:https://doi.org/10.1016/j.metabol.2022.155397

      Highlights

      • Components of the Activins - Follistatins axis follow an opposite pattern of correlations for age and BMI vs. BMD
      • Follistatin (but not FSTL 3) and its ratios with activins are inversely associated with lumbar spine BMD
      • Follistatin (but not FSTL 3) and its ratios with activins are inversely associated with the presence of osteoporosis
      • Inhibin B levels were lower in postmenopausal osteoporotic women

      Abstract

      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.

      Graphical abstract

      Abbreviations:

      ActRIIA (activin receptor type IIA), AFI (activins-follistatins-inhibins system), BMD (bone mineral density), BMI (body mass index), FN (femoral neck), FSH (follicle-stimulating hormone), FSTL3 (follistatin-like 3), LS (lumbar spine), TGF-β (transforming growth factor-β)

      Keywords

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