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

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.

Keywords: Activin; Follistatin; Hip fracture; Inhibin; Myokine; Postmenopausal osteoporosis.