The comparative effect of teriparatide and denosumab on activins, follistatins, and inhibins in women with postmenopausal osteoporosis

Abstract The activins–follistatins–inhibins (AFI) hormonal system affects bone metabolism. Treatments that alter bone metabolism may also alter the AFI molecules. In this non-randomized, open-label, head-to-head comparative study, circulating levels of the AFI system were evaluated in postmenopausal women with osteoporosis treated for 12 mo with either teriparatide (n = 23) or denosumab (n = 22). Τeriparatide treatment increased activin B (P=.01) and activin AB (P=.004) and the ratios activin A/follistatin (P=.006), activin B/follistatin (P=.007), activin AB/follistatin (P<.001), and activin AB/ follistatin-like 3 (FSTL3) (P=.034). The significant P for trend in group × time interactions of activins B and AB and of the ratio activin AB/FSTL3 remained robust after adjustment for BMI and LS BMD but it was lost for activin B after adjustment for previous antiresorptive treatment. The effect of teriparatide on BMD was attenuated when it was adjusted for baseline activins levels or their 12-mo changes. No changes were observed after denosumab treatment. In conclusion, activins B and AB, as well as the ratios of all activins to follistatin and of activin AB to FSTL3 increased with teriparatide treatment, possibly in a compensatory manner. Future studies are needed to study the potentially important role activins may play in bone biology and any associations with the effect of teriparatide on BMD. Clinical Trials identifier: NCT04206618. ClinicalTrials.gov https://clinicaltrials.gov/search?term=NCT04206618.