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 months with either teriparatide (n = 23) or denosumab (n = 22). Τeriparatide treatment increased activin B (p = 0.01) and activin AB (p = 0.004) and the ratios activin A/follistatin (p = 0.006), activin B/follistatin (p = 0.007), activin AB/follistatin (p < 0.001) and activin AB/FSTL3 (p = 0.034). 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 body mass index (BMI) and lumbar spine bone mineral density (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-month 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.
Bone and the muscle, comprise two tissues that are considered to interact with each other, not only through mechanical but also through endocrine signals. Several components of the activins-follistatins-inhibins (AFI) hormonal system have been shown to be secreted by the muscle and affect the bone possibly contributing to this interplay. We have previously investigated levels of the AFI molecules in case–control studies and reported differences between osteoporotic versus osteopenic versus postmenopausal and premenopausal women with normal bone mineral density (BMD). In this 12-month, non-randomized, open-labeled, head-to-head comparative study, we prospectively compared the effect of antiosteoporotic agents with opposite effect on bone metabolism, i.e., teriparatide versus denosumab, on the circulating concentrations of all known molecules of the AFI system in postmenopausal women with osteoporosis. We observed increases of activins after teriparatide treatment, but no effect after denosumab treatment on any of the AFI molecules studied. Since activins are mainly acting in an autocrine way and since activin B and AB have not been extensively studied, further studies in the basic research, preclinical and clinical research fields are required to expand these observations and fully elucidate physiology and any therapeutic potential.
摘要:
活化素-叶酸抑制素-抑制素(AFI)激素系统影响骨代谢。改变骨代谢的治疗也可以改变AFI分子。在这个非随机的,开放标签,头对头比较研究,在接受特立帕肽(n=23)或地诺舒马(n=22)治疗12个月的绝经后骨质疏松症女性中,我们评估了AFI系统的循环水平.塞立帕肽治疗增加了活化素B(p=0.01)和活化素AB(p=0.004)以及活化素A/卵泡抑素的比例(p=0.006),活化素B/卵泡抑素(p=0.007),活化素AB/卵泡抑素(p<0.001)和活化素AB/FSTL3(p=0.034)。在调整体重指数(BMI)和腰椎骨矿物质密度(LSBMD)后,活化素B和AB的时间相互作用以及活化素AB/FSTL3比率的趋势的显着p保持稳健,但在调整之前的抗再吸收治疗后,活化素B消失了。当调整基线活化素水平或其12个月变化时,特立帕肽对BMD的影响减弱。denosumab治疗后未观察到变化。总之,活化素B和AB,以及所有活化素与卵泡抑素和活化素AB与FSTL3的比率随着特立帕肽治疗而增加,可能是补偿性的。需要进一步的研究来研究激活素可能在骨生物学中发挥的潜在重要作用以及与特立帕肽对BMD的影响的任何关联。
骨骼和肌肉,包括两个被认为相互作用的组织,不仅通过机械,而且通过内分泌信号。活化素-叶酸抑制素-抑制素(AFI)激素系统的几种成分已被证明是由肌肉分泌的,并影响可能导致这种相互作用的骨骼。我们以前曾在病例对照研究中研究过AFI分子的水平,并报道了骨质疏松性,骨质减少性,绝经后和绝经前正常骨矿物质密度(BMD)的女性之间的差异。在这12个月里,非随机化,开放标签,头对头比较研究,我们前瞻性比较了抗骨质疏松药物对骨代谢的相反作用,即,特立帕肽与地诺舒马,绝经后骨质疏松症妇女AFI系统所有已知分子的循环浓度。我们观察到特立帕肽治疗后激活素的增加,但denosumab治疗后对任何研究的AFI分子都没有影响。由于活化素主要以自分泌方式起作用,并且由于活化素B和AB尚未得到广泛研究,基础研究的进一步研究,临床前和临床研究领域需要扩大这些观察,并充分阐明生理学和任何治疗潜力。