Anastasilakis Athanasios D, Yavropoulou Maria P, Makras Polyzois, Sakellariou Grigorios T, Papadopoulou Fotini, Gerou Spyridon, Papapoulos Socrates E
Department of Endocrinology424 General Military Hospital, Thessaloniki, Greece.
1st Department of Internal MedicineLaboratory of Clinical and Molecular Endocrinology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Eur J Endocrinol. 2017 Jun;176(6):677-683. doi: 10.1530/EJE-16-1027. Epub 2017 Mar 10.
To test the hypothesis that rebound of bone remodeling is responsible for clinical vertebral fractures reported in a few patients with osteoporosis after cessation of denosumab treatment.
In this case-control study we compared clinical and biochemical characteristics of postmenopausal women with clinical vertebral fractures 8-16 months after the last injection of denosumab (Dmab/Fx+, = 5) with those of treatment-naïve women with such fractures (Fx+, = 5). In addition, 5 women who discontinued denosumab treatment but did not sustain vertebral fractures 18-20 months after the last injection were studied (Dmab/Fx-, = 5).
We measured serum microRNAs, gene expression of mRNAs of factors regulating formation and activity of osteoclasts and biochemical markers of bone and mineral metabolism. In Dmab/Fx+ and Fx+ women, blood was taken 4-8 weeks after the fracture.
Compared to Fx+ women, Dmab/Fx+ women had higher serum P1NP and CTx levels, and significantly lower serum miR-503 and miR-222-2 that downregulate osteoclastogenesis and osteoclast activity, and higher RANK (13-fold) and (2.6-fold) mRNA. The respective values of Dmab/Fx- women were in the same direction as those of Dmab/Fx+ women but of a lesser magnitude.
Bone fragility in women with clinical vertebral fractures after stopping denosumab therapy is pathophysiologically different from that of treatment-naïve women with osteoporosis and clinical vertebral fractures and it is associated with upregulation of markers of osteoclast formation and activity. The small number of women with this rare event studied is a limitation.
验证以下假说，即骨重塑的反弹是导致少数接受地诺单抗治疗的骨质疏松症患者停药后发生临床椎体骨折的原因。
在这项病例对照研究中，我们比较了最后一次注射地诺单抗后8 - 16个月发生临床椎体骨折的绝经后女性（Dmab/Fx +，n = 5）与未接受过治疗但发生此类骨折的女性（Fx +，n = 5）的临床和生化特征。此外，还研究了5名停止地诺单抗治疗但在最后一次注射后18 - 20个月未发生椎体骨折的女性（Dmab/Fx -，n = 5）。
我们检测了血清微小RNA、调节破骨细胞形成和活性的因子的mRNA基因表达以及骨和矿物质代谢的生化标志物。在Dmab/Fx +和Fx +组女性中，骨折后4 - 8周采集血液样本。
与Fx +组女性相比，Dmab/Fx +组女性血清P1NP和CTx水平更高，而下调破骨细胞生成和破骨细胞活性的血清miR - 503和miR - 222 - 2水平显著更低，RANK（13倍）和 （2.6倍）mRNA水平更高。Dmab/Fx -组女性的相应值与Dmab/Fx +组女性的方向相同，但幅度较小。
停止地诺单抗治疗后发生临床椎体骨折的女性的骨脆性在病理生理上与未接受过治疗的骨质疏松症和临床椎体骨折女性不同，并且与破骨细胞形成和活性标志物的上调有关。本研究中研究这一罕见事件的女性数量较少是一个局限性。
