Changes of Circulating MicroRNAs in Response to Treatment With Teriparatide or Denosumab in Postmenopausal Osteoporosis
Changes of Circulating MicroRNAs in Response to Treatment With Teriparatide or Denosumab in Postmenopausal Osteoporosis
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DOI：
10.1210/jc.2017-02406
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发表时间：
2018-03-01
影响因子：
5.8
通讯作者：
Yavropoulou, Maria P.
中科院分区：
文献类型：
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作者：
Anastasilakis, Athanasios D.;Makras, Polyzois;Yavropoulou, Maria P.
内容：血清中与骨代谢相关的microRNA（miRs）的表达可能受到抗骨质疏松治疗的影响。目的：研究两种对骨代谢具有相反作用的抗骨质疏松剂对血清中miRs表达谱的影响。设计：观察性、开放标签、非随机临床试验。设置：希腊塞萨洛尼基424总军事医院代谢性骨病门诊。患者和干预措施：低骨量绝经后妇女用特立帕妥治疗（TPTD; n = 30）或地舒单抗（n = 30）治疗12个月。主要结果测量：在治疗3个月和12个月时与骨代谢相关的选定miR的血清表达的变化。二次测量：测量的miR与12个月时的骨矿物质密度（BMD）变化以及3个月和12个月时的骨转换标志物（BTM）I型胶原的C-末端交联端肽和I型前胶原N-末端前肽的相关性。我们发现TPTD治疗3个月时miR-33- 3 p的相对表达显著降低（P = 0.03），12个月时miR-133 a的相对表达显著降低（P = 0.042）。TPTD治疗12个月时的BMD值与3个月时的miR-124- 3 p表达显著负相关（P = 0.008）。miR-24- 3 p和miR-27 a的相对表达与TPTD治疗期间BTM的变化相关，miR-21- 5 p、miR-23 a-3 p、miR-26 a-5 p、miR-27 a、miR-222- 5 p和miR-335- 5 p的相对表达与狄诺塞单抗治疗期间BTM的变化相关。TPTD影响与RUNX-2（miR-33）和DKK-1基因（miR-133）表达相关的miR的相对表达。
Context: Expression of microRNAs (miRs) related to bone metabolism in the serum may be affected by antiosteoporotic treatment.Objective: To investigate the effect of two antiosteoporotic agents with opposite effects on bone metabolism on miR expression profile in the serum.Design: Observational, open label, nonrandomized clinical trial.Setting: The outpatient clinics for Metabolic Bone Diseases of 424 General Military Hospital, Thessaloniki, Greece.Patients and Interventions: Postmenopausal women with low bone mass were treated with either teriparatide (TPTD; n = 30) or denosumab (n = 30) for 12 months.Main Outcome Measures: Changes in the serum expression of selected miRs linked to bone metabolism at 3 and 12 months of treatment. Secondary measurements: associations of measured miRs with changes in bone mineral density (BMD) at 12 months and the bone turnover markers (BTMs) C-terminal cross-linking telopeptide of type I collagen and procollagen type I N-terminal propeptide at 3 and 12 months.Results: We found significantly decreased relative expression of miR-33-3p at 3 months (P = 0.03) and of miR-133a at 12 months (P = 0.042) of TPTD treatment. BMD values at 12 months of TPTD treatment were significantly and inversely correlated with miR-124-3p expression at 3 months (P = 0.008). Relative expression of miR-24-3p and miR-27a was correlated with changes in BTMs during TPTD treatment and of miR-21-5p, miR-23a-3p, miR-26a-5p, miR-27a, miR-222-5p, and miR-335-5p with changes in BTMs during denosumab treatment.Conclusions: Circulating miRs are differentially affected by treatment with TPTD and denosumab. TPTD affects the relative expression of miRs related to the expression of RUNX-2 (miR-33) and DKK-1 gene (miR-133).