类风湿性关节炎患者在denosumab治疗期间骨吸收,主要免疫标志物阳性

П.С. Коваленко, И.С. Дыдыкина, А.В. Смирнов, Евгений Львович Насонов, P. Kovalenko, I. S. Dydykina, Alexander V. Smirnov, E. L. Nasonov, V. A. N. Research
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引用次数: 1

摘要

目标。类风湿性关节炎(RA)的炎症导致局部和全身性骨质流失的发展。类风湿因子(RF)和抗环瓜氨酸肽抗体(ACCP)被认为在RA的放射学进展中起负作用。使用denosumab - RANKL(核因子κ b配体受体激活剂)单克隆抗体等抗吸收治疗,可降低破骨细胞的活性,增加骨矿物质密度(BMD),并可能影响RA的侵蚀过程。本研究的目的是考虑血清RF和ACCP阳性以及基线RA活性,评估denosumab治疗对RA和骨质疏松症(OP)患者BMD和糜烂计数的影响。材料和方法。对denosumab治疗RA和OP患者(每6个月皮下注射60mg)疗效的为期12个月的前瞻性研究包括66名绝经后妇女;年龄59.4±7.5岁,RA病程17.8±10.6年,rf阳性47例(72%),accp阳性48例(74%)。在基线和12个月后,进行双能x线骨密度测量,评估腰椎(L1 - L4)、股骨近端(髋颈和全髋)、前臂远端的骨密度;手部和足部远端x光片直接投影,然后根据Sharp/van der Heijde方法评估侵蚀-破坏性变化。结果。尽管RF和ACCP呈阳性,但所有研究部位的骨密度均显著增加(髋颈部p=0.05),而RF和ACCP阴性组的骨密度仅在L1-L4部位显著增加。在RF和accp阳性组中,侵蚀计数增加的进展被注意到,而在RF和accp阴性组中,该指标没有变化。无论RA的基线活动度如何(DAS28(疾病活动度评分28)),骨骼大部分的BMD都是稳定的。在中度RA活动度的患者中,RF-和accp阳性和阴性两组的L1-L4的BMD显著增加,RF-和accp阳性组的BMD也显著增加。RA患者糜烂计数的动态不依赖于DAS28活性的基线程度,在分析组中未检测到显著变化。结论。在接受denosumab治疗的RA和OP患者中,血清RF和ACCP阳性对BMD动力学没有负面影响,但侵蚀数量增加。在大多数亚组中,基线RA活动水平不影响侵蚀计数的动态变化和骨密度的动态变化——骨密度水平已经增加或稳定。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bone resorption during therapy with denosumab in patients with rheumatoid arthritis, positive for the main immunological markers
Objective. Inflammation in rheumatoid arthritis (RA) leads to the development of local and generalized bone loss. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACCP) are believed to play a negative role in the radiological progression of RA. The use of such antiresorptive therapy as denosumab – monoclonal antibodies to RANKL (receptor activator of nuclear factor kappa-B ligand), reduces the activity of osteoclasts, increases bone mineral density (BMD), and also potentially affects the erosive process at RA. The aim of the study is to evaluate the effect of denosumab therapy on BMD and erosion count in patients with RA and osteoporosis (OP) in consideration of the positivity in the RF and ACCP in serum and the baseline RA activity. Materials and methods. The 12-month prospective study of the efficacy of denosumab therapy (60 mg subcutaneously every 6 months) in patients with RA and OP included 66 postmenopausal women; age – 59.4±7.5 years, duration of RA – 17.8±10.6 years, RF-positive – 47 (72%) patients, ACCP-positive – 48 (74%) patients. At baseline and after 12 months, dual-energy X-ray absorptiometry was performed with an assessment of BMD in the lumbar spine (L1– L4), proximal femur (hip neck and total hip), distal forearm; X-ray of the hands and distal parts of the feet in direct projection, followed by assessment of erosive-destructive changes according to the Sharp/van der Heijde method. Results. A significant increase in BMD was established in all studied sites of the skeleton despite the positivity of the RF and ACCP (for the hip neck p=0.05), while a significant increase in BMD in the RF- and ACCP-negative group was detected only in L1–L4 site. The progression of the increase in erosion count was noted in the RF- and ACCP-positive group while in the RF- and ACCP-negative group this indicator did not change. Regardless of the baseline activity of RA (by DAS28 (Disease Activity Score 28)) the BMD of most parts of the skeleton were stabilized. In patients with moderate RA activity, BMD increased significantly in L1–L4 in both groups: RF- and ACCP-positive and -negative , as well as in the total hip – in RF- and ACCP-positive group. The dynamics of the erosion count in RA patients did not depend on the baseline degree of DAS28 activity, no significant changes were detected in the analyzed groups. Conclusions. RF and ACCP positivity in serum in patients with RA and OP treated with denosumab did not have a negative effect on the dynamics of BMD, while the number of erosions increased. The baseline RA activity level did not affect the dynamics of the erosion count and the dynamics of BMD in most subgroups – BMD levels have been increased or stabilized.
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