Rheumatology department, CHRU Cavale Blanche, Brest, France; Lymphocytes B et autoimmunité, UMR1227, INSERM, Université de Bretagne Occidentale, Brest, France.
Radiology department, CHRU Cavale Blanche, Brest, France.
Joint Bone Spine. 2021 May;88(3):105117. doi: 10.1016/j.jbspin.2020.105117. Epub 2020 Dec 7.
This study explores changes in the bone homeostasis by testing the N-terminal collagen type I extension propeptide (PINP) marker for osteo-formation and the carboxy-terminal region of collagen type I (CTX-I) marker for osteo-resorption in patients taking tocilizumab for polymyalgia rheumatica (PMR).
Twenty patients were included in the prospective open-label TENOR study (Clinicaltrials.gov NCT01713842) and received three monthly tocilizumab infusions, followed by corticosteroids starting at week (W) 12. PINP and CTX-I were tested at inclusion (W0), after tocilizumab but before steroid initiation (W12), at the end of the protocol (W24) and were compared to healthy controls. Information regarding disease activity, bone mineral density using scanographic bone attenuation correlation (SBAC), inflammatory parameters and interleukin (IL)-6 levels were collected during the follow-up of the patients.
PMR patients were characterised by a reduction in bone mineral density and a higher level of CTX-I relative to healthy controls matched in age and sex at baseline. PINP levels increased at W12 (P< 0.001, versus W0) following tocilizumab introduction and CTX-I levels decreased at W24 and after steroid initiation (P=0.001, versus W0). Such modifications explain the altered correlation observed between PINP and CTX-I at W0 (r=0.255 at W0 versus r=0.641 in healthy controls) and its correction after treatment (r=0.760 at W12 and r=0.767 at W24). Finally, greater changes in PINP were observed in patients whose circulating IL-6 levels decreased after tocilizumab therapy.
Control of bone turnover, in part through the inhibition of the IL-6 axis, is observed during tocilizumab and subsequent steroid treatment of PMR.
通过检测成骨标志物 N 端胶原 I 型前肽（PINP）和破骨标志物 I 型胶原 C 端肽（CTX-I），探讨托珠单抗治疗巨细胞动脉炎（PMR）患者骨稳态的变化。
20 例 PMR 患者纳入前瞻性开放标签 TENOR 研究（Clinicaltrials.gov NCT01713842），每 3 个月接受托珠单抗静脉输注，随后于第 12 周开始使用皮质类固醇。在入组时（第 0 周，W0）、托珠单抗治疗但皮质类固醇未起始时（第 12 周，W12）、方案结束时（第 24 周，W24）检测 PINP 和 CTX-I，并与健康对照组进行比较。在患者随访期间收集疾病活动度、使用扫描骨衰减相关性（SBAC）检测的骨密度、炎症参数和白细胞介素（IL）-6 水平等信息。
与年龄和性别匹配的健康对照组相比，PMR 患者的骨密度降低，CTX-I 水平升高。托珠单抗治疗后第 12 周（P<0.001，与 W0 相比），PINP 水平升高，第 24 周和皮质类固醇起始后（P=0.001，与 W0 相比）CTX-I 水平降低。这些变化解释了 W0 时观察到的 PINP 和 CTX-I 之间改变的相关性（W0 时 r=0.255，健康对照组时 r=0.641），以及治疗后的校正（W12 时 r=0.760，W24 时 r=0.767）。此外，托珠单抗治疗后 IL-6 水平降低的患者的 PINP 变化更大。
在托珠单抗和随后的皮质类固醇治疗 PMR 期间，观察到骨转换得到控制，部分原因是通过抑制 IL-6 轴。
