ACR2010_依那西普改善RA患者骨代谢

研究显示与对照组相比，RA患者血清CTX和硬骨素水平较低，这提示骨吸收速度较慢，以及骨生成较慢。依那西普治疗后，骨转换标记物升高，炎性指标下降。因此我们认为依那西普在抑制炎症的同时，能刺激RA患者降低的骨代谢。
             

原文

译文

[1813] - Etanercept Normalizes Systemic Bone Metabolism in Rheumatoid Arthritis Patients.

Won Park, MD, PhD ¹,Mie Jin Lim, MD²,Seong Ryul Kwon, M.D, PhD.²,Ji Yeol Yoon, M.D²,Chang Gi Moon, M.D²,Go Eun Ju, M.D.². ¹Medicine/Rheumatology, IN-HA University Hospital, Choong-Gu Incheon,²IN-HA University Hospital, Incheon

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by bone loss. Etanercept is soluble TNF-α receptor which is effective in suppressing RA activity.
Objective: Our aim is to assess bone metabolism in TNF naïve RA patients and to figure out effects of etanercept on bone turnover markers and inflammatory mediators.

Methods: Twenty-one RA patients (19 women and 2 men; age 46.29 ± 11.6 years) were included. They were required to be active RA, thus meeting the criteria of DAS28 ≥ 3.2 and either ESR ≥ 28 mm/hr or CRP ≥ 2.0 mg/dL and morning stiffness ≥ 45 minutes.
Age and sex matched control group were recruited.
Etanercept was administered at standard dose, twice a week.

Venous blood was drawn at baseline in both groups and at week 14-16 after etanercept use in RA patient. Bone metabolism was assessed using bone specific alkaline phosphatase (BSAP), osteoprotegerin (OPG), sclerostin for bone formation and receptor activator for nuclear factor κB ligand (RANKL), serum c-telopeptide (CTX) for bone resorption. Serum level of inflammatory mediators including ESR, CRP and IL-6 were also determined.

Differences between two groups were examined for statistical difference by Wilkoxon signed ranks test. A p value of less than 0.05 was denoted statistically significant.
Results: At baseline the sclerostin level was significantly decreased in RA patients than in control group while serum CTX was decreasing. However after etanercept use, both serum CTX and sclerostin markedly increased (Table 1).

BSAP and OPG were slightly affected by etanercept. RANKL mildly decreased after treatment.
Inflammatory mediators responded to the treatment as ESR, CRP and IL-6 all significantly decreased (Table 2).

Conclusions: Our study showed lower level of serum CTX and sclerostin in RA patients than in control group, which suggested slow bone resorption rate coupled with low bone production. However after etanercept use, bone turnover markers rose while inflammation was decreasing. Therefore we conclude that etanercept stimulates depressed bone metabolism in RA patients as it suppresses inflammation.

Table 1. Bone metabolism in TNF naïve RA patients and changes observed after etanercept use.Table 2. Bone turnover markers and inflammatory mediators after etanercept administration in RA patients.
         

Table 1

Table 2

依那西普改善RA患者骨代谢

 

Park W, et al. ACR 2010. Present No: 1813.

 

背景：RA是一种慢性炎性疾病，伴有骨丢失。依那西普是可溶性TNF-α受体，能有效抑制RA疾病活动度。

目的：评估未使用过TNF拮抗剂的RA患者骨代谢，明确依那西普对骨转换标记物和炎性指标的影响。

方法：共纳入21例RA患者，19例女性，2例男性，年龄46.29 ± 11.6岁。均为活动性RA患者，DAS28 ≥ 3.2，ESR ≥ 28 mm/hr或 CRP ≥ 2.0 mg/dL，晨僵≥ 45分钟。选择年龄、性别匹配的对照组。依那西普按照标准剂量，每周2次。RA组在基线期和依那西普治疗14～16周后、对照组在基线期抽取静脉血。采用骨特异性碱性磷酸酶（BSAP）、骨保护素（OPG）、代表骨形成的硬骨素(sclerostin)、RANKL、代表骨吸收的血清C端肽（CTX）评估骨代谢。同时检测ESR、CRP和IL-6水平。采用Wilcoxon符号秩检验检测两组间差异。P值小于0.05认为有统计学意义。

结果：与对照组相比，RA组患者基线期硬骨素显著下降，血清CTX也有所下降。使用依那西普治疗后，血清CTX和硬骨素明显增高（表1）。依那西普对BSAP和OPG有轻度影响。治疗后RANKL稍有下降。ESR、CRP和IL-6等炎性指标治疗后显著下降（表2）。

结论：研究显示与对照组相比，RA患者血清CTX和硬骨素水平较低，这提示骨吸收速度较慢，以及骨生成较慢。依那西普治疗后，骨转换标记物升高，炎性指标下降。因此我们认为依那西普在抑制炎症的同时，能刺激RA患者降低的骨代谢。

 

表1 未使用TNF拮抗剂的RA患者的骨代谢及其在使用依那西普后的变化

	年龄与性别匹配的对照者	基线期RA患者	P (对照者与基线期RA患者相比)	依那西普治疗14-16周后	P (基线期RA患者与14-16周相比)
Sclerostin (pg/mL)	2.2±1.61	1.63±2.26	0.03	2.95±4.18	0.046
血清CTX (ng/mL)	0.38±0.18	0.28±0.13	0.114	0.34±0.17	0.048

 

 

表2  RA患者接受依那西普治疗后骨转换标记物和炎性指标的变化

	基线期	依那西普治疗14-16周后	P
ESR(mm/hr)	39 ± 31.2	26 ± 25	0.013
CRP(mg/dL)	0.98 ± 0.866	0.43 ± 1.118	0.013
IL-6(pg/mL)	3.58 ± 3.371	0.77 ± 0.726	0.001
OPG(pmol/L)	2.36 ± 1.081	2.2 ± 0.786	0.619
BSAP(U/L)	20 ± 6.97	20.3 ± 7.45	0.887
RANKL(pmol/L)	0.25 ± 0.37	0.22 ± 0.422	0.07