Department of Rheumatology, Aarhus University Hospital, Nørrebrogade 44, byg 3, 8000 Aarhus C, Denmark; Department of Clinical Medicine, Aarhus University, Incuba/Skejby, bygning 2, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Denmark.
Department of Rheumatology, Aarhus University Hospital, Nørrebrogade 44, byg 3, 8000 Aarhus C, Denmark; Department of Clinical Medicine, Aarhus University, Incuba/Skejby, bygning 2, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Denmark.
Bone. 2018 Sep;114:172-180. doi: 10.1016/j.bone.2018.06.008. Epub 2018 Jun 18.
The role of glucocorticoids in the treatment of rheumatoid arthritis (RA) is widely debated. Impairment of bone formation may be counter-balanced by reduced systemic inflammation. This review aims to assess the effect of prednisolone/prednisone on bone mineral density (BMD) in patients with RA analyzed in randomized, controlled trials.
We performed a systematic literature search and identified randomized, double-blinded placebo-controlled studies including patients with RA and using prednisolone or prednisone as the intervention. We selected studies that measured BMD by DXA at baseline and at least once thereafter. Two authors independently performed reference review, data extraction and risk of bias assessment. Primary outcome was mean change in BMD from baseline to follow-up. Secondary endpoints included radiographic scores, RA disease activity indices and fractures. We rated the quality of evidence using the GRADE approach. Outcomes were standardized for meta-analyses and 95% confidence intervals (95% CI) were calculated.
We identified 7 studies and included previously unpublished data. Studies were similar regarding study population and intervention. Standard mean difference (SMD) in change in BMD from 0 to 24 months was -0.02 (95%CI -0.16, 0.12) at the lumbar spine and -0.11 (95% CI -0.25, 0.02) at the hip (both high quality evidence) between patients treated with prednisolone/prednisone or not. Data completeness was low in some studies, concomitant treatment of RA differed between studies and differences in use of anti-osteoporotic medication may have influenced the results. However, sensitivity analyses excluding studies in which participants used either the most or the least potent concomitant RA treatment or used anti-osteoporotic therapies did not alter the estimates.
In patients with early and active RA, we found no difference in change in BMD between patients treated with prednisone/prednisolone versus placebo, suggesting that at least through 24 months, the suppression of inflammation by glucocorticoids may counterbalance their adverse effects on bone remodeling.
糖皮质激素在类风湿关节炎（RA）治疗中的作用存在广泛争议。骨形成的受损可能会被全身炎症的减轻所抵消。本综述旨在评估在随机对照试验中分析的 RA 患者使用泼尼松龙/泼尼松治疗对骨密度（BMD）的影响。
我们进行了系统的文献检索，并确定了包括 RA 患者在内的随机、双盲、安慰剂对照研究，使用泼尼松龙或泼尼松作为干预措施。我们选择了在基线和此后至少一次测量 DXA 骨密度的研究。两位作者独立进行参考文献审查、数据提取和偏倚风险评估。主要结局是从基线到随访时 BMD 的平均变化。次要结局包括影像学评分、RA 疾病活动指数和骨折。我们使用 GRADE 方法评估证据质量。使用标准化均值差（SMD）进行汇总分析，并计算 95%置信区间（95%CI）。
我们确定了 7 项研究，包括以前未发表的数据。研究在研究人群和干预措施方面相似。泼尼松龙/泼尼松治疗与未治疗患者在 0 至 24 个月时 BMD 变化的标准均数差（SMD）在腰椎为-0.02（95%CI -0.16，0.12），在髋关节为-0.11（95%CI -0.25，0.02）（均为高质量证据）。一些研究的数据完整性较低，研究之间 RA 的伴随治疗不同，抗骨质疏松药物的使用差异可能影响了结果。然而，排除参与者使用最有效或最无效的伴随 RA 治疗或使用抗骨质疏松药物治疗的研究的敏感性分析并未改变估计值。
在早期和活动期 RA 患者中，我们发现接受泼尼松龙/泼尼松治疗与安慰剂治疗的患者之间 BMD 变化无差异，这表明至少在 24 个月内，糖皮质激素对炎症的抑制可能抵消了其对骨重塑的不利影响。
