Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
J Clin Densitom. 2020 Apr-Jun;23(2):223-236. doi: 10.1016/j.jocd.2019.05.003. Epub 2019 May 10.
Osteoporosis is a common complication of primary biliary cholangitis (PBC) yet evidence for effective therapy is lacking. We sought to review all randomized controlled trials evaluating pharmacotherapy against placebo or no intervention for treatment of osteoporosis in PBC.
A comprehensive database search was conducted from inception through 29 March 2017. The primary outcome was incidence of fractures; secondary outcomes were change in bone mineral density (BMD) and adverse events. We assessed studies for risk of bias, graded quality of evidence, and used meta-analysis to obtain overall effect by pooling studies of the same drug class.
We identified 11 randomized controlled trials evaluating bisphosphonates (3), hormone replacement therapy (2), ursodeoxycholic acid (1), obeticholic acid (1), cyclosporin A (1), vitamin K (1), calcitriol (1), and sodium fluoride (1). No intervention significantly reduced fractures compared to control. Although significant improvement in BMD was seen in one study with alendronate, a third-generation bisphosphonate, no significant improvement was seen on pooled analysis of all bisphosphonates including first-generation bisphosphonates (standard mean difference 0.41, p = 0.68). On pooled analysis, hormone replacement therapy modestly improved lumbar BMD (standard mean difference 0.69, p = 0.02), but with significantly increased adverse events (odds ratio 8.82, p = 0.01).
There is a lack of high-quality evidence supporting the efficacy of any treatment of osteoporosis in PBC. This may be explained by lack of power in the included studies. However, our current understanding of PBC-related osteoporosis indicates that it results from decreased bone formation, which may explain the attenuated effect of traditional antiresorptive agents. Future studies should investigate newer anabolic bone agents.
骨质疏松症是原发性胆汁性胆管炎（PBC）的常见并发症，但缺乏有效的治疗证据。我们旨在回顾所有评估药物治疗与安慰剂或不干预治疗 PBC 相关骨质疏松症的随机对照试验。
从研究开始到 2017 年 3 月 29 日，我们进行了全面的数据库检索。主要结局是骨折的发生率；次要结局是骨密度（BMD）的变化和不良事件。我们评估了研究的偏倚风险，分级证据质量，并使用荟萃分析来汇总相同药物类别的研究以获得总体效果。
我们确定了 11 项评估双膦酸盐（3）、激素替代疗法（2）、熊去氧胆酸（1）、奥贝胆酸（1）、环孢素 A（1）、维生素 K（1）、骨化三醇（1）和氟化钠（1）治疗骨质疏松症的随机对照试验。与对照组相比，不干预显著降低了骨折的发生率。虽然一项关于阿仑膦酸盐（第三代双膦酸盐）的研究显示 BMD 有显著改善，但所有双膦酸盐（包括第一代双膦酸盐）的汇总分析并未显示出显著改善（标准化均数差 0.41，p=0.68）。在汇总分析中，激素替代疗法适度改善了腰椎 BMD（标准化均数差 0.69，p=0.02），但不良事件显著增加（比值比 8.82，p=0.01）。
缺乏高质量的证据支持任何治疗 PBC 相关骨质疏松症的疗效。这可能是由于纳入的研究缺乏效力。然而，我们目前对 PBC 相关骨质疏松症的认识表明，其源于成骨减少，这可能解释了传统抗吸收剂作用减弱的原因。未来的研究应调查新型合成代谢骨剂。
