Abstract

Background: Chronic kidney disease (CKD) is associated with bone and mineral metabolism. In this study we evaluated the comparative efficacies and safety of osteoporosis medications in patients with CKD or a history of kidney transplantation, and make recommendations for the best choice of osteoporosis treatment among patients with CKD or a history of kidney transplantation. Methods: We systemically searched for randomized controlled trials published in PubMed, Embase, and Cochrane databases up to June 2020. Network-meta analysis was used to compare the relative effectiveness of different treatments. A random-effects model was used when heterogeneity was expected. The safety of different treatments was also evaluated in terms of reported major adverse events. Results: A total of 17 studies with data from 10,214 patients who had stage 2–5 CKD, were receiving dialysis, or had a history of kidney transplantation were included in the network meta-analysis. Treatment with teriparatide, denosumab, alendronate, and raloxifene were all associated with a significantly reduced risk of fractures compared to treatment with placebos [teriparatide: odds ratio (OR) = 0.19, 95% confidence interval (CI): 0.10–0.35; denosumab: OR = 0.40, 95% CI: 0.27–0.58; alendronate: OR = 0.61, 95% CI: 0.40–0.92; raloxifene: OR = 0.52, 95% CI: 0.41–0.67]. The rank probability and the surface under the cumulative ranking (SUCRA) values suggested that teriparatide ranked the highest for improvement in vertebral bone mineral density (BMD) (SUCRA = 97.8%), whereas denosumab ranked the highest for improvement in femoral neck BMD (SUCRA = 88.3%). Conclusion: Teriparatide and denosumab seem to be the most effective treatments for preventing bone loss and reducing the risk of fracture in our network comparison. However, because of the limitations and potential biases in the reviewed studies, there is still some uncertainty about the best treatment options for osteoporosis in patients with CKD or a history of kidney transplantation. Systematic Review Registration: [PROSPERO], identifier [CRD42020209830].

Highlights

  • Chronic kidney disease (CKD) is a major global public health issue, affecting an estimated 700 million people worldwide (Bikbov et al, 2020)

  • Five of the randomized controlled trials included patients diagnosed as having stage 3–5 CKD and patients receiving dialysis (Toussaint et al, 2010; Haghverdi et al, 2014; Shigematsu et al, 2017; Iseri et al, 2019; Sugimoto et al, 2019), and seven studies included patients who had received kidney transplants (Coco et al, 2003; Walsh et al, 2009; Torregrosa et al, 2010; Smerud et al, 2012; Sánchez-Escuredo et al, 2015; Bonani et al, 2016; Marques et al, 2019)

  • With respect to new vertebral or clinical fracture events, treatment with alendronate, denosumab, raloxifene, or teriparatide were all associated with a significantly lower risk of new vertebral or clinical fractures compared to treatment with placebos [alendronate: odds ratio (OR) = 0.61, 95% confidence intervals (CIs): 0.40–0.92; raloxifene: OR = 0.52, 95% CI: 0.41–0.67; denosumab: OR = 0.40, 95% CI: 0.27–0.58; teriparatide: OR = 0.19, 95% CI: 0.10–0.35]

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Summary

Introduction

Chronic kidney disease (CKD) is a major global public health issue, affecting an estimated 700 million people worldwide (Bikbov et al, 2020). The prevalence of CKD has almost doubled over the last 2 decades, driven by population growth, aging, and an increased number of people with hypertension and diabetes (Bikbov et al, 2020). The growing number of CKD cases and kidney transplantation may lead to a potential increase in the burden of bone and mineral metabolism disorders. Studies of patients with CKD or a history of kidney transplantation have shown that there is a higher incidence of hip fracture among patients with progressive CKD compared to patients without CKD (System URD, 2013). Chronic kidney disease (CKD) is associated with bone and mineral metabolism. In this study we evaluated the comparative efficacies and safety of osteoporosis medications in patients with CKD or a history of kidney transplantation, and make recommendations for the best choice of osteoporosis treatment among patients with CKD or a history of kidney transplantation

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