Benefits and harms of osteoporosis medications in patients with chronic kidney disease: A systematic review and meta-analysis

Background: Complications of chronic kidney disease (CKD) include weak bones and increased fracture risk. Purpose: To review the benefits and harms of osteoporosis medications (bisphosphonates, teriparatide, raloxifene, and denosumab) compared with placebo, usual care, or active control in terms of bone mineral density (BMD), fractures, and safety in patients with CKD. Data Sources: PubMed and the Cochrane Central Register of Controlled Trials from December 2006 through December 2016. Study Selection: Paired reviewers independently screened abstracts and full-text articles for English-language, randomized, controlled trials that had at least 6 months of follow-up; evaluated osteoporosis medications among patients with CKD; and reported on BMD, fractures, or safety (mortality and adverse events). Data Extraction: Two reviewers serially abstracted data and independently assessed risk of bias and graded the strength of evidence (SOE). Data Synthesis: There were 13 trials (n = 9850) that included kidney transplant recipients (6 trials), patients who had stage 3 to 5 CKD or were receiving dialysis (3 trials), or postmenopausal women with CKD (4 trials). Evidence showed that bisphosphonates may slow loss of BMD among transplant recipients (moderate SOE), but their effects on fractures and safety in transplant recipients and others with CKD are unclear. Raloxifene may prevent vertebral fractures but may not improve BMD (low SOE). Effects of teriparatide and denosumab on BMD and fractures are unclear (very low SOE), and these medications may increase risk for some safety outcomes. Limitation: Unclear rigor of evidence, possible reporting biases, and scant evidence among patients with stage 3 to 5 CKD. Conclusion: Effects of osteoporosis medications on BMD, fracture risk, and safety among patients with CKD are not clearly established. Primary Funding Source: Kidney Disease: Improving Global Outcomes.