The Efficacy and Safety of Bisphosphonate Therapy for Osteopenia/Osteoporosis in Patients With Chronic Kidney Disease: A Systematic Review and Individual Patient-Level Meta-Analysis of Placebo-Controlled Randomized Trials

Abstract

Background: The efficacy and safety of bisphosphonate therapy for the treatment of osteoporosis and osteopenia in the setting of chronic kidney disease (CKD) is unclear. Objective: To determine the effect of bisphosphonate therapy on fractures, bone mineral density (BMD), and adverse events in adults across the spectrum of CKD and dialysis. Design: Systematic review and individual patient-level meta-analysis. Setting: Searches of Ageline, CINAHL, the Cochrane Library, EMBASE, and Medline from inception to August 25, 2016, supplemented with manual screening and clinicalstudydatarequest.com . Authors were contacted for individual patient-level data. Patients: Randomized, placebo-controlled trials with 100 or more participants that evaluated the treatment of primary osteoporosis/osteopenia in adult men and women with bisphosphonate therapy. Measurements: Study characteristics, quality, and data were assessed independently by 2 reviewers. Outcome measures were fractures, BMD, and adverse events including decline in estimated glomerular filtration rate (eGFR) and hypocalcemia (calcium 0.05). Limitations: Clinically significant heterogeneity among studies, lack of long-term follow-up and bone biopsy results, limited representation of stage G4 and G5 CKD patients. Conclusions: Chronic kidney disease potentially modifies the efficacy but not the safety of bisphosphonate therapy in osteopenia and osteoporosis. Registration: PROSPERO CRD42020145613