• Tatiane Vilaca, Syazrah Salam, Marian Schini, Susan Harnan, Anthea Sutton, Edith Poku, Isabel Elaine Allen, Steven R Cummings, and Richard Eastell.
• Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom. Electronic address: tvilaca1@sheffield.ac.uk.
• Am. J. Kidney Dis. 2020 Oct 1; 76 (4): 521-532.

Rationale & ObjectiveDisordered mineral metabolism complicates chronic kidney disease (CKD), but the effect of reduced kidney function on fracture risk has not been fully established. We conducted a systematic review and meta-analysis of the risks for hip and nonvertebral fractures in people with CKD. We also investigated the effects of age, sex, and CKD stage.Study DesignSystematic review and meta-analysis.Study PopulationAdults with CKD glomerular filtration rate (GFR) categories 3a-5D (G3a-G5D) compared with adults without CKD G3a-G5D.Selection Criteria For StudiesObservational studies.Data ExtractionData extraction was conducted by 1 reviewer and checked by a second reviewer.Analytical ApproachMEDLINE, EMBASE, and Cochrane databases were searched in March 2018 and an update was conducted in November 2019. We used random-effects models to calculate pooled risk estimates and 95% CIs.Results17 studies met the inclusion criteria. We included 13 studies in the hip fracture systematic review and 10 studies in the meta-analysis. Studies reported data from 250,440,035 participants; 5,798,566 with CKD G3a-G5D and 363,410 with hip fractures. 4 studies were included in the nonvertebral fracture analysis, reporting data from 1,396,976 participants; 464,978 with CKD G3a-G5D and 115,284 fractures. Studies reported data from participants aged 18 to older than 90 years. We found a significant increase in fracture risk both for hip (relative risk [RR], 2.36; 95% CI, 1.64-3.39) and nonvertebral fractures (RR, 1.47; 95% CI, 1.15-1.88). For hip fractures, younger patients (<65 years) had higher relative risk (RR, 7.66; 95% CI, 2.76-21.26) than older patients (>65 years; RR, 2.11; 95% CI, 1.41-3.16). Greater GFR loss was associated with higher relative risk for fractures.LimitationsWe could not assess the effects of bone mineral density, biochemical abnormalities, renal osteodystrophy, frailty, falls, or medications on risk for fractures.ConclusionsRisks for hip and nonvertebral fractures are increased in CKD G3a-G5D. The relative risk of hip fracture is greater in the younger than the older population and increases progressively with loss of GFR. We suggest that fracture prevention should be a consideration in CKD at any age.Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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