Advertisement

Risks of Hip and Nonvertebral Fractures in Patients With CKD G3a-G5D: A Systematic Review and Meta-analysis

      Rationale & Objective

      Disordered 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 Design

      Systematic review and meta-analysis.

      Study Population

      Adults with CKD glomerular filtration rate (GFR) categories 3a-5D (G3a-G5D) compared with adults without CKD G3a-G5D.

      Selection Criteria for Studies

      Observational studies.

      Data Extraction

      Data extraction was conducted by 1 reviewer and checked by a second reviewer.

      Analytical Approach

      MEDLINE, 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.

      Results

      17 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.

      Limitations

      We could not assess the effects of bone mineral density, biochemical abnormalities, renal osteodystrophy, frailty, falls, or medications on risk for fractures.

      Conclusions

      Risks 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.

      Index Words

      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Coresh J.
        • Astor B.C.
        • Greene T.
        • Eknoyan G.
        • Levey A.S.
        Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.
        Am J Kidney Dis. 2003; 41: 1-12
        • Tentori F.
        • McCullough K.
        • Kilpatrick R.D.
        • et al.
        High rates of death and hospitalization follow bone fracture among hemodialysis patients.
        Kidney Int. 2014; 85: 166-173
        • Elliott M.J.
        • James M.T.
        • Quinn R.R.
        • et al.
        Estimated GFR and fracture risk: a population-based study.
        Clin J Am Soc Nephrol. 2013; 8: 1367-1376
        • Kim S.M.
        • Long J.
        • Montez-Rath M.
        • Leonard M.
        • Chertow G.M.
        Hip fracture in patients with non-dialysis-requiring chronic kidney disease.
        J Bone Miner Res. 2016; 31: 1803-1809
        • Malluche H.H.
        • Porter D.S.
        • Monier-Faugere M.C.
        • Mawad H.
        • Pienkowski D.
        Differences in bone quality in low- and high-turnover renal osteodystrophy.
        J Am Soc Nephrol. 2012; 23: 525-532
      1. Higgins J. Green S. Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, 2011
        www.handbook.cochrane.org
        Version: Version 5.1.0 [updated March 2011]
        Date accessed: April 1, 2019
        • Akers J.
        • Aguiar-Ibáñez R.
        • Baba-Akbari Sari AJYCfR, Dissemination
        CRD’s Guidance for Undertaking Reviews in Health Care.
        Centre for Reviews and Dissemination, York2009
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        PLoS Med. 2009; 6e1000097
        • Stroup D.F.
        • Berlin J.A.
        • Morton S.C.
        • et al.
        Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.
        JAMA. 2000; 283: 2008-2012
        • Pimentel A.
        • Urena-Torres P.
        • Zillikens M.C.
        • Bover J.
        • Cohen-Solal M.
        Fractures in patients with CKD-diagnosis, treatment, and prevention: a review by members of the European Calcified Tissue Society and the European Renal Association of Nephrology Dialysis and Transplantation.
        Kidney Int. 2017; 92: 1343-1355
        • Torres P.A.U.
        • Cohen-Solal M.
        Evaluation of fracture risk in chronic kidney disease.
        J Nephrol. 2017; 30: 653-661
      2. Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawas scale (NOS) for assessing the quality of non randomised studies in meta-analysis. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. 2014. Accessed April 22, 2019.

      3. Higgins J, Green S, eds. Identifying and measuring heterogeneity. 2011. In: Cochrane Handbook for Systematic Reviews of Interventions. Version 510. https://handbook-5-1.cochrane.org/index.htm#chapter_9/9_5_2_identifying_and_measuring_heterogeneity.htm. Accessed April 22, 2019.

      4. Hutchon DJ. 2005. http://www.hutchon.net/CompareRR.htm. Accessed April 1, 2019.

        • Alem A.M.
        • Sherrard D.J.
        • Gillen D.L.
        • et al.
        Increased risk of hip fracture among patients with end-stage renal disease.
        Kidney Int. 2000; 58: 396-399
        • Dooley A.C.
        • Weiss N.S.
        • Kestenbaum B.
        Increased risk of hip fracture among men with CKD.
        Am J Kidney Dis. 2008; 51: 38-44
        • Ensrud K.E.
        • Lui L.Y.
        • Taylor B.C.
        • et al.
        Renal function and risk of hip and vertebral fractures in older women.
        Arch Intern Med. 2007; 167: 133-139
        • Ensrud K.E.
        • Parimi N.
        • Fink H.A.
        • et al.
        Estimated GFR and risk of hip fracture in older men: comparison of associations using cystatin C and creatinine.
        Am J Kidney Dis. 2014; 63: 31-39
        • Fried L.F.
        • Biggs M.L.
        • Shlipak M.G.
        • et al.
        Association of kidney function with incident hip fracture in older adults.
        J Am Soc Nephrol. 2007; 18: 282-286
        • Hall R.K.
        • Sloane R.
        • Pieper C.
        • et al.
        Competing risks of fracture and death in older adults with chronic kidney disease.
        J Am Geriatr Soc. 2018; 10: 532-538
        • LaCroix A.Z.
        • Lee J.S.
        • Wu L.
        • et al.
        Cystatin-C, renal function, and incidence of hip fracture in postmenopausal women.
        J Am Geriatr Soc. 2008; 56: 1434-1441
        • Maravic M.
        • Ostertag A.
        • Torres P.U.
        • Cohen-Solal M.
        Incidence and risk factors for hip fractures in dialysis patients.
        Osteoporos Int. 2014; 25: 159-165
        • McCarthy J.T.
        • Rule A.D.
        • Achenbach S.J.
        • Bergstralh E.J.
        • Khosla S.
        • Melton 3rd, L.J.
        Use of renal function measurements for assessing fracture risk in postmenopausal women.
        Mayo Clin Proc. 2008; 83: 1231-1239
        • Naylor K.L.
        • McArthur E.
        • Leslie W.D.
        • et al.
        The three-year incidence of fracture in chronic kidney disease.
        Kidney Int. 2014; 86: 810-818
        • Wakasugi M.
        • Kazama J.J.
        • Taniguchi M.
        • et al.
        Increased risk of hip fracture among Japanese hemodialysis patients.
        J Bone Miner Metab. 2013; 31: 315-321
        • Whitlock R.H.
        • Leslie W.D.
        • Shaw J.
        • et al.
        The Fracture Risk Assessment Tool (FRAX(R)) predicts fracture risk in patients with chronic kidney disease.
        Kidney Int. 2019; 95: 447-454
        • Yenchek R.H.
        • Ix J.H.
        • Shlipak M.G.
        • et al.
        Bone mineral density and fracture risk in older individuals with CKD.
        Clin J Am Soc Nephrol. 2012; 7: 1130-1136
        • Ensrud K.E.
        • Barbour K.
        • Canales M.T.
        • et al.
        Renal function and nonvertebral fracture risk in multiethnic women: the Women's Health Initiative (WHI).
        Osteoporos Int. 2012; 23: 887-899
        • Reyes C.
        • Estrada P.
        • Nogues X.
        • et al.
        The impact of common co-morbidities (as measured using the Charlson index) on hip fracture risk in elderly men: a population-based cohort study [erratum in Osteoporos Int. 2014;25(9):2333].
        Osteoporos Int. 2014; 25: 1751-1758
        • Cummings P.
        The relative merits of risk ratios and odds ratios.
        Arch Pediatr Adolesc Med. 2009; 163: 438-445
        • Jamal S.A.
        • Hayden J.A.
        • Beyene J.
        Low bone mineral density and fractures in long-term hemodialysis patients: a meta-analysis.
        Am J Kidney Dis. 2007; 49: 674-681
        • Bucur R.C.
        • Panjwani D.D.
        • Turner L.
        • Rader T.
        • West S.L.
        • Jamal S.A.
        Low bone mineral density and fractures in stages 3-5 CKD: an updated systematic review and meta-analysis.
        Osteoporos Int. 2015; 26: 449-458
        • Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group
        KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD).
        Kidney Int Suppl. 2009; 113: S1-S130
        • Vestergaard P.
        Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes - a meta-analysis.
        Osteoporos Int. 2007; 18: 427-444
        • Tan J.
        • Li Y.
        • Wu Z.
        • Zhao J.
        Risk of hip fracture in patients on dialysis or kidney transplant: a meta-analysis of 14 cohort studies.
        Ther Clin Risk Manag. 2018; 14: 1747-1755
        • Boonpheng B.
        • Thongprayoon C.
        • Mao M.A.
        • et al.
        Risk of hip fracture in patients on hemodialysis versus peritoneal dialysis: a meta-analysis of observational studies.
        J Evid Based Med. 2019; 12: 98-104
        • Sidibe A.
        • Auguste D.
        • Desbiens L.C.
        • et al.
        Fracture risk in dialysis and kidney transplanted patients: a systematic review.
        JBMR Plus. 2019; 3: 45-55
        • Nickolas T.L.
        • Stein E.M.
        • Dworakowski E.
        • et al.
        Rapid cortical bone loss in patients with chronic kidney disease.
        J Bone Miner Res. 2013; 28: 1811-1820
        • Urena P.
        • De Vernejoul M.C.
        Circulating biochemical markers of bone remodeling in uremic patients.
        Kidney Int. 1999; 55: 2141-2156
        • Block G.A.
        • Klassen P.S.
        • Lazarus J.M.
        • Ofsthun N.
        • Lowrie E.G.
        • Chertow G.M.
        Mineral metabolism, mortality, and morbidity in maintenance hemodialysis.
        J Am Soc Nephrol. 2004; 15: 2208-2218
        • Bowling C.B.
        • Plantinga L.
        • Phillips L.S.
        • et al.
        Association of multimorbidity with mortality and healthcare utilization in chronic kidney disease.
        J Am Geriatr Soc. 2017; 65: 704-711
        • Naylor K.L.
        • Garg A.X.
        • Zou G.
        • et al.
        Comparison of fracture risk prediction among individuals with reduced and normal kidney function.
        Clin J Am Soc Nephrol. 2015; 10: 646-653
        • Wilson L.M.
        • Rebholz C.M.
        • Jirru E.
        • et al.
        Benefits and harms of osteoporosis medications in patients with chronic kidney disease: a systematic review and meta-analysis.
        Ann Intern Med. 2017; 166: 649-658

      Linked Article

      • Risks of Hip and Nonvertebral Fractures in Patients With CKD
        American Journal of Kidney DiseasesVol. 77Issue 4
        • Preview
          We read with interest the systematic review and meta-analysis by Vilaca et al.1 The authors mentioned several factors that could contribute to the increase in risk for hip and nonvertebral fractures in chronic kidney disease (CKD), such as low bone mineral density, CKD mineral and bone disorder, previous inflammation, glucocorticoid treatment, and diabetes mellitus, although none of these factors were analyzed in the meta-analysis. We suggest adding chronic hyponatremia as a novel risk factor for fractures in CKD patients, as it is a very frequent electrolyte abnormality in this population.
        • Full-Text
        • PDF