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
Authors: Ana Pimentel, Pablo Ureña-Torres, M. Carola Zillikens, Jordi Bover, Martine Cohen-Solal
Journal: Kidney International (2017)

Mineral and bone disease is omnipresent in patients with chronic kidney disease (CKD) and leads to a diverse range of clinical manifestations, including bone pain and fractures. The accumulation of traditional clinical risk factors, in addition to those related to CKD, enhances the risk of comorbidity and mortality. Despite significant advances in understanding bone disease in CKD, most clinical and biochemical targets used in clinical practice remain controversial, resulting in an undermanagement of bone fragility. Vitamin D supplementation is widely used, but only a few studies have shown beneficial effects and a reduced risk of fracture and mortality. The achievement of serum levels of 25-hydroxyvitamin D is recommended for CKD patients to reduce a high parathyroid hormone level, which is associated with skeletal fractures. Optimal control of parathyroid hormone also improves bone mineralization and lowers circulating bone biomarkers such as alkaline phosphatase and cross-linked collagen type I peptide. The potential value of more recent biomarkers such as sclerostin and fibroblast growth factor 23, as surrogates for bone fragility, is an encouraging new direction in clinical research but is far from being firmly established. This article reviews the literature related to the pathophysiological role of various mineral and biochemical factors involved in renal osteodystrophy. To better understand bone fragility in CKD, new information related to the impact of disturbances of mineral metabolism on bone strength is urgently needed. The combined expertise of clinicians from various medical disciplines appears crucial for the most successful prevention of fractures in these patients. Mineral and bone disease is omnipresent in patients with chronic kidney disease (CKD) and leads to a diverse range of clinical manifestations, including bone pain and fractures. The accumulation of traditional clinical risk factors, in addition to those related to CKD, enhances the risk of comorbidity and mortality. Despite significant advances in understanding bone disease in CKD, most clinical and biochemical targets used in clinical practice remain controversial, resulting in an undermanagement of bone fragility. Vitamin D supplementation is widely used, but only a few studies have shown beneficial effects and a reduced risk of fracture and mortality. The achievement of serum levels of 25-hydroxyvitamin D is recommended for CKD patients to reduce a high parathyroid hormone level, which is associated with skeletal fractures. Optimal control of parathyroid hormone also improves bone mineralization and lowers circulating bone biomarkers such as alkaline phosphatase and cross-linked collagen type I peptide. The potential value of more recent biomarkers such as sclerostin and fibroblast growth factor 23, as surrogates for bone fragility, is an encouraging new direction in clinical research but is far from being firmly established. This article reviews the literature related to the pathophysiological role of various mineral and biochemical factors involved in renal osteodystrophy. To better understand bone fragility in CKD, new information related to the impact of disturbances of mineral metabolism on bone strength is urgently needed. The combined expertise of clinicians from various medical disciplines appears crucial for the most successful prevention of fractures in these patients. Preventing or delaying the progressive metabolic complications related to chronic kidney disease (CKD) is essential to reduce the high morbidity and mortality rates associated with it. The mineral and bone disorder (MBD) associated with CKD (CKD-MBD) is an evolving entity. Guidelines from the 2009 Kidney Disease Improving Global Outcomes (KDIGO)1Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work GroupKDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).Kidney Int Suppl. 2009 Aug; : S1-S130Google Scholar and the 2017 revised version (in press) have incorporated recommendations on the assessment and treatment of bone, biochemical, and cardiovascular abnormalities. In addition to the initial criteria for renal osteodystrophy based on bone biopsy findings, bone volume and mineralization have been added as other bone markers of fragility. The new CKD-MBD definition aims at a better awareness of bone events. Skeletal fractures are the main clinical outcome, and their prevention should be a major target of renal osteodystrophy. The evaluation of fracture risk is required in light of high mortality and hospitalization costs related to fractures in dialysis patients,2Beaubrun A.C. Kilpatrick R.D. Freburger J.K. et al.Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.J Am Soc Nephrol. 2013; 24: 1461-1469Crossref PubMed Scopus (0) Google Scholar, 3Hansen D. Olesen J.B. Gislason G.H. et al.Risk of fracture in adults on renal replacement therapy: a Danish national cohort study.Nephrol Dial Transplant. 2016; 31: 1654-1662Crossref PubMed Google Scholar, 4Maravic M. Ostertag A. Torres P.U. et al.Incidence and risk factors for hip fractures in dialysis patients.Osteoporos Int. 2014; 25: 159-165Crossref PubMed Scopus (50) Google Scholar, 5Tentori F. McCullough K. Kilpatrick R.D. et al.High rates of death and hospitalization follow bone fracture among hemodialysis patients.Kidney Int. 2014; 85: 166-173Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 6Danese M.D. Kim J. Doan Q.V. et al.PTH and the risks for hip, vertebral, and pelvic fractures among patients on dialysis.Am J Kidney Dis. 2006; 47: 149-156Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar which enhances the economic burden of CKD-MBD. In contrast to the 2009 KDIGO guidelines, systematic bone mineral density (BMD) measurement is recommended in CKD patients by the revised 2017 KDIGO guidelines because this might influence treatment decisions. CKD patients are living longer at present than at the end of the past century. Because bone loss increases with aging, the prevalence of skeletal fractures has increased in recent years. Table 1 summarizes several longitudinal studies reporting the incidence of fractures.4Maravic M. Ostertag A. Torres P.U. et al.Incidence and risk factors for hip fractures in dialysis patients.Osteoporos Int. 2014; 25: 159-165Crossref PubMed Scopus (50) Google Scholar, 7Alem A. Sherrard D. Gillen D. et al.Increased risk of hip fracture among patients with end-stage renal disease.Kidney Int. 2000; 58: 396-399Abstract Full Text Full Text PDF PubMed Scopus (431) Google Scholar, 8Coco M. Rush H. Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone.Am J Kidney Dis. 2000; 36: 1115-1121Abstract Full Text Full Text PDF PubMed Google Scholar, 9Stehman-Breen C.O. Sherrard D.J. Alem A.M. et al.Risk factors for hip fracture among patients with end-stage renal disease.Kidney Int. 2000; 58: 2200-2205Abstract Full Text Full Text PDF PubMed Google Scholar, 10Dukas L. Schacht E. Stähelin H.B. In elderly men and women treated for osteoporosis a low creatinine clearance of <65 ml/min is a risk factor for falls and fractures.Osteoporos Int. 2005; 16: 1683-1690Crossref PubMed Scopus (0) Google Scholar, 11Jadoul M. Albert J.M. Akiba T. et al.Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study.Kidney Int. 2006; 70: 1358-1366Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 12Nickolas T.L. McMahon D.J. Shane E. Relationship between moderate to severe kidney disease and hip fracture in the United States.J Am Soc Nephrol. 2006; 17: 3223-3232Crossref PubMed Scopus (156) Google Scholar, 13Ensrud 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: 133Crossref PubMed Scopus (157) Google Scholar, 14Fried 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: 282-286Crossref PubMed Scopus (0) Google Scholar, 15Dooley A.C. Weiss N.S. Kestenbaum B. Increased risk of hip fracture among men with CKD.Am J Kidney Dis. 2008; 51: 38-44Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 16LaCroix 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: 1434-1441Crossref PubMed Scopus (0) Google Scholar, 17Ambrus C. Almasi C. Berta K. et al.Vitamin D insufficiency and bone fractures in patients on maintenance hemodialysis.Int Urol Nephrol. 2011; 43: 475-482Crossref PubMed Scopus (0) Google Scholar, 18Iimori S. Mori Y. Akita W. et al.Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients-a single-center cohort study.Nephrol Dial Transplant. 2012; 27: 345-351Crossref PubMed Scopus (0) Google Scholar, 19Wakasugi M. Kazama J.J. Taniguchi M. et al.Increased risk of hip fracture among Japanese hemodialysis patients.J Bone Miner Metab. 2013; 31: 315-321Crossref PubMed Scopus (31) Google Scholar, 20Arneson T.J. Li S. Liu J. et al.Trends in hip fracture rates in US hemodialysis patients, 1993-2010.Am J Kidney Dis. 2013; 62: 747-754Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 21Elliott 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: 1367-1376Crossref PubMed Scopus (0) Google Scholar, 22Nair S.S. Mitani A.A. Goldstein B.A. et al.Temporal trends in the incidence, treatment, and outcomes of hip fracture in older patients initiating dialysis in the United States.Clin J Am Soc Nephrol. 2013; 8: 1336-1342Crossref PubMed Scopus (0) Google Scholar, 23Mathew A.T. Hazzan A. Jhaveri K.D. et al.Increasing hip fractures in patients receiving hemodialysis and peritoneal dialysis.Am J Nephrol. 2014; 40: 451-457Crossref PubMed Scopus (0) Google Scholar, 24Delgado C. Shieh S. Grimes B. et al.Association of self-reported frailty with falls and fractures among patients new to dialysis.Am J Nephrol. 2015; 42: 134-140Crossref PubMed Scopus (12) Google Scholar, 25Yamamoto S. Kido R. Onishi Y. et al.Use of renin-angiotensin system inhibitors is associated with reduction of fracture risk in hemodialysis patients.PLoS One. 2015; 10: e0122691Google Scholar Most of them found the fracture incidence to progressively increase by 15.0, 20.5, 24.2, 31.2, and 46.3 per 1000 person-years for CKD stages 1 to 2, 3a, 3b, and 4, respectively.26Naylor 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: 646-653Crossref PubMed Scopus (0) Google Scholar The risk of skeletal fracture is up to 5 times higher in individuals with an estimated glomerular filtration rate (eGFR) <15 versus >60 ml/min per 1.73 m2. Patients with CKD and older than 65 years of age exhibit a particularly high rate of fractures, with 1 in 10 women and 1 in 20 men experiencing at least 1 fracture in the subsequent 3 years of follow-up.27Naylor K.L. McArthur E. Leslie W.D. et al.The three-year incidence of fracture in chronic kidney disease.Kidney Int. 2014; 86: 810-818Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar In a recent Dialysis Outcomes and Practice Patterns Study (DOPPS) report, the incidence of fractures was significantly higher for patients receiving hemodialysis therapy than in the general population, with a 3.7-fold increase in the unadjusted relative risk of death.5Tentori F. McCullough K. Kilpatrick R.D. et al.High rates of death and hospitalization follow bone fracture among hemodialysis patients.Kidney Int. 2014; 85: 166-173Abstract Full Text Full Text PDF PubMed Scopus (0) Google ScholarTable 1Fracture incidence per 1000 persons-years and increased risk in CKD populationStudyType of studyTotal no. of patientsFracture (N)Fracture typeCKD stageIncidence of fractures (1000 person-years)Incidence (1000 person-years)Global OR fracture risk95% CIMenWomenMen RRWomen RRAlem et al.7Alem A. Sherrard D. Gillen D. et al.Increased risk of hip fracture among patients with end-stage renal disease.Kidney Int. 2000; 58: 396-399Abstract Full Text Full Text PDF PubMed Scopus (431) Google ScholarRC326,4646542Hip5DNR7.4513.63NR4.44 (4.16–4.75)4.40 (4.17–4.64)Coco and Rush8Coco M. Rush H. Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone.Am J Kidney Dis. 2000; 36: 1115-1121Abstract Full Text Full Text PDF PubMed Google ScholarRC127256Hip5D HD13.911.724.1NR14.2 (9.3–28.6)17.2 (7.1–19.4)Stehman-Breen et al.9Stehman-Breen C.O. Sherrard D.J. Alem A.M. et al.Risk factors for hip fracture among patients with end-stage renal disease.Kidney Int. 2000; 58: 2200-2205Abstract Full Text Full Text PDF PubMed Google ScholarRC4952103Hip5D HDNRNRNRNR3.12 (2.13–4.59)3.35 (2.59–4.40)Dukas et al.10Dukas L. Schacht E. Stähelin H.B. In elderly men and women treated for osteoporosis a low creatinine clearance of <65 ml/min is a risk factor for falls and fractures.Osteoporos Int. 2005; 16: 1683-1690Crossref PubMed Scopus (0) Google ScholarCS5313NRHip<65NRNRNR1.57 (1.18–2.09)NRNRWristNRNRNR1.79 (1.39–2.31)NRNRVertebralNRNRNR1.31 (1.19–1.55)NRNRJadoul et al.11Jadoul M. Albert J.M. Akiba T. et al.Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study.Kidney Int. 2006; 70: 1358-1366Abstract Full Text Full Text PDF PubMed Scopus (0) Google ScholarRC12,782174Hip5D HD8.9 (8.4–9.4)NR1.41 (1. –1.89)NRNRNR489Any25.6 (24.4–27.0)NR1.59 (1.32–1.92)NRNRNRNickolas et al.12Nickolas T.L. McMahon D.J. Shane E. Relationship between moderate to severe kidney disease and hip fracture in the United States.J Am Soc Nephrol. 2006; 17: 3223-3232Crossref PubMed Scopus (156) Google ScholarCS6270159Hip<60NRNRNR2.32 (1.13–4.74)NRNREnsrud et al.13Ensrud 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: 133Crossref PubMed Scopus (157) Google ScholarPC9704149Hip<45NRNANRNANA2.32 (1.15–4.68)Trochanteric<45NRNANRNANA7.17 (1.93–26.67)150Vertebral<45NRNANRNANA1.33 (0.63–2.80)Fried et al.14Fried 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: 282-286Crossref PubMed Scopus (0) Google ScholarPC4699274Hip3–5NR5.99.7NR1.48 (0.95–2.31)1.74 (1.33–2.28)Cystatin CNRNRNRNR1.14 (0.86–1.52)1.16 (1.01–1.33)Dooley et al.15Dooley A.C. Weiss N.S. Kestenbaum B. Increased risk of hip fracture among men with CKD.Am J Kidney Dis. 2008; 51: 38-44Abstract Full Text Full Text PDF PubMed Scopus (0) Google ScholarRC33,091176Hip3NRNRNANA1.28 (0.88–1.66)NA4NRNRNANA3.98 (2.25–7.74)NALaCroix et al.16LaCroix 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: 1434-1441Crossref PubMed Scopus (0) Google ScholarPC397NRHip3–5NRNANRNRNA2.50 (1.32–4.72)Ambrus et al.17Ambrus C. Almasi C. Berta K. et al.Vitamin D insufficiency and bone fractures in patients on maintenance hemodialysis.Int Urol Nephrol. 2011; 43: 475-482Crossref PubMed Scopus (0) Google ScholarRC13021AllHD30.51748.8NRNRNRIimori et al.18Iimori S. Mori Y. Akita W. et al.Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients-a single-center cohort study.Nephrol Dial Transplant. 2012; 27: 345-351Crossref PubMed Scopus (0) Google ScholarPC48546All5D HD1.9 each 100 patient-yearNRNRNRNRNRWakasugi et al.19Wakasugi M. Kazama J.J. Taniguchi M. et al.Increased risk of hip fracture among Japanese hemodialysis patients.J Bone Miner Metab. 2013; 31: 315-321Crossref PubMed Scopus (31) Google ScholarRC128,1411437HipHDNR7.517.43NR6.2 (5.7–6.8)4.9 (4.6–5.3)Arneson et al.20Arneson T.J. Li S. Liu J. et al.Trends in hip fracture rates in US hemodialysis patients, 1993-2010.Am J Kidney Dis. 2013; 62: 747-754Abstract Full Text Full Text PDF PubMed Scopus (0) Google ScholarRC86,387831HipHD1993: 11.9NRNRNRNR–NR146,83532562004: 21.9NRNRNRNRNR203,85729122010: 16.6NRNRNRNRNRElliott et al.21Elliott 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: 1367-1376Crossref PubMed Scopus (0) Google ScholarRC1,815,94310,188Hip65–74 yr6702NRNA279.86NRNA2.25 (1.78–2.72)4252NR274.15NANR1.48 (1.12–1.84)NA18,762Wrist>85 yr2792NRNA31.27NRNA8.02 (5.66–10.38)462NR14.07NANR2.58 (0.69–4.47)NA12,070Vertebral65–74 yr7662NRNA278.95NRNA2.68 (1.98–3.39)5602NR273.78NANR1.82 (1.24–2.40)NANair et al.22Nair S.S. Mitani A.A. Goldstein B.A. et al.Temporal trends in the incidence, treatment, and outcomes of hip fracture in older patients initiating dialysis in the United States.Clin J Am Soc Nephrol. 2013; 8: 1336-1342Crossref PubMed Scopus (0) Google ScholarPC409,04017,887Hip1–533.3NRNRNR1.50 (1.45–1.55)1.03 (1.03–1.03)Maravic et al.4Maravic M. Ostertag A. Torres P.U. et al.Incidence and risk factors for hip fractures in dialysis patients.Osteoporos Int. 2014; 25: 159-165Crossref PubMed Scopus (50) Google ScholarRC68,953362Hip5DNR1.1%1.40%NRNRNR68,5911–5NR0.16%0.41%NRNRNRMathew et al.23Mathew A.T. Hazzan A. Jhaveri K.D. et al.Increasing hip fractures in patients receiving hemodialysis and peritoneal dialysis.Am J Nephrol. 2014; 40: 451-457Crossref PubMed Scopus (0) Google ScholarRC929,114842,028Hip5D HD18.4NRNRNRNRNRDelgado et al.24Delgado C. Shieh S. Grimes B. et al.Association of self-reported frailty with falls and fractures among patients new to dialysis.Am J Nephrol. 2015; 42: 134-140Crossref PubMed Scopus (12) Google ScholarPC1646283All5D HDNonfrail: 66NRNRNRNRNRFrail: 126NRNR1.6 (1.16–2.20)NRNRYamamoto et al.25Yamamoto S. Kido R. Onishi Y. et al.Use of renin-angiotensin system inhibitors is associated with reduction of fracture risk in hemodialysis patients.PLoS One. 2015; 10: e0122691Google ScholarPC3276178All use ACEI/ARB5D HD1.48/100 patient-yearsNRNR0.65 (0.45–0.92)NRNRAll do not use ACEI/ARB2.33/100 patient-yearsNRNRNRNRNRACEI/ARB, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker; CI, confidence interval; CKD, chronic kidney disease; CS, cross-sectional; HD, hemodialysis; NA, not applied; NR, not reported; OR, odds ratio; PC, prospective cohort study; RC, retrospective cohort study; RR, relative risk. Open table in a new tab ACEI/ARB, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker; CI, confidence interval; CKD, chronic kidney disease; CS, cross-sectional; HD, hemodialysis; NA, not applied; NR, not reported; OR, odds ratio; PC, prospective cohort study; RC, retrospective cohort study; RR, relative risk. The incidence of hip fractures is also 4-fold higher for dialysis patients than for the general population after adjustment for age, sex, and ethnicity.7Alem A. Sherrard D. Gillen D. et al.Increased risk of hip fracture among patients with end-stage renal disease.Kidney Int. 2000; 58: 396-399Abstract Full Text Full Text PDF PubMed Scopus (431) Google Scholar, 28Maravic M. Ostertag A. Urena P. et al.Dementia is a major risk factor for hip fractures in patients with chronic kidney disease.Osteoporos Int. 2016; 27: 1665-1669Crossref PubMed Scopus (3) Google Scholar The incidence of hip fracture in CKD patients differs by ethnicity and sex, being 3 times higher for Caucasian than African-American individuals2Beaubrun A.C. Kilpatrick R.D. Freburger J.K. et al.Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.J Am Soc Nephrol. 2013; 24: 1461-1469Crossref PubMed Scopus (0) Google Scholar and twice as high for women than men.4Maravic M. Ostertag A. Torres P.U. et al.Incidence and risk factors for hip fractures in dialysis patients.Osteoporos Int. 2014; 25: 159-165Crossref PubMed Scopus (50) Google Scholar, 9Stehman-Breen C.O. Sherrard D.J. Alem A.M. et al.Risk factors for hip fracture among patients with end-stage renal disease.Kidney Int. 2000; 58: 2200-2205Abstract Full Text Full Text PDF PubMed Google Scholar, 15Dooley A.C. Weiss N.S. Kestenbaum B. Increased risk of hip fracture among men with CKD.Am J Kidney Dis. 2008; 51: 38-44Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 29Brauer C.A. Incidence and mortality of hip fractures in the United States.JAMA. 2009; 302: 1573Crossref PubMed Scopus (512) Google Scholar Demographic risk factors include older age, low body mass index, and long dialysis vintage; a history of a hip fracture is also highly associated with an increased risk of hip fracture.11Jadoul M. Albert J.M. Akiba T. et al.Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study.Kidney Int. 2006; 70: 1358-1366Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar US Medicare data on hemodialysis patients identified downward hip fracture incidence trends from 2000 to late 2009,2Beaubrun A.C. Kilpatrick R.D. Freburger J.K. et al.Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.J Am Soc Nephrol. 2013; 24: 1461-1469Crossref PubMed Scopus (0) Google Scholar most prominent in older adults of both sexes.30Wright N.C. Saag K.G. Curtis J.R. et al.Recent trends in hip fracture rates by race/ethnicity among older US adults.J Bone Miner Res. 2012; 27: 2325-2332Crossref PubMed Scopus (58) Google Scholar Indeed, the incidence of hip fracture increased when dialysis treatment was initiated from 1996 to 2004 and then declined until 2009, although it remained higher than in 1996.22Nair S.S. Mitani A.A. Goldstein B.A. et al.Temporal trends in the incidence, treatment, and outcomes of hip fracture in older patients initiating dialysis in the United States.Clin J Am Soc Nephrol. 2013; 8: 1336-1342Crossref PubMed Scopus (0) Google Scholar The relative risk of hip fractures starts to increase as early as age 55 years and is high for CKD patients with high bone turnover rather than with low turnover disease.11Jadoul M. Albert J.M. Akiba T. et al.Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study.Kidney Int. 2006; 70: 1358-1366Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 15Dooley A.C. Weiss N.S. Kestenbaum B. Increased risk of hip fracture among men with CKD.Am J Kidney Dis. 2008; 51: 38-44Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar The mortality risk after a hip fracture is high in CKD patients,31Bass E. French D.D. Bradham D.D. et al.Risk-adjusted mortality rates of elderly veterans with hip fractures.Ann Epidemiol. 2007; 17: 514-519Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar, 32Fransen M. Woodward M. Norton R. et al.Excess mortality or institutionalization after hip fracture: men are at greater risk than women.J Am Geriatr Soc. 2002; 50: 685-690Crossref PubMed Scopus (0) Google Scholar but has essentially not changed after 1998 for either sex.29Brauer C.A. Incidence and mortality of hip fractures in the United States.JAMA. 2009; 302: 1573Crossref PubMed Scopus (512) Google Scholar The risk of skeletal fractures combines classic risk factors with those associated with CKD. After 4 years of dialysis, the age-standardized incidence ratio of hip fracture was 9.83 (95% confidence interval 8.61–11.2) for men and 8.10 (95% confidence interval 7.23–9.07) for women.7Alem A. Sherrard D. Gillen D. et al.Increased risk of hip fracture among patients with end-stage renal disease.Kidney Int. 2000; 58: 396-399Abstract Full Text Full Text PDF PubMed Scopus (431) Google Scholar Even in renal transplant recipients, previous dialysis vintage is associated with an increased risk of hip fracture.3Hansen D. Olesen J.B. Gislason G.H. et al.Risk of fracture in adults on renal replacement therapy: a Danish national cohort study.Nephrol Dial Transplant. 2016; 31: 1654-1662Crossref PubMed Google Scholar, 33Ball AM, Gillen DL, Weiss NS, et al. Risk of hip fracture among dialysis and renal transplant recipients. 2002;288:3014–3018.Google Scholar The 30-day mortality rate after hip fracture is 16% for CKD patients initiating dialysis after age 67 years in the United States.22Nair S.S. Mitani A.A. Goldstein B.A. et al.Temporal trends in the incidence, treatment, and outcomes of hip fracture in older patients initiating dialysis in the United States.Clin J Am Soc Nephrol. 2013; 8: 1336-1342Crossref PubMed Scopus (0) Google Scholar Hip fracture–related mortality risk is 2 times higher with an eGFR <45 than with an eGFR ≥45 ml/min per 1.73 m2.34Nitsch D. Mylne A. Roderick P.J. et al.Chronic kidney disease and hip fracture-related mortality in older people in the UK.Nephrol Dial Transplant. 2009; 24: 1539-1544Crossref PubMed Scopus (0) Google Scholar In 2010, the French national database exhibited significantly higher mortality rates after hip fracture in patients on dialysis therapy than in those without dialysis, as high as 12% for men and 8% for women, as well as a longer hospital stay in the intensive care unit.4Maravic M. Ostertag A. Torres P.U. et al.Incidence and risk factors for hip fractures in dialysis patients.Osteoporos Int. 2014; 25: 159-165Crossref PubMed Scopus (50) Google Scholar Several risk factors were associated, particularly vascular-related diseases and dementia. The prevalence of vertebral fractures is poorly documented in cohorts and dialysis registries. This has been reported to be low, ranging from 7% to 20%,35Atsumi K. Kushida K. Yamazaki K. et al.Risk factors for vertebral fractures in renal osteodystrophy.Am J Kidney Dis. 1999; 33: 287-293Abstract Full Text Full Text PDF PubMed Google Scholar, 36Ureña P. Bernard-Poenaru O. Ostertag A. et al.Bone mineral density, biochemical markers and skeletal fractures in haemodialysis patients.Nephrol Dial Transplant. 2003; 18: 2325-2331Crossref PubMed Scopus (0) Google Scholar and only 1% of patients had vertebral fractures based on clinical diagnosis in 1 clinical trial.37Moe S.M. Abdalla S. Chertow G.M. et al.Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis: The EVOLVE trial.J Am Soc Nephrol. 2015; 26: 1466-1475Crossref PubMed Scopus (0) Google Scholar This may be an underestimation because radiographic imaging is not systematically performed. In case-control studies with a small number of dialysis patients, low BMD at the lumbar spine was associated with vertebral and prevalent or self-reported peripheral fractures.38Jamal S.A. Gilbert J. Gordon C. et al.Cortical pQCT measures are associated with fractures in dialysis patients.J Bone Miner Res. 2006; 21: 543-548Crossref PubMed Scopus (120) Google Scholar However, in these patients, lumbar BMD did not have the same predictive value as in those without CKD. In a meta-analysis of 13 studies,39Bucur R.C. Panjwani D.D. Turner L. et al.Low bone mineral density and fractures in stages 3-5 CKD: an updated systematic review and meta-analysis.Osteoporos Int. 2015; 26: 449-458Crossref PubMed Scopus (0) Google Scholar only 1 study mentioned a relationship between vertebral fracture and dialysis vintage, but did not find any association between risk of fracture and BMD.17Ambrus C. Almasi C. Berta K. et al.Vitamin D insufficiency and bone fractures in patients on maintenance hemodialysis.Int Urol Nephrol. 2011; 43: 475-482Crossref PubMed Scopus (0) Google Scholar This indicates that low BMD could not be considered as strong a risk factor as it is in patients without CKD. The 2017 KDIGO guidelines recommend using BMD measurement in patients with stages 3a to 5D CKD for predicting peripheral fractures, but we have no evidence that BMD could predict vertebral fractures in them. The evaluation of bone strength includes several factors that influence the quality of bone extracellular matrix. Bone quantity might be estimated by bone density, whereas bone quality might be estimated by the microarchitecture, both leading to a reduced mechanical bone adaptation (Figure 1). Occurrence of a fracture is the result of a fall in addition to failure in mechanical strength. Several imaging and biochemical tests are available and used to assess the fracture risk in the non-CKD population (Figure 2). These factors are reviewed in the following with regard to CKD.Figure 2Assessment of fracture risk in chronic kidney disease. In the presence of a fracture, investigations include the collection of clinical risk factors, imaging (dual-energy X-ray absorptiometry [DEXA], high-resolution peripheral quantitative computed tomography [HRpQCT], if available) and biochemical tests. The 3 are required to properly evaluate the risk of further fractures. CTX, cross-linked collagen type I peptide; FRAX, Fracture Risk Assessment Tool; P1NP, procollagen type 1 N-terminal pro-peptide; PTH, parathyroid hormone; TRAP5B, tartrate-resistant acid phosphatase 5B. To optimize viewing of this image, please see the online version of this article at www.kidney-international.org.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The KDIGO Working Group recommended using the same definition of osteoporosis for CKD patients as that advocated by the WHO for the general population. WHO defines osteoporosis as a bone disorder resulting in decreased bone strength and increased fracture risk. We believe that this definition could be