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American Journal of Kidney Diseases

Declining Hip Fracture Rates in Dialysis Patients: Is This Winning the War?

      Related Article, p. 173
      Fracture rates in patients with chronic kidney disease (CKD) are remarkably higher than in the general population.
      • Nickolas T.L.
      • McMahon D.J.
      • Shane E.
      Relationship between moderate to severe kidney disease and hip fracture in the United States.
      • Alem A.M.
      • Sherrard D.J.
      • Gillen D.L.
      • et al.
      Increased risk of hip fracture among patients with end-stage renal disease.
      • Dooley A.C.
      • Weiss N.S.
      • Kestenbaum B.
      Increased risk of hip fracture among men with CKD.
      • Fried L.F.
      • Biggs M.L.
      • Shlipak M.G.
      • et al.
      Association of kidney function with incident hip fracture in older adults.
      • Naylor K.L.
      • McArthur E.
      • Leslie W.D.
      • et al.
      The three-year incidence of fracture in chronic kidney disease.
      • Coco M.
      • Rush H.
      Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone.
      • Denburg M.R.
      • Kumar J.
      • Jemielita T.
      • et al.
      Fracture burden and risk factors in childhood CKD: results from the CKiD Cohort Study.
      All studies of adults and children with CKD stages 3 and 4 on dialysis therapy and after kidney transplantation demonstrate that fracture incidence is 2- to 100-fold higher compared with age- and sex-matched individuals without CKD.
      • Nickolas T.L.
      • McMahon D.J.
      • Shane E.
      Relationship between moderate to severe kidney disease and hip fracture in the United States.
      • Alem A.M.
      • Sherrard D.J.
      • Gillen D.L.
      • et al.
      Increased risk of hip fracture among patients with end-stage renal disease.
      • Dooley A.C.
      • Weiss N.S.
      • Kestenbaum B.
      Increased risk of hip fracture among men with CKD.
      • Denburg M.R.
      • Kumar J.
      • Jemielita T.
      • et al.
      Fracture burden and risk factors in childhood CKD: results from the CKiD Cohort Study.
      • Nair S.S.
      • Mitani A.A.
      • Goldstein B.A.
      • Chertow G.M.
      • Lowenberg D.W.
      • Winkelmayer W.C.
      Temporal trends in the incidence, treatment, and outcomes of hip fracture in older patients initiating dialysis in the United States.
      • Wagner J.
      • Jhaveri K.D.
      • Rosen L.
      • Sunday S.
      • Mathew A.T.
      • Fishbane S.
      Increased bone fractures among elderly United States hemodialysis patients.
      • Arneson T.J.
      • Li S.
      • Liu J.
      • Kilpatrick R.D.
      • Newsome B.B.
      • St Peter W.L.
      Trends in hip fracture rates in US hemodialysis patients, 1993-2010.
      Fracture incidence increases in a graded manner with more severely reduced kidney function,
      • Naylor K.L.
      • McArthur E.
      • Leslie W.D.
      • et al.
      The three-year incidence of fracture in chronic kidney disease.
      and even declines in estimated glomerular filtration rates have been demonstrated to predict future fracture.
      • Isakova T.
      • Craven T.E.
      • Scialla J.J.
      • et al.
      Change in estimated glomerular filtration rate and fracture risk in the Action to Control Cardiovascular Risk in Diabetes Trial.
      To make matters worse, after any type of fracture, morbidity, mortality, and health care–associated economic costs are substantially higher for patients with kidney disease than for the general population.
      • Kim S.M.
      • Long J.
      • Montez-Rath M.
      • Leonard M.
      • Chertow G.M.
      Hip fracture in patients with non-dialysis-requiring chronic kidney disease.
      • Beaubrun A.C.
      • Kilpatrick R.D.
      • Freburger J.K.
      • Bradbury B.D.
      • Wang L.
      • Brookhart M.A.
      Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.
      After fracture, patients with CKD experience longer hospitalizations and are more commonly discharged to a skilled nursing facility than patients without CKD. More than 80% of patients with CKD were reported to be discharged to a long-term care facility after fracture,
      • Kim S.M.
      • Long J.
      • Montez-Rath M.
      • Leonard M.
      • Chertow G.M.
      Hip fracture in patients with non-dialysis-requiring chronic kidney disease.
      representing more skilled-nursing facility admissions than any other CKD complication (eg, heart disease).
      • Doan Q.V.
      • Gleeson M.
      • Kim J.
      • Borker R.
      • Griffiths R.
      • Dubois R.W.
      Economic burden of cardiovascular events and fractures among patients with end-stage renal disease.
      In 2010, hip fractures in patients with non–dialysis-dependent CKD and end-stage kidney disease resulted in >$600 million in health care expenditures.
      • Kim S.M.
      • Long J.
      • Montez-Rath M.
      • Leonard M.
      • Chertow G.M.
      Hip fracture in patients with non-dialysis-requiring chronic kidney disease.
      During the past several decades, the body of literature regarding CKD-associated fractures has compelled us to better understand their pathogenesis to develop antifracture strategies. However, we have a paucity of therapeutic agents or clinical trials targeted specifically for our patients. In the future, as our patient population ages and fracture rates increase, we will be forced to make hard decisions, without primary efficacy and safety data, to prevent fracture occurrence in our high-risk population. However, in this issue of AJKD, Wakasugi et al
      • Wakasugi M.
      • Kazama J.J.
      • Wada A.
      • Hamano T.
      • Masakane I.
      • Narita I.
      Hip fracture trends in Japanese dialysis patients, 2008-2013.
      report that hip fracture rates in female Japanese dialysis patients declined from 2008 to 2013. By itself, this analysis is an interesting addition to the body of literature on CKD-associated fractures. However, in the context of a growing literature in other populations suggesting similar decreasing trends in hip fracture incidence, this study raises important questions regarding our approach to fracture prevention in CKD.
      Several other studies have reported that hip fracture incidence in patients receiving dialysis is on the decline.
      • Nair S.S.
      • Mitani A.A.
      • Goldstein B.A.
      • Chertow G.M.
      • Lowenberg D.W.
      • Winkelmayer W.C.
      Temporal trends in the incidence, treatment, and outcomes of hip fracture in older patients initiating dialysis in the United States.
      • Wagner J.
      • Jhaveri K.D.
      • Rosen L.
      • Sunday S.
      • Mathew A.T.
      • Fishbane S.
      Increased bone fractures among elderly United States hemodialysis patients.
      • Arneson T.J.
      • Li S.
      • Liu J.
      • Kilpatrick R.D.
      • Newsome B.B.
      • St Peter W.L.
      Trends in hip fracture rates in US hemodialysis patients, 1993-2010.
      • Beaubrun A.C.
      • Kilpatrick R.D.
      • Freburger J.K.
      • Bradbury B.D.
      • Wang L.
      • Brookhart M.A.
      Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.
      Wagner et al
      • Wagner J.
      • Jhaveri K.D.
      • Rosen L.
      • Sunday S.
      • Mathew A.T.
      • Fishbane S.
      Increased bone fractures among elderly United States hemodialysis patients.
      used the US Renal Data System (USRDS) to study incidence rates of both central (hip and spine) and peripheral (arm and leg) fractures resulting in hospitalizations in US hemodialysis patients from 1992 to 2009. They reported a nonsignificant decline in rates of central fractures from 2006 (25.1/1,000 person-years) to 2009 (21.4/1,000 person-years). However, rates of peripheral fractures experienced a significant steady increase and more than doubled during that same period from 3.2/1,000 person-years in 1992 to 7.7/1,000 person-years in 2009. Furthermore, Wagner et al
      • Wagner J.
      • Jhaveri K.D.
      • Rosen L.
      • Sunday S.
      • Mathew A.T.
      • Fishbane S.
      Increased bone fractures among elderly United States hemodialysis patients.
      also reported that fracture rates were more than 3- and 7-fold higher for patients with end-stage kidney disease aged 65 to 85 years and older than 85 years, respectively, than for younger patients with end-stage kidney disease.
      Beaubrun et al
      • Beaubrun A.C.
      • Kilpatrick R.D.
      • Freburger J.K.
      • Bradbury B.D.
      • Wang L.
      • Brookhart M.A.
      Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.
      used USRDS data to assess rates of both in- and outpatient fractures among prevalent in-center hemodialysis patients from 2000 to 2009. Pelvis and hip fractures represented the most common type of fracture, and their incidence declined nonsignificantly during the study period, from 29.6/1,000 person-years in 2000 to 20.6/1,000 person-years in 2009. In contrast, rates of all other types of fracture remained stable.
      Nair et al
      • Nair S.S.
      • Mitani A.A.
      • Goldstein B.A.
      • Chertow G.M.
      • Lowenberg D.W.
      • Winkelmayer W.C.
      Temporal trends in the incidence, treatment, and outcomes of hip fracture in older patients initiating dialysis in the United States.
      used USRDS data to study hip fractures resulting in hospitalizations for incident dialysis patients 67 years and older from 1996 to 2009. Hip fracture rates increased by 43% in 2004 from 29.3/1,000 person-years in 1996; thereafter, hip fracture rates declined but remained 27% higher in 2009 than in 1996.
      Finally, Arneson et al
      • Arneson T.J.
      • Li S.
      • Liu J.
      • Kilpatrick R.D.
      • Newsome B.B.
      • St Peter W.L.
      Trends in hip fracture rates in US hemodialysis patients, 1993-2010.
      used USRDS data to study hip fractures resulting in hospitalizations in US hemodialysis patients between 1993 and 2010. Between 1993 and 2004, there was a yearly increase in hip fracture incidence of 4.6%, and hip fracture incidence rates doubled during that 10-year period. However, in contrast to that first decade, between 2004 and 2010, there was a yearly decline in hip fracture incidence of 5.2% and a reduction in hip fracture incidence from 21.9/1,000 person-years to 16.6/1,000 person-years during that entire 6-year period. Arneson et al
      • Arneson T.J.
      • Li S.
      • Liu J.
      • Kilpatrick R.D.
      • Newsome B.B.
      • St Peter W.L.
      Trends in hip fracture rates in US hemodialysis patients, 1993-2010.
      then compared hip fracture incidence rates in patients with end-stage kidney disease older than 66 years to a similarly aged cohort from the general population. Not only was hip fracture incidence in the general population less than half that of patients with end-stage kidney disease, but the general population experienced a yearly decline in hip fracture rates between 1996 and 2010.
      In this issue of AJKD, Wakasugi et al perform a similar investigation in Japanese dialysis patients. They used data from the Japanese Society for Dialysis Therapy Renal Data Registry database from 2007 to 2013 to study secular trends in age-standardized hip fracture incidence rates. They included both incident and prevalent hemodialysis and peritoneal dialysis patients 20 years and older and without a history of hip fracture. Inclusion of data for the use of cinacalcet and vitamin D agents was available only for 2009. During the study period, they noted that mean age and dialysis vintage increased. They reported 4,963 and 6,625 hip fractures in male and female dialysis patients, respectively. Incidence rates were higher in older compared with younger patients and were not influenced by dialysis vintage. Due to low numbers of events in peritoneal dialysis patients, they did not stratify on dialysis modality. In analyses that pooled men and women, there was no change in hip fracture incidence during the study period. In contrast, sex-stratified models detected a 3.6% (95% confidence interval, −6.9% to −0.2%; P < 0.01) per year decline in hip fracture incidence in women, but changes were not significant in men.
      What do these studies mean and how might they influence our efforts to prevent CKD-associated fractures? Although none of these studies were able to link drug prescribing patterns directly to trends in hip fracture incidence, they all suggested that declines in hip fracture rates tracked with the 2004 KDIGO (Kidney Disease: Improving Global Outcomes) guideline changes on the management of CKD–mineral and bone disorder (CKD-MBD). Therefore, the temporal relationships between the change in the KDIGO guideline and the decline in fracture rates could be interpreted as the outcome of a natural experiment, designed to test whether improved management of vitamin D deficiency and hyperparathyroidism could have favorable effects on bone health. However, other variables, such as improved dialysis adequacy and an increase in public awareness of the benefits of exercise, may be contributing factors. Mitigating the skeletal effects of CKD-MBD should be the standard of care in CKD and can be broadly implemented for all patients.
      What these studies do not do is suggest that the fight to prevent CKD-associated fractures is being won. On the contrary, they indicate that we continue to fail: all studies report that fracture rates are shockingly higher in patients with end-stage kidney disease relative to the general population. Nair et al
      • Nair S.S.
      • Mitani A.A.
      • Goldstein B.A.
      • Chertow G.M.
      • Lowenberg D.W.
      • Winkelmayer W.C.
      Temporal trends in the incidence, treatment, and outcomes of hip fracture in older patients initiating dialysis in the United States.
      reported that with increasing dialysis vintage, hip fracture rates increased that 30-day mortality after fracture in incident dialysis patients was more than 5 times higher than in the general incident dialysis population. Wagner et al
      • Wagner J.
      • Jhaveri K.D.
      • Rosen L.
      • Sunday S.
      • Mathew A.T.
      • Fishbane S.
      Increased bone fractures among elderly United States hemodialysis patients.
      reported that rates of painful and disabling fractures of the leg and arm more than doubled during the study period. Also, Beaubrun et al
      • Beaubrun A.C.
      • Kilpatrick R.D.
      • Freburger J.K.
      • Bradbury B.D.
      • Wang L.
      • Brookhart M.A.
      Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.
      reported that rates of other serious fracture types (eg, spine and lower leg) did not change over time, and compared with matched individuals without CKD, postfracture mortality was more than 2-fold greater.
      How do we succeed in treating osteoporosis in patients with CKD? The updated 2017 KDIGO guideline for the management of bone and mineral disorders is a great place to start.
      • Ketteler M.
      • Block G.A.
      • Evenepoel P.
      • et al.
      Executive summary of the 2017 KDIGO chronic kidney disease–mineral and bone disorder (CKD-MBD) guideline update: what’s changed and why it matters.
      In 2013, the KDIGO Bone Quality Working Group reviewed the state of the literature on bone health assessment in CKD. A major goal of the group was to recommend evidence-based changes to the 2009 KDIGO guideline, which stated that assessment of fracture risk by measuring bone mineral density using dual-energy x-ray absorptiometry was not warranted due to a lack of primary efficacy and treatment data. In 2013, the committee reviewed 4 prospective cohort studies that demonstrated that measurement of bone mineral density by dual-energy x-ray absorptiometry predicted fractures in adults with CKD grades 3a to 5D.
      • Iimori 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.
      • Naylor K.L.
      • Garg A.X.
      • Zou G.
      • et al.
      Comparison of fracture risk prediction among individuals with reduced and normal kidney function.
      • West S.L.
      • Lok C.E.
      • Langsetmo L.
      • et al.
      Bone mineral density predicts fractures in chronic kidney disease.
      • Yenchek R.H.
      • Ix J.H.
      • Shlipak M.G.
      • et al.
      Bone mineral density and fracture risk in older individuals with CKD.
      The updated guideline was a marked departure from the 2009 recommendation and is both important and prescient as we look ahead to improving our patients’ morbidity and mortality through fracture prevention. The new guideline gives us a tool to stratify risk in adult patients for fracture and target them for antifracture strategies. Nevertheless, the guideline is controversial given the lack of treatments proved to prevent fractures in patients with CKD-associated osteoporosis. Cinacalcet, a drug designed to specifically target a critical component in the pathogenesis of renal osteodystrophy, failed to prevent fractures in patients with hyperparathyroidism receiving hemodialysis.
      • Moe S.M.
      • Abdalla S.
      • Chertow G.M.
      • et al.
      Effects of cinacalcet on fracture events in patients receiving hemodialysis: the EVOLVE Trial.
      Although post hoc analyses of the US Food and Drug Administration (FDA) registration trials for antiosteoporotic treatments suggested safety and efficacy in participants with CKD stages 3a through 4,
      • Jamal S.A.
      • Ljunggren O.
      • Stehman-Breen C.
      • et al.
      Effects of denosumab on fracture and bone mineral density by level of kidney function.
      • Miller P.D.
      • Schwartz E.N.
      • Chen P.
      • Misurski D.A.
      • Krege J.H.
      Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment.
      • Miller P.D.
      • Roux C.
      • Boonen S.
      • Barton I.P.
      • Dunlap L.E.
      • Burgio D.E.
      Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials.
      • Ishani A.
      • Blackwell T.
      • Jamal S.A.
      • Cummings S.R.
      • Ensrud K.E.
      • MORE Investigators.
      The effect of raloxifene treatment in postmenopausal women with CKD.
      • Jamal S.A.
      • Bauer D.C.
      • Ensrud K.E.
      • et al.
      Alendronate treatment in women with normal to severely impaired renal function: an analysis of the Fracture Intervention Trial.
      extrapolation of these studies to patients with CKD-MBD is considered a stretch by many nephrologists. The tested pharmacologic agents were not designed for patients with renal osteodystrophy, it is unlikely that the participants in those trials can be classified as having had CKD-MBD, none of the participants were receiving dialysis, bone-tissue safety was incompletely assessed in patients with lower glomerular filtration rates, and these were secondary and not primary analyses.
      How do we start winning the war against CKD-associated fractures? A good place to look for inspiration is the non-CKD population. Since 1995, fracture incidence has decreased by ∼20% due to the introduction of fracture screening, prevention, and treatment programs in the general American population.
      • Brauer C.A.
      • Coca-Perraillon M.
      • Cutler D.M.
      • Rosen A.B.
      Incidence and mortality of hip fractures in the United States.
      • Wright N.C.
      • Saag K.G.
      • Curtis J.R.
      • et al.
      Recent trends in hip fracture rates by race/ethnicity among older US adults.
      Why can’t we start there? KDIGO now provides us with the justification and rationale to use a widely available and inexpensive screening tool that quantifies risk in all patients with CKD.
      • Ketteler M.
      • Block G.A.
      • Evenepoel P.
      • et al.
      Executive summary of the 2017 KDIGO chronic kidney disease–mineral and bone disorder (CKD-MBD) guideline update: what’s changed and why it matters.
      All patients at risk can be managed with the same nonpharmacologic strategies with proven antifracture efficacy used in the general population because 60% of the observed reduction in fracture incidence in the general population has been attributed to lifestyle interventions, including calcium and vitamin D supplementation, smoking cessation, weight-bearing exercise, fall prevention,
      • West S.L.
      • Jamal S.A.
      • Lok C.E.
      Tests of neuromuscular function are associated with fractures in patients with chronic kidney disease.
      improved nutrition,
      • Schurch M.A.
      • Rizzoli R.
      • Slosman D.
      • Vadas L.
      • Vergnaud P.
      • Bonjour J.P.
      Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial.
      and moderating alcohol intake.
      • Brauer C.A.
      • Coca-Perraillon M.
      • Cutler D.M.
      • Rosen A.B.
      Incidence and mortality of hip fractures in the United States.
      Our patients with CKD who fit the profiles of participants included in the FDA registration trials can be initiated on treatment with antiresorptive or osteoanabolic agents. However, many patients will not fit these profiles and will be denied treatment even though they are at risk for severe debilitation and death if they sustain any type of fracture.
      • Beaubrun A.C.
      • Kilpatrick R.D.
      • Freburger J.K.
      • Bradbury B.D.
      • Wang L.
      • Brookhart M.A.
      Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.
      To win this war, we need funding agencies and manufacturers to focus on the many individuals with CKD who are at risk for fractures and to work with bone health experts to devise effective treatments and clinical trials to prevent fractures and their associated morbidity.

      References

        • Nickolas 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: 3223-3232
        • 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
        • 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
        • 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
        • Coco M.
        • Rush H.
        Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone.
        Am J Kidney Dis. 2000; 36: 1115-1121
        • Denburg M.R.
        • Kumar J.
        • Jemielita T.
        • et al.
        Fracture burden and risk factors in childhood CKD: results from the CKiD Cohort Study.
        J Am Soc Nephrol. 2016; 27: 543-550
        • Nair S.S.
        • Mitani A.A.
        • Goldstein B.A.
        • Chertow G.M.
        • Lowenberg D.W.
        • Winkelmayer W.C.
        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: 1336-1342
        • Wagner J.
        • Jhaveri K.D.
        • Rosen L.
        • Sunday S.
        • Mathew A.T.
        • Fishbane S.
        Increased bone fractures among elderly United States hemodialysis patients.
        Nephrol Dial Transplant. 2014; 29: 146-151
        • Arneson T.J.
        • Li S.
        • Liu J.
        • Kilpatrick R.D.
        • Newsome B.B.
        • St Peter W.L.
        Trends in hip fracture rates in US hemodialysis patients, 1993-2010.
        Am J Kidney Dis. 2013; 62: 747-754
        • Isakova T.
        • Craven T.E.
        • Scialla J.J.
        • et al.
        Change in estimated glomerular filtration rate and fracture risk in the Action to Control Cardiovascular Risk in Diabetes Trial.
        Bone. 2015; 78: 23-27
        • 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
        • Beaubrun A.C.
        • Kilpatrick R.D.
        • Freburger J.K.
        • Bradbury B.D.
        • Wang L.
        • Brookhart M.A.
        Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.
        J Am Soc Nephrol. 2013; 24: 1461-1469
        • Doan Q.V.
        • Gleeson M.
        • Kim J.
        • Borker R.
        • Griffiths R.
        • Dubois R.W.
        Economic burden of cardiovascular events and fractures among patients with end-stage renal disease.
        Curr Med Res Opin. 2007; 23: 1561-1569
        • Wakasugi M.
        • Kazama J.J.
        • Wada A.
        • Hamano T.
        • Masakane I.
        • Narita I.
        Hip fracture trends in Japanese dialysis patients, 2008-2013.
        Am J Kidney Dis. 2018; 71: 173-181
        • Ketteler M.
        • Block G.A.
        • Evenepoel P.
        • et al.
        Executive summary of the 2017 KDIGO chronic kidney disease–mineral and bone disorder (CKD-MBD) guideline update: what’s changed and why it matters.
        Kidney Int. 2017; 92: 26-36
        • Iimori 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: 345-351
        • 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
        • West S.L.
        • Lok C.E.
        • Langsetmo L.
        • et al.
        Bone mineral density predicts fractures in chronic kidney disease.
        J Bone Miner Res. 2015; 30: 913-919
        • 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
        • Moe 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: 1466-1475
        • Jamal S.A.
        • Ljunggren O.
        • Stehman-Breen C.
        • et al.
        Effects of denosumab on fracture and bone mineral density by level of kidney function.
        J Bone Miner Res. 2011; 26: 1829-1835
        • Miller P.D.
        • Schwartz E.N.
        • Chen P.
        • Misurski D.A.
        • Krege J.H.
        Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment.
        Osteoporos Int. 2007; 18: 59-68
        • Miller P.D.
        • Roux C.
        • Boonen S.
        • Barton I.P.
        • Dunlap L.E.
        • Burgio D.E.
        Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials.
        J Bone Miner Res. 2005; 20: 2105-2115
        • Ishani A.
        • Blackwell T.
        • Jamal S.A.
        • Cummings S.R.
        • Ensrud K.E.
        • MORE Investigators.
        The effect of raloxifene treatment in postmenopausal women with CKD.
        J Am Soc Nephrol. 2008; 19: 1430-1438
        • Jamal S.A.
        • Bauer D.C.
        • Ensrud K.E.
        • et al.
        Alendronate treatment in women with normal to severely impaired renal function: an analysis of the Fracture Intervention Trial.
        J Bone Miner Res. 2007; 22: 503-508
        • Brauer C.A.
        • Coca-Perraillon M.
        • Cutler D.M.
        • Rosen A.B.
        Incidence and mortality of hip fractures in the United States.
        JAMA. 2009; 302: 1573-1579
        • Wright 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: 2325-2332
        • West S.L.
        • Jamal S.A.
        • Lok C.E.
        Tests of neuromuscular function are associated with fractures in patients with chronic kidney disease.
        Nephrol Dial Transplant. 2012; 27: 2384-2388
        • Schurch M.A.
        • Rizzoli R.
        • Slosman D.
        • Vadas L.
        • Vergnaud P.
        • Bonjour J.P.
        Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial.
        Ann Intern Med. 1998; 128: 801-809

      Linked Article

      • Hip Fracture Trends in Japanese Dialysis Patients, 2008-2013
        American Journal of Kidney DiseasesVol. 71Issue 2
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          Contrary to observations of decreasing rates in Western nations for the past 2 decades, age-adjusted rates of hip fracture in the general population in Japan have continually increased. This study aimed to analyze recent changes in trends of hip fracture incidence among Japanese dialysis patients between 2008 and 2013.
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