Discriminants of Prevalent Fractures in Chronic Kidney Disease

Nickolas, Thomas L.; Cremers, Serge; Zhang, Amy; Thomas, Valeri; Stein, Emily; Cohen, Adi; Chauncey, Ryan; Nikkel, Lucas E.; Yin, Michael T.; Liu, X. Sherry; Boutroy, Stéphanie; Staron, Ronald B.; Leonard, Mary B.; McMahon, Donald J.; Dworakowski, Elzbieta; Shane, Elizabeth

doi:10.1681/asn.2010121275

Cited by 123 publications

(136 citation statements)

References 66 publications

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“…Serum concentrations of TRAP-5b have been shown to be related to osteoclast number more than osteoclast activity (29,30). Comparing patients with CKD with bone fractures with patients without fractures, TRAP-5b was found to be 29% higher in patients with fractures (31). These findings are extended by our results, which identify elevated TRAP-5b as an independent predictor for bone loss.…”

Section: Discussionsupporting

confidence: 80%

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Malluche¹,

Davenport

Cantor³

et al. 2014

Clinical Journal of the American Society of Nephrology

122

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Background and objectives Use of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is controversial for diagnosing bone loss in CKD patients on dialysis. The alternative quantitative computed tomography (QCT) is expensive and requires high radiation exposure. This study compared the two techniques and evaluated serum biochemical parameters for prediction of bone loss.Design, setting, participants, & measurements This prospective study enrolled patients from dialysis centers throughout Kentucky. BMD of the spine and hip was measured at baseline and after 1 year by DXA and QCT. Customary and novel serum biochemical parameters were obtained at the same times, including calcium, phosphorus, whole and intact parathyroid hormone, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide, tartrate-resistant acid phosphatase-5b, Dickkopf-1, fibroblast growth factor, and sclerostin. Rates of detection of osteoporosis by DXA and QCT were compared. Correlations were calculated between baseline biochemical parameters and BMD at baseline and changes over 1 year. Multivariable regression was performed to adjust for age, sex, body mass index, and race.Results Eighty-one patients completed the study (mean age=52.6612.3 years, 56% men, 53% African American, and median dialysis vintage=41 months). At baseline, QCT and DXA of the spine identified similar rates of osteoporosis (13.6% and 13.6%), but at the hip, DXA identified more osteoporosis (22.2% versus 13.6%). At any site and by either method, 33.3% of the patients were osteoporotic. Baseline BMD correlated with sclerostin, intact parathyroid hormone, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase-5b, and fibroblast growth factor. At 1 year, hip QCT identified a higher number of patients experiencing bone loss (51.3%) than DXA (38.5%). After multivariable adjustment, baseline sclerostin and tartrate-resistant acid phosphatase-5b predicted bone loss measured by QCT of the hip; procollagen type 1 N-terminal propeptide predicted cortical spine bone gain by QCT.Conclusions QCT identified prospectively more bone loss at the hip than DXA. The baseline serum biochemical parameters sclerostin and tartrate-resistant acid phosphatase-5b were noninvasive independent predictors of bone loss in CKD patients on dialysis.

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Section: Discussionsupporting

confidence: 80%

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Malluche¹,

Davenport

Cantor³

et al. 2014

Clinical Journal of the American Society of Nephrology

122

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“…(26) In a more recent study that enrolled 82 individuals with stage 3 to 5 CKD (n ¼ 23 with fracture), BMD by DXA at the lumbar spine, total hip, femoral neck, 1/3 radius, and ultradistal radius were significantly lower in those with fractures compared to those without. (27) A potential limitation of BMD by DXA at traditional sites (ie, the hip and spine) is the inability of DXA (because of resolution) to discriminate between cortical and trabecular bone compartments. This limitation is particularly relevant in CKD because these individuals typically have elevations in serum PTH-so called "secondary hyperparathyroidism"-which has an anabolic effect on trabecular bone and a catabolic effect on cortical bone.…”

Section: Discussionmentioning

confidence: 99%

Retracted: Bone Mineral Density Predicts Fractures in Chronic Kidney Disease

West

Lok

Langsetmo

et al. 2014

Journal of Bone and Mineral Research

167

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Fractures are common in chronic kidney disease (CKD). The optimal methods by which to assess fracture risk are unknown, in part, due to a lack of prospective studies. We determined if bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), and/ or high-resolution peripheral quantitative computed tomography (HRpQCT) could predict fractures in men and women !18 years old with stages 3 to 5 CKD. BMD was measured by DXA (at the total hip, lumbar spine, ultradistal, and 1/3 radius) and by HRpQCT (at the radius), and subjects were followed for 2 years for incident morphometric spine fractures and low-trauma clinical fractures. The mean age of the subjects was 62 years with equal numbers having stages 3, 4, and 5 CKD. Over 2 years there were 51 fractures in 35 subjects. BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without. For example, the mean BMD at the total hip in those with incident fractures was 0.77 g/cm 2 (95% confidence interval [CI], 0.73 to 0.80) and in those without fracture was 0.95 g/cm 2 (95% CI, 0.92 to 0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without. For example, volumetric BMD in those with incident fractures was 232 mg HA/cm 3 (95% CI, 213 to 251) and in those without fracture was 317.6 mg HA/cm 3 (95% CI, 306 to 329.1). Bone loss occurred in all subjects, but was significantly greater among those with incident fractures. Our data demonstrate that low BMD (by DXA and HRpQCT) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD.

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“…8,9 Risk factors associated with fractures in patients with CKD include older age, female sex, lower serum albumin, prior kidney transplantation, peripheral vascular disease, muscle weakness, falls, and the administration of psychoactive medications. 2,3,[10][11][12][13][14] Thus, abnormalities of bone in terms of both quality and quantity, variable biochemical abnormalities, and multiple comorbid conditions are likely to contribute to the pathogenesis of fractures in ESRD. The complexity and nature of CKD-mineral and bone disorder (MBD) may also render conventional therapy for osteoporosis and osteopenia ineffective or possibly harmful in CKD or ESRD.…”

mentioning

confidence: 99%

Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis

Moe

Abdalla

Chertow

et al. 2015

Journal of the American Society of Nephrology

177

116

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Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for #64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%. 26: 146626: -147526: , 201526: . doi: 10.1681 Patients with end stage renal disease (ESRD) on dialysis have increased risk of fractures compared with the general population. 1 Fracture incidence rates vary by geographic region, although rates are consistently higher in patients with CKD than matched controls from the same country. [2][3][4][5][6] Depending on the study, 10%-52% of patients receiving dialysis J Am Soc Nephrol

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Discriminants of Prevalent Fractures in Chronic Kidney Disease

Cited by 123 publications

References 66 publications

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Retracted: Bone Mineral Density Predicts Fractures in Chronic Kidney Disease

Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis

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