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      Bone fragility in patients with chronic kidney disease

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          Abstract

          Mineral and bone diseases (MBD) are predominant in patients with chronic kidney disease (CKD) and lead to several bone manifestations, from pain to skeletal fractures. Cumulative traditional clinical risk factors, such as age and gender, in addition to those related to CKD, enhance the risk of comorbidity and mortality related to fractures. Despite great advances in understanding MBD in CKD, clinical and biological targets are lacking, which leads to under-management of fractures. Optimal PTH control results in a net improvement in defining the levels of bone remodeling. In addition, circulating biomarkers such as bone-specific alkaline phosphatase and cross-linked collagen type I peptide will also provide additional information about remodeling rate, bone mineralization and the evaluation of fracture risk. Imaging techniques identify patients at risk by measurement of bone mineral density by DEXA or by high peripheral QCT, which allow the discrimination of trabecular and cortical bone. Here, we have reviewed the literature related to epidemiology and the pathophysiological role of mineral and biochemical factors involved in CKD-MBD with a special focus on fracture risk. We also provide an algorithm that could be used for the management of bone diseases and to guide treatment decisions. Finally, the combined expertise of clinicians from various disciplines is crucial for the best prevention of fractures.

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          Most cited references51

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          Timing of onset of CKD-related metabolic complications.

          Chronic kidney disease (CKD) guidelines recommend evaluating patients with GFR <60 ml/min per 1.73 m(2) for complications, but little evidence supports the use of a single GFR threshold for all metabolic disorders. We used data from the NephroTest cohort, including 1038 adult patients who had stages 2 through 5 CKD and were not on dialysis, to study the occurrence of metabolic complications. GFR was measured using renal clearance of (51)Cr-EDTA (mGFR) and estimated using two equations derived from the Modification of Diet in Renal Disease study. As mGFR decreased from 60 to 90 to <20 ml/min per 1.73 m(2), the prevalence of hyperparathyroidism increased from 17 to 85%, anemia from 8 to 41%, hyperphosphatemia from 1 to 30%, metabolic acidosis from 2 to 39%, and hyperkalemia from 2 to 42%. Factors most strongly associated with metabolic complications, independent of mGFR, were younger age for acidosis and hyperphosphatemia, presence of diabetes for acidosis, diabetic kidney disease for anemia, and both male gender and the use of inhibitors of the renin-angiotensin system for hyperkalemia. mGFR thresholds for detecting complications with 90% sensitivity were 50, 44, 40, 39, and 37 ml/min per 1.73 m(2) for hyperparathyroidism, anemia, acidosis, hyperkalemia, and hyperphosphatemia, respectively. Analysis using estimated GFR produced similar results. In summary, this study describes the onset of CKD-related complications at different levels of GFR; anemia and hyperparathyroidism occur earlier than acidosis, hyperkalemia, and hyperphosphatemia.
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            Rapid cortical bone loss in patients with chronic kidney disease.

            Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described. In this longitudinal study of 53 patients with CKD Stages 2 to 5D, we used dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT), and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton. Median follow-up was 1.5 years (range 0.9 to 4.3 years); bone changes were annualized and compared with baseline. By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius: -1.3% (95% confidence interval [CI] -2.1 to -0.6) and -2.4% (95% CI -4.0 to -0.9), respectively. By HRpQCT at the distal radius, there were significant declines in cortical area, density, and thickness and increases in porosity: -2.9% (95% CI -3.7 to -2.2), -1.3% (95% CI -1.6 to -0.6), -2.8% (95% CI -3.6 to -1.9), and +4.2% (95% CI 2.0 to 6.4), respectively. Radius trabecular area increased significantly: +0.4% (95% CI 0.2 to 0.6), without significant changes in trabecular density or microarchitecture. Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration. Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity. These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover. Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates. Copyright © 2013 American Society for Bone and Mineral Research.
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              Relationship between moderate to severe kidney disease and hip fracture in the United States.

              People with ESRD are at a high risk for hip fracture. However, the effect of moderate to severe chronic kidney disease (CKD) on hip fracture risk has not been well studied. As part of the Third National Health and Nutrition Examination Survey, information on both kidney function and history of hip fracture was obtained. This survey is a complex, multistage, probability sample of the US noninstitutionalized civilian population and was conducted between 1988 and 1994. A history of hip fracture was identified from the response to a questionnaire that was administered to all participants. There were 159 cases of hip fracture. There was a significantly increased likelihood of reporting a hip fracture in participants with estimated GFR <60 ml/min (odds ratio [OR] 2.12; 95% confidence interval [CI] 1.18 to 3.80). In younger participants (aged 50 to 74 yr), the prevalence of CKD was approximately three-fold higher in those with a history of hip fracture versus in those without a history of hip fracture (19.0 versus 6.2%, respectively; P = 0.04). In multivariate logistic regression analysis, only the presence of CKD (OR 2.32; 95% CI 1.13 to 4.74), a reported history of osteoporosis (OR 2.52; 95% CI 1.08 to 5.91), and low physical activity levels (OR 2.10; 95% CI 1.03 to 4.27) were associated with a history of hip fracture. There is a significant association between hip fracture and moderate to severe degrees of CKD, particularly in younger individuals, that is independent of traditional risk factors for hip fracture.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                April 2020
                13 March 2020
                : 9
                : 4
                : R93-R101
                Affiliations
                [1 ]Department of Skeletal Diseases , INSERM U1132 & Université de Paris, Hôpital Lariboisière, Paris, France
                [2 ]AURA Nord , Saint Ouen, France
                [3 ]Department of Renal Physiology , Necker Hospital, Université de Paris, Paris, France
                Author notes
                Correspondence should be addressed to M Cohen-Solal: martine.cohen-solal@ 123456inserm.fr
                Article
                EC-20-0039
                10.1530/EC-20-0039
                7219138
                32168473
                5d125e1f-fc1b-426d-a92b-6e81317e143c
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 20 February 2020
                : 13 March 2020
                Categories
                Review

                bone,skeleton,fracture,bone mineral density,ckd-mbd,phosphate,calcium,parathyroid hormone,vitamin d

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