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      Avances en la valoración de la salud ósea en el trasplantado renal Translated title: Advances in the evaluation of bone health in kidney transplant patients

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          Abstract

          Resumen La enfermedad ósea asociada a la enfermedad renal crónica, y en particular en el paciente trasplantado renal, representa una causa de frecuente morbimortalidad, sobre todo porque predispone a un mayor riesgo de fractura osteoporótica. Este hecho, bien conocido desde hace décadas, no ha estimulado lo suficiente hasta la fecha el desarrollo de una adecuada estrategia diagnóstica. Si dejamos aparte la biopsia ósea, técnica invasiva y escasamente utilizada, no disponemos de herramientas capaces de estimar de manera precisa el riesgo de fractura en el paciente renal. La escasa validación externa de técnicas aplicadas en la población general como la densitometría ósea hace que su uso tampoco sea sistemático. Por tanto, la identificación de qué pacientes tienen mayor riesgo de fractura y son susceptibles de intervención preventiva es una necesidad no cubierta. La resistencia ósea, definida como la capacidad del hueso para resistir la fractura, viene determinada por la cantidad de material mineral (medida como densidad mineral ósea por densitometría ósea), la arquitectura trabecular y la calidad del tejido óseo. El score trabecular óseo estima la microarquitectura ósea y valores bajos se han demostrado como predictores independientes de mayor riesgo de fractura. La microindentación ósea es una técnica mínimamente invasiva capaz de medir la resistencia ósea que el hueso opone a la apertura de micro-cracks (separación microscópica de fibras de colágena mineralizada), y con ello, las propiedades biomecánicas del tejido óseo. La buena correlación con el riesgo de fractura de los parámetros medidos con el score trabecular óseo o la microindentación en diversas poblaciones, superior a la propia densitometría ósea, nos ha estimulado a desarrollar su potencial aplicación en los pacientes con enfermedad renal crónica y trasplantados renales.

          Translated abstract

          Abstract Bone disease related to chronic kidney disease and, particularly, to kidney transplant patients is a common cause or morbidity and mortality, especially due to a higher risk of osteoporotic fractures. Despite the fact that this has been known for decades, to date, an appropriate diagnostic strategy has yet to be established. Apart from bone biopsy, which is invasive and scarcely used, no other technique is available to accurately establish the risk of fracture in kidney patients. Techniques applied to the general population, such as bone densitometry, have not been subjected to sufficient external validation and their use is not systematic. This means that the identification of patients at risk of fracture and therefore those who are candidates for preventive strategies is an unmet need. Bone strength, defined as the ability of the bone to resist fracture, is determined by bone mineral density (measured by bone densitometry), trabecular architecture and bone tissue quality. The trabecular bone score estimates bone microarchitecture, and low values have been described as an independent predictor of increased fracture risk. Bone microindentation is a minimally invasive technique that measures resistance of the bone to micro-cracks (microscopic separation of mineralised collagen fibres), and therefore bone tissue biomechanical properties. The superiority over bone densitometry of the correlation between the parameters measured by trabecular bone score and microindentation with the risk of fracture in diverse populations led us to test its feasibility in chronic kidney disease and kidney transplant patients.

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          In vivo assessment of bone quality in postmenopausal women with type 2 diabetes.

          Although patients with type 2 diabetes (T2D) are at significant risk for well-recognized diabetic complications, including macrovascular disease, retinopathy, nephropathy, and neuropathy, it is also clear that T2D patients are at increased risk for fragility fractures. Furthermore, fragility fractures in patients with T2D occur at higher bone mineral density (BMD) values compared to nondiabetic controls, suggesting abnormalities in bone material strength (BMS) and/or bone microarchitecture (bone "quality"). Thus, we performed in vivo microindentation testing of the tibia to directly measure BMS in 60 postmenopausal women (age range, 50-80 years) including 30 patients diagnosed with T2D for >10 years and 30 age-matched, nondiabetic controls. Regional BMD was measured by dual-energy X-ray absorptiometry (DXA); cortical and trabecular bone microarchitecture was assessed from high-resolution peripheral quantitative computed tomography (HRpQCT) images of the distal radius and tibia. Compared to controls, T2D patients had significantly lower BMS: unadjusted (-11.7%; p<0.001); following adjustment for body mass index (BMI) (-10.5%; p<0.001); and following additional adjustment for age, hypertension, nephropathy, neuropathy, retinopathy, and vascular disease (-9.2%; p=0.022). By contrast, after adjustment for confounding by BMI, T2D patients had bone microarchitecture and BMD that were not significantly different than controls; however, radial cortical porosity tended to be higher in the T2D patients. In addition, patients with T2D had significantly reduced serum markers of bone turnover (all p<0.001) compared to controls. Of note, in patients with T2D, the average glycated hemoglobin level over the previous 10 years was negatively correlated with BMS (r=-0.41; p=0.026). In conclusion, these findings represent the first demonstration of compromised BMS in patients with T2D. Furthermore, our results confirm previous studies demonstrating low bone turnover in patients with T2D and highlight the potential detrimental effects of prolonged hyperglycemia on bone quality. Thus, the skeleton needs to be recognized as another important target tissue subject to diabetic complications. © 2014 American Society for Bone and Mineral Research. © 2014 American Society for Bone and Mineral Research.
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            Bone mineralization density distribution in health and disease.

            Human cortical and trabecular bones are formed by individual osteons and bone packets, respectively, which are produced at different time points during the (re)modeling cycle by the coupled activity of bone cells. This leads to a heterogeneously mineralized bone material with a characteristic bone mineralization density distribution (BMDD) reflecting bone turnover, mineralization kinetics and average bone matrix age. In contrast to BMD, which is an estimate of the total amount of mineral in a scanned area of whole bone, BMDD describes the local mineral content of the bone matrix throughout the sample. Moreover, the mineral content of the bone matrix is playing a pivotal role in tuning its stiffness, strength and toughness. BMDD of healthy individuals shows a remarkably small biological variance suggesting the existence of an evolutionary optimum with respect to its biomechanical performance. Hence, any deviations from normal BMDD due to either disease and/or treatment might be of significant biological and clinical relevance. The development of appropriate methods to sensitively measure the BMDD in bone biopsies led to numerous applications of BMDD in the evaluation of diagnosis and treatment of bone diseases, while advancing the understanding of the bone material, concomitantly. For example, transiliacal bone biopsies of postmenopausal osteoporotic women were found to have mostly lower mineralization densities than normal, which were partly associated by an increase of bone turnover, but also caused by calcium and Vit-D deficiency. Antiresorptive therapy causes an increase of degree and homogeneity of mineralization within three years of treatment, while normal mineralization levels are not exceeded. In contrast, anabolic therapy like PTH decreases the degree and homogeneity of matrix mineralization, at least transiently. Osteogenesis imperfecta is generally associated with increased matrix mineralization contributing to the brittleness of bone in this disease, though bone turnover is usually increased suggesting an alteration in the mineralization kinetics. Furthermore, BMDD measurements combined with other scanning techniques like nanoindentation, Fourier transform infrared spectroscopy and small angle X-ray scattering can provide important insights into the structure-function relation of the bone matrix, and ultimately a better prediction of fracture risk in diseases, and after treatment.
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              Microindentation for In Vivo Measurement of Bone Tissue Mechanical Properties in Humans

              Bone tissue mechanical properties are deemed a key component of bone strength, but their assessment requires invasive procedures. Here we validate a new instrument, a reference point indentation (RPI) instrument, for measuring these tissue properties in vivo. The RPI instrument performs bone microindentation testing (BMT) by inserting a probe assembly through the skin covering the tibia and, after displacing periosteum, applying 20 indentation cycles at 2 Hz each with a maximum force of 11 N. We assessed 27 women with osteoporosis-related fractures and 8 controls of comparable ages. Measured total indentation distance (46.0 ± 14 versus 31.7 ± 3.3 µm, p = .008) and indentation distance increase (18.1 ± 5.6 versus 12.3 ± 2.9 µm, p = .008) were significantly greater in fracture patients than in controls. Areas under the receiver operating characteristic (ROC) curve for the two measurements were 93.1% (95% confidence interval [CI] 83.1–100) and 90.3% (95% CI 73.2–100), respectively. Interobserver coefficient of variation ranged from 8.7% to 15.5%, and the procedure was well tolerated. In a separate study of cadaveric human bone samples (n = 5), crack growth toughness and indentation distance increase correlated (r = –0.9036, p = .018), and scanning electron microscope images of cracks induced by indentation and by experimental fractures were similar. We conclude that BMT, by inducing microscopic fractures, directly measures bone mechanical properties at the tissue level. The technique is feasible for use in clinics with good reproducibility. It discriminates precisely between patients with and without fragility fracture and may provide clinicians and researchers with a direct in vivo measurement of bone tissue resistance to fracture. © 2010 American Society for Bone and Mineral Research.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                nefrologia
                Nefrología (Madrid)
                Nefrología (Madr.)
                Sociedad Española de Nefrología (Cantabria, Santander, Spain )
                0211-6995
                1989-2284
                February 2018
                : 38
                : 1
                : 27-33
                Affiliations
                [5] Madrid orgnameInstituto Carlos III orgdiv1CIBERFES España
                [4] Oxford orgnameUniversity of Oxford orgdiv1Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences orgdiv2Oxford NIHR Musculoskeletal Biomedical Research Unit United Kingdom
                [1] Barcelona orgnameHospital del Mar orgdiv1Servicio de Nefrología España
                [2] Barcelona orgnameInstitut Mar d’Investigacions Mediques España
                [6] Cataluña orgnameUniversitat Autónoma de Barcelona orgdiv1Hospital del Mar orgdiv2Servicio de Medicina Interna Spain
                [3] Madrid orgnameInstituto Carlos III orgdiv1REDinREN España
                Article
                S0211-69952018000100027
                10.1016/j.nefro.2017.04.002
                a963d331-f46f-40e7-bd5f-faf39fa33404

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

                History
                : 05 April 2017
                : 04 January 2017
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 42, Pages: 7
                Product

                SciELO Spain


                Score trabecular óseo,Microindentación ósea,Bone mineral disease,Kidney transplant,Fractures,Bone strength,Trabecular bone score,Bone microindentation,Enfermedad mineral ósea,Trasplante renal,Fracturas,Resistencia ósea

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