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Abnormal bone metabolism is an integral part of the chronic kidney disease-mineral bone disorder (CKD-MBD). For several reasons, the difficult bone compartment was neglected for some time, but there has been renewed interest as a result of the conception of bone as a new endocrine organ, the increasing recognition of the cross-talk between bone and vessels, and, especially, the very high risk of osteoporotic fractures (and associated mortality) demonstrated in patients with CKD. Therefore, it has been acknowledged in different guidelines that action is needed in respect of fracture risk assessment and the diagnosis and treatment of osteoporosis in the context of CKD and CKD-MBD, even beyond renal osteodystrophy. These updated guidelines clearly underline the need to improve a non-invasive approach to these bone disorders in order to guide treatment decisions aimed at not only controlling CKD-MBD but also decreasing the risk of fracture. In this report, we review the current role of the most often clinically used or promising biochemical circulating biomarkers such as parathyroid hormone, alkaline phosphatases, and other biochemical markers of bone activity as alternatives to some aspects of bone histomorphometry. We also mention the potential role of classic and new imaging techniques for CKD patients. Information on many aspects is still scarce and heterogeneous, but many of us consider that it is indeed time for action, recognizing our definitely limited ability to base certain treatment decisions only on our current non-comprehensive knowledge.

Resumen: La osteoporosis (OP) y la enfermedad renal crónica (ERC) influyen independientemente en la salud ósea. Numerosos pacientes con ERC presentan una disminución de densidad mineral ósea (DMO), un elevado riesgo de fracturas por fragilidad ósea y un incremento de su morbimortalidad. Con el envejecimiento de la población estos hechos no son dependientes solo de la «osteodistrofia renal» sino también de la OP asociada. Dado que la DMO tiene capacidad predictiva en pacientes con ERC (parte I), ahora analizaremos las implicaciones terapéuticas derivadas. Análisis post hoc de estudios aleatorizados han mostrado que fármacos como alendronato, risedronato, raloxifeno, teriparatida o denosumab tienen una eficacia comparable a la población general en pacientes con una disminución leve-moderada del filtrado glomerular (especialmente ERC-3). Estos estudios tienen limitaciones, pues incluyen mayoritariamente mujeres «sanas», sin diagnóstico conocido de ERC y habitualmente con parámetros normales de laboratorio; sin embargo, también existen datos positivos preliminares en estadios más avanzados (ERC-4) y más limitados en ERC-5D. Por todo ello, al menos en ausencia de alteraciones significativas del metabolismo mineral (i.e., hiperparatiroidismo severo), el beneficio potencial de dichos fármacos debería ser considerado en pacientes que presenten un riesgo de fractura elevado o muy elevado. Es novedad importante que las nuevas guías no condicionan su uso a la práctica de una biopsia ósea previa y que el beneficio/riesgo de estos fármacos podría estar justificado. Sin embargo, debemos considerar que la mayoría de estudios no son consistentes y tienen un bajo grado de evidencia, por lo que la indicación farmacológica (riesgo/beneficio) debe ser individualizada y prudente. Abstract: Osteoporosis (OP) and chronic kidney disease (CKD) both independently affect bone health. A significant number of patients with CKD have decreased bone mineral density (BMD), are at high risk of fragility fractures and have an increased morbidity and mortality risk. With an ageing population, these observations are not only dependent on “renal osteodystrophy” but also on the associated OP. As BMD predicts incident fractures in CKD patients (part I), we now aim to analyse the potential therapeutic consequences. Post-hoc analyses of randomised studies have shown that the efficacy of drugs such as alendronate, risedronate, raloxifene, teriparatide and denosumab is similar to that of the general population in patients with a mild/moderate decline in their glomerular filtration rate (especially CKD-3). These studies have some flaws however, as they included mostly “healthy” women with no known diagnosis of CKD and generally with normal lab test results. Nevertheless, there are also some positive preliminary data in more advanced stages (CKD-4), even though in CKD-5D they are more limited. Therefore, at least in the absence of significant mineral metabolism disorders (i.e. severe hyperparathyroidism), the potential benefit of these drugs should be considered in patients with a high or very high fracture risk. It is an important change that the new guidelines do not make it a requirement to first perform a bone biopsy and that the risk/benefit ratio of these drugs may be justified. However, we must also be aware that most studies are not consistent and the level of evidence is low. Consequently, any pharmacological intervention (risk/benefit) should be prudent and individualised. Palabras clave: Osteoporosis, CKD-MBD, Densidad mineral ósea, Fracturas, ERC, DEXA, Bisfosfonatos, Denosumab, Romosozumab, Keywords: Osteoporosis, CKD-MBD, Bone mineral density, Fractures, CKD, DEXA, Bisphosphonates, Denosumab, Romosozumab

Background and Aims Bone fragility fractures (bone fractures) are extremely frequent in haemodialysis (HD) patients. Serum phosphate (P) has been suggested as a risk factor for bone fracture, nonetheless, evidence is poor. The aim of this study was to assess the association between incidence of bone fractures and serum phosphate (P), calcium (Ca) and parathyroid hormone (PTH) in patients from the COSMOS study. Method COSMOS is an observational, prospective, open cohort study with 3 years of follow-up including 6797 haemodialysis patients from 227 centres randomly selected from 20 European countries. At baseline, demographics, comorbidities, treatments, serum biochemical parameters of the previous six months and bone fractures of the previous 12 months were collected. Every 6 months, all these variables, outcomes, and incident bone fractures, were collected. Patients who had at least one bone fracture during follow-up were compared with those who had not. Multivariate binary logistic regression and Poisson regression were used to assess the association between incidence of bone fractures and serum P, Ca and PTH. Time to fracture (and possible re-fracture) was also evaluated using Cox regression and Cox regression for recurrent events. All the results were adjusted by 23 variables including Ca, P, PTH, albumin and haemoglobin (full adjusted model). Results Analysis included 6274 patients who had follow-up data and non-missing information regarding bone fractures at baseline and during follow-up; 252 patients (4.0%), suffered at least one incident bone fracture. The fractured patients were older (68.1±12.9 vs. 63.8±14.5 years, p Multivariate binary logistic regression showed that “well known risk factors for bone fracture”, such as a previous bone fracture (OR: 7.78[95%CI:4.83-12.55], p 800 pg/mL (OR: 1.60[95%CI: 1.01-2.55], p=0.047), were associated with a higher incidence of follow-up bone fractures. In addition to the “well known bone risk factors for fracture”, serum P > 6.1 mg/dL (OR: 1.50[95% CI: 1.07-2.11], p=0.02) and serum Ca > 9.7 mg/dL (OR: 1.42[95%CI: 1.01-2.03], p=0.043), were also associated with a higher incidence of bone fractures in the full-adjusted model. These findings were partly consistent with Poisson regression for serum P >6.1 mg/dL (IRR: 1.46[95% CI: 1.00-2.13], p=0.0085) and serum Ca > 9.7 mg/dL (IRR: 1.49[95%CI: 1.06-2.08], p=0.0047), but not for PTH. In addition, Cox regression analysis showed association between bone fractures and serum P >6.1 mg/dl (HR: 1.61 [95%CI: 1.16-2.24], p=0.0049) and 1.60 [95%CI: 1.14-2.24] (p=0.0066) for simple and recurrent events respectively, but no association was found with serum Ca and PTH in the 2 full-adjusted models for the Cox regression analyses. Conclusion In COSMOS, a large haemodialysis patient’s cohort with 3 years follow up, serum P was the only biochemical parameter that remained as a significant risk factor for bone fractures after 4 statistic approaches. Thus, for the first time, in a large scale well controlled study, high serum P has been identified as a new independent potential risk factor for incident bone fractures in haemodialysis patients.

BackgroundIn chronic kidney disease, serum phosphorus (P) elevations stimulate parathyroid hormone (PTH) production, causing severe alterations in the bone–vasculature axis. PTH is the main regulator of the receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, which is essential for bone maintenance and also plays an important role in vascular smooth muscle cell (VSMC) calcification. The discovery of a new RANKL receptor, leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), which is important for osteoblast differentiation but with an unknown role in vascular calcification (VC), led us to examine the contribution of LGR4 in high P/high PTH–driven VC.MethodsIn vivo studies were conducted in subtotally nephrectomized rats fed a normal or high P diet, with and without parathyroidectomy (PTX). PTX rats were supplemented with PTH(1–34) to achieve physiological serum PTH levels. In vitro studies were performed in rat aortic VSMCs cultured in control medium, calcifying medium (CM) or CM plus 10−7 versus 10−9 M PTH.ResultsRats fed a high P diet had a significantly increased aortic calcium (Ca) content. Similarly, Ca deposition was higher in VSMCs exposed to CM. Both conditions were associated with increased RANKL and LGR4 and decreased OPG aorta expression and were exacerbated by high PTH. Silencing of LGR4 or parathyroid hormone receptor 1 (PTH1R) attenuated the high PTH–driven increases in Ca deposition. Furthermore, PTH1R silencing and pharmacological inhibition of protein kinase A (PKA), but not protein kinase C, prevented the increases in RANKL and LGR4 and decreased OPG. Treatment with PKA agonist corroborated that LGR4 regulation is a PTH/PKA-driven process.ConclusionsHigh PTH increases LGR4 and RANKL and decreases OPG expression in the aorta, thereby favouring VC. The hormone’s direct pro-calcifying actions involve PTH1R binding and PKA activation.

Resumen Objetivos Valorar si la fuerza de agarre y la dificultad para realizar actividades cotidianas podrían ser predictores de caídas y fracturas osteoporóticas. Material y métodos Se seleccionaron aleatoriamente 624 hombres y mujeres mayores de 50 años, que fueron seguidos durante 8 años para conocer la incidencia de caídas y fracturas osteoporóticas no vertebrales. Al inicio se midió la fuerza de agarre en manos y se cumplimentó un cuestionario con variables clínicas, factores de riesgo relacionados con la osteoporosis y cuestiones relativas a la dificultad o incapacidad para realizar actividades cotidianas. Resultados La fuerza de agarre en manos no se asoció con la incidencia de caídas y fracturas. Sin embargo, la imposibilidad o dificultad de “estar sentado más de 1 hora en silla dura”, “quitarse los calcetines o las medias” e “inclinarse desde una silla para coger un objeto del suelo” se asoció con caídas: 1,83 (1,16-2,89); 1,85 (1,14-3,00) y 1,68 (1,04-2,70), respectivamente. Del mismo modo, la imposibilidad o dificultad de “llevar durante 10 metros un objeto de 10 kilos” y “levantar una caja con 6 botellas y ponerlas sobre una mesa” se asoció con fractura: 2,82 (1,21-6,59) y 2,54 (1,12-5,81) respectivamente. Conclusiones No se encontró asociación entre la fuerza de agarre e incidencia de caídas y fracturas osteporóticas, pero sí con dificultad o incapacidad para realizar actividades cotidianas. Las relacionadas con mayor fuerza se asociaron con fractura, mientras que las relacionadas con capacidad funcional se asociaron con caídas. Realizar cuestionarios sencillos podría ayudar a predecir eventos antes de que ocurran.

Inflammation is central to chronic kidney disease (CKD) pathogenesis and vascular outcomes, but the exact players remain unidentified. Since low density granulocytes (LDGs) are emerging mediators in inflammatory conditions, we aimed to evaluate whether LDGs may be altered in CKD and related to clinical outcomes as biomarkers. To his end, LDGs subsets were measured in peripheral blood by flow cytometry and confocal microscopy in 33 CKD patients undergoing peritoneal dialysis and 15 healthy controls (HC). Analyses were replicated in an additional cohort. DEF3 (marker of early granulopoiesis) gene expression on PBMCs was quantified by qPCR. Total CD15+ LDGs and both CD14lowCD16+ and CD14−CD16− subsets were expanded in CKD. The relative frequency of the CD14−CD16− subpopulation was higher among the CD15+ pool in CKD. This alteration was stable over-time. The increased CD14−CD16−CD15+ paralleled Kauppila scores and DEF3 expression, whereas no association was found with CD14lowCD16+ CD15+. Both subsets differed in their CD11b, CD10, CD35, CD31, CD62L, IFNAR1 and CD68 expression, FSC/SSC features and nuclear morphology, pointing to different origins and maturation status. In conclusion, LDGs were expanded in CKD showing a skewed distribution towards a CD14−CD16−CD15+ enrichment, in association with vascular calcification. DEF3 expression in PBMC can be a marker of LDG expansion. Fil: Rodríguez Carrio, Javier. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA). Bone and Mineral Research Unit; España. Universidad de Oviedo; España Fil: Carrillo López, Natalia. Hospital Universitario Central de Asturias; España Fil: Ulloa, Catalina. Hospital Universitario Central de Asturias; España Fil: Seijo, Mariana. Hospital Universitario Central de Asturias; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Rodríguez García, Minerva. Hospital Universitario Central de Asturias; España Fil: Rodríguez Suárez, Carmen. Hospital Universitario Central de Asturias; España Fil: Díaz-Corte, Carmen. Hospital Universitario Central de Asturias; España Fil: Cannata Andía, Jorge B.. Universidad de Oviedo; España. Hospital Universitario Central de Asturias; España Fil: Suárez, Ana. Universidad de Oviedo; España Fil: Dusso, Adriana. Hospital Universitario Central de Asturias; España

Osteoporosis (OP) and chronic kidney disease (CKD) independently influence bone and cardiovascular health. A considerable number of patients with CKD, especially those with stages 3a to 5D, have a significantly reduced bone mineral density leading to a high risk of fracture and a significant increase in associated morbidity and mortality. Independently of classic OP related to age and/or gender, the mechanical properties of bone are also affected by inherent risk factors for CKD ("uraemic OP"). In the first part of this review, we will analyse the general concepts regarding bone mineral density, OP and fractures, which have been largely undervalued until now by nephrologists due to the lack of evidence and diagnostic difficulties in the context of CKD. It has now been proven that a reduced bone mineral density is highly predictive of fracture risk in CKD patients, although it does not allow a distinction to be made between the causes which generate it (hyperparathyroidism, adynamic bone disease and/or senile osteoporosis, etc.). Therefore, in the second part, we will analyse the therapeutic indications in different CKD stages. In any case, the individual assessment of factors which represent a higher or lower risk of fracture, the quantification of this risk (i.e. using tools such as FRAX

Aims Our aim was to evaluate the long-term effect of cinacalcet in patients with hypercalcaemic secondary hyperparathyroidism (SHPT) after renal transplantation (RT) in order to expand real-world data in this population. Methods We performed a multicentre, observational, retrospective study in 17 renal transplant units from Spain. We collected data from renal recipients with hypercalcaemic (calcium >10.2 mg/dL) SHPT (intact parathyroid hormone (iPTH) > 120 pg/mL) who initiated cinacalcet in the clinical practice. Results We included 193 patients with a mean (standard deviation (SD)) age of 52 (12) years, 58% men. Cinacalcet treatment was initiated at a median of 20 months after RT (median dose 30 mg/day). Mean calcium levels decreased from a mean (SD) of 11.1 (0.6) at baseline to 10.1 (0.8) at 6 months (9.0% reduction, P

Aims: Iberian pigs are bred in Spain for the production of high-value dry-cured products, whose export volumes are increasing. Animals are typically reared outdoors, although indoor farming is becoming popular. We compared carriage of methicillin-resistant Staphylococcus aureus (MRSA) in Iberian pigs, raised indoors and outdoors, with intensively farmed Standard White pigs. Methods and Results: From June 2007 to February 2008, 106 skin swabs were taken from Iberian pigs and 157 samples from SWP at slaughterhouses in Spain. We found that Iberian pigs carried MRSA, although with a significantly lower prevalence (30/106; 28%) than SWP (130/157; 83%). A higher prevalence of indoor Iberian pigs compared with animals reared under outdoor conditions was not significant; however, all but one positive indoor Iberian pig samples were detected from one slaughterhouse. Overall, 16 different spa types were identified, with t011 predominating in all three animal populations. A subset of isolates was characterized by MLST. Most of these belonged to ST398. MRSA isolates from Iberian pigs presented a higher susceptibility to antibiotics than those isolated from SWP. Conclusions: Despite limited contact with humans, pigs raised outdoors are colonized by an MRSA population that genetically overlaps with that of intensively farmed pigs, although antimicrobial resistance is lower. Significance and Impact of the Study: To our knowledge, this is the first detection of MRSA in food animals raised in free-range conditions. © 2012 The Authors. Letters in Applied Microbiology © 2012 The Society for Applied Microbiology.

Background. Vascular calcifications and the bone fractures caused by abnormal bone fragility, also called osteoporotic fractures, are frequent complications associated with chronic kidney diseases (CKD). The aim of this study was to investigate the association between vascular calcifications, osteoporotic bone fractures and survival in haemodialysis (HD) patients. Methods. A total of 193 HD patients were followed up to 2 years. Vascular calcifications and osteoporotic vertebral fractures (quoted just as vertebral fractures in the text) were assessed by thoracic, lumbar spine, pelvic and hand X-rays and graded according to their severity. Clinical, biochemical and therapeutic data gathered during the total time spent on HD were collected. Results. The prevalence of aortic calcifications was higher in HD patients than in a random-based general population (79% versus 37.5%, P < 0.001). Total time on any renal replacement therapy (RRT) and diabetes were positively associated with a higher prevalence of vascular calcifications. In addition to these factors, time on HD was also positively associated with the severity of vascular calcifications, and higher haemoglobin levels were associated with a lower prevalence of severe vascular calcifications in large and medium calibre arteries. The prevalence of vertebral fractures in HD patients was similar to that of the general population (26.5% versus 24.1%). Age and time on HD showed a positive and statistically significant association with the prevalence of vertebral fractures. Vascular calcifications in the medium calibre arteries were associated with a higher rate of prevalent vertebral fractures. In women, severe vascular calcifications and vertebral fractures were positively associated with mortality [RR = 3.2 (1.0–10.0) and RR = 4.8 (1.7–13.4), respectively]. Conclusions. Positive associations between vascular calcifications, vertebral fractures and mortality have been found in patients on HD.

Background: Abnormalities in serum phosphorus, calcium and parathyroid hormone (PTH) have been associated with poor survival in haemodialysis patients. This COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) analysis assesses the association of high and low serum phosphorus, calcium and PTH with a relative risk of mortality. Furthermore, the impact of changes in these parameters on the relative risk of mortality throughout the 3-year follow-up has been investigated. Methods: COSMOS is a 3-year, multicentre, open-cohort, prospective study carried out in 6797 adult chronic haemodialysis patients randomly selected from 20 European countries. Results: Using Cox proportional hazard regression models and penalized splines analysis, it was found that both high and low serum phosphorus, calcium and PTH were associated with a higher risk of mortality. The serum values associated with the minimum relative risk of mortality were 4.4 mg/dL for serum phosphorus, 8.8 mg/dL for serum calcium and 398 pg/mL for serum PTH. The lowest mortality risk ranges obtained using as base the previous values were 3.6-5.2 mg/dL for serum phosphorus, 7.9-9.5 mg/dL for serum calcium and 168-674 pg/mL for serum PTH. Decreases in serum phosphorus and calcium and increases in serum PTH in patients with baseline values of >5.2 mg/dL (phosphorus), >9.5 mg/dL (calcium) and

The predisposition to vascular calcifications in patients with chronic kidney disease (CKD) has gained great interest in recent years as many studies have described its likely impact on morbidity and mortality. The mechanism by which the process of vascular calcification is produced is complex, and it does not consist in a simple precipitation of calcium and phosphate but is instead an active and modifiable process. Several "modifiable and nonmodifiable" factors that are able to promote vascular calcification are extremely frequent in patients with CKD. Most of the present strategies to decrease vascular calcifications are based in the control of the more prevalent modifiable risk factors. Unfortunately, the extremely important nonmodifiable risk factors, which are highly prevalent, such as older age, time on dialysis, and diabetes, are not under one's control. Recent studies also have shown that vascular calcifications in some localizations were associated with increased osteoporotic fractures not only in dialysis patients but also in the general population, and interestingly, mortality also was associated significantly and positively with vascular calcifications and nontraumatic bone fractures. Despite that new strategies may improve the management of vascular diseases and specifically have a positive impact on the high prevalence of vascular calcifications, still the best possible control of the bone metabolic and inflammatory parameters are in the primary line. The horizon of the coming decade looks promising, but solid clinical and epidemiologic data are needed to manage better the bone- and cardiovascular-related disorders in patients with CKD.

The key players of the CKD–MBD are calcium, phosphorus, PTH, FGF23, and the vitamin D hormonal system. The progressive reduction of kidney function greatly modified the tightly interrelated mechanisms controlling these parameters. As a result, important changes occurred in the bone and mineral hormonal axis leading to changes in bone turnover with consequences in relevant clinical outcomes, such as decrease in bone mass with increased bone fragility and bone fractures and increased vascular and valvular calcification with great impact in the cardiovascular outcomes.

Background: The effect of cinacalcet in patients with persistent secondary hyperparathyroidism (SHPT) after kidney transplantation (KT) has mainly been reported in patients with secondary hypercalcaemia. Objectives: Our objective was to assess the long-term effect of cinacalcet on patients with a KT and normocalcaemic SHPT. Methods: A one-year multicentre, observational, retrospective study that included kidney recipients with SHPT (intact parathyroid hormone [iPTH] > 120pg/ml) and calcium levels within the normal range (8.4-10.2mg/dl). Patients began treatment with cinacalcet in clinical practice. Results: 32 patients with a mean age (standard deviation [SD] of 54 (11) years, 56% male, were included in the study. Treatment with cinacalcet began a median of 16 months after KT (median dose of 30mg/day). Levels of iPTH decreased from a median (P25, P75) of 364 (220, 531) pg/ml at the start of the study to 187 (98, 320) after 6 months (48.6% reduction, P=.001) and to 145 (91, 195) after 12 months (60.2% reduction, P=.001), without there being changes in calcium and phosphorus levels (P=.214 and P=.216, respectively). No changes were observed in kidney function or anti-calcineuric drug levels. 3.1% of patients discontinued cinacalcet due to intolerance and 6.2% due to a lack of efficacy. Conclusions: In patients with normocalcaemic SHPT after KT cinacalcet improves the control of serum PTH values without causing changes to calcaemia, phosphataemia or kidney function. Cinacalcet showed good tolerability.

Our aim was to evaluate the long-term effect of cinacalcet in patients with hypercalcaemic secondary hyperparathyroidism (SHPT) after renal transplantation (RT) in order to expand real-world data in this population.We performed a multicentre, observational, retrospective study in 17 renal transplant units from Spain. We collected data from renal recipients with hypercalcaemic (calcium10.2 mg/dL) SHPT (intact parathyroid hormone (iPTH) 120 pg/mL) who initiated cinacalcet in the clinical practice.We included 193 patients with a mean (standard deviation (SD)) age of 52 (12) years, 58% men. Cinacalcet treatment was initiated at a median of 20 months after RT (median dose 30 mg/day). Mean calcium levels decreased from a mean (SD) of 11.1 (0.6) at baseline to 10.1 (0.8) at 6 months (9.0% reduction, P 0.0001). Median iPTH was reduced by 23.0% at 6 months (P = 0.0005) and mean phosphorus levels increased by 11.1% (P 0.0001). The effects were maintained up to 3-years. No changes were observed in renal function or anticalcineurin drug levels. Only 4.1% of patients discontinued cinacalcet due to intolerance and 1.0% due to lack of efficacy.In renal transplant patients with hypercalcaemic SHPT, cinacalcet controlled serum calcium, iPTH and phosphorus levels up to 3 years. Tolerability was good.

Background. Chronic kidney disease–mineral and bone disorders (CKD–MBD) are important complications of CKD5D patients that are associated with mortality. Methods. COSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005–07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions. Results. The haemodialysis population in Europe is an aged population (mean age 64.8 ± 14.2 years) with a high prevalence of diabetes (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on haemodialysis more than 5 years. Patients from the former Eastern countries are younger (59.3 ± 14.3 versus 66.0 ± 13.9), having a lower proportion of diabetics (24.1 versus 30.7%). There were relevant differences in the frequency of measurement of the main CKD–MBD biochemical parameters [Ca, P and parathyroid hormone (PTH)] and the Eastern countries showed a poorer control of these biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the haemodialysis patients received active vitamin D treatment. Calcitriol use doubled that of alfacalcidiol in the Mediterranean countries, whereas the opposite was found in the non-Mediterranean countries. The criteria followed to perform parathyroidectomy were different across Europe. In the Mediterranean countries, the level of serum PTH considered to perform parathyroidectomy was higher than in non-Mediterranean countries; as a result, in the latter, more parathyroidectomies were performed in the year previous to inclusion to COSMOS. Conclusions. The COSMOS baseline results show important differences across Europe in the management of CKD–MBD.

Vascular calcification plays a major role in cardiovascular disease, which is one of the main causes of mortality in chronic kidney disease patients. Vascular calcification is determined by prevalent traditional and uraemia-related (non-traditional) risk factors. It occurs mainly in the arteries, which are classified into three types according to their size and structural characteristics. In addition, vascular calcification has been associated with bone loss and fractures in chronic kidney disease patients and the general population, stressing the fact that both disorders can share pathogenetic pathways. The strategies to control vascular calcification involve several measures, chief among them the control of hyperphosphataemia. Furthermore, it has been recently described that strategies that reduce bone resorption and increase bone mineralization may decrease the risk of vascular calcifications; however, this approach still remains controversial. The mechanisms involved in vascular calcification are complex and not yet fully understood. Phosphorus plays a major role, while other factors related to bone formation have been recently identified.

El objetivo del estudio fue analizar el riesgo de fractura calculado mediante la herramienta FRAX® y sus determinantes, en pacientes con trasplante renal remitidos a nuestra consulta para control de las repercusiones óseas. Se estudiaron 113 pacientes, 42 hombres y 71 mujeres portadores de trasplante renal funcionante a los que se les realizó una encuesta general. A todos los pacientes se les hizo una densitometría ósea en columna lumbar PA (L2 - L4) y cadera (cuello femoral y cadera total) con un densitómetro Hologic QDR 1000®. Con los datos recogidos de la encuesta se calculó el riesgo de fractura mediante la herramienta FRAX®. La edad media de los pacientes fue 57±9 años y un tiempo medio trasplantados de 4,6±4,4 años. El riesgo de presentar fractura osteoporótica mayor a los 10 años fue del 6,54±4,9% y de fractura de cadera de 2,06±2,67%. Cuando analizamos el riesgo según el sexo observamos como en las mujeres la probabilidad de presentar fractura osteoporótica mayor a los 10 años fue significativamente superior que en los hombres (7,6±5,2% vs 4,8±3,7%, p=0,001). El riesgo de fractura de cadera a los 10 años fue también ligeramente superior en las mujeres que en los hombres, pero no de forma significativa (2,3±2,8% vs1,6±2,4%).

At present, new compounds are available to treat secondary hyperparathyroidism, namely calcimimetics, novel phosphorus binders and also novel vitamin D receptor activators. Calcimimetics increase the sensitivity of the parathyroid gland to calcium through spatial configurational changes of the calcium-sensing receptor. In addition, experimental studies have demonstrated that calcimimetics also upregulate both the calcium-sensing receptor and the vitamin D receptor. They are efficacious in children, though the experience in paediatric chronic kidney disease is still limited. Sevelamer, lanthanum carbonate and magnesium iron hydroxycarbonate are novel phosphorus binders available on the market. Several studies have demonstrated their efficacy and safety up to 6 years, though costs are the main limitation for a wider use. Since almost all the experience available on the new phosphorus binders comes from its use in adults, studies on children are needed in order to confirm the efficacy and safety of these products. Other new salts and polymers are also being developed. New vitamin D receptor activators, such as paricalcitol, are as effective at suppressing parathyroid hormone (PTH) as the traditional vitamin D receptor activators used for the past two decades, but they have a better and safer profile, showing fewer calcaemic and phosphoraemic effects while preserving the desirable effects of the vitamin D receptor activators on the cardiovascular system, hypertension, inflammation and fibrosis. Their use in children with chronic kidney disease has revealed similar responses to those of adults. The novel compounds discussed in this review should facilitate and improve the management of mineral and bone disorders in children with chronic kidney disease.

In this prospective study, we found a positive relationship between the prevalence of aortic calcifications and age. Aortic calcifications at baseline were positively associated with osteoporotic fractures. In addition, progression of aortic calcifications was also positively associated with the rate of decline in BMD at lumbar spine.The aim of this study was to analyze the relationship between the progression of abdominal aortic calcification and osteoporosis in a Spanish cohort of men and women older than 50.Men and women (n=624) aged 50 and over underwent two lateral X-rays of thoracic and lumbar spine and a dual X-ray absorptiometry (DXA) study at lumbar spine and hip, and were followed during 4 years. Abdominal aortic calcifications were classified as absent, mild-moderate and severe.There was a positive relationship between the prevalence of aortic calcifications and age. In both sexes, prevalent severe aortic calcifications were positively associated with prevalent osteoporotic fractures [odds ratio (OR)=1.93 (1.02-3.65)]. The association was stronger when only vertebral fracture was considered [OR=2.45 (1.23-4.87)]. In addition, progression of aortic calcifications showed a positive association with the rate of decline in bone mineral density (BMD) at lumbar spine.Aortic calcifications at baseline were positively associated with osteoporotic fractures. The progression of aortic calcifications was also positively associated with the rate of decline in BMD at lumbar spine.

Advantages of adjusting the initial dose of intravenous calcitriol according to PTH levels.BackgroundTo assess the usefulness of starting calcitriol therapy with a dose proportional to the degree of hyperparathyroidism, 141 patients from 28 centers were treated with intravenous calcitriol for 6 months. The aim was to achieve a final PTH between 125 and 250 pg/mL. Patients with serum PTH>250 pg/mL were included in the study and divided into 4 groups according to baseline PTH levels.MethodsThe study was completed by 100 patients, a third of which were treated strictly according to the protocol, labeled “compliants”; thus, calcitriol was started according to baseline PTH levels. Two thirds of patients, labeled “noncompliants,” showed one or more violation in the dosage regimen.ResultsAfter 2 months of treatment with calcitriol, 59% of the “compliants” and 35% of the “noncompliants” decreased their PTH levels>40% (P = 0.022), 70%, and 49%, respectively after 3 months of treatment. After 3 months of treatment, 67% of the “compliants” reached the target (PTH 125 to 250 pg/mL) in contrast with 23% of the “noncompliants” (P < 0.001). The number of hypercalcemic and hyperphosphatemic episodes was significantly lower in the “compliants” group (P < 0.006).ConclusionThese results demonstrate several advantages when calcitriol therapy is started with a dose proportional to the severity of hyperparathyroidism.

Hyperphosphataemia is a frequent and important cardiovascular risk factor in patients with chronic kidney disease (CKD). High phosphate levels may influence vascular calcifications by two separate mechanisms: by worsening secondary hyperparathyroidism, which in turn facilitates calcification, and by promoting calcium phosphate deposition in pre-formed endothelial plaques and in the arterial wall. Recent studies have shown that hyperphosphataemia induces the proliferation and differentiation of endothelial vascular cells into osteoblast-like cells, promoting vascular calcification. High phosphate levels also increase the risk of mortality in patients with CKD. To reduce the negative impact of high phosphate, serum phosphate levels should be

There is little data concerning the morbidity, mortality, and epidemiology of vertebral fracture. The aim of this study was to evaluate the effect of prevalent and incident vertebral fractures as risk factors for further osteoporotic fractures and mortality. The study was performed on a cohort of 316 women and 308 men older than 50 belonging to the EVOS study, randomly selected from our city register. At the beginning of the study and 4 years later, lateral dorsal and lumbar X-rays were performed. In addition, evaluation of the incidence of osteoporotic nonvertebral fractures was performed throughout 8 years. The incidence of all osteoporotic fractures was higher in women than in men (two-fold increase in vertebral fracture incidence and five-fold increase in Colles' and femur incidence). Vertebral fracture was a strong risk factor for a new vertebral fracture [RR=4.7 (1.8-11.9)], hip fracture [RR=6.7 (2.0-22.7)] and Colles' fracture [RR=3.0 (1.1-7.8)]. Prevalent and incident vertebral fractures were associated with a higher risk of having a hip fracture [RR=10.0 (2.0-50.2)] and Colles' fracture [RR=5.5 (1.3-23.4)]. In addition, in women, the vertebral fracture was associated with a higher mortality. By contrast, no association was found in men. These results demonstrate the association between a previous vertebral fracture with increments in the incidence of osteoporotic fractures of any type. In addition, we found a significantly higher mortality rate in women having vertebral fractures. These findings support the necessity of preventing the occurrence of vertebral fractures to limit their strong negative impact on mortality.