Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease-Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows.

Shortly after the discovery of Klotho, interest grew in its potential role in chronic kidney disease (CKD). There are three isoforms of the Klotho protein: αKlotho, ßKlotho and γKlotho. This review will focus on αKlotho due to its relevance as a biomarker in CKD. αKlotho is synthesized mainly in the kidneys, but it can be released into the bloodstream and urine as soluble Klotho (sKlotho), which undertakes systemic actions, independently or in combination with FGF23. It is usually accepted that sKlotho levels are reduced early in CKD and that lower levels of sKlotho might be associated with the main chronic kidney disease-mineral bone disorders (CKD-MBDs): cardiovascular and bone disease. However, as results are inconsistent, the applicability of sKlotho as a CKD-MBD biomarker is still a matter of controversy. Much of the inconsistency can be explained due to low sample numbers, the low quality of clinical studies, the lack of standardized assays to assess sKlotho and a lack of consensus on sample processing, especially in urine. In recent decades, because of our longer life expectancies, the prevalence of accelerated-ageing diseases, such as CKD, has increased. Exercise, social interaction and caloric restriction are considered key factors for healthy ageing. While exercise and social interaction seem to be related to higher serum sKlotho levels, it is not clear whether serum sKlotho might be influenced by caloric restriction. This review focuses on the possible role of sKlotho as a biomarker in CKD-MBD, highlighting the difference between solid knowledge and areas requiring further research, including the role of sKlotho in healthy ageing.

Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients.

BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.

A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D-a randomised multicentre international clinical trial.

BACKGROUND: Vitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed. METHODS: The COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed. RESULTS: In the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0-10.5] vs. 9.5 [95%CI 9.0-10.5] days), admission to ICU (17.2% [95%CI 13.0-22.3] vs. 16.4% [95%CI 12.3-21.4]) and death rate (8.0% [95%CI 5.2-12.1] vs. 5.6% [95%CI 3.3-9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes. CONCLUSIONS: The randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes. TRIAL REGISTRATION: COVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov ( NCT04552951 ).

The Non-invasive Diagnosis of Bone Disorders in CKD.

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.

Multiple vertebral fractures after suspension of denosumab. A series of 56 cases.

BACKGROUND: Denosumab is a monoclonal antibody approved for the treatment of postmenopausal osteoporosis. The withdrawal of denosumab produces an abrupt loss of bone mineral density and may cause multiple vertebral fractures (MVF). OBJECTIVE: The objective of this study is to study the clinical, biochemical, and densitometric characteristics in a large series of postmenopausal women who suffered MVF after denosumab withdrawal. Likewise, we try to identify those factors related to the presence of a greater number of vertebral fractures (VF). PATIENTS AND METHODS: Fifty-six patients (54 women) who suffered MVF after receiving denosumab at least for three consecutive years and abruptly suspended it. A clinical examination was carried out. Biochemical bone remodelling markers (BBRM) and bone densitometry at the lumbar spine and proximal femur were measured. VF were diagnosed by magnetic resonance imaging MRI, X-ray, or both at dorsal and lumbar spine. RESULTS: Fifty-six patients presented a total of 192 VF. 41 patients (73.2%) had not previously suffered VF. After discontinuation of the drug, a statistically significant increase in the BBRM was observed. In the multivariate analysis, only the time that denosumab was previously received was associated with the presence of a greater number of VF (P = .04). CONCLUSIONS: We present the series with the largest number of patients collected to date. 56 patients accumulated 192 new VF. After the suspension of denosumab and the production of MVF, there was an increase in the serum values of the BBRM. The time of denosumab use was the only parameter associated with a greater number of fractures.

Is vitamin-D supplementation not useful in patients at risk of fractures and falls?

To evaluate numerous publications that question the bone and extraosseous benefits of vitamin D diet supplementation based on results, which often transcend to public opinion, but are not well interpreted. This may have negative consequences on compliance of patients under vitamin D supplementation. Critical appraisal of several articles on vitamin D supplementation and its relationship with fractures, falls, cardiovascular diseases, and cancer incidence. Such publications have certain limitations (i.e. patients excluded because of a diagnosis of osteoporosis, or at a higher risk for fractures and falls, or because they have a vitamin D deficiency, etc.), and conclusions and/or subsequent recommendations should be approached with caution. Our research shows that patients with osteoporosis, vitamin D deficiency, and at high risk of fractures and falls should not discontinue vitamin D supplementation (often associated with calcium). It is becoming increasingly evident that patients with hypovitaminosis D are those that gain a maximal benefit from vitamin D supplementation.

Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care.

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD ("Chronic Kidney Disease-Mineral and Bone Disorders") complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism.

No association between perception of family functioning and treatment modality for chronic renal disease secondary to diabetes mellitus.

INTRODUCTION: This work was undertaken with the aim of studying the association between perception of family functioning and mode of medical treatment in Mexicans between 40 and 65 years whose suffer from chronic kidney disease. MATERIAL AND METHODS: Participants 37 patients, 22 men, 40 to 65 years of age with chronic renal disease secondary to diabetes mellitus. Patients were assigned to three groups, diet, diet + dialysis and diet + hemodialysis, they responded to four self-administered questionnaires, a demographic questionnaire and three questionnaires to assess family functioning, the Apgar family test, the family functioning perception test, and the scale of Garcia et al. RESULTS: There was no relationship between perception of family functioning of patients with chronic kidney disease secondary to diabetes mellitus and type of medical treatment. CONCLUSIONS: The perception of family functioning was not associated with the type of medical treatment of adults with chronic renal failure secondary to diabetes mellitus. The use of various instruments to explore family functioning is important to identify areas to address the psychotherapeutic management of the family. Key words: Family functioning, Diabetes mellitus type 2, Chronic renal disease, Middle adulthood.

Transition of patients with metabolic bone disease from paediatric to adult healthcare services: current situation and proposals for improvement.

BACKGROUND: There are currently no models for the transition of patients with metabolic bone diseases (MBDs) from paediatric to adult care. The aim of this project was to analyse information on the experience of physicians in the transition of these patients in Spain, and to draw up consensus recommendations with the specialists involved in their treatment and follow-up. METHODS: The project was carried out by a group of experts in MBDs and included a systematic review of the literature for the identification of critical points in the transition process. This was used to develop a questionnaire with a total of 48 questions that would determine the degree of consensus on: (a) the rationale for a transition programme and the optimal time for the patient to start the transition process; (b) transition models and plans; (c) the information that should be specified in the transition plan; and (d) the documentation to be created and the training required. Recommendations and a practical algorithm were developed using the findings. The project was endorsed by eight scientific societies. RESULTS: A total of 86 physicians from 53 Spanish hospitals participated. Consensus was reached on 45 of the 48 statements. There was no agreement that the age of 12 years was an appropriate and feasible point at which to initiate the transition in patients with MBD, nor that a gradual transition model could reasonably be implemented in their own hospital. According to the participants, the main barriers for successful transition in Spain today are lack of resources and lack of coordination between paediatric and adult units. CONCLUSIONS: The TEAM Project gives an overview of the transition of paediatric MBD patients to adult care in Spain and provides practical recommendations for its implementation.

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial.

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

[Incidence of cesarean section in a regional general hospital]. / Incidencia de cesáreas en un hospital general de zona.

BACKGROUND: the high incidence of cesarean section is a world health problem, and Mexico is not the exception. The purpose of the clinical practice guidelines is to establish accurate directions on delivery by cesarean section, diminishing its unjustified practice. The Regional General Hospital and Medical Family Unit 2 of the Instituto Mexicano del Seguro Social in Zacapu, Michoacán has 70 % of cesarean section rate, it is the double of the country average. The aim was to know causes of cesarean section. METHODS: a retrospective, non-probabilistic analysis of 127 patients attended along two months. The incidence of cesarean section and causes were recorded. A statical descriptive analysis was done. RESULTS: ninety cesareans (70.9) % were performed in 127 patients; 44.4 % of these were performed in primiparous women. The most frequent reason was repeated cesarean in 27.8 %, cephalopelvic disproportion in 25.6 %, and fetal distress in 14.4 %. CONCLUSIONS: the high incidence of cesarean section in primiparous women suggests a careful review of its indications, mainly the cephalopelvic disproportion diagnosis.

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial.

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

[Anthropometric parameters as predictors of insulin resistance in overweight and obese adults]. / Parámetros antropométricos como predictores de resistencia a la insulina en adultos con sobrepeso y obesidad.

OBJECTIVE: To evaluate which of the anthropometric parameters that estimate overweight and obesity are the best predictors of insulin resistance (IR) in adults from Family Medicine Unit N degrees 80 of IMSS in Morelia, Michoacán, México. DESIGN: Descriptive cross-sectional study. SETTING: Family Medicine Unit N 80 of Mexican Social Security Institute in Morelia, Michoacán, Mexico. PARTICIPANTS: A random sample of 147 adults with overweight or obesity. MAIN MEASUREMENTS: Age and sex. Anthropometrics: weight, body mass index (BMI), waist and mid arm circumference, % corporal fat; Skin folds thickness: bicipital, tricipital, subscapularis, abdominal skin folds; analyses: glucose, lipid profile, insulin; clinical: diastolic and systolic pressure, cardiovascular risk and insulin resistance by HOMA > or =2.5. RESULTS: IR was found in 41.49% of patients. ROC curves were made and the cut off point of bicipital skin fold > or =4.50mm, mid arm > or =27.50 cm were predictors of IR in 97.4%; BMI > or =25kg/m(2) was a predictor of IR in 92.3%, and by linear regression these parameters were the better predictors of IR. CONCLUSIONS: A total of 41.49% of patients were identified with IR (HOMA > or =2.5). BMI, bicipital skins fold and mid arm were the better predictors of IR. Specific studies are needed to determine the optimum cut off point of different parameters for estimating overweight and obesity in each sector in México.

Paediatric Metabolic Bone Disease: A Lifetime Ahead.

Beyond its functions in locomotion, support and protection of vital organs, bone also interacts with other organs to adjust mineral balance in response to physiological requirements. Bone remodelling is a continuous process of bone resorption and formation for the purpose of maintaining healthy bone mass and growth. Any derangement in this process can cause bone disorders with important clinical consequences. The most prominent features of bone diseases in children include early bone fractures, deformities and pain, which can persist and worsen later in life if an accurate and timely diagnosis is not achieved. Biochemical and genetic testing usually help to discriminate the aetiology of the disease, which determines the subsequent management and follow-up. This review focuses on major genetic metabolic bone diseases in children, their pathophysiological mechanisms, the potential therapeutic interventions and the possible consequences in adulthood of the disease and its treatments.

Educational strategy based on the NutrIMSS program in patients with prediabetes. / Estrategia educativa basada en el programa NutrIMSS en pacientes con prediabetes.

BACKGROUND: Prediabetes is an altered metabolic state of glucose; it does not present symptoms, it is considered an intermediate stage in the progression to diabetes; it is possible to detect it early to avoid or delay the disease. NutrIMSS strategy was implemented so that these patients achieve a healthy lifestyle. OBJECTIVE: To evaluate the impact of an educational intervention based on the NutrIMSS strategy on somatometric and biochemical parameters in patients with prediabetes. METHOD: Quasi-experimental study in the Family Medicine Unit No. 80 of Morelia, Michoacán, Mexico, in patients 20 to 59 years of age, with diagnosis of prediabetes (impaired fasting glucose 100-125 mg/dL). The educational intervention included three educational sessions, six consultations with nutrition and inclusion to the social security center, from March to August 2017. Initial anthropometric and biochemical measurements were taken and in the sixth month. The data were presented as median and interquartile range or mean ± standard deviation, and Student's t and Wilcoxon tests, with a significance value of p < 0.05. RESULTS: 45 patients, 66.7% women. Previous and after the intervention parameters were, respectively: weight (kg), 79.9 (56.5-114) and 77.5 (54.6-110) (p = 0.001); body mass index (kg/m2), 30.89 (23.2-39.9) and 29.0 (21.5-39.1) (p < 0.001); glucose (mg/dL), 111 ± 6.3 and 95.8 ± 9.2 (p < 0.001); and total cholesterol (mg/dL): 171 (120-223) and 170 (90-205) (p = 0.01). CONCLUSIONS: The educational intervention based on the NutrIMSS strategy has a positive impact on the metabolic control of patients with prediabetes.

INTRODUCCIÓN: La prediabetes es un estado metabólico alterado de la glucosa, no presenta síntomas, se considera un estadio intermedio en la progresión a diabetes y es posible detectarla tempranamente para evitar o retrasar la enfermedad. La estrategia NutrIMSS se implementó para que estos pacientes alcancen un estilo de vida saludable. OBJETIVO: Evaluar el impacto de una intervención educativa basada en la estrategia NutrIMSS sobre parámetros somatométricos y bioquímicos en pacientes con prediabetes. MÉTODO: Estudio cuasiexperimental en la Unidad de Medicina Familiar No. 80 de Morelia, Michoacán, en el que participaron pacientes de 20-59 años, con diagnóstico de prediabetes (glucosa alterada de ayuno 100-125 mg/dl). La intervención educativa incluyó tres sesiones educativas, seis consultas con nutrición e inclusión al centro de seguridad social de marzo a agosto de 2017. Se realizaron mediciones antropométricas y bioquímicas iniciales y al sexto mes. Los datos se presentaron como mediana (con rangos intercuartílicos) o media ± desviación estándar, pruebas de Wilcoxon y t de Student, con una significación de p < 0.05. RESULTADOS: Fueron 45 pacientes, con un 66.7% de mujeres. Los parámetros previos y posteriores a la intervención fueron los siguientes, respectivamente: peso (kg), 79.9 (56.5-114) y 77.5 (54.6-110) (p = 0.001); índice de masa corporal (kg/m2), 30.89 (23.2-39.9) y 29.0 (21.5-39.1) (p < 0.001); glucosa (mg/dl), 111 ± 6.3 y 95.8 ± 9.2 (p < 0.001); y colesterol total (mg/dl), 171 (120-223) y 170 (90-205) (p = 0.01). CONCLUSIONES: La intervención educativa basada en la estrategia NutrIMSS impacta de manera positiva en el control metabólico de los pacientes con prediabetes.

Vascular calcifications, vertebral fractures and mortality in haemodialysis patients.

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.

The next step after anti-osteoporotic drug discontinuation: an up-to-date review of sequential treatment.

Several antiresorptive drugs, like bisphosphonates and denosumab, are currently available for the treatment of osteoporosis due to their evidenced efficacy in reducing fracture risk at mid-term. Osteoanabolic therapies, like teriparatide, whose treatment duration is limited to 2 years, have also shown efficacy in the reduction of fracture risk. However, depending on the severity of osteoporosis and the presence of other associated risk factors for fracture, some patients may require long-term treatment to preserve optimal bone strength and minimize bone fracture risk. Given the limited duration of some treatments, the fact that most of the antiresorptive drugs have not been assessed beyond 10 years, and the known long-term safety issues of these drugs, including atypical femoral fractures or osteonecrosis of the jaw, the long-term management of these patients may require an approach based on drug discontinuation and/or switching. In this regard, interest in sequential osteoporosis therapy, wherein drugs are initiated and discontinued over time, has grown in recent years, although the establishment of an optimal and individualized order of therapies remains controversial. This review reports the currently available clinical evidence on the discontinuation effects of different anti-osteoporotic drugs, as well as the clinical outcomes of the different sequential treatment regimens. The objective of this article is to present up-to-date practical knowledge on this area in order to provide guidance to the clinicians involved in the management of patients with osteoporosis.

Tissue-specific effect of VDR gene polymorphisms on the response to calcitriol.

In the last decade, the likely role of vitamin D receptor (VDR) polymorphisms in different diseases has been extensively discussed. In this paper we review several studies carried out in this field to investigate the possible influence of VDR polymorphisms on different aspects of bone and parathyroid gland metabolism. On one hand, most of the epidemiological studies showed that the BAt haplotype, from BsmI, ApaI and TaqI polymorphisms in VDR, is associated with a lower bone mineral density (BMD) in women and a higher risk of osteoporotic fractures. On the other hand, experimental studies carried out in both human primary osteoblasts and human parathyroid glands showed that while in osteoblasts the BAt haplotype showed a worse response to calcitriol, in parathyroid glands the results were the opposite, and BAt was the haplotype associated with better responses. Overall, the results reinforce the suggestion that VDR polymorphisms play an important role in bone and parathyroid gland behavior, leading to different response patterns due to a likely tissue-specific effect of the VDR response to calcitriol.