Manejo de la osteoporosis en el paciente con enfermedad renal crónica (Estudio ERCOS): un desafío en la asistencia nefrológica / Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care

La valoración del riesgo de fractura del paciente con enfermedad renal crónica (ERC) ha sido incluida en el complejo Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD) en guías nefrológicas internacionales y nacionales, sugiriéndose por primera vez la evaluación de la densidad mineral ósea (DMO) si los resultados pueden condicionar la toma de decisiones terapéuticas. Sin embargo, existe muy poca información en práctica clínica real en esta población. El objetivo principal del estudio ERC-Osteoporosis (ERCOS) es describir el perfil de los pacientes con ERC G3-5D con osteoporosis (OP) y/o fracturas por fragilidad atendidos en consultas especializadas de nefrología, reumatología y medicina interna en España. Participaron 15 centros y se incluyeron 162 pacientes (siendo en su mayoría mujeres [71,2%] posmenopáusicas [98,3%]) con una mediana de edad de 77 años. La mediana del filtrado glomerular estimado (FGe) fue de 36ml/min/1,73m2 y el 38% de pacientes incluidos estaban en diálisis. Destacamos la elevada frecuencia de fracturas por fragilidad prevalentes ([37,7%), principalmente vertebrales [52,5%] y de cadera 24,6%]), el antecedente desproporcionado de pacientes con enfermedad glomerular en comparación con series puramente nefrológicas (corticoides) y el infratratamiento para la prevención de fracturas, fundamentalmente en consultas nefrológicas. Este estudio supone una inmediata llamada a la acción con la difusión de las nuevas guías clínicas, más proactivas, y subraya la necesidad de homogeneizar el enfoque asistencial/terapéutico multidisciplinar coordinado de estos pacientes de un modo eficiente para evitar las actuales discrepancias y el nihilismo terapéutico. (AU)

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD) complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results will impact treatment decisions. However, there is very little information on actual clinical practice in this population. The main objective of the ERC-Osteoporosis (ERCOS) 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 36ml/min/1.73m2 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 efficient multidisciplinary care/therapeutic approach to these patients to avoid current discrepancies and therapeutic nihilism. (AU)

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.

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.

Asociación de la gamma glutamil transferasa con la presencia y progresión de calcificaciones aórticas abdominales y con cambios en densidad mineral ósea / Association of gamma glutamyl transferase in the presence and progression of abdominal aortic calcifications and changes to bone mineral density

Introducción y objetivo: la calcificación aórtica abdominal (CAA) es predictora de eventos cardiovasculares. El objetivo de este trabajo fue valorar la asociación de la gamma glutamil transferasa (GGT) con presencia y progresión de CAA y los cambios en densidad mineral ósea (DMO) en columna lumbar y cuello femoral. Material y métodos: se seleccionaron 326 hombres y mujeres mayores de 50 años que realizaron un cuestionario, dos radiografías laterales dorso-lumbares y DMO, repitiendo a los 4 años las mismas pruebas y un estudio analítico. Resultados: la presencia y progresión de CAA (nuevas o mayor severidad) fue inferior en el cuartil 1 (Q1) de GGT respecto a los otros cuartiles (40 % vs. 58 %, p = 0,021; 24 % vs. 44 %, p = 0,022). Comparado con Q1, el análisis de regresión logística ajustado por confusores mostró que los Q2 y Q4 se asociaron con aumentos en la presencia de CAA [odds ratio (OR) = 2,53, intervalo de confianza del 95 % (IC 96 %) = (1,22-5,25) y OR = 3,04, IC 95 % = (1,36-6,77)] y Q2, Q3 y Q4 se asociaron con aumentos en progresión de CAA [OR = 2,24, IC 95 % = (1,07-4,67); OR = 2,35, IC 95 % = (1,09-5,07) y OR = 3,47, IC 95 % = (1,56-7,70)]. El análisis multivariante por sexos mostró que tanto en hombres como mujeres el Q4 de GGT se asoció con progresión de CAA [OR = 3,27, IC 95 % = (1,14-9,36) y OR = 3,26, IC 95 % = (1,03-10,29) respectivamente] y en mujeres con mayores pérdidas de DMO a nivel lumbar. No hubo efecto con respecto a la prevalencia de CAA. Conclusiones: valores elevados de GGT podrían ser un indicador de presencia y progresión de CAA en población mayor de 50 años. De forma separada por sexo, los mayores niveles de GGT se asociaron con progresión de CAA, siendo un marcador pronóstico de daño cardiovascular.(AU)

Introduction and objective: abdominal aortic calcification (AAC) is a predictor of cardiovascular events. This study aimedto assess the association of gamma glutamyl transferase (GGT) in the presence and progression of AAC, as well as changesto bone mineral density (BMD) in the lumbar spine and femoral neck.Materials and methods: a total of 326 men and women over 50 years of age were selected for this study. They completeda questionnaire, underwent two lateral dorso-lumbar spine X-rays, and BMD measurements. The same tests and 1 analyticalassessment were repeated after 4 years.Results: the presence and progression of AAC (new occurrences or increased severity) were lower in GGT quartile 1 (Q1)compared with the other quartiles (40 % vs 58 %; p = 0.021; 24 % vs 44 %; p = 0.022). Compared with Q1, the confound -ers-adjusted logistic regression analysis showed that Q2 and Q4 were associated with more presence of AAC [odds ratio(OR), 2.53; 95 % confidence interval (95 % CI), 1.22-5.25 and OR, 3.04; 95 % CI, 1.36-6.77]. Additionally, Q2, Q3, and Q4were associated with more AAC progression [OR, 2.24; 95 % CI, 1.07-4.67; OR, 2.35; 95 % CI, 1.09-5.07; and OR, 3.47;95 % CI, 1.56-7.70]. The gender-stratified multivariate analysis revealed that in both men and women, the Q4 of GGT wasassociated with AAC progression [OR, 3.27; 95 % CI, 1.14-9.36, and OR, 3.26; 95 % CI, 1.03-10.29, respectively], and inwomen alone, with greater lumbar BMD losses. There were no effects regarding the prevalence of AAC.Conclusions: elevated GGT levels could serve as an indicator of the presence and progression of AAC in individuals olderthan 50 years. When analyzed separately by gender, higher GGT levels were associated with AAC progression, which actedas a prognostic marker for cardiovascular disease.(AU)

¿Debería la herramienta FRAX tener en cuenta otras variables para evaluar la fractura osteoporótica por fragilidad? / Should the FRAX tool include other variables to assess fragility-related osteoporotic fractures?

Introducción y objetivo: el objetivo fue valorar la relevancia de variables no contenidas en el FRAX sobre la incidencia de fractura osteoporótica. Material y métodos: participaron 316 mujeres > 50 años seguidas 8 años. Se evaluaron variables que recoge FRAX (edad, IMC, fractura previa, antecedentes parentales de fractura de cadera, hábito tabáquico, glucocorticoides, DMO cuello femoral) y que no recoge (edad de menarquia, menopausia, años fértiles y nuliparidad). Resultados: edad y antecedentes parentales de fractura de cadera se asociaron con fractura de cadera, pero también edad de menopausia y años fértiles. La edad [odds ratio (OR) = 1,09, Intervalo de confianza del 95 % (IC 95 %) = (1,01-1,17)] y edad de menopausia [OR = 0,90, IC 95 % = (0,82-0,99)] se asociaron con fractura de cadera tras análisis multivariante ajustado por edad e IMC. IMC, DMO en cuello femoral y nuliparidad se asociaron con fractura de Colles. En el análisis multivariante, solo nuliparidad se asoció con fractura de Colles [OR = 4,59, IC 95 % = (1,59-13,26)]. La fractura mayor osteoporótica se asoció significativamente con antecedentes parentales de fractura de cadera, nuliparidad y años fértiles. En el análisis multivariante, antecedentes parentales de fractura de cadera [OR = 3,26, IC 95 % = (1,23-8,61)], nuliparidad [OR = 3,07; IC 95 % = (1,48-6,37)] y años fértiles [OR = 0,92, IC 95 % = (0,87-0,98)] se asociaron con fractura mayor osteoporótica. Conclusiones: de las variables del FRAX, edad y antecedentes parentales de fractura de cadera se asociaron con incidencia de fractura mayor osteoporótica y de cadera, pero otras variables ginecológicas tuvieron un peso similar, lo que sugiere que deben ser tenidas muy en cuenta a la hora de realizar la anamnesis de las pacientes.(AU)

Introduction and objective: the objective of this study was to assess the significance of variables not included in the FRAXtool regarding the incidence of osteoporotic fractures.Materials and methods: a total of 316 women older than 50 years were followed for 8 years. The variables collected (age,BMI, previous fracture, parental history of hip fracture, smoking habit, use of glucocorticoids, femoral neck BMD) and thosenot collected by the FRAX tool (age at menarche, menopause, fertile years, nulliparity) were studied.Results: age and parental history of hip fracture were associated with hip fractures, but so were age at menopause andfertile years. Age [odds ratio (OR), 1.09; 95 % confidence interval (CI), 1.01-1.17] and age at menopause [OR, 0.90; 95 %CI,0.82-0.99] were associated with hip fractures after the multivariate analysis adjusted for age and BMI. BMI, femoral neckBMD and nulliparity were associated with the occurrence of Colles fractures. According to the multivariate analysis, onlynulliparity was associated with Colles fractures [OR, 4.59; 95 %CI, 1.59-13.26)]. Major osteoporotic fractures were signifi-cantly associated with parental history of hip fracture, nulliparity, and fertile years. According to the multivariate analysis,the parental history of hip fracture [OR, 3.26; 95 %CI, 1.23-8.61], nulliparity [OR, 3.07; 95 %CI, 1.48-6.37], and fertile years[OR, 0.92; 95 %CI, 0.87-0.98] were associated with the occurrence of major osteoporotic fractures.Conclusions: among the FRAX variables, age and parental history of hip fracture were associated with the incidence ofmajor osteoporotic and hip fractures. However, the significance of other gynecological variables was similar, which is indic-ative that they should certainlay be taken into consideration during patient history assessment.(AU)

Las células senescentes como factores patogénicos y posibles dianas terapéuticas en osteoporosis / Cellular senescence as a pathogenic factor and potential therapeutic target in osteoporosis

La senescencia celular es un proceso inducido por varios tipos de estrés que causan una detención irreversible del ciclo celular y un cambio en las características y la funcionalidad de las células, además de la adquisición de un fenotipo secretor que genera un ambiente proinflamatorio. Si bien en determinados contextos es beneficiosa para los tejidos y promueve el desarrollo del organismo, la senescencia es un destino celular implicado en el proceso de envejecimiento y en las patologías degenerativas relacionadas con la edad. Los senolíticos son fármacos que eliminan específicamente a las células senescentes y los senomórficos son fármacos que suprimen su fenotipo secretor asociado a senescencia (SASP) sin inducir la muerte celular. Así, las estrategias terapéuticas enfocadas en las células senescentes (senolíticos y senomórficos) como mecanismo subyacente al envejecimiento, se erigen en una alternativa con gran potencial para luchar contra las enfermedades relacionadas con la edad en su conjunto, y no de forma individual. Una de estas patologías es la osteoporosis, donde además se han descrito, a nivel experimental, que fármacos como el ácido zoledrónico tiene efecto sobre los preosteoblastos y actúa sobre las células senescentes, prolongando la supervivencia y abriendo la puerta a la posibilidad de tratar las enfermedades relacionadas con la edad con fármacos que ya se empleen en la práctica, y que puedan tener un efecto más allá del propio hueso y aumentar la supervivencia. En este trabajo se va a realizar una revisión en este campo de vertiginoso crecimiento en los últimos años y con indudable interés traslacional.(AU)

Cellular senescence is a process induced by various types of stress that irreversibly cause cell cycle arrest and changes tothe characteristics and functionality of cells, as well as the acquisition of a secretory phenotype that generates a pro-in-flammatory environment. While, in certain contexts, it is beneficial for tissues and promotes organism development, senes-cence is a cellular fate implicated in the process of aging and age-related degenerative conditions. Senolytics are drugs thatspecifically eliminate senescent cells, and senomorphics are drugs that suppress their senescence-associated secretoryphenotype (SASP) without inducing cell death. Therefore, therapeutic strategies targeting senescent cells (senolytics andsenomorphics) as an underlying mechanism of aging emerge as an alternative with great potential to fight age-relateddiseases as a whole rather than individually. One of these conditions is osteoporosis where it has been experimentallydescribed that drugs such as zoledronic acid have effects on preosteoblasts and act on senescent cells extending survivaland opening up the possibility of treating age-related diseases with drugs already used in practice, which may have effectsbeyond the bone itself and increase overall survival. In this study, a review will be conducted in this rapidly growing fieldin recent years of undeniable translational interest.(AU)

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).

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 ).

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.

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).

Evaluación del desarrollo infantil en niños de 2 a 4 años en el primer nivel de atención / Evaluation of child development in children from 2 to 4 years old in the first level of care

Introducción: actualmente es posible evaluar el desarrollo infantil y, con ello, proporcionar señales de las posibles alteraciones que pueden existir en los niños menores de 5 años. Objetivo: evaluar el desarrollo infantil e identificar las áreas del desarrollo afectadas en los niños de 2 a 4 años en el primer nivel de atención. Metodología: estudio transversal descriptivo en 69 niños de ambos sexos de 2 a 4 años y 11 meses de edad, a quienes se les aplicó en el consultorio la prueba Evaluación del Desarrollo Infantil. Los datos se expresaron como media ± desviación estándar, porcentajes y prueba de ji al cuadrado, considerando como significancia estadística p < 0.05. Resultados: se incluyeron 44 (63.7%) niños y 25 (36.3%) niñas, con una edad media de 2.57 ± 0.63. El desarrollo infantil fue normal en 49 niños (71%), se observó rezago en el desarrollo en 9 niños (13%) y riesgo de retraso en 11 niños (16%). Las áreas que más afectaron el resultado global fueron motor grueso (p = 0.001), motor fino (p = 0.00) y lenguaje (p = 0.00). Conclusiones: es importante evaluar el desarrollo infantil en los niños menores de 5 años, ya que el riesgo de retraso en el desarrollo se sigue detectando en una proporción considerable, lo que a futuro puede aumentar el costo de su atención.

Introduction: Currently it is possible to evaluate child development and with it, provide signs of the possible alterations that may exist in children under 5 years of age. Objective: To evaluate child development and identify affected areas of development in children from 2 to 4 years of age who attended UMF. Method: Descriptive study, we included 69 patients, both sexes from 2 to 4 years 11 months of age who agreed to participate. The Child Development Assessment test was used. The data were expressed + SD, and percentages, Chi square, significance p < 0.05. Results: 44 (63.7%) men and 25 (36.2%) women were included, mean age 2.57 + 0.63; child development was normal in 49 children (71%), developmental delay in 9 children (13%) and risk of delay in 11 children (16%); The areas that most affected the overall result were: gross motor (p = 0.001), fine motor (p = 0.00) and language (p = 0.00). Conclusions: It is important to carry out the Evaluation of Child Development in children under 5 years of age, since the risk of delay in development continues to be detected in a considerable proportion, which in the future may increase the cost of their care.

Evaluación del desarrollo infantil en niños menores de 1 año en una unidad médica / Evaluation of child development in children under 1 year in a medical unita

Introducción: el desarrollo psicomotor es un fenómeno de adquisición continua y progresiva de habilidades a lo largo de la infancia, afectado por la herencia genética y factores psicosociales y biológicos. Objetivo: evaluar el desarrollo infantil en niños menores de 1 año mediante la prueba Evaluación del Desarrollo Infantil en una unidad de medicina familiar. Metodología: estudio descriptivo con 62 niños menores de 1 año, en el módulo de PREVENIMSS, de octubre de 2018 a octubre de 2019. Se realizó un muestreo no probabilístico. Para el análisis de los datos se utilizó estadística descriptiva (media, desviación estándar, frecuencias y porcentajes); el análisis inferencial se realizó mediante la prueba de ji al cuadrado, considerando como significancia estadística p < 0.05. Resultados: el 42% (26) fueron niños y el 58% (36) niñas. En el resultado global, el 68% (42) obtuvieron desarrollo normal, el 29% (18) rezago en el desarrollo y el 3% (2) riesgo de retraso en el desarrollo. Las áreas del desarrollo afectadas fueron motricidad fina y lenguaje. Conclusiones: es necesario implementar estrategias institucionales para que se cumplan las políticas públicas de la primera infancia y que todos los niños derechohabientes del Instituto Mexicano del Seguro Social cuenten con evaluaciones periódicas de su desarrollo.

Introduction: Psychomotor development is a phenomenon of continuous and progressive acquirement of skills throughout childhood, affected by genetic inheritance and psychosocial and biological factors. Objective: To evaluate child development to children under 1 year old, through the Child Development Assessment test in a family medicine unit. Methods: Descriptive study in 62 children under 1 year of age, in the PREVENIMSS module, from October 2018 to October 2019. A non-probability sampling was carried out. Descriptive statistics (mean, standard deviation, frequencies and percentages) were used for data analysis, inferential analysis was performed using Chi Square, statistical significance of p < 0.05. Results: 42% (26) were men and 58% (36) women. In the overall result: 68% (42) obtained normal development, 29% (18) lag in development and 3% (2) risk of delay in development. The developmental areas affected were fine motor skills and language. Conclusions: It is necessary to implement institutional strategies so that early childhood public policies are complied with and that all IMSS eligible children have periodic evaluations of their development.