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      Efecto de la suplementación con vitamina D en los efectos secundarios musculoesqueléticos relacionados con los inhibidores de la aromatasa para el cáncer de mama: cohorte B-ABLE Translated title: Effect of vitamin D supplementation on aromatase inhibitor-related musculoskeletal side effects for breast cancer: B-ABLE cohort

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          Abstract

          Resumen Objetivo Evaluar el efecto de la suplementación con vitamina D en las complicaciones musculoesqueléticas relacionadas con el tratamiento con inhibidores de la aromatasa (IA) en pacientes con cáncer de mama. Material y métodos Estudio observacional prospectivo de mujeres en tratamiento con IA, reclutadas en la cohorte B-ABLE. Las pacientes con niveles séricos iniciales de 25(OH)D (25-hidroxivitamina D) <30 ng/ml recibieron una dosis de 16.000 UI de calcifediol oral cada 2 semanas. La artralgia y la pérdida ósea relacionadas con los IA se evaluaron a los 3 meses y al año de seguimiento, respectivamente. Los análisis de asociación del status de vitamina D a los 3 meses con eventos musculoesqueléticos se realizaron mediante modelos de regresión lineal multivariante ajustados. Además, se evaluó la asociación del dolor incidente, definido como pacientes sin dolor articular inicial, pero con una escala visual analógica (EVA) >0 a los 3 meses, mediante regresión logística. Resultados La suplementación con vitamina D al inicio del tratamiento con IA disminuyó el riesgo tanto de artralgia incidente como de su empeoramiento. El umbral efectivo de 25(OH)D en suero para reducir el dolor articular se estableció en 40 ng/ml. Sin embargo, este umbral no se relacionó significativamente con los cambios óseos al año de seguimiento. No obstante, los niveles de vitamina D se correlacionaron inversamente con la pérdida ósea de la columna lumbar (CL) (β=0,177% [IC 95%: 0,014 a 0,340]). Conclusiones La administración de suplementos de vitamina D con el objetivo de alcanzar niveles séricos de 25OHD de al menos 40 ng/ml es protectora para la artralgia. Los niveles de vitamina D a los tres meses podrían predecir el riesgo de pérdida ósea en CL al año de tratamiento con IA. Por lo tanto, se recomiendan dosis altas de vitamina D en estas pacientes, que son más propensas a sufrir afecciones musculoesqueléticas.

          Translated abstract

          Summary Objetive To assess the effect of vitamin D supplementation on musculoskeletal complications related to aromatase inhibitor (AI) treatment in patients with breast cancer. Material and methods Prospective observational study of women undergoing AI treatment, recruited in the B-ABLE cohort. Patients with baseline serum 25 (OH) D (25-hydroxyvitamin D) levels <30 ng/ml received a 16,000 IU dose of oral calcifediol every 2 weeks. Arthralgia and bone loss related to AIs were assessed at 3 months and 1 year of followup, respectively. The association analyzes of vitamin D status at 3 months with musculoskeletal events were carried out using adjusted multivariate linear regression models. In addition, the association of incident pain, defined as patients without initial joint pain, but with a visual analog scale (VAS) >0 at 3 months, was evaluated using logistic regression. Results Vitamin D supplementation at the start of AI treatment decreased the risk of both incident arthralgia and its worsening. The effective threshold of 25 (OH) D in serum to reduce joint pain was established at 40 ng/ml. However, this threshold was not significantly related to bone changes at one year of follow-up. However, vitamin D levels were inversely correlated with lumbar spine bone loss (LS) (β=0.177% [95% CI: 0.014 to 0.340]). Conclusions Vitamin D supplementation aimed at achieving serum 25(OH)D levels of at least 40 ng/ml is protective for arthralgia. Vitamin D levels at three months could predict the risk of bone loss in LS at one year of AI treatment. Therefore, high doses of vitamin D are recommended in these patients, who are more prone to musculoskeletal conditions.

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          Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer.

          Aromatase inhibitors (AIs) improve survival in postmenopausal women with hormone-sensitive breast cancer, but can cause joint pain and stiffness. The purpose of the current study was to evaluate the prevalence of and identify risk factors for AI-related joint symptoms. We performed a cross-sectional survey of consecutive postmenopausal women receiving adjuvant AI therapy for early-stage hormone-sensitive breast cancer at an urban academic breast oncology clinic. Patients completed a 25-item self-administered questionnaire assessing the presence of joint symptoms that started or worsened after initiating AIs. Multivariate regression was used to compare those with AI-related arthralgia with those who did not report symptoms, adjusting for demographic and clinical factors. Of 200 patients who completed the survey, 94 (47%) reported having AI-related joint pain and 88 (44%) reported AI-related joint stiffness. In multiple logistic regression analysis, being overweight (body mass index of 25 to 30 kg/m(2)) and prior tamoxifen therapy were inversely associated with AI-related joint symptoms. Patients who received taxane chemotherapy were more than four times more likely than other patients to have AI-related joint pain and stiffness (odds ratio [OR] = 4.08, 95% CI, 1.58 to 10.57 and OR = 4.76; 95% CI, 1.84 to 12.28, respectively). Our study suggests that AI-related joint symptoms are more prevalent than what has been described previously in clinical trials. The success of AI therapy depends on patients' ability to adhere to treatment recommendations; therefore, additional studies of interventions that may alleviate these symptoms are needed.
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            Optimal vitamin D status: a critical analysis on the basis of evidence-based medicine.

            Public health authorities around the world recommend widely variable supplementation strategies for adults, whereas several professional organizations, including The Endocrine Society, recommend higher supplementation. We analyzed published randomized controlled clinical trials to define the optimal intake or vitamin D status for bone and extraskeletal health. The extraskeletal effects of vitamin D are plausible as based on preclinical data and observational studies. However, apart from the beneficial effects of 800 IU/d of vitamin D3 for reduction of falls in the elderly, causality remains yet unproven in randomized controlled trials (RCTs). The greatest risk for cancer, infections, cardiovascular and metabolic diseases is associated with 25-hydroxyvitamin D (25OHD) levels below 20 ng/mL. There is ample evidence from RCTs that calcium and bone homeostasis, estimated from serum 1,25-dihydroxyvitamin D and PTH, calcium absorption, or bone mass, can be normalized by 25OHD levels above 20 ng/mL. Moreover, vitamin D supplementation (800 IU/d) in combination with calcium can reduce fracture incidence by about 20%. Such a dose will bring serum levels of 25OHD above 20 ng/mL in nearly all postmenopausal women. Based on calculations of the metabolic clearance of 25OHD, a daily intake of 500-700 IU of vitamin D3 is sufficient to maintain serum 25OHD levels of 20 ng/mL. Therefore, the recommendations for a daily intake of 1500-2000 IU/d or serum 25OHD levels of 30 ng or higher for all adults or elderly subjects, as suggested by The Endocrine Society Task Force, are premature. Fortunately, ongoing RCTs will help to guide us to solve this important public health question.
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              Consensus statement from 2 nd International Conference on Controversies in Vitamin D

              The 2nd International Conference on Controversies in Vitamin D was held in Monteriggioni (Siena), Italy, September 11-14, 2018. The aim of this meeting was to address ongoing controversies and timely topics in vitamin D research, to review available data related to these topics and controversies, to promote discussion to help resolve lingering issues and ultimately to suggest a research agenda to clarify areas of uncertainty. Several issues from the first conference, held in 2017, were revisited, such as assays used to determine serum 25-hydroxyvitamin D [25(OH)D] concentration, which remains a critical and controversial issue for defining vitamin D status. Definitions of vitamin D nutritional status (i.e. sufficiency, insufficiency and deficiency) were also revisited. New areas were reviewed, including vitamin D threshold values and how they should be defined in the context of specific diseases, sources of vitamin D and risk factors associated with vitamin D deficiency. Non-skeletal aspects related to vitamin D were also discussed, including the reproductive system, neurology, chronic kidney disease and falls. The therapeutic role of vitamin D and findings from recent clinical trials were also addressed. The topics were considered by 3 focus groups and divided into three main areas: 1) “Laboratory”: assays and threshold values to define vitamin D status; 2) “Clinical”: sources of vitamin D and risk factors and role of vitamin D in non-skeletal disease and 3) “Therapeutics”: controversial issues on observational studies and recent randomized controlled trials. In this report, we present a summary of our findings.
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                Author and article information

                Journal
                romm
                Revista de Osteoporosis y Metabolismo Mineral
                Rev Osteoporos Metab Miner
                Sociedad Española de Investigaciones Óseas y Metabolismo Mineral (Madrid, Madrid, Spain )
                1889-836X
                2173-2345
                June 2021
                : 13
                : 2
                : 66-71
                Affiliations
                [02] Barcelona orgnameInstituto Hospital del Mar de Investigaciones Médicas orgdiv1Programa de Investigación en Cáncer España
                [04] Barcelona Cataluña orgnameUniversitat Autónoma de Barcelona orgdiv1Hospital del Mar orgdiv2Departamento de Medicina Interna Spain
                [01] Barcelona orgnameInstituto Hospital del Mar de Investigaciones Médicas orgdiv1Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable España
                [03] Guipúzcoa orgnameHospital Alto Deba orgdiv1Departamento de Traumatología y Cirugía Ortopédica España
                Article
                S1889-836X2021000200004 S1889-836X(21)01300200004
                10.4321/s1889-836x2021000200004
                ac679034-fa75-40e4-bd69-d8948b323159

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 22 May 2021
                : 01 April 2021
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 23, Pages: 6
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                SciELO Spain

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                arthralgia,inhibidores de la aromatasa,vitamina D,cáncer de mama,pérdida ósea,artralgia,propensity score matching,densidad ósea,aromatase inhibitors,vitamin D,osteoporosis,breast cancer,bone loss

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