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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) 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.

Objetivo: Evaluar la persistencia a la terapia con inhibidores de la aromatasa (IA), la mortalidad asociada a la discontinuidad al tratamiento y la influencia de los bifosfonatos (BF) orales, en la práctica clínica habitual. Material y métodos: Estudio prospectivo observacional de mujeres con cáncer de mama en tratamiento con IA entre enero de 2006 y diciembre de 2015, registradas en la base de datos SIDIAP. Se excluyeron aquellas tratadas previamente con tamoxifeno. Se estudió la persistencia al tratamiento con IA con un análisis de supervivencia: se calculó el estimador de Kaplan-Meier, y se realizó un modelo de los riesgos proporcionales (regresión de Cox) entre usuarias y no usuarias de BF ajustando por edad. Se llevó a cabo un análisis de sensibilidad teniendo en cuenta la mortalidad como riesgo competitivo (modelos de Fine y Gray). Se comparó la diferencia de mortalidad entre grupos mediante una prueba Chi cuadrado. Resultados: Se observó una persistencia a los IA del 87% a 5 años de tratamiento, con una mortalidad global del 19,75%. Se registró un 7,7% menos de mortalidad en aquellas pacientes que completaron los 5 años de tratamiento respecto a las que no. Las pacientes con BF mostraron una disminución de la mortalidad (6,6%) y una disminución del riesgo de abandono de la terapia (SHR ajustado: 0,62 [IC 95%: 0,55 a 0,70]) respecto a las no usuarias. Conclusiones: La permanencia a los IA y el uso de BF está asociada a una disminución de la mortalidad global. Además, el uso de BF resulta en un aumento de la adherencia al tratamiento con IA.

Objetivo: Los inhibidores de la aromatasa (IA) se han asociado con una pérdida de masa ósea acelerada y un mayor riesgo de fracturas osteoporóticas. Con este trabajo se pretendió evaluar los factores de riesgo de fractura incidente en pacientes con cáncer de mama que reciben IA. Material y métodos: Estudio prospectivo-observacional de cohorte de mujeres con cáncer de mama que inician tratamiento con IA (cohorte B-ABLE). Las pacientes realizaron tratamiento durante 5 años o bien 2 ó 3 años si habían recibido previamente tamoxifeno. Se les evaluó la salud ósea desde el inicio del tratamiento hasta un año después de finalizar dicho tratamiento mediante densitometría ósea, marcadores de remodelado óseo, niveles de vitamina D y una radiografía antero-posterior y otra lateral de columna. Se realizó el cálculo de riesgo de fractura mediante la herramienta FRAX® antes de iniciar IA. Se utilizaron modelos de Cox para calcular los ratios de riesgo (HR [IC 95%]) de fractura. Resultados: Un total de 943 pacientes fueron incluidas en el estudio. El 5,4% sufrieron una fractura incidente, la mayoría durante el tratamiento con IA, aunque un 21,5% ocurrieron durante el primer año después de finalizar la terapia. La mayoría de las fracturas incidentes fueron vertebrales clínicas (29,4%) y de Colles (31,4%). El 86,3% de las pacientes tenían un diagnóstico de osteopenia u osteoporosis en el momento de la fractura y el 33% tenían los niveles de β-CTX (isómero β del telopéptido carboxiterminal del colágeno tipo I) por encima de la normalidad. Las pacientes diagnosticadas de osteoporosis o con riesgo de fractura al inicio del estudio fueron tratadas con antirresortivos óseos. No se encontraron diferencias significativas en el riesgo de fractura entre pacientes con y sin tratamiento antirresortivo: HR=1,75 [IC 95%: 0,88 a 3,46]. Tampoco se encontraron diferencias entre las pacientes que habían hecho tratamiento previo con tamoxifeno respecto a las que no (HR=1,00 [IC 95%: 0,39 a 2,56]). La herramienta FRAX® dio valores de media dentro del rango de riesgo intermedio, con 13 pacientes con valores de alto riesgo de fractura principal. Conclusiones: El principal factor de riesgo detectado para fractura incidente en pacientes tratadas con IA es el diagnóstico de osteopenia u osteoporosis. El cálculo de la herramienta FRAX® y la determinación de los niveles de β-CTX son herramientas útiles para identificar a pacientes de alto riesgo.

Objetivos: Los inhibidores de la aromatasa (AI) son terapias endocrinas adyuvantes eficaces para pacientes con cáncer de mama, aunque se han asociado a un mayor riesgo de fractura osteoporótica. Previamente se ha demostrado una pérdida en el Trabecular Bone Score (TBS) que puede variar entre las pacientes tratadas con IA. El estudio pretendió identificar la base genética asociada al cambio en el TBS mediante el estudio de genes de la vía esteroidogénica. Material y métodos: La cohorte B-ABLE estudia de forma prospectiva a mujeres postmenopáusicas con cáncer de mama en tratamiento con IA. Se calculó el TBS a partir de los datos adquiridos en la densitometría mediante absorciometría radiológica dual (DXA) realizada al inicio y al final del tratamiento con IA. El cambio relativo del TBS se calculó como la variación porcentual del valor de TBS al final de tratamiento respecto al TBS basal. Para estudiar la posible asociación genética se genotiparon los polimorfismos de cambio de un nucleótido (SNPs) en los genes CYP11A1, CYP17A1, HDE3B2, HDE17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, GC, CYP27B1, VDR y CYP24A1. Se estudió mediante regresión lineal múltiple la posible relación entre genes y cambios en TBS contemplando los modelos de herencia genética dominante, recesivo y aditivo. Resultados: Se incluyeron en el estudio un total de 212 mujeres no tratadas con bisfosfonatos en las que pudo calcularse el TBS. La mitad de las pacientes habían recibido tratamiento previo con tamoxifeno. El porcentaje de cambio intra-individual del TBS fue del -0,04% [IC del 95%: -0,05 a -0,03; p

Objetivos: Identificar putativas variantes funcionales en los genes CYP11A1 y CYP17A1 asociadas a efectos musculoesqueléticos (pérdida acelerada de la masa ósea y artralgias) derivados del tratamiento con inhibidores de la aromatasa (IA). Material y métodos: La cohorte B-ABLE es un estudio prospectivo de mujeres postmenopáusicas con cáncer de mama en tratamiento con IA. La densidad mineral ósea en columna lumbar y cuello femoral se midió mediante densitometría, y el dolor articular mediante escala analógica visual. A partir de polimorfismos de cambio de un nucleótido (SNPs) en los genes CYP11A1 (rs4077581, rs11632698 y rs900798) y CYP17A1 (rs4919686, rs4919683, rs4919687, rs3781287, rs10786712, rs6163, rs743572), asociados previamente con eventos musculoesqueléticos, se construyeron los haplotipos para cada paciente de la cohorte, y se seleccionaron aquellos que mostraron mayor diferencia fenotípica (p

Objetive: Aromatase inhibitors (AI) have been associated with an accelerated loss of bone mass and an increased risk of osteoporosis fractures. This study assesses the risk factors for incident fracture in breast cancer patients receiving AI. Material and methods: Prospective-observational cohort study of women with breast cancer who begin treatment with AI (B-ABLE cohort). Patients were treated for 5 years or 2 or 3 years if they had previously received tamoxifen. Bone health was assessed from the beginning of the treatment until one year post treatment by bone densitometry, bone remodeling markers, vitamin D levels and an anteroposterior and lateral spine radiography. The fracture risk calculation was performed using the FRAX® tool before starting AI. Cox models were used to calculate the risk ratios (HR [95% CI]) of fracture. Results: A total of 943 patients were included in the study. 5.4% suffered an incident fracture, most during AI treatment, although 21.5% occurred during the first year after the end of therapy. Most of the incident fractures were clinical vertebral (29.4%) and Colles (31.4%). 86.3% of the patients had a diagnosis of osteopenia or osteoporosis at the time of the fracture and 33% had the levels of β-CTX (β isomer of the carboxyterminal telopeptide of type I collagen) above normal. Patients diagnosed with osteoporosis or at risk of fracture at the start of the study were treated with bone antiresorptives. No significant differences in fracture risk were found between patients with and without antiresorptive therapy: HR=1.75 [95% CI: 0.88 to 3.46]. Nor were differences found among patients who had previously treated with tamoxifen compared to those who did not (HR=1.00 [95% CI 0.39 to 2.56]). The FRAX® tool gave average values within the intermediate risk range, with 13 patients with high risk of major fracture values. Conclusions: The main risk factor detected for incident fracture in patients treated with AI is the diagnosis of osteopenia or osteoporosis. The calculation of the FRAX® tool and the determination of β-CTX levels are useful tools to identify high-risk patients. [ABSTRACT FROM AUTHOR]

Objectives: Aromatase inhibitors (AI) are effective adjuvant endocrine therapies for breast cancer patients, although they have been associated with an increased risk of osteoporotic fracture. Trabecular Bone Score (TBS) loss has been previously demonstrated, although it may vary among AI-treated patients. This study aims to identify the genetic basis associated with TBS change by studying steroidogenic pathway genes. Material and methods: The B-ABLE cohort studies prospectively postmenopausal women with breast cancer under treatment with AI. TBS is calculated from the raw data acquired in dual-energy x-ray absorptiometry (DXA) scan at the outset of the study and at the end of AI-treatment. The relative TBS change was calculated as the percentage variation of the TBS value at the end of treatment from baseline. To study the possible genetic association, nucleotide polymorphisms (SNPs) were genotyped in genes CYP11A1, CYP17A1, HDE3B2, HDE17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, GC, CYP27B1, VDR and CYP24A1. The possible relationship between genes and TBS changes was studied by multiple linear regression, considering models of dominant, recessive and additive genetic inheritance. Results: The study included 212 women that had not been treated with bisphosphonates and had available TBS data. Half of the patients had been treated previously with tamoxifen. The percentage of intraindividual TBS change was -0.04% [95% CI: -0.05 to -0.03; p<0.001] at the end of AI treatment. The SNP rs6013897 in the gene CYP24A1 showed a significant association with TBS reduction [p=0.03565; coefficient ß (95% CI) = -1.55 (-2.98 to -0.11)]. Conclusions: The CYP24A1 gene could be involved in the phenotypic variability found in bone microarchitecture deterioration during AI treatment. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic had collateral effects on many health systems. Cancer screening and diagnostic tests were postponed, resulting in delays in diagnosis and treatment. This study assessed the impact of the pandemic on screening, diagnostics and incidence of breast, colorectal, lung, and prostate cancer; and whether rates returned to pre-pandemic levels by December, 2021., Methods: This is a cohort study of electronic health records from the United Kingdom (UK) primary care Clinical Practice Research Datalink (CPRD) GOLD database. The study included individuals registered with CPRD GOLD between January, 2017 and December, 2021, with at least 365 days of clinical history. The study focused on screening, diagnostic tests, referrals and diagnoses of first-ever breast, colorectal, lung, and prostate cancer. Incidence rates (IR) were stratified by age, sex, and region, and incidence rate ratios (IRR) were calculated to compare rates during and after lockdown with rates before lockdown. Forecasted rates were estimated using negative binomial regression models., Results: Among 5,191,650 eligible participants, the first lockdown resulted in reduced screening and diagnostic tests for all cancers, which remained dramatically reduced across the whole observation period for almost all tests investigated. There were significant IRR reductions in breast (0.69 [95% CI: 0.63-0.74]), colorectal (0.74 [95% CI: 0.67-0.81]), and prostate (0.71 [95% CI: 0.66-0.78]) cancer diagnoses. IRR reductions for lung cancer were non-significant (0.92 [95% CI: 0.84-1.01]). Extrapolating to the entire UK population, an estimated 18,000 breast, 13,000 colorectal, 10,000 lung, and 21,000 prostate cancer diagnoses were missed from March, 2020 to December, 2021., Discussion: The UK COVID-19 lockdown had a substantial impact on cancer screening, diagnostic tests, referrals, and diagnoses. Incidence rates remained significantly lower than pre-pandemic levels for breast and prostate cancers and associated tests by December, 2021. Delays in diagnosis are likely to have adverse consequences on cancer stage, treatment initiation, mortality rates, and years of life lost. Urgent strategies are needed to identify undiagnosed cases and address the long-term implications of delayed diagnoses., Competing Interests: Author DP-A has performed paid consultancy services for the following commercial entities: European Medicines Agency; the Innovative Medicines Initiative; Amgen, Chiesi, and UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, and UCB Biopharma. Author NB has received paid consultancy fees for Theramex and Lindus Health; and provides research consultancy services for Sleep Universal Limited. All of these activities were independent from the research reported here. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Barclay, Pineda Moncusí, Jödicke, Prieto-Alhambra, Raventós, Newby, Delmestri, Man, Chen and Català.)

Intersectional social determinants including ethnicity are vital in health research. We curated a population-wide data resource of self-identified ethnicity data from over 60 million individuals in England primary care, linking it to hospital records. We assessed ethnicity data in terms of completeness, consistency, and granularity and found one in ten individuals do not have ethnicity information recorded in primary care. By linking to hospital records, ethnicity data were completed for 94% of individuals. By reconciling SNOMED-CT concepts and census-level categories into a consistent hierarchy, we organised more than 250 ethnicity sub-groups including and beyond "White", "Black", "Asian", "Mixed" and "Other, and found them to be distributed in proportions similar to the general population. This large observational dataset presents an algorithmic hierarchy to represent self-identified ethnicity data collected across heterogeneous healthcare settings. Accurate and easily accessible ethnicity data can lead to a better understanding of population diversity, which is important to address disparities and influence policy recommendations that can translate into better, fairer health for all., (© 2024. The Author(s).)

The objective of this work was to estimate the incidence rate of cardiovascular disease (CVD) events (myocardial infarction, stroke, or CVD death) at 1 year among three cohorts of patients at high risk of fracture (osteoporosis, previous fracture, and anti-osteoporosis medication) and to identify the key risk factors of CVD events in these three cohorts. To do so, this prospective cohort study used data from the Clinical Practice Research Datalink, a primary care database from United Kingdom. Major adverse cardiovascular events (MACE, a composite outcome for the occurrence of either myocardial infarction [MI], stroke, or CVD death) were identified in patients aged 50 years or older at high or imminent fracture risk identified in three different cohorts (not mutually exclusive): recently diagnosed with osteoporosis (OST, n = 65,295), incident fragility fracture (IFX, n = 67,065), and starting oral bisphosphonates (OBP, n = 145,959). About 1.90%, 4.39%, and 2.38% of the participants in OST, IFX, and OBP cohorts, respectively, experienced MACE events. IFX was the cohort with the higher risk: MACE incidence rates (cases/1000 person-years) were 19.63 (18.54-20.73) in OST, 52.64 (50.7-54.5) in IFX, and 26.26 (25.41-27.12) in OBP cohorts. Risk of MACE events at 1 year was predicted in the three cohorts. Models using a set of general, CVD, and fracture candidates selected by lasso regression had a good discrimination (≥70%) and internal validity and generally outperformed the models using only the CVD risk factors of general population listed in QRISK tool. Main risk factors common in all MACE models were sex, age, smoking, alcohol, atrial fibrillation, antihypertensive medication, prior MI/stroke, established CVD, glomerular filtration rate, systolic blood pressure, cholesterol levels, and number of concomitant medicines. Identified key risk factors highlight the differences of patients at high risk of fracture versus general population. Proposed models could improve prediction of CVD events in patients with osteoporosis in primary care settings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

The availability of anti-osteoporosis medications with rapid onset and high potency requires tools to identify patients at high imminent fracture risk (IFR). There are few tools that predict a patient's IFR. We aimed to develop and validate tools for patients with a recent fracture and for patients initiating oral bisphosphonate therapy. Models for two separate cohorts, those with incident fragility fracture (IFx) and with incident oral bisphosphonate prescription (OBP), were developed in primary care records from Spain (SIDIAP database), UK (Clinical Practice Research Datalink GOLD), and Denmark (Danish Health Registries). Separate models were developed for hip, major, and any fracture outcomes. Only variables present in all databases were included in Lasso regression models for the development and logistic regression models for external validation. Discrimination was tested using area under curve (AUC) and calibration was assessed using observed versus predicted risk plots stratified by age, sex, and previous fracture history. The development analyses included 35,526 individuals in the IFx and 41,401 in the OBP cohorts, with 671,094 in IFx and 330,256 in OBP for the validation analyses. Both the IFx and OBP models demonstrated similarly good performance for hip fracture at 1 year (with AUCs of 0.79 [95% CI 0.75 to 0.82] and 0.87 [0.83 to 0.91] in Spain, 0.71 [0.71 to 0.72] and 0.73 [0.72 to 0.74] in the UK, and 0.70 [0.70 to 0.70] and 0.69 [0.68 to 0.70] in Denmark), and lower discrimination for major osteoporotic and any fracture sites. Calibration was good across all three countries. Discrimination and calibration for the 2-year models was similar. The proposed IFR prediction models could be used to identify more precisely patients at high imminent risk of fracture and inform anti-osteoporosis treatment selection. The freely available model parameters permit local validation and implementation. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

Context: COVID-19 is a major health problem because of saturation of intensive care units (ICU) and mortality. Vitamin D has emerged as a potential treatment able to reduce the disease severity., Objective: This work aims to elucidate the effect of 25(OH)D3 (calcifediol) treatment on COVID-19-related outcomes., Methods: This observational cohort study was conducted from March to May 2020, among patients admitted to COVID-19 wards of Hospital del Mar, Barcelona, Spain. A total of 930 patients with COVID-19 were included; 92 were excluded because of previous calcifediol intake. Of the remaining 838, a total of 447 received calcifediol (532 μg on day 1 plus 266 μg on days 3, 7, 15, and 30), whereas 391 were not treated at the time of hospital admission (intention-to-treat). Of the latter, 53 patients were treated later during ICU admission and were allocated in the treated group in a second analysis. In healthy individuals, calcifediol is about 3.2-fold more potent on a weight basis than cholecalciferol. Main outcome measures were ICU admission and mortality., Results: ICU assistance was required by 102 (12.2%) participants. Out of 447 patients treated with calcifediol at admission, 20 (4.5%) required the ICU, compared to 82 (21%) out of 391 nontreated (P < .001). Logistic regression of calcifediol treatment on ICU admission, adjusted by age, sex, linearized 25-hydroxyvitamin D levels at baseline, and comorbidities showed that treated patients had a reduced risk of requiring the ICU (odds ratio [OR] 0.13; 95% CI 0.07-0.23). Overall mortality was 10%. In the intention-to-treat analysis, 21 (4.7%) out of 447 patients treated with calcifediol at admission died compared to 62 patients (15.9%) out of 391 nontreated (P = .001). Adjusted results showed a reduced mortality risk with an OR of 0.21 (95% CI, 0.10-0.43). In the second analysis, the obtained OR was 0.52 (95% CI, 0.27-0.99)., Conclusion: In patients hospitalized with COVID-19, calcifediol treatment significantly reduced ICU admission and mortality., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The DKK1 gene encodes an extracellular inhibitor of the Wnt pathway with an important role in bone tissue development, bone homeostasis, and different critical aspects of bone biology. Several BMD genome-wide association studies (GWASs) have consistently found association with SNPs in the DKK1 genomic region. For these reasons, it is important to assess the functionality of coding and regulatory variants in the gene. Here, we have studied the functionality of putative regulatory variants, previously found associated with BMD in different studies by others and ourselves, and also six missense variants present in the general population. Using a Wnt-pathway-specific luciferase reporter assay, we have determined that the variants p.Ala41Thr, p.Tyr74Phe, p.Arg120Leu, and p.Ser157Ile display a reduced DKK1 inhibitory capacity as compared with WT. This result agrees with the high-bone-mass (HBM) phenotype of two women from our cohort who carried mutations p.Tyr74Phe or p.Arg120Leu. On the other hand, by means of a circularized chromosome conformation capture- (4C-) sequencing experiment, we have detected that the region containing 24 BMD-GWA variants, located 350-kb downstream of DKK1 , interacts both with DKK1 and the LNCAROD (LncRNA-activating regulator of DKK1, AKA LINC0148 ) in osteoblastic cells. In conclusion, we have shown that some rare coding variants are partial loss-of-function mutations that may lead to a HBM phenotype, whereas the common SNPs associated with BMD in GWASs belong to a putative long-range regulatory region, through a yet unknown mechanism involving LNCAROD . © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Background: Tamoxifen (TAM) and aromatase inhibitor (AI) therapies have been associated with increased risk of thromboembolic and cardiovascular events, respectively, in addition to other side effects. This study analysed the risk of these events and the overall survival (OS) benefit in breast cancer patients treated with AI, compared with TAM-treated patients, in a large population-based cohort., Methods: This observational cohort study included women diagnosed with breast cancer and treated with TAM or AI. Data were extracted from primary care records in a population database (SIDIAP, System for the Development of Research in Primary Care). Incidence rates of study outcomes are reported. Survival analyses included Kaplan-Meier estimation and Cox proportional hazards models. Sensitivity analysis was carried out, using Fine and Gray models to account for competing risk of death. Confounding was minimized using propensity score adjustment and inverse probability weighting (IPW) adjustment., Results: Data from 3082 postmenopausal women treated with TAM, and 18,455 treated with AI, were available. Adjusted hazard ratios (HRs) [95% confidence interval (CI)] for AI users, compared with TAM group, were 0.93 (95%CI 0.69-1.26) for thromboembolic events (TEEs); 1.13 (95%CI 0.79-1.63) for cardiovascular events, and 0.76 (95%CI 0.70-0.82) for mortality. Additional analyses using competing risk analysis had similar results, while IPW adjustment showed a potential risk of pulmonary embolism (PE) [2.26 (95%CI 1.02-4.97)] in AI-treated patients., Conclusions: AI users had >20% lower all-cause mortality compared with TAM users, without increasing risk to experience cardiovascular and TEEs. This would locate AI therapy on the first line in clinical practice. Thus, AI might be the most preferable option in adjuvant hormonal therapy choice., Competing Interests: Conflict of interest statement: ADP reports grants from Amgen, personal fees from UCB, Mereo, Sandoz, Gilead, and other from Active Life Sci, outside the submitted work. DPA reports unrestricted research funding from UCB, Amgen, and Servier Laboratoires outside of the submitted work; DPA’s department has received fees for speaker services from Amgen outside of the submitted work. MPM, NGG, IT, SS, JA and XN have nothing to disclose., (© The Author(s), 2020.)

Aromatase inhibitors have been associated with accelerated bone loss and an increased risk of osteoporotic fractures. Currently, bisphosphonates are recommended to reduce fracture risk in these patients. The aim of this study is to evaluate the fracture risk in breast cancer patients receiving aromatase inhibitors, compared to tamoxifen users, and to assess the effectiveness of oral bisphosphonates in reducing fracture risk. We performed an observational cohort study up to 10 years of follow-up. Data were extracted from primary care records in a population database. Women diagnosed with breast cancer between 2006 and 2015 and treated with tamoxifen or aromatase inhibitors (n = 36,472) were stratified according to low (without osteoporosis diagnosis nor bisphosphonates exposure) or high (with osteoporosis and/or treated with bisphosphonates) fracture risk. Cox models were used to calculate hazard ratios (HR [95% CI]) of fracture from the propensity score-matched patients. Sensitivity analyses account for competing risk of death were performed (subdistribution hazard ratio [SHR] [95% CI]). In postmenopausal women, fracture risk in aromatase inhibitor users showed an HR 1.40 [95% CI,1.05 to 1.87] and SHR 1.48 [95% CI, 1.11 to 1.98], compared to tamoxifen. Observing aromatase inhibitors patients at high risk of fracture, bisphosphonate-treated patients had an HR 0.73 [95% CI, 0.51 to 1.04] and SHR 0.69 [95% CI, 0.48 to 0.98] compared to nontreated. In conclusion, fracture risk in postmenopausal women during aromatase inhibitor treatment, in real-life conditions, was >40% compared to tamoxifen, corroborating previous randomized controlled trials results. In high-risk patients, bisphosphonate users had lower significant fracture incidence during aromatase inhibitor therapy than nonbisphosphonate users. Monitoring fracture risk and related risk factors in aromatase inhibitor patients is advisable. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)