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J Bone Miner Res ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596961


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.

Breast Cancer Res Treat ; 177(1): 53-60, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31127467


PURPOSE: The most frequent adverse effects of aromatase inhibitors (AI) are arthralgia and bone loss induction. These reduce the quality of life of patients and their adherence to the treatment. This study evaluates the early AI cessation caused by AI intolerance, and the evolution of joint pain and health-related quality of life (HRQoL) during AI treatment until 1-year after AI completion. METHODS: Data of 910 women diagnosed with early breast cancer and candidates for AI were recruited in B-ABLE cohort. AI discontinuation was analyzed by survival analysis, including Kaplan-Meier estimation and Cox regression. Patients were distributed in three groups of the study according to previous tamoxifen (TAM) exposure and length of AI treatment: TAM-2yAI, TAM-3yAI, and 5yAI. Evolution of joint pain and HRQoL in osteoporosis was evaluated using Visual Analog Scale (VAS) and ECOS-16 tests, respectively, from baseline to 1-year after AI completion through repeated-measures ANOVA. RESULTS: Risk of AI discontinuation was increased in patients previously exposed to tamoxifen compared to non-exposed (adjusted HR 5.30 [95% CI 2.23 to 12.57]). VAS and ECOS-16 scores of TAM-2yAI and TAM-3yAI groups increased during AI treatment, mainly during the first 3-12 months. After 1-year from AI completion, values tend to decrease to baseline levels. In 5yAI group, VAS and ECOS-16 levels increased at three months, and VAS remained significantly higher at 1-year post-treatment. CONCLUSIONS: AI therapy increased joint pain and reduced HRQoL, mainly during the first year of treatment. Patients previously treated with tamoxifen experienced greater pain when they switched to AI therapy and had an excess risk of discontinuation during the first 12 months. TRIAL REGISTRATION: NCT03811509. Registered 28 January 2018-Retrospectively registered, .

J Antimicrob Chemother ; 74(5): 1381-1388, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30768163


BACKGROUND: The mechanisms behind ART-induced bone changes in HIV-infected patients are poorly known. We aimed to analyse changes in inflammatory and bone markers in HIV after tenofovir disoproxil fumarate initiation, and the associations with changes in the bone strength parameters. METHODS: HIV-positive participants starting tenofovir disoproxil fumarate-based ART underwent dual-energy X-ray absorptiometry (QDR 4500 SL®, Hologic, Waltham, MA, USA) for bone mineral density (BMD), a microindentation test (OsteoProbe®, Active Life Scientific, Santa Barbara, CA, USA) for bone quality [bone material strength index (BMSi)] and phlebotomy at baseline and 48 weeks after ART. A panel of inflammatory biomarkers and bone turnover markers were measured by ELISA. HIV-negative controls underwent identical procedures once. Values are expressed as medians and IQRs, and non-parametric tests were used to perform the analysis. RESULTS: Twenty HIV-infected individuals and 20 HIV-negative control individuals were matched in terms of age and gender. HIV individuals showed higher levels of inflammatory markers. We found no differences in bone turnover markers. HIV-positive individuals presented lower BMSi values at baseline compared with controls [86 (83-90) versus 89 (88-93), respectively; P = 0.034]. We found no difference in BMD (at either of the sites evaluated). BMSi tended to increase with treatment. IL-1ß at baseline was positively correlated with changes in BMSi after ART (rho = 0.564, P = 0.014). Baseline levels of sclerostin tended to be negatively correlated with changes in BMSi (rho = -0.402, P = 0.097). We found a negative correlation between time since HIV diagnosis and changes in BMSi (rho = -0.466, P = 0.04). CONCLUSIONS: We observed a correlation between changes in bone quality and the inflammatory environment in HIV-positive individuals. Moreover, among the underlying mechanisms we highlight the Wnt pathway as having a potentially significant role in ART bone quality recovery.

Bone ; 117: 54-59, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30223134


INTRODUCTION: Breast cancer patients treated with aromatase inhibitors (AIs) experience increased bone loss during their treatment. However, there is little information about bone mineral density (BMD) after completing AI-treatment. The present study aimed to assess BMD changes one year after AI-therapy completion. METHODS: Data were collected from 864 postmenopausal women treated with AI during 5 years (5y-AI group), or during 2-3 years after taking tamoxifen therapy (pTAM-AI group). Participants with osteoporosis were treated with oral bisphosphonates (BP). BMD changes in lumbar spine (LS), femoral neck (FN) and total hip (TH) between baseline, end of treatment, and at one year post-treatment were assessed using repeated-measures ANOVA. RESULTS: At the end of AI-treatment, 382 patients had available BMD values and 316 also had post-treatment BMD values. As expected, BMD levels were decreased at AI-completion in non-BP treated patients. After one year, LS BMD increased in both groups (5y-AI: +2.11% [95%CI: 1.55 to 2.68], p < 0.001; pTAM-AI: +1.00% [95%CI: 0.49 to 1.51], p < 0.001) compared with the end of AI-therapy, while values at FN and TH remained stable. On the other hand, BMD values of BP-treated patients were increased or maintained at the end of AI-treatment and also at post-treatment. CONCLUSIONS: At one year after AI-completion, FN and TH BMD remained reduced in non-BP treated women, while LS BMD was recovered in the 5y-AI group and partially recovered in the pTAM-AI group. BP treatment increased or maintained BMD values at the end of therapy and at one year post-treatment.

Maturitas ; 116: 83-88, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30244785


OBJECTIVES: To evaluate the vitamin D status of postmenopausal women with early estrogen-receptor-positive breast cancer and to compare it with that of healthy postmenopausal women from the same Mediterranean region. STUDY DESIGN AND OUTCOME MEASURES: Data from 691 breast cancer (BC) patients in the B-ABLE cohort were analyzed after recent cancer intervention (recent-BC) or after a minimum of two years since this intervention (long-term-BC). Patients were also stratified by previous chemotherapy exposure (ChT+ and ChT-). Plasma levels of 25-hydroxyvitamin D [25(OH)D] (25(OH)D) were compared with data from 294 healthy women (non-BC) by linear regression to estimate ß-coefficients using non-BC participants as the reference group. Age, body mass index and season of blood extraction were selected as potential confounders. RESULTS: Of the recent-BC patients, 23.7% had 25(OH)D deficiency, compared with 17.7% of the long-term-BC group, and just 1.4% of the non-BC participants. Most of the women were located in the insufficient 25(OH)D category regardless of study group. BC patients had significantly lower 25(OH)D levels than non-BC participants (adjusted ß-coefficients: -4.84 [95%CI -6.56 to -3.12] in recent-BC, and -2.05 [95%CI -4.96 to -0.14] in long-term-BC). Among BC patients, the lowest 25(OH)D levels were found in the recent-BC (ChT+) group (p < 0.001). No differences were found between the long-term-BC (ChT-), long-term-BC (ChT+) and recent-BC (ChT-) groups. Among the BC ChT+ patients, the recent-BC group had significantly lower 25(OH)D levels than the long-term-BC group (p < 0.001). CONCLUSION: Severely reduced 25(OH)D levels were detected in patients with breast cancer, particularly after recent chemotherapy. These 25(OH)D levels had partially recovered over the long term, but still remained much lower than in the healthy population.

Neoplasias da Mama/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Idoso , Feminino , Humanos , Região do Mediterrâneo , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Vitamina D/sangue