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      Prediction of vertebral fractures in cancer patients undergoing hormone deprivation therapies: Reliability of who fracture risk assessment tool (frax) and bone mineral density in real-life clinical practice

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          Highlights

          • In females under estrogen-deprivation therapies, risk of vertebral fractures was associated with FRAX score for major fractures, with the best therapeutic threshold of 6.5%.

          • In males under androgen-deprivation therapy, risk of vertebral fractures was high when BMD T-score was lower than −1.0 SD or when subjects were treated with abiraterone.

          • High body mass index was an independent risk factor for vertebral fractures in males exposed to androgen-deprivation therapy.

          • In the setting of hormonal deprivation therapies, FRAX and BMD thresholds were lower than those used in post-menopausal osteoporosis and primary male osteoporosis.

          Abstract

          Background and Objective

          Prediction of fractures in cancer survivors exposed to hormone-deprivation therapies (HDTs) is a challenge since bone loss is rapid and severe, and determinants of fractures in this setting are still largely unknown. In this study we investigated reliability of the WHO Fracture Risk Assessment Tool (FRAX) and bone mineral density (BMD) to identify subjects developing vertebral fractures during HDTs.

          Design

          Five-hundred-twenty-seven consecutive subjects (429 females with breast cancer, 98 males with prostate cancer; median age 61 years), under HDTs for at least 6 months, were evaluated for vertebral fractures by a radiological and morphometric approach, in relationship with FRAX score, body mass index (BMI), BMD, age and duration of HDTs.

          Results

          Vertebral fractures were found in 140 subjects (26.6%) and spine deformity index was significantly associated with duration of HDTs (rho 0.38; p < 0.001). Only in females, vertebral fractures were significantly associated with FRAX score for major fractures [OR 1.08; P < 0.001]. The best cut-off of FRAX score for major fractures, as calculated by receiving operating characteristic (ROC) analysis was 6.35%. In males, however, vertebral fractures were significantly and independently associated with BMI ≥ 25 Kg/m 2 (OR 17.63; P < 0.001), BMD T-score below −1.0 SD at any skeletal site (OR 7.79; P < 0.001) and gonadotropin-releasing hormone agonists (GnRHa) plus abiraterone treatment (OR 11.51; P = 0.001).

          Conclusions

          FRAX and BMD may be useful for predicting vertebral fractures in subjects undergoing HDTs, but the thresholds seem to be lower than those used in the general population. High BMI is a determinant of vertebral fractures in males under HDT.

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          Most cited references52

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          The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies

          Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study’s generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control and cross-sectional studies. We convened a two-day workshop, in September 2004, with methodologists, researchers and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the web sites of PLoS Medicine, Annals of Internal Medicine and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.
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            European guidance for the diagnosis and management of osteoporosis in postmenopausal women

            Summary Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk of fractures due to osteoporosis. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2008. This manuscript updates these in a European setting. Methods Systematic literature reviews. Results The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk, general and pharmacological management of osteoporosis, monitoring of treatment, assessment of fracture risk, case finding strategies, investigation of patients and health economics of treatment. Conclusions A platform is provided on which specific guidelines can be developed for national use.
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              FRAX™ and the assessment of fracture probability in men and women from the UK

              Summary A fracture risk assessment tool (FRAX™) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK. Introduction The aim of this study was to apply an assessment tool for the prediction of fracture in men and women with the use of clinical risk factors (CRFs) for fracture with and without the use of femoral neck bone mineral density (BMD). The clinical risk factors, identified from previous meta-analyses, comprised body mass index (BMI, as a continuous variable), a prior history of fracture, a parental history of hip fracture, use of oral glucocorticoids, rheumatoid arthritis and other secondary causes of osteoporosis, current smoking, and alcohol intake 3 or more units daily. Methods Four models were constructed to compute fracture probabilities based on the epidemiology of fracture in the UK. The models comprised the ten-year probability of hip fracture, with and without femoral neck BMD, and the ten-year probability of a major osteoporotic fracture, with and without BMD. For each model fracture and death hazards were computed as continuous functions. Results Each clinical risk factor contributed to fracture probability. In the absence of BMD, hip fracture probability in women with a fixed BMI (25 kg/m2) ranged from 0.2% at the age of 50 years for women without CRF’s to 22% at the age of 80 years with a parental history of hip fracture (approximately 100-fold range). In men, the probabilities were lower, as was the range (0.1 to 11% in the examples above). For a major osteoporotic fracture the probabilities ranged from 3.5% to 31% in women, and from 2.8% to 15% in men in the example above. The presence of one or more risk factors increased probabilities in an incremental manner. The differences in probabilities between men and women were comparable at any given T-score and age, except in the elderly where probabilities were higher in women than in men due to the higher mortality of the latter. Conclusion The models provide a framework which enhances the assessment of fracture risk in both men and women by the integration of clinical risk factors alone and/or in combination with BMD.
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                Author and article information

                Contributors
                Journal
                J Bone Oncol
                J Bone Oncol
                Journal of Bone Oncology
                Elsevier
                2212-1366
                2212-1374
                09 March 2022
                April 2022
                09 March 2022
                : 33
                : 100421
                Affiliations
                [a ]Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy
                [b ]Endocrinology, Diabetology and Andrology Unit, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy
                [c ]Biostatistics Unit, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy
                [d ]Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy
                [e ]Department of Radiology, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy
                [f ]Medical Oncology Unit, ASST Spedali Civili di Brescia, Brescia, Italy
                [g ]Radiology Unit, ASST Spedali Civili di Brescia, Brescia, Italy
                [h ]Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Italy
                Author notes
                [* ]Corresponding author at: Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele, MI, Italy. andrea.lania@ 123456hunimed.eu
                Article
                S2212-1374(22)00011-2 100421
                10.1016/j.jbo.2022.100421
                8928084
                35310388
                71aee0f9-de7c-4f56-9d3b-b5c0dfda6615
                © 2022 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 26 December 2021
                : 4 March 2022
                : 5 March 2022
                Categories
                Research Paper

                bone mineral density,breast cancer,frax score,fractures,hormone deprivation therapy,osteoporosis,prostate cancer,vertebral fractures

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