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      Fracture Risk in Trans Women and Trans Men Using Long‐Term Gender‐Affirming Hormonal Treatment: A Nationwide Cohort Study

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          ABSTRACT

          Concerns about bone health in transgender people using gender‐affirming hormonal treatment (HT) exist, but the fracture risk is not known. In this nationwide cohort study, we aimed to compare the fracture incidence in transgender people using long‐term HT with an age‐matched reference population. All adult transgender people who started HT before 2016 at our gender‐identity clinic were included and were linked to a random population‐based sample of 5 age‐matched reference men and 5 age‐matched reference women per person. Fracture incidence was determined using diagnoses from visits to hospital emergency rooms nationwide between 2013 and 2015. A total of 1089 trans women aged <50 years (mean 38 ± 9 years) and 934 trans women aged ≥50 years (mean 60 ± 8 years) using HT for median 8 (interquartile range [IQR] 3–16) and 19 (IQR 11–29) years, respectively, were included. A total of 2.4% of the trans women aged <50 years had a fracture, whereas 3.0% of the age‐matched reference men (odds ratio [OR] = 0.78, 95% confidence interval [CI] 0.51–1.19) and 1.6% of the age‐matched reference women (OR = 1.49, 95% CI 0.96–2.32) experienced a fracture. In trans women aged ≥50 years, 4.4% experienced a fracture compared with 2.4% of the age‐matched reference men (OR = 1.90, 95% CI 1.32–2.74) and 4.2% of the age‐matched reference women (OR = 1.05, 95% CI 0.75–1.49). A total of 1036 trans men (40 ± 14 years) using HT for median 9 (IQR 2–22) years were included. Fractures occurred in 1.7% of the trans men, 3.0% of the age‐matched reference men (OR = 0.57, 95% CI 0.35–0.94), and 2.2% of the age‐matched reference women (OR = 0.79, 95% CI 0.48–1.30). In conclusion, fracture risk was higher in older trans women compared with age‐matched reference men. In young trans women, fracture risk tended to be increased compared with age‐matched reference women. Fracture risk was not increased in young trans men. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

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          Estrogen prevents osteoporotic bone loss by attenuating bone resorption; however, the molecular basis for this is unknown. Here, we report a critical role for the osteoclastic estrogen receptor alpha (ERalpha) in mediating estrogen-dependent bone maintenance in female mice. We selectively ablated ERalpha in differentiated osteoclasts (ERalpha(DeltaOc/DeltaOc)) and found that ERalpha(DeltaOc/DeltaOc) females, but not males, exhibited trabecular bone loss, similar to the osteoporotic bone phenotype in postmenopausal women. Further, we show that estrogen induced apoptosis and upregulation of Fas ligand (FasL) expression in osteoclasts of the trabecular bones of WT but not ERalpha(DeltaOc/DeltaOc) mice. The expression of ERalpha was also required for the induction of apoptosis by tamoxifen and estrogen in cultured osteoclasts. Our results support a model in which estrogen regulates the life span of mature osteoclasts via the induction of the Fas/FasL system, thereby providing an explanation for the osteoprotective function of estrogen as well as SERMs.
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                Author and article information

                Contributors
                m.denheijer@amsterdamumc.nl
                Journal
                J Bone Miner Res
                J. Bone Miner. Res
                10.1002/(ISSN)1523-4681
                JBMR
                Journal of Bone and Mineral Research
                John Wiley & Sons, Inc. (Hoboken, USA )
                0884-0431
                1523-4681
                07 October 2019
                January 2020
                : 35
                : 1 ( doiID: 10.1002/jbmr.v35.1 )
                : 64-70
                Affiliations
                [ 1 ] Department of Endocrinology Amsterdam UMC, VU University Medical Center Amsterdam the Netherlands
                [ 2 ] Center of Expertise on Gender Dysphoria, Amsterdam UMC, VU University Medical Center Amsterdam the Netherlands
                Author notes
                [*] [* ]Address correspondence to: Martin den Heijer, MD, PhD, Department of Internal Medicine, Section Endocrinology, Amsterdam UMC, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands. E‐mail: m.denheijer@ 123456amsterdamumc.nl
                Author information
                https://orcid.org/0000-0002-8280-0065
                https://orcid.org/0000-0002-1137-0862
                https://orcid.org/0000-0001-8414-3938
                Article
                JBMR3862
                10.1002/jbmr.3862
                7003754
                31487065
                8c11c18b-e201-455a-b7f4-78b009a1a213
                © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 May 2019
                : 16 August 2019
                : 23 August 2019
                Page count
                Figures: 2, Tables: 2, Pages: 7, Words: 6316
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:06.02.2020

                Human biology
                bone,fractures,gender‐affirming hormonal treatment,osteoporosis,transgender
                Human biology
                bone, fractures, gender‐affirming hormonal treatment, osteoporosis, transgender

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