18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Utility of Preclinical Models in Understanding the Bone Health of Transgender Individuals Undergoing Gender-Affirming Hormone Therapy

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose of Review

          To summarise the evidence regarding the effects of gender-affirming hormone therapy (GAHT) on bone health in transgender people, to identify key knowledge gaps and how these gaps can be addressed using preclinical rodent models.

          Recent Findings

          Sex hormones play a critical role in bone physiology, yet there is a paucity of research regarding the effects of GAHT on bone microstructure and fracture risk in transgender individuals. The controlled clinical studies required to yield fracture data are unethical to conduct making clinically translatable preclinical research of the utmost importance. Novel genetic and surgical preclinical models have yielded significant mechanistic insight into the roles of sex steroids on skeletal integrity.

          Summary

          Preclinical models of GAHT have the potential inform clinical approaches to preserve skeletal integrity and prevent fractures in transgender people undergoing GAHT. This review highlights the key considerations required to ensure the information gained from preclinical models of GAHT are informative.

          Related collections

          Most cited references131

          • Record: found
          • Abstract: found
          • Article: not found

          Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr.

          We employed a whole body magnetic resonance imaging protocol to examine the influence of age, gender, body weight, and height on skeletal muscle (SM) mass and distribution in a large and heterogeneous sample of 468 men and women. Men had significantly (P < 0.001) more SM in comparison to women in both absolute terms (33.0 vs. 21.0 kg) and relative to body mass (38.4 vs. 30.6%). The gender differences were greater in the upper (40%) than lower (33%) body (P < 0.01). We observed a reduction in relative SM mass starting in the third decade; however, a noticeable decrease in absolute SM mass was not observed until the end of the fifth decade. This decrease was primarily attributed to a decrease in lower body SM. Weight and height explained approximately 50% of the variance in SM mass in men and women. Although a linear relationship existed between SM and height, the relationship between SM and body weight was curvilinear because the contribution of SM to weight gain decreased with increasing body weight. These findings indicate that men have more SM than women and that these gender differences are greater in the upper body. Independent of gender, aging is associated with a decrease in SM mass that is explained, in large measure, by a decrease in lower body SM occurring after the fifth decade.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts.

            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.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Sex differences in human adipose tissues – the biology of pear shape

              Women have more body fat than men, but in contrast to the deleterious metabolic consequences of the central obesity typical of men, the pear-shaped body fat distribution of many women is associated with lower cardiometabolic risk. To understand the mechanisms regulating adiposity and adipose tissue distribution in men and women, significant research attention has focused on comparing adipocyte morphological and metabolic properties, as well as the capacity of preadipocytes derived from different depots for proliferation and differentiation. Available evidence points to possible intrinsic, cell autonomous differences in preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the microenvironment within each adipose tissue, and developmental factors. Gluteal-femoral adipose tissues of women may simply provide a safe lipid reservoir for excess energy, or they may directly regulate systemic metabolism via release of metabolic products or adipokines. We provide a brief overview of the relationship of fat distribution to metabolic health in men and women, and then focus on mechanisms underlying sex differences in adipose tissue biology.
                Bookmark

                Author and article information

                Contributors
                r.davey@unimelb.edu.au
                Journal
                Curr Osteoporos Rep
                Curr Osteoporos Rep
                Current Osteoporosis Reports
                Springer US (New York )
                1544-1873
                1544-2241
                14 September 2023
                14 September 2023
                2023
                : 21
                : 6
                : 825-841
                Affiliations
                [1 ]GRID grid.1008.9, ISNI 0000 0001 2179 088X, Department of Medicine, , Austin Health, The University of Melbourne, ; Heidelberg, Victoria 3084 Australia
                [2 ]Department of Endocrinology, Austin Health, ( https://ror.org/05dbj6g52) Heidelberg, Victoria 3084 Australia
                Author information
                http://orcid.org/0000-0001-5121-0209
                Article
                818
                10.1007/s11914-023-00818-2
                10724092
                37707757
                fc0506b0-46e1-453c-9d48-0651f2486a7d
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 August 2023
                Funding
                Funded by: University of Melbourne
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2023

                Orthopedics
                transgender,gender-affirming hormone therapy (gaht),bone microstructure,bone strength,preclinical rodent models

                Comments

                Comment on this article