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The effects of gender affirming hormone therapy (GAHT) on bone microarchitecture and fracture risk in adult transgender women is unclear. To investigate the concept that skeletal integrity and strength in trans women may be improved by treatment with a higher dose of GAHT than commonly prescribed, we treated adult male mice with a sustained, high dose of estradiol. Adult male mice at 16 weeks of age were administered ~1.3 mg estradiol by silastic implant, implanted intraperitoneally, for 12 weeks. Controls included vehicle treated intact females and males. High-dose estradiol treatment in males stimulated the endocortical deposition of bone at the femoral mid-diaphysis, increasing cortical thickness and bone area. This led to higher stiffness, maximum force, and the work required to fracture the bone compared to male controls, while post-yield displacement was unaffected. Assessment of the material properties of the bone showed an increase in both elastic modulus and ultimate stress in the estradiol treated males. Treatment of male mice with high dose estradiol was also anabolic for trabecular bone, markedly increasing trabecular bone volume, number and thickness in the distal metaphysis which was accompanied by an increase in the histomorphometric markers of bone remodelling, mineralizing surface/bone surface, bone formation rate and osteoclast number. In conclusion, a high dose of estradiol is anabolic for cortical and trabecular bone in a male to female transgender mouse model, increasing both stiffness and strength. These findings suggest that increasing the current dose of GAHT administered to trans women, while considering other potential adverse effects, may be beneficial to preserving their bone microstructure and strength., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rachel A Davey reports financial support was provided by Sir Edward Dunlop Medical Research Foundation. Rachel A Davey reports financial support was provided by Austin Health Medical Research Foundation. Rachel A Davey and Jeffrey D Zajac reports financial support was provided by Les and Eva Erdi Research Grant. Tian Nie reports financial support was provided by Endocrine Society of Australia. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Traditional quantitative analysis of bone microstructure in micro-computed tomography (microCT) is dependent on animal scale and requires parametric tuning in new implementations. This study aims to develop an automated and resolution-invariant 3D image processing workflow for quantitative assessment of osteophytes., Methods: In this workflow, cortical bone was segmented from microCT scans, and a 3D sphere-fitting transform was performed to obtain a thickness map, for which each voxel is assigned a thickness value corresponding to the size of the largest sphere containing the voxel that fits entirely within the cortical bone. From the thickness map, a 1-voxel thick outer surface was extracted to model surface roughness. The thickness values of the outer surface were empirically estimated by a series of known statistical distributions. Resulting parameters describing best-fit distributions, along with other cortical bone metrics, were analysed to determine sensitivity to osteoarthritis and the presence of osteophytes., Results: The workflow was validated using microCT scans and histological gradings of rabbit and rat tibiofemoral joints. Visual inspection shows that samples with osteoarthritis and the presence of osteophytes have more surface voxels assigned small thickness values. The distribution of surface thickness values for each animal is best described by Gamma distributions, whose shape parameter is consistently sensitive to osteoarthritis and the presence of osteophytes., Conclusion: Combining traditional image processing with empirical distribution fitting provides an automated, objective, and resolution-invariant workflow for osteophyte assessment., Significance: The proposed method is simple, yet elegant in its implementation, and can be readily used in new implementations.

Objectives: The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Emerging Leaders Program (ELP) aims to cultivate a cohort of skilled leaders within the OMERACT community empowering them with expertise and knowledge to help shape and steer the organization into the future. This publication highlights the significance of the ELP in driving leadership excellence, its impact on OMERACT's evolution, and the outcomes and learnings from the OMERACT 2023 ELP., Methods: Insights from the 2018 ELP report informed 2023 program improvements. Engagement was measured by attendance and WhatsApp interactions. Positive program aspects, areas for improvement and ideas for enhancing future ELPs were captured via anonymous survey and participant focus groups., Results: Engagement with the ELP was high with 9 participants, 96 % attendance at all workshops, 154 WhatsApp interactions. All program components were highly rated, with the highest being the 'Psychological Safety' and 'Methodology/Process/Politics' workshops. Future enhancements included creating further networking, connection and support activities, practical leadership and methodological skill development opportunities, and a new stream focussing on organisational advancement., Conclusions: The 2023 OMERACT ELP was well received and successfully addressed areas previously identified as requiring improvement. New educational enhancements were valued, and the importance of fostering psychological safety at all levels was highlighted. The ELP fortifies OMERACT by nurturing a diverse array of skilled leaders who embody OMERACTs core values. Continuing to refine and evolve the ELP over time will help OMERACT sustain its global influence in patient-centered outcome research., Competing Interests: Declaration of competing interest None of the authors has any competing interests to declare., (Copyright © 2024. Published by Elsevier Inc.)

Glycosaminoglycans (GAGs) are ubiquitous components in the cartilage extracellular matrix (ECM). Ultrastructural arrangement of ECM and GAG-mediated interactions with collagen are known to govern the mechanics in articular cartilage, but these interactions are less clear in other cartilage types. Therefore, this article reviews the current literature on ultrastructure of articular, auricular, meniscal, and nasal septal cartilage, seeking insight into GAG-mediated interactions influencing mechanics. Ultrastructural features of these cartilages are discussed to highlight differences between them. GAG-mediated interactions are reviewed under two categories: interactions with chondrocytes and interactions with other fibrillar macromolecules of the ECM. Moreover, efforts to replicate GAG-mediated interactions to improve mechanical integrity of tissue-engineered cartilage constructs are discussed. In conclusion, studies exploring cartilage specific GAGs are poorly represented in the literature, and the ultrastructure of nasal septal and auricular cartilage is less studied compared with articular and meniscal cartilages. Understanding the contribution of GAGs in cartilage mechanics at the ultrastructural level and translating that knowledge to engineered cartilage will facilitate improvement of cartilage tissue engineering approaches.

The effects of gender-affirming hormone therapy on the skeletal integrity and fracture risk in transitioning adolescent trans girls are unknown. To address this knowledge gap, we developed a mouse model to simulate male-to-female transition in human adolescents in whom puberty is first arrested by using gonadotrophin-releasing hormone analogs with subsequent estradiol treatment. Puberty was suppressed by orchidectomy in male mice at 5 weeks of age. At 3 weeks post-surgery, male-to-female mice were treated with a high dose of estradiol (~0.85 mg) by intraperitoneal silastic implantation for 12 weeks. Controls included intact and orchidectomized males at 3 weeks post-surgery, vehicle-treated intact males, intact females and orchidectomized males at 12 weeks post-treatment. Compared to male controls, orchidectomized males exhibited decreased peak bone mass accrual and a decreased maximal force the bone could withstand prior to fracture. Estradiol treatment in orchidectomized male-to-female mice compared to mice in all control groups was associated with an increased cortical thickness in the mid-diaphysis, while the periosteal circumference increased to a level that was intermediate between intact male and female controls, resulting in increased maximal force and stiffness. In trabecular bone, estradiol treatment increased newly formed trabeculae arising from the growth plate as well as mineralizing surface/bone surface and bone formation rate, consistent with the anabolic action of estradiol on osteoblast proliferation. These data support the concept that skeletal integrity can be preserved and that long-term fractures may be prevented in trans girls treated with GnRHa and a sufficiently high dose of GAHT. Further study is needed to identify an optimal dose of estradiol that protects the bone without adverse side effects., (© 2023. The Author(s).)

Objective: To systematically review the published parameters for the assessment of subchondral bone in human osteoarthritis (OA) using computed tomography (CT) and gain an overview of current practices and standards., Design: A literature search of Medline, Embase and Cochrane Library databases was performed with search strategies tailored to each database (search from 2010 to January 2023). The search results were screened independently by two reviewers against pre-determined inclusion and exclusion criteria. Studies were deemed eligible if conducted in vivo/ex vivo in human adults (>18 years) using any type of CT to assess subchondral bone in OA. Extracted data from eligible studies were compiled in a qualitative summary and formal narrative synthesis., Results: This analysis included 202 studies. Four groups of CT modalities were identified to have been used for subchondral bone assessment in OA across nine anatomical locations. Subchondral bone parameters measuring similar features of OA were combined in six categories: (i) microstructure, (ii) bone adaptation, (iii) gross morphology (iv) mineralisation, (v) joint space, and (vi) mechanical properties., Conclusions: Clinically meaningful parameter categories were identified as well as categories with the potential to become relevant in the clinical field. Furthermore, we stress the importance of quantification of parameters to improve their sensitivity and reliability for the evaluation of OA disease progression and the need for standardised measurement methods to improve their clinical value., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)