High-fat and high-carbohydrate diets increase bone fragility through TGF-ß-dependent control of osteocyte function.

Obesity can increase the risk of bone fragility, even when bone mass is intact. This fragility stems from poor bone quality, potentially caused by deficiencies in bone matrix material properties. However, cellular and molecular mechanisms leading to obesity-related bone fragility are not fully understood. Using male mouse models of obesity, we discovered TGF-ß signaling plays a critical role in mediating the effects of obesity on bone. High-carbohydrate and high-fat diets increase TGF-ß signaling in osteocytes, which impairs their mitochondrial function, increases cellular senescence, and compromises perilacunar/canalicular remodeling and bone quality. By specifically inhibiting TGF-ß signaling in mouse osteocytes, some of the negative effects of high-fat and high-carbohydrate diets on bones, including the lacunocanalicular network, perilacunar/canalicular remodeling, senescence, and mechanical properties such as yield stress, were mitigated. DMP1-Cre-mediated deletion of TGF-ß receptor II also blunted adverse effects of high-fat and high-carbohydrate diets on energy balance and metabolism. These findings suggest osteocytes are key in controlling bone quality in response to high-fat and high-carbohydrate diets. Calibrating osteocyte function could mitigate bone fragility associated with metabolic diseases while reestablishing energy balance.

Leadership development training for orthopaedic trauma surgeons: an international survey.

Purpose: This study examined the leadership development themes that global orthopaedic surgeons in differently resourced countries perceive as essential components and evaluated barriers to attending leadership development programs. Methods: This multinational, 45-question survey engaged orthopaedic surgeons (one expert per country). The questionnaire collected participants' demographics, perception of effective leadership traits, and valuation of various leadership themes based on importance and interest. Results: The survey was completed by 110 orthopaedic surgeons worldwide. Respondents most commonly reported holding a leadership position (87%) in hospital settings (62%), clinical settings (47%), and national orthopaedic societies (46%). The greatest proportion of participants reported having never attended a leadership course (42%). Participants regarded "high performing team-building," "professional ethics," and "organizational structure and ability to lead" as the most important leadership themes. No significant (P ≤ 0.05) differences were identified among perceived importance or interest in leadership themes between income levels; however, statistically significant differences were identified in the questionnaire; respondents in low- and middle-income countries (LICs/LMICs) demonstrated a stronger interest in attending a leadership course than those in high-income countries (HICs) (98% vs. 79%, P = 0.013), and fewer surgeons in LICs/LMICs had taken personality assessment tests than those in HICs (22% vs. 49%, P = 0.019). The most common barriers to attending leadership courses were lack of opportunities and invitations (57%), difficulty missing work (22%), and cost of course attendance (22%). Conclusions: These findings can better inform the development of effective curricula and provide a framework for a successful model for the future. Level of Evidence: V.

Therapeutic approaches to activate the canonical Wnt pathway for bone regeneration.

Activation of the canonical Wingless-related integration site (Wnt) pathway has been shown to increase bone formation and therefore has therapeutic potential for use in orthopedic conditions. However, attempts at developing an effective strategy to achieve Wnt activation has been met with several challenges. The inherent hydrophobicity of Wnt ligands makes isolating and purifying the protein difficult. To circumvent these challenges, many have sought to target extracellular inhibitors of the Wnt pathway, such as Wnt signaling pathway inhibitors Sclerostin and Dickkopf-1, or to use small molecules, ions and proteins to increase target Wnt genes. Here, we review systemic and localized bioactive approaches to enhance bone formation or improve bone repair through antibody-based therapeutics, synthetic Wnt surrogates and scaffold doping to target canonical Wnt. We conclude with a brief review of emerging technologies, such as mRNA therapy and Clustered Regularly Interspaced Short Palindromic Repeats technology, which serve as promising approaches for future clinical translation.

International Orthopaedic Volunteer Opportunities in Low and Middle-Income Countries.

ABSTRACT: Globally, the burden of musculoskeletal conditions continues to rise, disproportionately affecting low and middle-income countries (LMICs). The ability to meet these orthopaedic surgical care demands remains a challenge. To help address these issues, many orthopaedic surgeons seek opportunities to provide humanitarian assistance to the populations in need. While many global orthopaedic initiatives are well-intentioned and can offer short-term benefits to the local communities, it is essential to emphasize training and the integration of local surgeon-leaders. The commitment to developing educational and investigative capacity, as well as fostering sustainable, mutually beneficial partnerships in low-resource settings, is critical. To this end, global health organizations, such as the Consortium of Orthopaedic Academic Traumatologists (COACT), work to promote and ensure the lasting sustainability of musculoskeletal trauma care worldwide. This article describes global orthopaedic efforts that can effectively address musculoskeletal care through an examination of 5 domains: clinical care, clinical research, surgical education, disaster response, and advocacy.

Orthopaedic trauma care during the early COVID-19 pandemic in the Asia-Pacific region.

The Asia-Pacific region countries, with their large and socioeconomically diverse populations and infrastructures, were amongst the earliest to have to respond to the COVID-19 pandemic. Although the disease is not one of surgical trauma, its effects on orthopaedic injuries have been significant. Medical systems had to adapt to better focus on patients with a highly communicable disease, while continuing to provide essential services. Even though many countries saw a decrease in traumatic injuries during the initial periods, orthopaedic trauma services nevertheless had to adapt accordingly to system-wide organizational changes. While each country took their individual approaches to address the pandemic, there were also consistencies in how musculoskeletal injuries and conditions were handled during these early stages of the pandemic. This article reviews those early management approaches to musculoskeletal injury care during the COVID-19 pandemic in different countries throughout the Asia-Pacific region following the initial outbreak in China: Australia, South Korea, and Japan.