Bone Phenotyping Approaches in Human, Mice and Zebrafish - Expert Overview of the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork").

A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research. This expert paper provides a comprehensive overview of state-of-the-art technologies to investigate bone properties in humans and animals - including their strengths and weaknesses. New research methodologies are outlined and future strategies are discussed to combine phenotypic with rapidly developing -omics data in order to advance musculoskeletal research and move towards "personalised medicine".

Genetics of Bone and Muscle Interactions in Humans.

PURPOSE OF REVIEW: To summarize the evidence from recent studies on the shared genetics between bone and muscle in humans. RECENT FINDINGS: Genome-wide association studies (GWAS) have successfully identified a multitude of loci influencing the variability of different bone or muscle parameters, with multiple loci overlapping between the traits. In addition, joint analyses of multiple correlated musculoskeletal traits (i.e., multivariate GWAS) have underscored several genes with possible pleiotropic effects on both bone and muscle including MEF2C and SREBF1. Notably, several of the proposed pleiotropic genes have been validated using human cells or animal models. It is clear that the study of pleiotropy may provide novel insights into disease pathophysiology potentially leading to the identification of new treatment strategies that simultaneously prevent or treat both osteoporosis and sarcopenia. However, the role of muscle factors (myokines) that stimulate bone metabolism, as well as osteokines that affect muscles, is in its earliest stage of understanding.

Structure, function, and control of the human musculoskeletal network.

The human body is a complex organism, the gross mechanical properties of which are enabled by an interconnected musculoskeletal network controlled by the nervous system. The nature of musculoskeletal interconnection facilitates stability, voluntary movement, and robustness to injury. However, a fundamental understanding of this network and its control by neural systems has remained elusive. Here we address this gap in knowledge by utilizing medical databases and mathematical modeling to reveal the organizational structure, predicted function, and neural control of the musculoskeletal system. We constructed a highly simplified whole-body musculoskeletal network in which single muscles connect to multiple bones via both origin and insertion points. We demonstrated that, using this simplified model, a muscle's role in this network could offer a theoretical prediction of the susceptibility of surrounding components to secondary injury. Finally, we illustrated that sets of muscles cluster into network communities that mimic the organization of control modules in primary motor cortex. This novel formalism for describing interactions between the muscular and skeletal systems serves as a foundation to develop and test therapeutic responses to injury, inspiring future advances in clinical treatments.

Estrés psicológico y problemática musculoesquelética. Revisión sistemática / Psychological stress and musculoskeletal problems. Systematic review

Objetivo. Analizar los diseños epidemiológicos más utilizados en el estudio de la relación entre estrés psicológico y problemática musculoesquelética. Metodología. Búsqueda bibliográfica con criterios de inclusión y exclusión específicos, en PubMed/Medline, EBSCOhost y revistas electrónicas de diversas disciplinas siguiendo las recomendaciones del estándar PRISMA. Se extrajeron 2782 artículos de los cuales fueron seleccionados 41 para la revisión. Resultados. Más del 80% de los estudios confirmaron la relación entre estrés psicológico y problemática musculoesquelética, determinando que los niveles de estrés mantenidos aumentan el riesgo de aparición de sintomatología, sobre todo en lumbares y cervicales. Del total de estudios, más del 50% fueron de diseño transversal y 77% sobre temática laboral. La población más vulnerable fue la femenina, especialmente funcionarios y trabajadores de oficina. Las “Demandas laborales” constituyeron el estresor psicosocial más descrito. Respecto a los instrumentos de medición más usados, destacan el “Stress Energy Questionnaire”, el “Job Content Questionnaire” y el “Standardized Nordic Musculoskeletal Questionnaire”. Conclusión: Los estudios sobre estrés psicológico y problemática musculoesquelética tienen diseños y resultados heterogéneos. Los hallazgos resaltaron múltiples estresores psicosociales y áreas corporales afectadas, siendo escasos los consensos en diagnósticos e instrumentos de medida. Aunque aparece una asociación entre estrés psicológico y problemas musculo esqueléticos, no se vislumbran relaciones causales claras. Dado el elevado coste de estos problemas, se considera necesario realizar más estudios con diseños y metodologías rigurosas (AU)

Objective: Analyze the epidemiological approach more used in the study of the relationship between psychological stress and musculoskeletal problems. Methodology: Bibliographic research with specific inclusion and exclusion criteria on PubMed / Medline, EBSCOhost and electronic journals from diverse disciplines following the recommendations of PRISMA standards. 2782 articles were extracted, of which 41 were selected for the revision. Results: More than 80% of the articles confirmed that maintained stress levels increase the risk of developing musculoskeletal symptoms, especially in the lower back and neck. Over 50% of the studies followed a transversal design, and 77% of them dealt with labour issues. The most vulnerable population were women working in civil service or white collars, and labour demands was the most described psychosocial stressor. Regarding measurement instruments, the most used were the Energy Stress Questionnaire, the Job Content Questionnaire, and the Standardized Nordic Musculoskeletal Questionnaire. Conclusion: Studies on psychological stress and musculoskeletal problems had heterogeneous results and designs. The findings highlight multiple psychosocial stressors and body areas affected and there was little consensus on diagnosis and measuring instruments. Although there was an association between psychological stress and musculoskeletal problems, their causal relationships are unclear. Given the higher cost of this problem, it is necessary to develop more studies with designs and rigorous methodologies (AU)