Current Osteoporosis Reports最新文献

Purpose of review: GWAS, as a largely correlational analysis, requires in vitro or in vivo validation. Zebrafish (Danio rerio) have many advantages for studying the genetics of human diseases. Since gene editing in zebrafish has been highly valuable for studying embryonic skeletal developmental processes that are prenatally or perinatally lethal in mammalian models, we are reviewing pros and cons of this model.

Recent findings: The true power for the use of zebrafish is the ease by which the genome can be edited, especially using the CRISPR/Cas9 system. Gene editing, followed by phenotyping, for complex traits such as BMD, is beneficial, but the major physiological differences between the fish and mammals must be considered. Like mammals, zebrafish do have main bone cells; thus, both in vivo stem cell analyses and in vivo imaging are doable. Yet, the "long" bones of fish are peculiar, and their bone cavities do not contain bone marrow. Partial duplication of the zebrafish genome should be taken into account. Overall, small fish toolkit can provide unmatched opportunities for genetic modifications and morphological investigation as a follow-up to human-first discovery.

Purpose of review: The integration of data from multiple genomic assays from humans and non-human model organisms is an effective approach to identify genes involved in skeletal fragility and fracture risk due to osteoporosis and other conditions. This review summarizes genome-wide genetic variation and gene expression data resources relevant to the discovery of genes contributing to skeletal fragility and fracture risk.

Recent findings: Genome-wide association studies (GWAS) of osteoporosis-related traits are summarized, in addition to gene expression in bone tissues in humans and non-human organisms, with a focus on rodent models related to skeletal fragility and fracture risk. Gene discovery approaches using these genomic data resources are described. We also describe the Musculoskeletal Knowledge Portal (MSKKP) that integrates much of the available genomic data relevant to fracture risk. The available genomic resources provide a wealth of knowledge and can be analyzed to identify genes related to fracture risk. Genomic resources that would fill particular scientific gaps are discussed.

Purpose of review: The purpose of this review paper is to summarize current weight-bearing guidelines for common geriatric fractures, around weight-bearing joints, of the upper and lower extremities.

Recent findings: There is an increasing amount of literature investigating the safety and efficacy of early weight-bearing in geriatric fractures, particularly of the lower extremity. Many recent studies, although limited, suggest that early weight-bearing may be safe for geriatric distal femur and ankle fractures. Given the limited data pertaining to early weight-bearing in geriatric fractures, it is difficult to establish concrete weight-bearing guidelines in this population. However, in the literature available, early weight-bearing appears to be safe and effective across most injuries. The degree and time to weight-bearing vary significantly based on fracture type and treatment method. Future studies investigating postoperative weight-bearing protocols should focus on the growing geriatric population and identify methods to address specific barriers to early weight-bearing in these patients such as cognitive impairment, dependence on caregivers, and variations in post-acute disposition.

Purpose of review: Orthodontic tooth movement is characterized by periodontal tissue responses to mechanical loading, leading to clinically relevant functional adaptation of jaw bone. Since osteocytes are significant in mechanotransduction and orchestrate osteoclast and osteoblast activity, they likely play a central role in orthodontic tooth movement. In this review, we attempt to shed light on the impact and role of osteocyte mechanotransduction during orthodontic tooth movement.

Recent findings: Mechanically loaded osteocytes produce signaling molecules, e.g., bone morphogenetic proteins, Wnts, prostaglandins, osteopontin, nitric oxide, sclerostin, and RANKL, which modulate the recruitment, differentiation, and activity of osteoblasts and osteoclasts. The major signaling pathways activated by mechanical loading in osteocytes are the wingless-related integration site (Wnt)/β-catenin and RANKL pathways, which are key regulators of bone metabolism. Moreover, osteocytes are capable of orchestrating bone adaptation during orthodontic tooth movement. A better understanding of the role of osteocyte mechanotransduction is crucial to advance orthodontic treatment. The optimal force level on the periodontal tissues for orthodontic tooth movement producing an adequate biological response, is debated. This review emphasizes that both mechanoresponses and inflammation are essential for achieving tooth movement clinically. To fully comprehend the role of osteocyte mechanotransduction in orthodontic tooth movement, more knowledge is needed of the biological pathways involved. This will contribute to optimization of orthodontic treatment and enhance patient outcomes.

Purpose of review: This review aims to explore the potential of biomimetic hydrogels as an alternative to bone cement in vertebral body stenting (VBS), a minimally invasive treatment for vertebral compression fractures.

Recent findings: The use of bone cement in VBS procedures can lead to complications such as incomplete fracture reduction and cement leakage. Biomimetic hydrogels have gained significant attention as potential biomaterial alternatives for VBS due to their unique properties, including tuneable therapeutic and mechanical properties. Over the past decade, there has been significant advancements in the development of biomimetic hydrogels for bone regeneration, employing a wide range of approaches to enhance the structural and functional properties of hydrogels. Biomimetic hydrogels hold significant promise as safer and reparative alternatives to bone cement for VBS procedures. However, further research and development in this field are necessary to explore the full potential of hydrogel-based systems for vertebral bone repair.

Purposeof review: To summarize what is known about the deleterious effect of hip fracture on muscle mass and strength as well as the scientific evidence for post-surgical nutrition supplementation to maintain muscle and improve function.

Recent findings: This review provides a discussion of the relationship between muscle mass, strength, and physical function following hip fracture, briefly describes the approaches to measuring lean mass, discusses prevalence of sarcopenia and malnutrition among older men and women with hip fracture, and reviews the effects of essential amino acids on muscle. Loss of muscle mass and strength following hip fracture is substantial with consequences for recovery of functional independence. EAA-based nutrition supplementation, which directly effects muscle, has potential to improve outcomes.

Purpose of review: The periosteum, the outer layer of bone, is a major source of skeletal stem/progenitor cells (SSPCs) for bone repair. Here, we discuss recent findings on the characterization, role, and regulation of periosteal SSPCs (pSSPCs) during bone regeneration.

Recent findings: Several markers have been described for pSSPCs but lack tissue specificity. In vivo lineage tracing and transcriptomic analyses have improved our understanding of pSSPC functions during bone regeneration. Bone injury activates pSSPCs that migrate, proliferate, and have the unique potential to form both bone and cartilage. The injury response of pSSPCs is controlled by many signaling pathways including BMP, FGF, Notch, and Wnt, their metabolic state, and their interactions with the blood clot, nerve fibers, blood vessels, and macrophages in the fracture environment. Periosteal SSPCs are essential for bone regeneration. Despite recent advances, further studies are required to elucidate pSSPC heterogeneity and plasticity that make them a central component of the fracture healing process and a prime target for clinical applications.

Purpose of review: The incidence of musculoskeletal disorders affecting bones, joints, and muscles is dramatically increasing in parallel with the increased longevity of the worldwide population, severely impacting on the individual's quality of life and on the healthcare costs. Inactivity and sedentary lifestyle are nowadays considered the main drivers of age-associated musculoskeletal disorders and exercise may counteract such alterations also in other bone- and muscle-centered disorders. This review aims at clarifying the potential use of exercise training to improve musculoskeletal health.

Recent findings: Both the skeletal muscle and the bone are involved in a complex crosstalk determining, in part through tissue-specific and inflammatory/immune released factors, the occurrence of musculoskeletal disorders. Exercise is able to modulate the levels of those molecules and several associated molecular pathways. Evidence from preclinical and clinical trials supports the adoption of exercise and the future use of exercise mimicking drugs will optimize the care of individuals with musculoskeletal disorders.