Sarcopenia

As the world's population ages, the prevalence of chronic diseases increases. Sarcopenia and osteoporosis are two conditions that are associated with aging, with similar risk factors that include genetics, endocrine function, and mechanical factors. Additionally, bone and muscle closely interact with each other not only anatomically, but also chemically and metabolically. Fat infiltration, a phenomenon observed in age-related bone and muscle loss, is highly prevalent and more severe in sarcopenic and osteoporotic subjects. Clinically, when individuals suffer a combination of both disorders, negative outcomes such as falls, fractures, loss of function, frailty, and mortality increase, thus generating significant personal and socio-economic costs. Therefore, it is suggested that when bone mineral density loss is synchronic with decreased muscle mass, strength, and function, it should be interpreted as a single diagnosis of osteosarcopenia, which may be preventable and treatable. Simple interventions such as resistance training, adequate protein and calcium dietary intake, associated with maintenance of appropriate levels of vitamin D, have a dual positive effect on bone and muscle, reducing falls, fractures, and, consequently, disability. It is essential that fracture prevention approaches-including postfracture management-involve assessment and treatment of both osteoporosis and sarcopenia. This is of particular importance as in older persons the combination of osteopenia/osteoporosis and sarcopenia has been proposed as a subset of frailer individuals at higher risk of institutionalization, falls, and fractures. This review summarizes osteosarcopenia epidemiology, pathophysiology, diagnosis, outcomes, and management strategies.

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Osteosarcopenia: where bone, muscle, and fat collide.

Osteosarcomas are the most frequent primary bone sarcomas, affecting mainly children, adolescents, and young adults, and with a second peak of incidence in elderly individuals. The current therapeutic management, a combined regimen of poly-chemotherapy and surgery, still remains largely insufficient, as patient survival has not improved in recent decades. Osteosarcomas are very heterogeneous tumors, both at the intra- and inter-tumor level, with no identified driver mutation. Consequently, efforts to improve treatments using targeted therapies have faced this lack of specific osteosarcoma targets. Nevertheless, these tumors are inextricably linked to their local microenvironment, composed of bone, stromal, vascular and immune cells and the osteosarcoma microenvironment is now considered to be essential and supportive for growth and dissemination. This review describes the different actors of the osteosarcoma microenvironment and gives an overview of the past, current, and future strategies of therapy targeting this complex ecosystem, with a focus on the role of extracellular vesicles and on the emergence of multi-kinase inhibitors.

The Osteosarcoma Microenvironment: A Complex But Targetable Ecosystem.

Purpose of reviewThis article reviews recently published evidence for common pathways explaining bone and muscle wasting in normal ageing and pathological conditions.Recent findingsNumerous studies support the concept of a bone–muscle unit, where constant cross-talking between the two tissues takes

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Osteoporosis and sarcopenia: two diseases or one?

The bone is a complex connective tissue composed of many different cell types such as osteoblasts, osteoclasts, chondrocytes, mesenchymal stem/progenitor cells, hematopoietic cells and endothelial cells, among others. The interaction between them is finely balanced through the processes of bone formation and bone remodeling, which regulates the production and biological activity of many soluble factors and extracellular matrix components needed to maintain the bone homeostasis in terms of cell proliferation, differentiation and apoptosis. Osteosarcoma (OS) emerges in this complex environment as a result of poorly defined oncogenic events arising in osteogenic lineage precursors. Increasing evidence supports that similar to normal development, the bone microenvironment (BME) underlies OS initiation and progression. Here, we recapitulate the physiological processes that regulate bone homeostasis and review the current knowledge about how OS cells and BME communicate and interact, describing how these interactions affect OS cell growth, metastasis, cancer stem cell fate and therapy outcome.

Bone microenvironment signals in osteosarcoma development

The complexity of cell interactions with their microenvironment and their ability to communicate at the autocrine, paracrine, and endocrine levels has gradually but significantly evolved in the last three decades. The musculoskeletal system has been historically recognized to be governed by a relationship of proximity and function, chiefly dictated by mechanical forces and the work of gravity itself. In this review article, we first provide a historical overview of the biomechanical theory of bone–muscle interactions. Next, we expand to detail the significant evolution in our understanding of the function of bones and muscles as secretory organs. Then, we review and discuss new evidence in support of a biochemical interaction between these two tissues. We then propose that these two models of interaction are complementary and intertwined providing for a new frontier for the investigation of how bone–muscle cross talk could be fully explored for the targeting of new therapies for musculoskeletal diseases, particularly the twin conditions of aging, osteoporosis and sarcopenia. In the last section, we explore the bone–muscle cross talk in the context of their interactions with other tissues and the global impact of these multi-tissue interactions on chronic diseases.

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Physiology of Mechanotransduction: How Do Muscle and Bone “Talk” to One Another?

Extracellular Membrane Vesicles Derived from 143B Osteosarcoma Cells Contain Pro-Osteoclastogenic Cargo: A Novel Communication Mechanism in Osteosarcoma Bone Microenvironment.

Jatropha curcas (JC) is a multipurpose perennial plant that belongs to the Euphorbiaceae family and is nativeto arid and semiarid tropical regions worldwide. It has many attributes and considerable potential for renewable energy,fish and livestock feeding. Despite its rich application as a renewable source and for animal feeding, JC has barely beenexplored for its medicinal potential. Here we review several patents related to JC that show it has been underused for medicinalpurposes. For example, only one invention disclosure to date utilizes JC, combined with three other plants, in apreparation for wound healing. Motivated by support from the Brazilian funding agencies and anecdotal accounts in Brazilof the medicinal value of JC, we performed a series of pilot studies that demonstrate that JC is able to protect skeletalmuscle cells in vitro against the deleterious effects of ethanol. We were able to determine that JC’s effects are mediated bythe up regulation of HSP60, a critical mitochondrial heat shock related protein that is essential for intracellular REDOXregulation. Given the fact that ethanol myopathy accounts for more than 50% of all cases of myopathy worldwide, wehope that our studies will sparkle new interest from the scientific community to explore the medicinal properties of Jatrophacurcas, including the development of new patents leading to new drugs and new targets for the treatment of musclediseases and other human diseases.

Jatropha curcas: from biodiesel generation to medicinal applications.

The endocrine nature of bones and skeletal muscles has become evident with the identification of several secreted molecules from these tissues. Cell based studies have demonstrated that conditioned media from one tissue can beneficially influence the other. Animal models of bone and muscle research have further supported the bone-muscle biochemical connection. This knowledge, in light of the tight developmental and genetic coupling of these tissues, large bivariate GWAS studies that have identified potentially pleiotropic bone-muscle genes, and the concurrence of osteoporosis and sarcopenia in older adults justifies a closer examination of the biochemical crosstalk between bones and muscles. In-depth understanding of the bone-muscle connection could pave the way to new treatments for musculoskeletal diseases.

Janalee Isaacson

Papers

Physiology of Mechanotransduction: How Do Muscle and Bone “Talk” to One Another?

Extracellular Membrane Vesicles Derived from 143B Osteosarcoma Cells Contain Pro-Osteoclastogenic Cargo: A Novel Communication Mechanism in Osteosarcoma Bone Microenvironment.

Jatropha curcas: from biodiesel generation to medicinal applications.

The Muscle-Bone Connection

Pinhão-manso (Jatropha curcas) demonstrates potent antibacterial properties in a rat model of third degree burns (1180.18)