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Various metabolic abnormalities, including obesity, insulin resistance, hypertension, dyslipidemia, hyperthyroidism and low vitamin D levels, have been linked to both osteopenia and sarcopenia. Osteosarcopenia is also commonly observed in older age groups, notably in postmenopausal women. Glucagon-like peptide-1 (GLP-1), a labile incretin secreted from the intestinal L-cells, stimulates insulin secretion and sensitivity, making it an effective anti-diabetic medication. GLP-1 binds to its receptor, the GLP-1 receptor, a G-protein-coupled receptor, and leads to the stimulation of adenylate cyclase, increasing the levels of cyclic AMP (cAMP). Elevated cAMP then activates protein kinase A and other downstream signaling pathways. These signaling cascades result in various cellular responses, such as enhanced insulin secretion from pancreatic beta cells, improved insulin sensitivity and modulation of appetite and gastric emptying. In addition, GLP-1 signaling can promote cell growth and survival, contributing to its effects on muscle and bone health. Its role as an anti-diabetic medication has been enhanced through various modifications to extend its half-life, thereby improving its effectiveness and druggability. GLP-1 analogs, initially developed for diabetes management, have also been harnessed for obesity treatment due to the effect of GLP-1 to induce satiety and slow gastric emptying. Beyond their well-known anti-diabetic and anti-obesity effects, GLP-1 agonists can enhance muscle mass and bone density, making them valuable in addressing conditions such as sarcopenia and osteoporosis. This review focuses on the effects of GLP-1 analogs on musculoskeletal health by critically assessing the underlying signaling mechanisms in order to understand their translational potential for the treatment of osteosarcopenia. [ABSTRACT FROM AUTHOR]

Contrary to the popular perception that bone is merely a structural organ, decades of research has established its functional importance in whole-body metabolism. Osteocytes, which comprise >80% of all bone cells, were also initially thought to be terminally differentiated dormant cells lacking metabolic functions. New research, however, is increasingly providing evidence that osteocytes not only play a role in the structural integrity of bone but also have secretory functions that regulate other bone cells and other organs, including skeletal muscle, the structural-mechanical neighbor of the bone, via paracrine and endocrine pathways. However, interpretations of the publicly available preclinical and clinical data pertaining to the factors secreted by osteocytes and their functions in the musculoskeletal system largely fail to reach a consensus. This review aimed to objectively collate all information available in the public domain for efficient access by researchers in the field. We strongly believe that this review will assist researchers attempting the unbiased design of therapeutic strategies for musculoskeletal disorders. [ABSTRACT FROM AUTHOR]