The bone-muscle-adipose tissue axis: mechanisms and clinical implications

Obesity and bone health: reconciling the density–fragility paradox

The need to move beyond BMD alone and adopt comprehensive, individualized approaches to fracture risk assessment and management in obesity is highlighted.

Shared mechanisms of musculoskeletal dysfunction in type 2 diabetes mellitus: Insights into future therapeutic directions (Review)

Type 2 diabetes mellitus (T2DM) profoundly affects the musculoskeletal system through multifactorial mechanisms. The present review systematically summarizes the impact of T2DM on skeletal muscle, tendon, tendon-bone interface (TBI), and bone, highlighting their shared and tissue-specific pathophysiological pathways. In skeletal muscle, impaired insulin signaling and mitochondrial dysfunction lead to reduced protein synthesis, enhanced proteolysis, and muscle atrophy. In tendons, advanced glycation end products accumulation and microangiopathy disrupt collagen metabolism and biomechanics. At the TBI, persistent hyperglycemia induces fibrocartilage fibrosis, impaired angiogenesis and disorganized stress transmission, ultimately weakening load-bearing capacity. In bone, the imbalance between osteoblast and osteoclast activity, coupled with microvascular dysfunction and metabolic acidosis, results in reduced bone formation and increased fragility. Although the manifestations of T2DM differ among skeletal muscle, tendon, TBI and bone, these tissues share common pathological drivers, including metabolic dysregulation, chronic inflammation, oxidative stress, extracellular matrix remodeling, and impaired regenerative capacity. A deeper understanding of these shared mechanisms may facilitate the identification of novel therapeutic targets. Emerging technologies, including single-cell RNA sequencing, regenerative medicine, and precision medicine, further provide new opportunities for early diagnosis and personalized management of diabetes-related musculoskeletal disorders.

Endocrine Factors in Sarcopenia: Lifestyle-Based Approaches with Nutrition, Exercise, and Circadian Health

Sarcopenia, the age-related skeletal muscle disorder characterized by declines in muscle mass, strength, and physical performance, has significant health consequences and represents a major global public health challenge. Age-related endocrine and peripheral anabolic-catabolic dysregulation plays a central role in sarcopenia development, and lifestyle factors interact with hormonal regulation to influence skeletal muscle homeostasis. In older adults, reduced hormone secretion capacity, receptor responsiveness, and peripheral metabolism impair hormonal systems, including the somatotropic, gonadal, adrenal, and thyroid axes, as well as insulin and peripheral mediators, such as adipokines, myokines, and inflammatory cytokines. These alterations promote anabolic resistance, a catabolic environment, and metabolic dysfunction, contributing to sarcopenia. Age-related changes in appetite, nutrient utilization, and food choice impair anabolic efficiency and metabolic homeostasis. Declines in physical activity and neuromuscular efficiency disrupt multiple signaling pathways required to maintain muscle mass, and psychosocial factors may increase the risk of a vicious cycle of inactivity. Alterations in the suprachiasmatic nucleus (SCN) and inconsistent behavioral zeitgebers disrupt physiological rhythms. These lifestyle domains influence skeletal muscle homeostasis independently and interact bidirectionally through shared endocrine pathways. Current pharmacological approaches remain adjunctive, limited to confirmed endocrine deficiencies. The coordinated optimization of nutrition, exercise, and circadian health, with attention to regularity and timing, may offer complementary benefits exceeding single-domain interventions. A stage-specific and individually tailored approach supported by multidimensional monitoring and digital technologies is recommended for effective sarcopenia prevention and management.

Glucose metabolism in osteoporosis: A potential therapeutic target (Review)

Osteoporosis is a systemic skeletal disease characterized by progressive bone loss and an increased risk of fracture, and it represents a major public health challenge worldwide. Osteoporosis has multiple pathogenic determinants, including age, endocrine disorders and medication. Current therapeutic approaches primarily aim to promote osteogenesis directly or inhibit osteoclast activity; however, these strategies may limit therapeutic efficacy and increase the risk of adverse effects. The present review provided an integrated perspective on the pathogenesis of osteoporosis from the standpoint of glucose metabolism. Glucose oxidation generates ATP and metabolic intermediates that are key to bone homeostasis. During early differentiation, mesenchymal stem cells rely predominantly on glycolysis during commitment toward pre-osteoblasts, whereas maturation into functional osteoblasts depends more notably on oxidative phosphorylation. The fusion and differentiation of osteoclasts require robust mitochondrial oxidation. Lactate derived from anaerobic metabolism has a dual role in bone metabolism. High-risk populations for osteoporosis include postmenopausal women, patients with type 2 diabetes mellitus and individuals with obesity. Estrogen exerts anti-inflammatory and antioxidant effects through receptor activation. Excessive production of advanced glycation end-products disrupts the bone matrix, whereas hyperlipidemia promotes inflammatory factor-induced bone resorption. These pathological changes disrupt the insulin receptor substrate/PI3K/AKT signaling pathway, compromise glucose transporter-mediated cellular glucose uptake and thus, contribute to relative insulin resistance and insufficiency compared with physiological states. In conclusion, the present review demonstrated that abnormal glucose metabolism is a key pathogenic mechanism in osteoporosis and that targeting insulin signaling may represent a fundamental strategy for correcting glucose metabolic abnormalities across diverse etiologies.

Regional adipose tissue redistribution and infiltration in primary osteoporosis: A comprehensive body composition study.

Endocrine-related osteoporosis: bone quality, clinical phenotype, and targeted management

A practical clinical framework is proposed that integrates endocrine phenotype, vertebral imaging, trabecular bone score, and biochemical assessment into fracture-risk stratification and therapeutic decision-making, enabling improved identification of high- and very-high-risk patients and facilitating the appropriate use of anabolic and antiresorptive therapies.