Natural Bioactive Compounds in Endocrine and Metabolic Bone Disorders: From Mechanisms to Translational Perspectives

Bone is a dynamic endocrine-responsive tissue that undergoes continuous remodeling to maintain skeletal strength and mineral homeostasis. This tightly regulated process depends on the coordinated activity of osteoblasts and osteoclasts and is influenced by complex interactions between hormonal signaling, immune responses, inflammatory mediators, and epigenetic regulation. Disruption of these pathways contributes to a wide range of endocrine and metabolic bone disorders, including osteoporosis, glucocorticoid-induced bone loss, diabetes-associated skeletal fragility, thyroid-related bone disease, and postmenopausal osteoporosis.While current pharmacological therapies have significantly improved the management of these conditions, long-term treatment may be associated with limitations including adverse effects, high costs, or incomplete restoration of bone quality. Consequently, naturally derived bioactive compounds have attracted growing interest as potential complementary or alternative therapeutic strategies. These include naturally occurring bioactive molecules and phytochemicals derived from plants, marine organisms, and microorganisms that exert measurable biological effects on pathways relevant to bone metabolism and endocrine bone disease. Such compounds have demonstrated the ability to regulate bone remodeling by modulating oxidative stress, inflammation, cytokine signaling, osteoblast and osteoclast activity, endocrine pathways, and epigenetic mechanisms. Emerging advances in targeted delivery systems may further improve the bioavailability, distribution, and therapeutic potential of natural compounds intended for bone disorders.Despite promising findings from experimental and preclinical studies, many questions remain regarding the molecular mechanisms underlying these compounds, their interactions with endocrine and immune signaling networks, and their translation into safe and effective clinical therapies. A more integrated understanding of their causal and biologically relevant effects on bone biology will be essential for identifying novel therapeutic targets and advancing natural compound-based interventions. Preclinical studies with clear mechanistic and translational relevance, alongside robust clinical evidence, are particularly important for bridging the gap between experimental findings and clinical application.This Research Topic aims to bring together basic, translational, and clinical research investigating natural bioactive compounds in endocrine and metabolic bone disorders. By integrating advances in endocrinology, bone biology, pharmacology, osteoimmunology, and epigenetics, this collection seeks to move beyond descriptive evidence by providing mechanistic insights into how natural compounds influence skeletal biology and evaluating their potential for clinical translation. Purely descriptive omics studies without biologically relevant functional or mechanistic validation are not considered within the scope of this Research Topic.We welcome submissions including, but not limited to:• Natural bioactive compounds and phytochemicals for the prevention and treatment of endocrine and metabolic bone disorders• Molecular and endocrine mechanisms through which bioactive compounds regulate bone remodeling• Natural bioactive compounds influencing osteoblast and osteoclast differentiation and function• Epigenetic, immunological, and cytokine signaling pathways targeted by natural bioactive compounds• Gut microbiota-mediated effects of natural compounds on bone metabolism• Randomized clinical trials, prospective studies, systematic reviews, and meta-analyses evaluating the efficacy, safety, pharmacokinetics, and clinical applicability of natural compounds in endocrine and metabolic bone disorders• Natural compound-based approaches for bone regeneration and fracture repair with clear relevance to endocrine and metabolic bone disease Topic editors: Katharina F. Kubatzky, Richa Ashma, Kok Lun Pang, Rupesh K. Srivastava Source: https://www.frontiersin.org/research-topics/84556/natural-bioactive-compounds-in-endocrine-and-metabolic-bone-disorders-from-mechanisms-to-translational-perspectives