{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:18:56Z","timestamp":1788787136671,"version":"build-2803163510"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Osteoporosis (OP) is increasingly recognized as a systemic disorder involving crosstalk among immune-inflammatory, endocrine, and metabolic axes, rather than a condition driven solely by bone-mineral imbalance. This review synthesizes recent advances in understanding these axes and their coupling mechanisms. The immune-inflammatory axis, centered on Th17\/Treg imbalance and cytokines such as IL-17 and IL-35, regulates osteoclastogenesis and osteogenesis while linking autoimmune diseases to bone loss. The endocrine axis, encompassing sex hormones, thyroid\/adrenal\/parathyroid hormones, and receptors such as LGR4, modulates bone remodeling through complex signaling networks and circadian rhythms. The metabolic axis, particularly glucose-lipid-uric acid homeostasis, influences bone fragility via energy metabolism, oxidative stress, and gut microbiota interactions. We propose that OP is best understood as a network disorder manifesting in the skeleton, necessitating a shift from single-target to multi-axis systems medicine approaches. However, much of the mechanistic evidence derives from preclinical models and observational studies; prospective clinical validation remains essential. Future research should prioritize elucidating inter-axis communication in human cohorts and developing integrated, biomarker-stratified therapeutic strategies to advance precision management of osteoporosis.<\/jats:p>","DOI":"10.3389\/fendo.2025.1705040","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T05:30:24Z","timestamp":1767591024000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Progress in multiaxial coupling mechanisms of osteoporosis: insights from systems medicine on immune-inflammatory interactions, hormonal regulation, and metabolic 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