The Gut-Bone Axis in Osteoporosis: A Multifaceted Interaction with Implications for Bone Health

Chunli Gu¹Hong Du²Ningying Li¹Yunlong Zhou³Sha Li³Yuchen Sun⁴Yiyang Han⁵Xuan Xu⁵Xianrong Li^1*

• ¹College of Nursing, Southwest Medical University, Luzhou, China
• ²Department of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan Province, China
• ³Department of Orthopedics, Leshan People’s Hospital, Leshan, China
• ⁴Department of Clinical Medicine, University of Hong Kong, Hongkong, China
• ⁵Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China

With the accelerated aging of population, degenerative orthopedic diseases represented by osteoporosis become a major public health challenge that threatens bone health and affects life quality. Existing anti-osteoporosis regime remains rather unitary or poorly adhered, which also limits the maintenance of bone health to some extent. Given the increasingly elucidated prominence of gut-related factors in osteoblast/osteoclast and bone formation/metabolism/maintenance, anchoring intestinal microecology and then targeting the distal bone tissue via the gut-bone axis has been recognized as a feasible intervention strategy. This review here systematically summarized the interaction of gut-bone axis, whilst highlighted the physiochemical barriers formed by intestinal intrinsic structures, gut microbiota and related molecules for bone health maintenance through immune and endocrine pathways. Meanwhile, we emphasized the ideal anti-osteoporotic property and individual achievability of measures like fecal microbiota transplantation, probiotic and prebiotic supplementation, and dietary pattern modification. The conceptual framework of gut-bone axis plus X were innovatively proposed given the potential synergy among different organs in disease characterization and pathogenesis, which may help better explain the etiology and manage other co-morbidities concurrent with or secondary to osteoporosis. Since the intersection of orthopedics with other subjects, we also supported the application of nano-biomaterials, bacterial synthetic biology and novel small molecules in anti-osteoporosis, which is expected to unlock broader prospects for multidisciplinary integration of the gut-bone axis.