REVIEW article
Front. Endocrinol.
Sec. Bone Research
The Role and Mechanisms of Bone Microenvironment Regulators in Osteoporosis: Novel Intervention Strategies for Addressing the Challenges of Aging
Provisionally accepted
- Second Affiliated Hospital of Jilin University, Changchun, China
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Osteoporosis is an increasingly important global health concern, particularly in aging populations, with prevalence rising markedly after the age of 60. Age-related alterations in the bone microenvironment play a pivotal role in disrupting skeletal homeostasis. Regulators of the bone microenvironment contribute centrally to osteoporosis pathogenesis by modulating bone remodeling through multiple, intersecting mechanisms. Accumulating evidence indicates that aging is accompanied by reduced levels of protective factors, such as osteoprotegerin and bone morphogenetic proteins (BMPs), alongside increases in pro-resorptive mediators, including receptor activator of nuclear factor-κB ligand (RANKL), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). This shift favors osteoclastogenesis and impairs osteoblast function, ultimately accelerating bone loss and increasing the risk of fragility fractures and disability. In this review, we synthesize current evidence on bone microenvironment regulatory factors in osteoporosis, with emphasis on their roles in bone remodeling and downstream cellular signaling pathways. We further discuss emerging intervention strategies that target these regulators to preserve or restore bone health in older adults. By clarifying age-associated microenvironmental changes and the interactions among key regulatory factors, this review aims to identify promising therapeutic targets and provide a conceptual framework to support osteoporosis prevention and treatment in the context of global population aging.
Keywords: Aging, Bone microenvironment, Bone Remodeling, Osteoporosis, regulatory factors
Received: 08 Jan 2026; Accepted: 03 Feb 2026.
Copyright: © 2026 Yao, Cui, Li, Sun, Peng and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dankai Wu
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