REVIEW article
Front. Aging
Sec. Musculoskeletal Aging
This article is part of the Research TopicFrailty Trajectories and Modifiable Determinants: From Biomarkers to Clinical GuidelinesView all articles
Targeting Innate Immunity to Modulate Bone Metabolism: A Novel Strategy for Osteoporosis Treatment
Provisionally accepted
Wenjie Kou Kou1
Xiaomin Lu Lu1Zhe Zhang Zhang1Kaiwen Liu Liu1Zhihuan Liu Liu1Bin Jiang Jiang1Hongping Wang Wang2Jishu Li Li1Hu Lu Lu1Chenglong Guo Guo3*Linzhong Cao Cao1Xiaogang Zhang Zhang3- 1Gansu University of Chinese Medicine, Lanzhou, China
- 2Longnan Maternal and Child Health Hospital, Longnan, Gansu, longann, China
- 3Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Osteoporosis is a systemic metabolic bone disorder characterized by reduced bone mass and impaired microarchitecture, with its core pathological mechanism being an imbalance between bone formation and resorption. Traditional therapies targeting osteoblast/osteoclast function have limited efficacy and safety concerns. Recent osteoimmunology advances reveal that the innate immune system regulates bone homeostasis via intercellular interactions, cytokine networks, and metabolic reprogramming. This systematic review examines the roles of innate immune cells (macrophages, neutrophils, NK cells, DCs), complement system, and emerging pathways (trained immunity, mitochondrial symbiosis disruption) in osteoporosis. It summarizes therapeutic strategies (immunometabolic modulators, complement antagonists, cytokine-targeted drugs, TCM components) and outlines challenges (target specificity, clinical translation) and future directions, providing theoretical foundations for novel OP treatments.
Keywords: bone metabolism, complement system, innate immunity, Macrophages, Osteoporosis, targetedtherapy, trainedimmunity
Received: 20 Nov 2025; Accepted: 13 Feb 2026.
Copyright: © 2026 Kou, Lu, Zhang, Liu, Liu, Jiang, Wang, Li, Lu, Guo, Cao and Zhang. 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: Chenglong Guo Guo
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.