Matrix Competence Failure in Osteoporosis: Mechanosensing, Osteoimmune Crosstalk, and Fragility Beyond Bone Mineral Density

Abstract

Osteoporosis is typically characterized by reduced bone mass and deterioration of microarchitecture. However, bone mineral density (BMD) does not fully account for the wide variations in skeletal fragility. In this study, we propose that matrix competence is the capacity of the mineralized extracellular matrix (ECM), the lacunar–canalicular network (LCN), and the osteocyte network to ensure material integrity, maintain network connectivity, and present appropriate cell–matrix adhesion cues. When these properties are degraded, matrix-to-signal breakdown occurs: mechanical and inflammatory inputs are no longer translated efficiently into coordinated remodeling. Research findings on bone material biology, osteocyte regulation, mechanotransduction, and osteoimmunology indicate that load-adaptive formation requires efficient signal amplification and propagation across matrix and cellular networks. During aging and unloading, the properties of collagen–mineral material decrease, LCN and osteocyte coupling decrease, and anabolic adaptation becomes blunted. Chronic low-grade inflammation and immune remodeling can further exploit altered ECM positioning and adhesion, reinforcing resorptive remodeling. We suggest that reduced matrix competence provides a tissue-level explanation for the relationships among BMD, fracture risk, and therapeutic response. This framework places matrix material properties, network structural integrity, and remodeling coordination at the center of osteoporosis phenotyping independent of BMD.

Keywords

Osteoporosis / Extracellular matrix remodeling / Matrix competence / Mechanotransduction / Osteoimmunology / Bone quality / Lacunar–canalicular network / Bone material properties

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Funding

National Natural Science Foundation of China(82405520)

Jiangsu Province Traditional Chinese Medicine Science and Technology Development Program(QN202322)

Jiangsu Commission of Health(MQ2025033)

Wang Jianwei Famous Traditional Chinese Medicine Doctor Studio

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to the Huazhong University of Science and Technology

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