Neuromuscular Remodeling in Knee Osteoarthritis Across Aging: An Evidence-Bounded Joint-Afferent-Motor Unit Framework.
- 1Department of Acupuncture and Tuina, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, People's Republic of China.
- 2Department of Traditional Chinese Medicine, The First People's Hospital of Baiyin City, Baiyin, Gansu, 730900, People's Republic of China.
Abstract
Quadriceps weakness is a major determinant of disability in knee osteoarthritis (KOA), particularly in later life, yet weakness often exceeds the loss of muscle size. This discrepancy is clinically important because joint-derived activation failure occurs against a background of declining neuromuscular and regenerative reserve. We critically examine an evidence-bounded joint-afferent-motor unit framework in which abnormal afferent input from the diseased knee reduces effective neural drive through arthrogenic muscle inhibition (AMI). Persistent under-recruitment may be associated with altered motor-unit behavior and loading, impaired muscle quality, and greater reliance on compensatory reinnervation. We deliberately distinguish demonstrated human observations from provisional transitions and hypothesis-generating mechanistic extensions. Human evidence supports AMI and impaired muscle quality and provides preliminary cross-sectional evidence of altered motor-unit behavior; however, human studies have not established a temporal sequence from persistent AMI to motor-unit remodeling or denervation-reinnervation. Direct KOA-related neuromuscular junction (NMJ) evidence remains predominantly preclinical, and progressive NMJ degeneration has not been demonstrated in humans with KOA. Aging, sex, obesity, diabetes, systemic inflammation, pain sensitization, inactivity, and other comorbidities are treated as effect modifiers and competing explanations rather than proof of causation. We propose a testable, multimodal validation strategy combining joint imaging, standardized voluntary-activation testing, neurophysiology, high-density electromyography, motor-unit-number estimation, muscle imaging, and, when justified, tissue-level NMJ phenotyping. For older adults, the practical implication is mechanism-directed care: restore joint-related activation when inhibition dominates, use neural augmentation to enable adequate loading, address muscle-quality and metabolic constraints when present, and reserve NMJ-directed interventions for future human subgroups defined by convergent structural and physiological evidence.
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BibTeX
@article{gao2026neuromuscular,
title = {{Neuromuscular Remodeling in Knee Osteoarthritis Across Aging: An Evidence-Bounded Joint-Afferent-Motor Unit Framework.}},
author = {Yaxiong Gao and Tiansheng Bu},
journal = {Clinical interventions in aging},
year = {2026},
month = oct,
doi = {10.2147/cia.s648376},
url = {https://europepmc.org/article/MED/42953747},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Neuromuscular Remodeling in Knee Osteoarthritis Across Aging: An Evidence-Bounded Joint-Afferent-Motor Unit Framework.
AU - Yaxiong Gao
AU - Tiansheng Bu
PY - 2026
DA - 2026/10/24
JO - Clinical interventions in aging
DO - 10.2147/cia.s648376
UR - https://europepmc.org/article/MED/42953747
AB - Quadriceps weakness is a major determinant of disability in knee osteoarthritis (KOA), particularly in later life, yet weakness often exceeds the loss of muscle size. This discrepancy is clinically important because joint-derived activation failure occurs against a background of declining neuromuscular and regenerative reserve. We critically examine an evidence-bounded joint-afferent-motor unit framework in which abnormal afferent input from the diseased knee reduces effective neural drive through arthrogenic muscle inhibition (AMI). Persistent under-recruitment may be associated with altered motor-unit behavior and loading, impaired muscle quality, and greater reliance on compensatory reinnervation. We deliberately distinguish demonstrated human observations from provisional transitions and hypothesis-generating mechanistic extensions. Human evidence supports AMI and impaired muscle quality and provides preliminary cross-sectional evidence of altered motor-unit behavior; however, human studies have not established a temporal sequence from persistent AMI to motor-unit remodeling or denervation-reinnervation. Direct KOA-related neuromuscular junction (NMJ) evidence remains predominantly preclinical, and progressive NMJ degeneration has not been demonstrated in humans with KOA. Aging, sex, obesity, diabetes, systemic inflammation, pain sensitization, inactivity, and other comorbidities are treated as effect modifiers and competing explanations rather than proof of causation. We propose a testable, multimodal validation strategy combining joint imaging, standardized voluntary-activation testing, neurophysiology, high-density electromyography, motor-unit-number estimation, muscle imaging, and, when justified, tissue-level NMJ phenotyping. For older adults, the practical implication is mechanism-directed care: restore joint-related activation when inhibition dominates, use neural augmentation to enable adequate loading, address muscle-quality and metabolic constraints when present, and reserve NMJ-directed interventions for future human subgroups defined by convergent structural and physiological evidence.
SN - 1176-9092
SN - 1178-1998
ER -