SA1 - Multi-Scale Biomarkers Differentiate Post-Traumatic and Primary TMJ Osteoarthritis and Inform Mechanism-Based Intervention

Abstract: Introduction: Post-traumatic osteoarthritis (PTOA) is a mechanically induced subtype of osteoarthritis (OA) caused by acute, high-impact forces that disrupt temporomandibular joint (TMJ) alignment and load distribution. In contrast to primary OA, which develops gradually under chronic functional overload and age-related degeneration, PTOA exhibits rapid, asymmetric condylar remodeling. Although these conditions may converge in end-stage morphology, their mechanical origins and spatiotemporal biological responses remain distinct. This divergence suggests that measurable structural and molecular biomarkers may differentiate acute trauma-induced degeneration from chronic load-mediated disease progression, providing a necessary framework to identify mechanism-based diagnosis for treatment stratification.

Objective: To identify multiscale structural and compositional biomarkers of mechanical trauma that distinguish acute impact-induced PTOA from chronic loading-associated OA, and to evaluate their potential relevance for earlier clinical intervention.

Methods: Condyles were collected from a patient who was undergoing bilateral total joint replacement due to ankylosis (PTOA; Left) and severe degeneration (OA; Right). Hierarchical analysis was conducted to understand microanatomical changes. Macro-scale joint biomarkers, evaluated with cone-beam computed tomography (CBCT), included jaw-occlusal alignment and the temporomandibular joint space. The condyles were also analyzed for micro-scale biomarkers such as condylar morphology, topography, and bone structure, using high-resolution micro-computed tomography (μCT). At the nano-scale, tissue-specific elemental composition was characterized using correlative scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDX), focusing on fibrosis and mineralization signatures.

Results: Macro-scale joint level biomarkers for the PTOA (high force over a short time) included severe malalignment of the jaw with non-uniform joint space with ankylosed regions, consistent with localized high-magnitude mechanical insult. However, in the OA, jaw alignment at a macroscale was preserved, but irregular joint space with surface roughness, pitting, and diffuse topographic degeneration were observed. Micro-scale structural biomarkers of the PTOA demonstrated increased mineral density (PTOA trended higher than OA: 1000-1300 mg/cc) and localized ectopic mineralization, particularly at ankylosed interfaces. OA showed more distributed architectural degradation without focal mineral bridging. Nanoscale compositional molecular biomarkers of the PTOA exhibited fibrotic tissue with mineral deposits in the ankylosed regions. Sites demonstrated increasing calcium (surrogate for inorganic constituents) to nitrogen and carbon (surrogates for organic constituents), compared to OA specimens with lower calcium to nitrogen and carbon. These compositional shifts represent candidate biomarkers of acute mechanical injury, distinct from the more gradual mineral changes in OA.

Discussion: These findings identify mechanically defined biomarker signatures that link force magnitude and duration to divergent pathways of condylar degeneration. Acute, high-magnitude impact (PTOA) is associated with rapid remodeling, as indicated by a fibrosis-to-mineral transition with focal ankylosis reminiscent of soft-to-hard tissue transformation in ligaments and associated enthesopathies. Chronic, lower-magnitude loading (OA) is associated with gradual surface degradation as illustrated by the absence of focal mineral bridging, but significant structural breakdown as indicated by differences between nitrogen and sulfur relative to calcium.

Conclusion: These findings support a model: mechanical trauma is encoded as multi-scale biomarkers spanning joint morphology, microstructure, and elemental composition, thereby distinguishing impact-induced degeneration from chronic load-mediated osteoarthritis. Clinically, the presence of ankylosis-related mineral biomarkers, when adjusted for nitrogen levels, tend to cluster with calcium and phosphorus (inorganic) in PTOA conditions. In contrast, OA samples tend to cluster with nitrogen and sulfur (organic). This distinction explains the faster progression and limited effectiveness of conservative treatments in PTOA, thereby supporting earlier surgical intervention. In the context of modern TMJ replacement, these biomarker-based trajectories offer a framework for mechanism-driven diagnosis and personalized treatment planning.


References:
1. Skabelund, Z., Acharya, D., Banks, J., et al. (2024). PTOA changes in condylar shape and bone microstructure. Bone, 189, 117263.
2. Cardoneanu, A., Macovei, L. A., Burlui, A. M., et al. Temporomandibular joint OA: Pathogenesis and therapeutic strategies.