242. Turning of the Tide: Does Tidemark Advancement Perpetuate Osteoarthritis
Bibliographic record
Abstract
Background: OA is a chronic debilitating condition marked by cartilage destruction and bone remodelling. Histopathologically OA is characterized by changes to the tidemark mineralization front, which marks the interface between the superficial viscoelastic hyaline layer and the deep calcified layer. Tidemark duplication (therefore, advancement) is a known histological feature of OA. This has been suggested to be a consequence of the reactivation of endochondral ossification leading to thickening of the calcified cartilage and neovascularization and neoinnervation of the cartilaginous cartilage potentially leading to mechanical pain. Methods: Femoral heads and tibial plateaus were taken from cadavers. Each femoral head was cut into four blocks exposing the articular surface, two superior to the fovea and two inferior. The tibial plateaus were cut into lateral or medial blocks. All blocks were demineralized by immersion in formal saline for a year, then embedded in wax and sliced into sections. These were divided into three even groups stained with toluidine blue, hematoxylin and eosin, and trichrome gomori. Each section was analysed by light microscopy and following the OARSI criteria set out by Pritzker et.al (2006) given a grade 0–6 based on changes to the matrix and/or cells. Student’s t-test explored associations between the presence of a dual tidemark and OARSI grade. Odds ratios were calculated for the occurrence of dual tidemarks by OARSI grade as independently defined by matrix and cells. Results: In total, 13 cadavers (8 male, 5 female, mean age 87) were used. Both femoral heads were removed from 5 cadavers, and one femoral head in two separate cadavers. The tibial plateau was removed from 6 different cadavers. 177 sections were produced (femoral heads left n = 72, right n = 72) (tibial plateaus right n = 22, left n = 11). A dual tidemark was associated with a higher OARSI grade than a single tidemark [mean (s.d.) 3.41 (1.59) vs 1.11 (1.04) respectively: P < 0.001]. A matrix with an OARSI score of ≥3 predicted a 96 fold increase in the association of a dual tidemark (P < 0.0001), whereas cellular changes resulting in an OARSI score ≥2 predicted a 17.7 fold increase in the occurrence of a dual tidemark (P < 0.001). Conclusion: We have demonstrated (for the first time) early changes in the matrix (OARSI ≥3) or chondrocytes (OARSI ≥2) strongly predict a dual tidemark. Pathologically, OA is regarded as a process that occurs from the wear and tear of articular surfaces. Our data suggest that tidemark advancement occurs at an early stage and may perpetuate further osteoarthritic change at the hyaline layer, thus mediating an alternative bottom-up mechanism. Further exploration of this may lead to novel systemic treatment strategies preventing tidemark advancement and thereby disease progression. Disclosure statement: The authors have declared no conflicts of interest.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".