Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older Adults
Bibliographic record
Abstract
Osteoarthritis (OA) is the most prevalent joint disorder characterized by joint structural pathological changes with the loss of articular cartilage as its hallmark. Tools that can predict cartilage loss would help identify people at high risk, thus preventing OA development. The recent advance of the metabolomics provides a new avenue to systematically investigate metabolic alterations in disease and identify biomarkers for early diagnosis. Using a metabolomics approach, the current study aimed to identify serum metabolomic signatures for predicting knee cartilage volume loss over 10 years in the Tasmania Older Adult Cohort (TASOAC). Cartilage volume was measured in the medial, lateral, and patellar compartments of the knee by MRI at baseline and follow-up. Changes in cartilage volume over 10 years were calculated as percentage change per year. Fasting serum samples collected at 2.6-year follow-up were metabolomically profiled using the TMIC Prime Metabolomics Profiling Assay and pairwise metabolite ratios as the proxies of enzymatic reaction were calculated. Linear regression was used to identify metabolite ratio(s) associated with change in cartilage volume in each of the knee compartments with adjustment for age, sex, and BMI. The significance level was defined at α = 3.0 × 10−6 to control multiple testing. A total of 344 participants (51% females) were included in the study. The mean age was 62.83 ± 6.13 years and the mean BMI was 27.48 ± 4.41 kg/m2 at baseline. The average follow-up time was 10.84 ± 0.66 years. Cartilage volume was reduced by 1.34 ± 0.72%, 1.06 ± 0.58%, and 0.98 ± 0.46% per year in the medial, lateral, and patellar compartments, respectively. Our data showed that the increased ratios of hexadecenoylcarnitine (C16:1) to tetradecanoylcarnitine (C14) and C16:1 to dodecanoylcarnitine (C12) were associated with 0.12 ± 0.02% reduction per year in patellar cartilage volume (both p < 3.03 × 10−6). In conclusion, our data suggested that alteration of long chain fatty acid β-oxidation was involved in patellar cartilage loss. While confirmation is needed, the ratios of C16:1 to C14 and C12 might be used to predict long-term cartilage loss.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.001 | 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".