Integrative Phenotyping of Knee Osteoarthritis: Linking WOMAC Cut-Offs, Kellgren–Lawrence Grades, and Cluster Analysis for Personalized Care
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design: Participants
2.2. Clinical Outcome Measures
2.3. Metabolic Assessments
2.4. Radiographic Assessments
2.5. Statistical Analysis
3. Results
Descriptive Analysis
- WOMAC Total Score: Mild OA patients had significantly lower scores than all other groups (p < 0.001), confirming increasing severity.
- WOMAC Pain Score: Mild OA cluster differed significantly from Moderate, Moderate-Severe, and Severe OA (p < 0.001).
- WOMAC Functional and Stiffness Scores: Stepwise increases were observed across groups, all of which were statistically significant (p < 0.001).
- Joint Space Narrowing and Osteophyte Scores: Progressively higher in more severe clusters (p < 0.001).
- BMI: Clusters 3 and 4 had significantly higher BMI than Clusters 1 and 2 (p < 0.001), consistent with a metabolic phenotype in more severe OA.
4. Discussion
4.1. Clinical Interpretation of WOMAC Cut-Offs and KL Grades
4.2. Psychological and Metabolic Influences on OA Severity
4.3. Inflammation, Depression, and OA Phenotype Overlap
4.4. Personalized Management Strategies for Identified Clusters
4.4.1. Non-Pharmacological Interventions
4.4.2. Pharmacological Management
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | Mean ± SD/n (%) |
---|---|
Age (years) | 52.84 ± 15.22 |
BMI (kg/m2) | 25.91 ± 5.61 |
Lequesne Index | 6.30 ± 2.58 |
WOMAC Pain | 12.74 ± 5.22 |
WOMAC Stiffness | 5.09 ± 2.18 |
WOMAC Function | 44.85 ± 15.18 |
WOMAC Total | 62.75 ± 22.10 |
VAS Pain (0–10) | 6.03 ± 2.14 |
HADS (total score) | 7.74 ± 4.34 |
KL | 2.35 ± 0.87 |
Joint space narrowing, grade (0–3) | 1.61 ± 1 |
Joint space narrowing present, n (%) | 84 (84.8%) |
Osteophytes, grade (0–3) | 1.67 ± 0.7 |
Osteophytes present, n (%) | 94 (94.9%) |
Hypertension (yes) | 40 (40.4%) |
Diabetes (yes) | 20 (20.2%) |
Category | WOMAC Score Interval | KL Grade Association | Specific Cut-Off (Youden J) | AUC (95% CI) | Clinical Interpretation |
---|---|---|---|---|---|
No symptoms | ≤24 | KL ≥ 1 vs. KL = 0 | 24 | 0.976 (0.938–1.000) | Minimal or no symptoms, no radiographic changes |
Mild | 25–41 | KL ≥ 2 vs. KL ≤ 1 | 41 | 1.000 (1.000–1.000) | Mild symptoms, early structural joint changes |
Moderate | 42–69 | KL ≥ 3 vs. KL ≤ 2 | 69 | 0.943 (0.892–0.980) | Clear pain and stiffness, moderate functional limitations |
Severe | 70–86 | KL = 4 vs. KL ≤ 3 | 87 | 0.944 (0.832–1.000) | Severe pain and significant mobility loss |
Extreme | ≥87 | KL 4 | 87 | 0.944 (0.832–1.000) | End-stage OA, high likelihood of disability. |
Variable | 1 Mild OA (n = 22) | 2 Moderate OA (n = 29) | 3 Moderate-Severe OA (n = 19) | 4 Severe OA (n = 29) |
---|---|---|---|---|
KL Grade | 0–2 | 2–3 | 3 | 3–4 |
WOMAC Total | 29.15 ± 9.18 | 56.81 ± 8.73 | 71.83 ± 7.22 | 88.64 ± 4.55 |
WOMAC Pain | 5.45 ± 2.35 | 10.74 ± 2.08 | 14.74 ± 2.07 | 19.20 ± 1.00 |
WOMAC Stiffness | 2.25 ± 1.25 | 4.29 ± 1.24 | 5.91 ± 1.04 | 7.60 ± 0.71 |
WOMAC Functional | 21.45 ± 6.59 | 41.58 ± 6.85 | 51.13 ± 5.22 | 61.84 ± 3.79 |
Joint Space Narrowing | 0.25 ± 0.44 | 1.23 ± 0.50 | 2.48 ± 0.51 | 2.40 ± 0.50 |
Osteophytes | 0.85 ± 0.59 | 1.32 ± 0.48 | 2.22 ± 0.42 | 2.24 ± 0.44 |
Lequesne Index | 2.40 ± 0.68 | 5.48 ± 0.85 | 7.65 ± 0.98 | 9.20 ± 0.96 |
BMI | 21.24 ± 2.41 | 23.95 ± 3.75 | 30.38 ± 5.30 | 27.97 ± 5.82 |
Age (Years) | 31.30 ± 8.30 | 50.58 ± 8.74 | 59.91 ± 8.58 | 66.36 ± 9.83 |
Pain (VAS) | 3.00 ± 0.86 | 5.16 ± 0.73 | 7.00 ± 0.74 | 8.64 ± 0.57 |
HADS | 1.75 ± 1.77 | 6.77 ± 1.63 | 10.26 ± 2.96 | 11.40 ± 3.46 |
Hypertension % | 0.00% | 19.35% | 69.57% | 72.00% |
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Pojala, C.-V.; Moga, M.A.; Pojala, C.-E.; Roman, N.A.; Necula, R.D.; Toma, S.I.; Manea, R.M.; Dima, L. Integrative Phenotyping of Knee Osteoarthritis: Linking WOMAC Cut-Offs, Kellgren–Lawrence Grades, and Cluster Analysis for Personalized Care. Life 2025, 15, 1542. https://doi.org/10.3390/life15101542
Pojala C-V, Moga MA, Pojala C-E, Roman NA, Necula RD, Toma SI, Manea RM, Dima L. Integrative Phenotyping of Knee Osteoarthritis: Linking WOMAC Cut-Offs, Kellgren–Lawrence Grades, and Cluster Analysis for Personalized Care. Life. 2025; 15(10):1542. https://doi.org/10.3390/life15101542
Chicago/Turabian StylePojala, Ciprian-Vasile, Marius Alexandru Moga, Cristiana-Elena Pojala, Nadinne Alexandra Roman, Radu Dan Necula, Sebastian Ionut Toma, Rosana Mihaela Manea, and Lorena Dima. 2025. "Integrative Phenotyping of Knee Osteoarthritis: Linking WOMAC Cut-Offs, Kellgren–Lawrence Grades, and Cluster Analysis for Personalized Care" Life 15, no. 10: 1542. https://doi.org/10.3390/life15101542
APA StylePojala, C.-V., Moga, M. A., Pojala, C.-E., Roman, N. A., Necula, R. D., Toma, S. I., Manea, R. M., & Dima, L. (2025). Integrative Phenotyping of Knee Osteoarthritis: Linking WOMAC Cut-Offs, Kellgren–Lawrence Grades, and Cluster Analysis for Personalized Care. Life, 15(10), 1542. https://doi.org/10.3390/life15101542