Progress is being made in understanding the causes of osteoarthritis (OA) of the knee. Age, obesity, and repetitive joint stress are well-known risk factors for the development of knee OA, among others. Insight into the pathophysiology of knee OA is increasing: pathophysiological processes in cartilage, bone and soft tissues are gradually being uncovered. Nevertheless, the exact causal pathways of knee OA remain elusive.
In an innovative study, Case et al.
1
looked at prodromal symptoms of knee OA. These scientists determined which symptoms preceded the development of radiographic knee OA, in a longitudinal study using data from the Osteoarthritis Initiative. Candidate prodromal symptoms were individual items from the WOMAC and KOOS questionnaires, available up to 4 years prior to the time of incident radiographic knee OA. Radiographic knee OA was defined as the new onset of combined definite osteophyte and joint space narrowing in the tibiofemoral joint. It was found that 31 out of 34 individual WOMAC/KOOS items were associated with the subsequent development of radiographic knee OA. The estimated length of the prodromal interval ranged from 47 months to 24 months. Perceived difficulty due to the knee in taking off sock/stockings, knee pain on stairs, and knee pain on twisting and pivoting were among the symptoms that appeared earliest. Self reported swelling of the knee occurred at an early stage as well.This is a highly innovative study. As pointed out by Case et al., until recently it was not possible to undertake a prospective investigation of the timing of prodromal symptoms, due to the lack of longitudinal studies that have obtained sufficiently frequent repeated measures of symptoms and images of the joint in persons at risk of developing radiographic OA. The Osteoarthritis Initiative provided the data to undertake such an investigation.
The results of this study provide important clues on ‘in whom’ and ‘when’ to look for causal pathways of osteoarthritis of the knee. The findings suggest to look for causal pathways in subjects reporting difficulty due to the knee in taking off sock/stockings, knee pain on stairs, knee pain on twisting and pivoting, swelling of the knee, or similar prodromal symptoms. With regard to timing, the findings suggest to look for causal pathways starting at least 47 months prior to the development of definite radiographic knee OA. In subjects reporting these symptoms and at that early stage, pathophysiological processes in cartilage, bone or soft tissues seem to be operating, eventually leading to radiographic knee OA. These processes first give rise to the observed prodromal symptoms, and eventually give rise to radiographic knee OA. In subjects reporting these symptoms and at that time, further research on pathophysiological processes, in interaction with joint loading parameters, may lead to the identification of causal pathways of knee OA.
Another recent study, also using data from the Osteoarthritis Initiative, showed that using stairs was the first activity to cause pain in subjects with knee OA or at risk of developing knee OA
2
. This finding is line with the result that pain using stairs is among the first prodromal symptoms in knee OA. However, Case et al.1
determined which symptoms precede the development of radiographic knee OA. The other study2
just looked at which symptoms appear first, without relating symptoms to subsequent radiographic knee OA. Additionally, Case et al. looked at a much broader range of prodromal symptoms. The assessment of prodromal symptoms preceding subsequent radiographic knee OA and the assessment of a broad range of symptoms are major strengths of the Case et al. study.Discordance between symptoms and radiographic knee OA is a well known fact. Patients may experience symptoms, without demonstrable signs of radiographic knee OA; conversely, signs of radiographic knee OA may be present, without patients experiencing symptoms. Case et al. seem to have identified a subgroup (phenotype) of patients who first experience symptoms and then go on to develop radiographic knee OA. Of course, the strategy on the identification of causal pathways of knee OA as suggested above applies only to patients in whom symptoms precede the development of radiographic knee OA. Other subgroups may exist; for example, patients who first develop radiographic knee OA, and who experience symptoms at a later stage. In the latter patients, different causal pathways seem to be operating. Full understanding of causal pathways requires research in patients characterized by various trajectories of symptoms, alterations in the joint (cartilage, bone, and soft tissue), joint loading, and other relevant processes.
Contributions
JD wrote the Editorial.
Conflict of interest
The author declares no conflict of interest.
References
- Prodromal symptoms in knee osteoarthritis: a nested case-control study using data from the osteoarthritis initiative.Osteoarthr Cartil. 2015; (accepted for publication)
- Toward a clinical definition of early osteoarthritis: onset of patient-reported knee pain begins on stairs. Data from the osteoarthritis initiative.Arthritis Care Res (Hoboken). 2015 January; 67: 40-47
Article info
Publication history
Published online: April 02, 2015
Accepted:
March 22,
2015
Received:
January 29,
2015
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© 2015 Osteoarthritis Research Society International. Published by Elsevier Inc.
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- Prodromal symptoms in knee osteoarthritis: a nested case–control study using data from the Osteoarthritis InitiativeOsteoarthritis and CartilageVol. 23Issue 7Open Access
