Mylène Jansen

408 Chapter 19 combined in such a way that structural repair is possible. Using this integrated ‘inside-out’ concept can provide as new insight which might be of value to better understanding of the OA degenerative process as well. Figure 2 : Instead of a conventional trial and error approach in a slowly progressing disease, we could learn from the relatively fast regenerative response with its integrated effects on all relevant tissues, pathways and molecules. With that, it could provide clues for long-standing questions in the field of OA. One of these questions is the relation between structural damage and pain where, despite many attempts, it has not yet been possible to identify with certainty specific characteristics of tissue damage that are associated with pain. 36 Some suggestions have been made, such as presence of bone marrow lesions, but results are often contradictory. 36–38 Using high rate, within-patient, structural alterations as seen after KJD to find a relation with changes in clinical outcome, characteristics could be identified that are important in the relationship between structure and pain in OA. A larger number of patients with standardized imaging would be required, not only restricted to KJD, so other cohorts showing significant cartilage repair should be included as well, such as patients treated with distraction of the ankle or thumb-base, or even those with potential spontaneous repair. 9,39 Even the beneficial effects observed by, for example, weight loss or physiotherapy could be included in such approaches. Identifying the cause of pain in patients could help better choosing the appropriate therapy, improving patient selection and increasing treatment success. This also highlights the importance of looking at individual patients, or at least distinguishing different groups of patients. Phenotyping, defining subtypes that share distinct underlying pathways and pain mechanisms, is another important challenge in the OA field that high rate repair processes could help with. 40 Different strategies have