Mylène Jansen

200 Chapter 10 induce bone formation. This combination with an overall increase in bone turnover might be the necessary circumstance under which cystic areas can be repaired. So far, no clear relations have been found between clinical improvement and overall bone changes. However, when specifically looking at the resolution of the cysts in relation to clinical improvement in case of ankle distraction, as determined by patient-reported outcome, a rather good correlation was demonstrated. 32 Cyst-related joint pain might be caused by increased pressure and fluid flow in the subchondral bone. During loading, compression of cartilage forces fluid into the bone through the damaged subchondral plate. 82 The hydraulic conductance of osteochondral tissue has been shown to be higher in OA patients. 83 When cysts and defects in the subchondral plate diminish, the subchondral bone is less subject to increased fluid flow and pressure decreasing joint pain. Cystic pores within the cortical plate close to the joint surface result in an increase in hydraulic conductance which might be responsible for joint pain. Bone cysts, as well as bone surface attrition, seem to evolve in regions of bone marrow lesions and are suggested to be the next level of bone marrow pathology. 84 The relationship between bone marrow lesions as seen on MRI and clinical symptoms is well-established, and it could also be explained by increased pressure within the bone in areas of excessive loading and mechanically compromised trabecular structure 84,85 , as such providing a rational for the deceased pain as a result of KJD. In addition to the mechanical effect, the significant changes in bone turnover inflicted by the osteopenia and later normalization most likely result in release of growth factors resided in large amounts in the bone. Bone is known to be a storage of factors that have been demonstrated to play a role in cartilage tissue repair. 86–88 These mechanical and biochemical interactions might not only be causative in the clinical and structural benefit of KJD (and joint distraction in general) but may also be valid to explain the tissue repair as observed by osteotomy, as this is an intervention which is accompanied by strong bone turnover as well. As the exact factors are not yet identified in the context of KJD (and HTO), we might learn a lot in the advances of understanding distraction histogenesis, a distraction technique which is successfully applied to overcome difficult orthopedic conditions such as limb deformities, non-union, and segmental bone defects. Though differently applied, it has been demonstrated that both local and systemic responses triggered by distraction contribute to bone regeneration and include bone morphogenetic proteins 89 , inflammatory factors 90 , and mechanotransduction signals (e.g, Hippo and Wnt signaling pathways) 91 , amongst others. Moreover, an animal study further supports the involvement of bone in the cartilage repair process under influence of KJD. 92 In this study, aimed to demonstrate the beneficial structural effect of KJD in dogs, an additional group was included in which only an external fixated frame without distraction was applied. Remarkably, this treatment group with clear bone turnover changes showed a moderate beneficial effect on the cartilage, as defined by an improved histology and cartilage proteoglycan turnover as compared to the untreated OA group, though inferior to the group treated with KJD. The improvement in this ‘frame non-distraction’ group might be due to the partial unloading with maintained joint mobility. The quadruple dogs loaded their treated