Altered Joint Mechanics and Biological Response in Osteoarthritic Knees.

Osteoarthritis (OA) stands out as the most prevalent joint disease. It manifests as a progressive degradation of articular cartilage, new bone growth and often synovial tissue proliferation, resulting in pain and compromised joint functionality, ultimately leading to disability. In 83% of OA patients the knee is affected limiting people from engaging in physical activities, which paves the way for the onset of cardiovascular diseases, obesity, and diabetes. Misalignment of the lower limb (varus or valgus knees) are recognised as a risk factor for osteoarthritis onset and progression. These misalignments of the lower limbs substantially influence the load distribution across the articular surface of the knee joint, and the load imbalance causes the most loaded compartment to wear out earlier. High tibial osteotomy (HTO) is a surgical technique that allows to shift the load from the affected area to other areas with intact cartilage. Similarly to HTO, braces realign the lower limb, without the need for surgical intervention. These corrective treatments are recommended for the youngest group of patients as it allows them to stay active, as opposed to Total Knee Replacement (TKR). However, long-term survivorship of HTO ranges from 40% to 85% and evidence of long-term efficacy of braces is limited. The specific reasons for failure are not well understood, but are probably linked to improper correction, as overcorrection can lead to instability while undercorrection may fail to alleviate symptoms, and no consensus on the optimal amount exist in literature. Until today, the effects of braces and HTO on the subchondral bone microstructure and cartilage are not well understood. Investigating these aspects to better understand treatment failures is becoming more and more crucial because global prevalence of knee OA is expected to increase with the ageing of populations.

Bone remodelling occurs as a consequence of the major change in loading condition, caused by the treatments, but the time frame and the extent to which this happens is unknown. Bone quality is typically evaluated by means of dual-energy X-ray absorptiometry (DXA), which is able to detect 2D changes in bone mineral density, but not suitable to measure regional differences in bone microstructure. High resolution pheripheral quantitative CT (HR-pQCT) is a widespread imaging technique in research context. It allows for 3D measurements and it was proven that it can accurately quantify bone remodelling at the wrist. However, HR-pQCT has a low clinical applicability, due to long scanning time and small field of view, that does not allow imaging of central sites, such as the knee. Photon Counting CT (PCCT) is one of the latest advancements in CT technique, with resolution comparable to HR-pQCT but higher clinical applicability. It was shown that PCCT is suitable to detect bone turnover in the same way as HR-pQCT, allowing for direct characterization of the microstructure at the knee.

Despite extensive in vitro and in vivo research, it remains unclear how the changes in cartilage composition and structure that occur during cartilage degeneration, interact. An in silico model to investigate the causal mechanisms by which the local mechanical environment of injured cartilage drives cartilage degeneration has been developed. The model predictions showed good agreement with previous experimental observations, however a more extensive validation with in vivo data would allow to investigate more physiological conditions.