A few weeks after joint trauma, subchondral bone may increase in volume, suggesting that bone turnover occurs early after a destabilizing joint injury.10 Gene dysregulation also happens very early in subchondral bone following traumatic injury, with gene signatures consistent with heavy bone turnover, MMP upregulation and osteoclast differentiation.11
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Explore This IssueFebruary 2019
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Post-traumatic OA inflammation is mechanically induced. After injury, “there is an effect on cartilage with matrix product release, and these can be acting as DAMPs [damage-associated molecular patterns] to activate cell population in the synovium. There is cytokine release, and subchondral bone turnover even in very early stages,” he said. Eleven cartilage-specific genes were dysregulated in the meniscus tissue of rats a few days after knee injury in one study, although not all at the same points in time.12 In post-traumatic OA, an early inflammatory response may be required to usher in a later wound healing response, and that may have important considerations for the timing and mechanism of treatment.
In early post-traumatic OA, cytokines and chemokines are dysregulated weeks after injury, as his research on surgically induced, CCL2-knockout mice shows.13 His group was interested in CCL2 as a potentially structure-modifying target. Blocking CCL2 and CCR2 can reduce cartilage degeneration, and CCR2 inhibition is only effective if used early in post-traumatic OA.14 Each type of OA has a different mechanism, so treatments should be tested in trials according to specific OA types, Dr. Appleton said.
Persistent Pain & Reduced Activity
Although many patients do well after joint injury, a considerable number of people still struggle with their symptoms even years later, said Jeffrey B. Driban, PhD, associate professor of medicine, Tufts University School of Medicine and Tufts Medical Center, Boston.
One-third of patients report they have unacceptable symptoms, such as knee pain, up to two years after an ACL injury and surgical treatment. Further, about 33% of patients develop tibiofemoral OA within 10 years after an ACL tear, with or without surgical repair, he said.15
“You can observe articular cartilage changes in the first two years after an ACL tear injury, including a thinning on the femoral trochlea, but a thickening at the central medial femur,” he said.16 “Composition of the articular cartilage is compromised, and this is more likely to be swelling” rather than a healthy adaptation. Cartilage changes happen consistently over several years after injury. Two years after injury, the posterior lateral meniscus recovers, but with persistent compositional changes in the medial meniscus that relate to articular cartilage changes.17