Post-Traumatic Osteoarthritis Following ACL Injury

Li-Juan Wang; Ni Zeng; Zhi-Peng Yan; Jie-Ting Li; Guo-Xin Ni


Arthritis Res Ther. 2020;22(57) 

In This Article

Conclusions and Future Directions

Patients with ACL injury have a high risk of developing PTOA.[5,6] Although much work has been done, the incidence of PTOA among patients with a history of ACL injury remains high due to the complexity of ACL injury progression to PTOA, the lack of sensitive and easily accessible diagnostic methods to detect OA development, and the limitations of current treatments.[1]

PTOA development is a chronic and progressive condition. At its late stages, the changes in the knee joint are irreversible, and arthroplasty might be the only treatment choice.[17,34] Therefore, early detection and assessment of OA severity is necessary to guide therapy and prevent irreparable damage to the knee joint.[34] Though detection methods such as imaging modalities and biomarkers now exist, none of them are both sensitive and easily accessible.[3,17] Future research directions should be the improvement of standardized and quantitative assessment techniques to detect PTOA at an early stage, monitor the progression and severity of OA development, and evaluate the efficacy of treatments.

At present, the way to prevent the progression of PTOA remains unclear, as a number of risk factors may be at play.[25] Animal models and experiments in vivo allow the study of pathological pathways triggered by ACL injury.[19,47] A complete understanding of its mechanisms to classify patients into different subgroups on the basis of risk factors is critical.[3] Treatments targeted toward different pathogenic pathways may be key to the management of PTOA in the future.

Unlike idiopathic OA, PTOA has a clear "starting point," which makes it possible to trace pathological pathways and intervene immediately after injury.[37] The improvement of conservative, surgical, and pharmacological treatments to diminish the deleterious impact of inflammation, delay PTOA, and promote optimal long-term health after ACL injury is imperative. An animal study shows that controlling knee stability plays a protective role in OA development.[48] After ACL injury, surgery to restabilize the knee joint is often recommended to mitigate knee rotational instability, restrain tibia anterior translation, and restore function.[6,8,9] The improvement of surgical techniques allows for better clinical outcomes. Novel approaches such as bio-enhanced ACL repair have been developed to produce similar structural properties in ACL grafts and provide protection of the articular cartilage in a porcine model.[49] Anatomic ACL-R with a minimum ACL-R scoring checklist score of 8 indicates a reduced incidence of OA compared with non-anatomic ACL-R in a minimum 10-year follow-up.[50] Thus, advanced anatomical reconstruction techniques should be developed to restore normal mechanics and reduce the risk of OA.[5]

The effect of pharmacological treatment has also been widely investigated in animal studies. As our knowledge of biological mechanisms triggered by ACL injury increases, selective inhibition of inflammatory chemokines such as IL-1 and TNF-α has shown potential for preventing the degradation of injured joints in animal studies.[3] Intra-articular injection of dexamethasone has been shown to decrease joint swelling, suppress catabolic gene expression, lower the histological grade, and reduce the formation of osteophytes in rabbit models.[13,32] AMD3100 can prevent trabecular bone loss and mitigate cartilage degeneration in PTOA mice by inhibiting the SDF-1α/CXCR4 signaling pathway.[27] Intra-articular injection of triamcinolone acetonide after ACL transection attenuates synovitis and collagen degradation in Yorkshire pigs.[51] Further work is warranted for clinical application of targeted therapy.

In future studies, standardized criteria should be developed to determine whether a patient needs to receive conservative treatment or surgery reconstruction, which may reduce the financial burden on the health care system and prolong joint health.[6] Finally, a better understanding of the course of specific inflammatory chemokine production and healing processes is of crucial importance in determining the duration of intervention.