Why ACL reconstruction fails to prevent post-traumatic osteoarthritis: A narrative review of mechanical and biological perspectives.

Anterior cruciate ligament (ACL) injury markedly increases the risk of post-traumatic osteoarthritis (PTOA), and anterior cruciate ligament reconstruction (ACLR), despite restoring knee stability and function, does not reliably prevent long-term cartilage degeneration. This narrative review aims to integrate current clinical and experimental evidence to clarify the multifactorial mechanisms responsible for PTOA development after ACLR, with particular emphasis on the interactions between mechanical, inflammatory, and subchondral bone-related factors. Recent epidemiological studies consistently demonstrate a high and time-dependent prevalence of PTOA following ACLR, frequently exceeding 50% at long-term follow-up. Residual anterior and rotatory instability and resulting altered joint loading remain important mechanical contributors, and emerging evidence suggests that lateral extra-articular tenodesis may reduce long-term PTOA risk by improving rotational control. Beyond biomechanics, ACLR itself induces a postoperative inflammatory response that acts as a secondary "inflammatory hit," re-triggering the degenerative pathways initiated by the primary injury, even when joint kinematics are restored. Increasing attention has also been directed toward subchondral bone remodeling and bone marrow adipose tissue, which actively mediate biochemical and biomechanical crosstalk within the osteochondral unit. In addition, patient age, concomitant meniscal or cartilage injury, surgical timing, and early postoperative loading conditions are known to critically influence PTOA progression. PTOA after ACLR arises from the temporal interplay between mechanical instability, surgery-induced inflammation, and subchondral bone alterations rather than from a single isolated factor. Effective long-term joint preservation will likely require an integrated strategy that addresses both mechanical and biological processes across different postoperative stages.