Pathologic Changes in Subchondral Bone Microarchitecture Differ Between ACLT, NIKI, and MMT Models of Post-Traumatic Osteoarthritis.

Abstract

Subchondral bone remodeling associated with symptomatic osteoarthritis (OA) is an error-driven response affected by abnormal joint loading. Since different injury models of pre-clinical OA may induce unique shifts in joint loading, comparing bone microstructural changes across different rat OA models may clarify the relationship between subchondral bone remodeling and the mechanisms of joint trauma. In this study, we compared bone microstructure measures across meniscal and anterior cruciate ligament models of late-stage rat OA. OA was induced in male Lewis rats using via medial meniscus transection (MMT), anterior cruciate ligament transection (ACLT), and non-invasive knee injury (NIKI, ACL rupture). At endpoint, microcomputed tomography was used to quantify trabecular and cortical bone microstructure. NIKI animals displayed unique changes in the subchondral bone plate and trabecular bone, where cortical (Ct.Th) and trabecular thickness (Tb.Th) decreased. In contrast, MMT and ACLT animals displayed varying levels of subchondral bone sclerosis with an increase in Ct.Th and Tb.Th compared to controls. Combined with the decreased bone volume (BV/TV), trabecular number (Tb.N), and increased trabecular separation (Tb.Sp), bone changes in NIKI animals indicated varying amounts of bone loss. End-stage bone changes differed across MMT, NIKI, and ACLT rat models of OA. Together, these data indicated that the mechanism of injury is an important consideration when evaluating OA pathophysiology at later time points of disease.