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Item Acute Bone Loss and Infrapatellar Fat Pad Fibrosis in the Knee After an In Vivo ACL Injury in Adolescent Mice(Sage, 2023) Ahn, Taeyong; Loflin, Benjamin E.; Nguyen, Nicholas B.; Miller, Ciena K.; Colglazier, Kaitlyn A.; Wojtys, Edward M.; Schlecht, Stephen H.; Orthopaedic Surgery, School of MedicineBackground: Young patients are 6 times more likely than adults to have a primary anterior cruciate ligament (ACL) graft failure. Biological factors (ie, tunnel osteolysis) may account for up to a third of these failures. Previous evaluations of patient ACL explants indicated significant bone loss within the entheseal regions. However, it remains unknown if the degree of bone loss within the ACL insertion regions, wherein ACL grafts are fixated, exceeds that of the femoral and tibial condylar bone. Hypothesis: Bone loss in the mineralized matrices of the femoral and tibial ACL entheses is distinct from that clinically reported across the whole knee after injury. Study design: Controlled laboratory study. Methods: We developed a clinically relevant in vivo mouse ACL injury model to cross-sectionally track the morphological and physiological postinjury changes within the ACL, femoral and tibial entheses, synovial joint space, and load-bearing epiphyseal cortical and trabecular bone components of the knee joint. Right ACLs of 10-week-old C57BL/6J female mice (N = 75) were injured in vivo with the contralateral ACLs serving as controls. Mice were euthanized at 1, 3, 7, 14, or 28 days after injury (n = 12/cohort). Downstream analyses included volumetric cortical and trabecular bone analyses and histopathologic assessments of the knee joint after injury. Gait analyses across all time points were also performed (n = 15 mice). Results: The majority of the ACL injuries in mice were partial tears. The femoral and tibial cortical bone volumes were 39% and 32% lower, respectively, at 28 days after injury than those of the uninjured contralateral knees (P < .01). Trabecular bone measures demonstrated little difference between injured and control knees after injury. Across all bone measures, bone loss was similar between the injured knee condyles and ACL entheses. There was also significant inflammatory activity within the knee after injury. By 7 days after injury, synovitis and fibrosis were sigificantly elevated in the injured knee compared with the controls (P < .01), which corresponded with significantly higher osteoclast activity in bone at this time point compared with the controls. This inflammatory response signficantly persisted throughout the duration of the study (P < .01). The hindlimb gait after injury deviated from normal, but mice habitually loaded their injured knee throughout the study. Conclusion: Bone loss was acute and persisted for 4 weeks after injury in mice. However, the authors' hypothesis was not confirmed, as bone quality was not significantly lower in the entheses compared with the condylar bone regions after injury. With relatively normal hindlimb loading but a significant physiological response after injury, bone loss in this model may be driven by inflammation. Clinical relevance: There is persistent bone resorption and fibrotic tissue development after injury that is not resolved. Inflammatory and catabolic activity may have a significant role in the postinjury decline of bone quality in the knee.Item State of the mineralized tissue comprising the femoral ACL enthesis in young women with an ACL failure(Wiley, 2021) Patton, Daniella M.; Ochocki, Danielle N.; Martin, Colin T.; Casden, Michael; Jepsen, Karl J.; Ashton-Miller, James A.; Wojtys, Edward M.; Schlecht, Stephen H.; Orthopaedic Surgery, School of MedicineDespite poor graft integration among some patients that undergo an ACL reconstruction, there has been little consideration of the bone quality into which the ACL femoral tunnel is drilled and the graft is placed. Bone mineral density of the knee decreases following ACL injury. However, trabecular and cortical architecture differences between injured and non-injured femoral ACL entheses have not been reported. We hypothesize that injured femoral ACL entheses will show significantly less cortical and trabecular mass compared to non-injured controls.Femoral ACL enthesis explants from 54 female patients (13 – 25 years) were collected during ACL reconstructive surgery. Control explants (n = 12) were collected from 7 donors (18 - 36 years). Injured (I) femoral explants differed from those of non-injured (NI) controls with significantly less (p ≤ 0.001) cortical volumetric bone mineral density (vBMD) (NI: 736.1 – 867.6 mg/cc; I: 451.2 – 891.9 mg/cc), relative bone volume (BV/TV) (NI: 0.674 – 0.867; I: 0.401 – 0.792) and porosity (Ct.Po) (NI: 0.133 – 0.326; I: 0.209 – 0.600). Injured explants showed significantly lesstrabecular vBMD (p = 0.013) but not trabecular BV/TV (p = 0.314), thickness (p = 0.412), or separation (p = 0.828). We found significantly less cortical bone within injured femoral entheses compared to non-injured controls.Lower cortical and trabecular bone mass within patient femoral ACL entheses may help explain poor ACL graft osseointegration outcomes in the young and may be a contributor to the osteolytic phenomenon that often occurs within the graft tunnel following ACL reconstruction.