Knee malalignment is a risk factor for patellar instability and patellofemoral osteoarthritis (PFOA), but etiologies remain unknown. We investigated the potential effects of decreased weight loading during growth on knee alignments and patellofemoral (PF) joint pathology. Hindlimb suspension (HS) was performed in 4-week-old female rats for 2, 4, and 8 weeks (HS groups). Age-matched rats were used as controls. Three-dimensional reconstructed images of the knee were obtained using X-ray computed tomography. Tibial tubercle-trochlear groove (TT-TG) distance, patellar tilt angle, and bisect offset were measured as indices of knee alignment. Histological analysis was also performed to evaluate the changes in cartilage and synovium in the PF joints. At Week 8, TT-TG distance, patella tilt angle, and bisect offset were significantly larger in the HS group than in the control group, respectively, indicating tibial external rotation, outward patellar tilt, and external displacement of the patella. Lateral patellar dislocation was frequently found in the HS group at Week 8 (five of eight knee joints, p < 0.05). Degenerative changes in the cartilage of the trochlear groove were observed at Week 8, and synovial changes such as hypertrophy and synovitis were observed at Weeks 4 and 8. Correlation analyses revealed significant relationships between the Mankin score and bisect offset, and between the OARSI synovitis score and all knee alignments indices. These results suggest that decreased weight loading on the lower extremities in growing rats resulted in knee malalignments characterized by external rotation of tibia and high incidence of lateral patellar dislocation with concomitant PFOA.© 2024 Orthopaedic Research Society.