This study provides a new scoring system, the Osteoarthritis Bone Score (OABS), that identifies as well as validly quantifies histopathological alterations linked with osteoarthritis (OA) bone marrow lesions (BMLs).

• From 10 knee OA patients, BML/non-BML tissues were harvested at total knee replacement (TKR), and osteochondral tissue were assessed from a further 140 TKR and 23 post-mortem (PM) cases; histological features differentiating magnetic resonance imaging-defined BML/non-BML tissues on qualitative analysis were categorized as present (0) or absent (1), summated for the OABS, validated by Rasch analysis and sensitivity to distinguish between sample groups.

• Cysts, fibrosis, hypervascularity, cartilage islands, trabecular thickening, loss of tidemark integrity and inflammatory cell infiltration were the subchondral features linked with BML tissues.

• PGP9.5 immunoreactive perivascular nerves were found to be related to BMLs.

• OABS displayed good performance as a measurement tool, and had good reliability (Cronbach alpha=0.68), had a 2-factor structure (trabecular/non-trabecular), with moderate correlation between the 2 factors.

• Higher OABS scores were identified in TKR compared to PM cases with chondropathy, median difference 1.5 (95% CI -2, 0).

• OABS and Mankin scores similarly differentiated TKR from non-OA controls, but only OABS was higher in BML compared to non-BML tissues, median difference -4 (95% CI -5 to -2).

• Overall, histopathology underlying BMLs could represent 2 inter-related pathological processes impacting trabecular/non-trabecular structures.

• A likely contributor to pain is increased vascularity/perivascular innervation in BMLs.