The osteoarthritis bone score (OABS): a new histological scoring system for the characterisation of bone marrow lesions in osteoarthritis

Abstract

Objectives: Bone marrow lesions (BMLs) are associated with pain in osteoarthritis (OA), but histological scores for OA focus on cartilage pathology. We developed a new scoring system, the Osteoarthritis Bone Score (OABS), to characterise OA-related BMLs.

Methods: BML/non-BML tissues identified by Magnetic Resonance Imaging (MRI) in 10 knee OA subjects were harvested at total knee replacement (TKR). Osteochondral tissue from a further 140 TKR and 23 post-mortem (PM) cases was assessed. Histological features distinguishing MRI-defined BML/non-BML tissues on qualitative analysis were classified as present (0) or absent (1), summated for the OABS, validated by Rasch analysis and sensitivity to distinguish between sample groups. Immunohistochemistry for PGP9.5 assessed innervation.

Results: Subchondral characteristics associated with BML tissues were cysts, fibrosis, hypervascularity, cartilage islands, trabecular thickening, loss of tidemark integrity and inflammatory cell infiltration. PGP9.5 immunoreactive perivascular nerves were associated with BMLs. OABS performed well as a measurement tool, displayed good reliability (Cronbach alpha = 0.68), had a 2-factor structure (trabecular/non-trabecular), with moderate correlation between the two factors (r = 0.56, 95% CI 0.46, 0.65). OABS scores were higher in TKR than PM cases with chondropathy, median difference 1.5 (95% CI -2, 0). OABS and Mankin scores similarly distinguished TKR from non-OA controls, but only OABS was higher in BML than non-BML tissues, median difference -4 (95% CI -5 to -2).

Conclusions: OABS identifies and validly quantifies histopathological changes associated with OA BMLs. Histopathology underlying BMLs may represent 2 inter-related pathological processes affecting trabecular/non-trabecular structures. Increased vascularity/perivascular innervation in BMLs might contribute to pain.

Keywords: Bone marrow lesions; Grading; Histology; Magnetic resonance imaging; Osteoarthritis; Scoring system.

Fig. 1

Co-localisation of MRI Images and joint tissue obtained at surgery. Representative images of Axial and Coronal views of target knee for co-localisation of knee biopsy tissue by MRI identification before tissue harvest at joint replacement surgery. MRI scans are shown alongside a macroscopic image of tibia for each subject harvested at the time of joint replacement. Each row represents an individual participant dataset for MRI and knee tissue. Yellow boxes represent BML tissue that was analysed. M: medial compartment; L: lateral compartment.

Fig. 2

Histological features of bone marrow lesions comprising the Osteoarthritis Bone Score (OABS). Appearances of the seven histological characteristics of BML regions, each scored as present (1) or absent (0) to constitute the OABS. Characteristic tissue changes are present within BML samples, but absent from the illustrated non-BML OA samples. Haematoxylin (blue) eosin (pink) or Safranin O (pink) and Fast Green staining. Typical histological changes shown in OA BML panel indicated by arrows are cysts, fibrosis, hypervascularity, cartilage islands (appears pink on Safranin O stain), thickened trabeculae, loss of tidemark integrity at the cartilage/bone interface and inflammation with increased presence of macrophages and osteoclasts. The panels on the right show non-BML OA tissue. Whole slide scanning with Nanozoomer technology is shown.

Fig. 3

Osteochondral histopathology in osteoarthritis. Representative stained sections of articular cartilage and subchondral bone showing BML (A) and non-BML (B) regions, localised by reference to preoperative MRI scans, and a sample from a patient without prior imaging (D), each from patients who underwent total knee replacement surgery for OA. Non-OA post-mortem control tissue is shown in (C). Subchondral pathology is most evident in regions identified as BMLs, and associated with more severe pathology in the overlying articular cartilage. Upper panels are stained with haematoxylin and eosin, with lower panels stained with Safranin O/Fast Green.

Fig. 4

Innervation of Bone Marrow Lesions. A: Nerve profiles in fibrotic OA BML tissue and perivascular staining. B: Perivascular PGP 9.5 immunoreactive nerves within subchondral BML bone. C: Box plots of subchondral vascular density in BML and non-BML OA samples, and in non-arthritic post-mortem (PM) controls. Number of blood vessels differed significantly between the three groups (Kruskall Wallis test, p < 0.0001). D: Box plots of percentage of blood vessels associated with PGP 9.5-immunoreactive nerves in subchondral bone of BML and non-BML OA samples (group 1), and in non-arthritic PM controls (Group 2). Percentage of blood vessels associated with PGP9.5 immunoreactivity differed significantly between the three groups (Kruskall Wallis test, p = 0.018). Box plots show maximum, minimum and IQR range of values. Nerves were visualised by immunoreactivity for PGP9.5 and counterstained with haematoxylin. To obtain the total number of blood vessels in the standardised subchondral region of interest (see methods), each blood vessel was counted by whole slide scanning using Nanozoomer technology.

Fig. 5

Box plots of Osteoarthritis Bone Scores and Mankin chondropathy scores. A: Box plots showing distribution of OABS scores in case groups corresponding to Table II. B: Box plots showing distribution of Mankin scores in case groups corresponding to Table II. Horizontal bars indicate median, IQR, maximum and minimum range of values.