Bone marrow lesions from osteoarthritis knees are characterized by sclerotic bone that is less well mineralized

Abstract

Introduction: Although the presence of bone marrow lesions (BMLs) on magnetic resonance images is strongly associated with osteoarthritis progression and pain, the underlying pathology is not well established. The aim of the present study was to evaluate the architecture of subchondral bone in regions with and without BMLs from the same individual using bone histomorphometry.

Methods: Postmenopausal female subjects (n = 6, age 48 to 90 years) with predominantly medial compartment osteoarthritis and on a waiting list for total knee replacement were recruited. To identify the location of the BMLs, subjects had a magnetic resonance imaging scan performed on their study knee prior to total knee replacement using a GE 1.5 T scanner with a dedicated extremity coil. An axial map of the tibial plateau was made, delineating the precise location of the BML. After surgical removal of the tibial plateau, the BML was localized using the axial map from the magnetic resonance image and the lesion excised along with a comparably sized bone specimen adjacent to the BML and from the contralateral compartment without a BML. Cores were imaged via microcomputed tomography, and the bone volume fraction and tissue mineral density were calculated for each core. In addition, the thickness of the subchondral plate was measured, and the following quantitative metrics of trabecular structure were calculated for the subchondral trabecular bone in each core: trabecular number, thickness, and spacing, structure model index, connectivity density, and degree of anisotropy. We computed the mean and standard deviation for each parameter, and the unaffected bone from the medial tibial plateau and the bone from the lateral tibial plateau were compared with the affected BML region in the medial tibial plateau.

Results: Cores from the lesion area displayed increased bone volume fraction but reduced tissue mineral density. The samples from the subchondral trabecular lesion area exhibited increased trabecular thickness and were also markedly more plate-like than the bone in the other three locations, as evidenced by the lower value of the structural model index. Other differences in structure that were noted were increased trabecular spacing and a trend towards decreased trabecular number in the cores from the medial location as compared with the contralateral location.

Conclusions: Our preliminary data localize specific changes in bone mineralization, remodeling and defects within BMLs features that are adjacent to the subchondral plate. These BMLs appear to be sclerotic compared with unaffected regions from the same individual based on the increased bone volume fraction and increased trabecular thickness. The mineral density in these lesions, however, is reduced and may render this area to be mechanically compromised, and thus susceptible to attrition.

Figure 1

Representative core sampling map as applied to the tibial plateau of a study participant. (a) Bone marrow lesions (BML) identified in the medial tibial plateau (arrow). (b) Regions from the BML area, from another area within the medial tibiofemoral compartment not affected by BMLs, and from the lateral tibiofemoral compartment as well as from matched locations from the lateral compartment were defined. (c) Multiple cores were machined from each region.

Figure 2

Bone volume fraction and average tissue mineral density for four locations from the entire core. (a) Bone volume fraction (BV/TV) and (b) average tissue mineral density (TMD) for the entire core for each of the four locations. HA, hydroxyapatite. Each bar represents the mean, and error bars represent one standard deviation. *Significant differences between groups (P < 0.05). Cores from the lesion area exhibited the highest volume fraction but lowest mineral density. (c) Longitudinal cut-away views of cores from each of the four locations. Each row contains cores from one donor.

Figure 3

Quantitative measures of the trabecular structure for each of the four locations. (a) Trabecular thickness (Tb.Th*). (b) Structure model index (SMI). (c) Trabecular spacing (Tb.Sp*). (d) Trabecular number (Tb.N*). Cores from the lesion area exhibited the highest Tb.Th* but lowest SMI. Differences in trabecular structure were also noted between the matched and medial locations. Each bar represents the mean, and error bars represent one standard deviation. *Significant differences between groups (P < 0.05). ^#A trend (0.05 ≤ P < 0.10).

Figure 4

Histopathological analyses of bone marrow lesion cores indicating a mixed pathology. (a) Diffuse granulation reaction in the marrow compartment. All blood vessels show signs of secondary remodeling with thickened walls. Some vessels show evidence of focal fibrinoid adhesion to the endothelium. (b) High-power view of focal granulation reaction. (c) Regional granulation reaction continuous with a focal fibrinoid reaction with thrombus inclusions. There is evidence of a low-grade inflammation peripheral to the fibrinoid edge. The marked vessel remodeling and the presence of fibrinoid inclusions in the granulation zone are consistent with a focal infarction. (d) Vascular leak with multiple thrombus inclusions. There is fibrinoid occupation and casting of the marrow stroma.