Does bone marrow Edema predict progression of Knee Osteoarthritis?
Summary written by Jon Giles, M.D.
The pathophysiology of osteoarthritis (OA) is incompletely understood. The currently accepted model, with pathologic processes centered primarily at the level of the articular cartilage, does not perfectly define many of the findings of OA, such as bone marrow edema in subchondral bone observed on MRI in affected joints. In a previous study, Felson et al defined a relationship between knee pain and bone marrow lesions observed on MRI (Ann Intern Med. 2001; 134:541), in which bone marrow lesions on MRI were present in 77.5% of patients with painful knee OA compared to only 30% of patients with painless knee OA. Expanding the concept that other aspects of knee OA can be mechanistically modeled at the level of subchondral bone rather than the articular cartilage, Felson et al seek to show a relationship between bone marrow edema, mechanical malalignment and risk of progression of OA of the knee (Ann Intern Med.2003; 139:330).
Methods: Patients were drawn from participants in the Veterans Health Study through four Veterans Administration sites in the Boston, Massachusetts area. Female participants were recruited from the Veterans Administration Womens Health Project, clinics at Boston Medical Center, and from advertisements in local newspapers. OA was defined by the presence of knee pain and an osteophyte on plain radiographs of the more symptomatic knee.
Eligible patients age 45 or older for men and age 50 or older for women without contraindications for MRI underwent MRI scanning of the more symptomatic knee with coronal T-2 weighted fat-saturated images read by a single, blinded radiologist. Bone marrow lesions were graded based on size. Participants also underwent fluoroscopically positioned plain radiographs of the more symptomatic knee, weight and height measurements, and questionnaires about severity of knee symptoms, including the Western Ontario McMaster Osteoarthritis (WOMAC) questionnaire. Follow-up visits occurred at 15 and 30 months and consisted of repeat plain radiographs, weight and height measurements, and follow-up questionnaires. Mechanical alignment at the knee was determined at the first follow-up visit with long-limb radiographs. Radiographs were evaluated unblinded to sequence.
Results: 223 patients who fulfilled inclusion criteria had at least one follow-up examination. Average age at baseline was 66.2 years. 41.7% of participants were women. Average weight at entry was 191.5 lbs with average body mass index of 31.1. Interestingly, although a definite osteophyte was required for inclusion, 25% of baseline knee radiographs were Kellegren-Lawrence grade of zero or one (normal or possible osteophyte). Of the remaining baseline knee radiographs, 44.4% were classified as Kellegren-Lawrence grade three.
In the cross-sectional baseline analysis, varus malalignment was significantly correlated with the presence of bone marrow lesion(s) in the medial compartment especially extreme varus malalignment (greater than or equal to 7 degrees of varus deformity). A similar but less striking relationship was found between neutral or valgus knee malalignment and bone marrow lesions in the lateral compartment.
In terms of progression of knee OA, of the 39 knees demonstrating progressive joint space narrowing (JSN) of the medial compartment, 27 (69.2%) had medial bone marrow lesions at baseline. Of the 75 knees with medial bone marrow lesions at baseline, 27 (36%) subsequently progressive JSN of the medial compartment, compared with 12(8.1%) of 148 knees without baseline medial bone marrow lesions who progressed(OR of 6.5 (95% CI 3.0-14.0) for baseline medial bone marrow lesions and subsequent medial progression of OA.). After adjusting for the effects of mechanical malalignment, the OR of medial progression in the setting of baseline medial bone marrow lesions remained significant at 5.6 (95% CI 2.1-14.8). Of the 20 knees demonstrating lateral progression, 10 (50%) had lateral bone marrow lesions at baseline. Of the 40 knees with lateral bone marrow lesions at baseline, 10 (25%) subsequently showed lateral progression, compared with 10 (5.5%) of 183 knees without baseline lateral bone marrow lesions that would go onto lateral progression (OR of 6.1(95% CI 2.2-16.5) for baseline lateral bone marrow lesions and subsequent lateral progression of OA). After adjusting for the effects of mechanical malalignment, the OR of lateral progression in the setting of baseline lateral bone marrow lesions was 2.8 (95% CI 0.8-10.1).
Knees with medial bone marrow lesions at baseline were less likely show lateral progression over the study period (Adjusted OR 0.3 (95% CI 0.1-1.0)) while knees with lateral bone marrow lesions at baseline were less likely to show medial progression over the study period (Adjusted OR 0.7(95% CI 0.2- 1.8)).
Conclusions: Baseline bone marrow edema is a predictor for progression of knee OA in the compartment ipsilateral to the bone marrow lesion. A parallel association of mechanical malalignment with ipsilateral bone marrow lesions exists in relation to progression of knee OA.
Editorial Comments: The correlation of bone marrow lesions with pain in knee OA has been convincingly established. Here, another compelling association is established between bone marrow (edema) lesions and risk for progression of knee OA. What remains to be established is the cause-and-effect relationship between the various variables. For instance, whether an initial insult to articular cartilage leads to mechanical malalignment and subsequent subchondral bone destruction or rather subchondral bone damage leads to mechanical malalignment and subsequent articular cartilage destruction is not explained by the current analysis. In addition, the evolution and natural history of the baseline bone marrow lesions on follow-up MRI studies with respect to progression of knee OA has yet to be investigated. It is interesting to note that, histologically, the lesions that appear as bone marrow edema on MRI contain very little edema at all. Rather, they demonstrate fibrosis, osteonecrosis, and extensive bony remodeling and are likely the result of contusions and focal micro-fractures. The clinician should be dissuaded from using these data to support routine use of MRI scanning or mechanical alignment measurements in order to risk stratify patients in terms of progression of knee OA. Nevertheless, these data contribute to a new understanding of the natural history of knee OA and suggests new areas of investigation and alternative treatment modalities to the few currently available.