Fluctuation of knee pain and changes in bone marrow lesions, effusions, and synovitis on magnetic resonance imaging

The number of adults in the US with clinical osteoarthritis grew from 21 million to nearly 27 million from 1995 to 20051. Of those, about 10 million people had symptomatic knee OA. Pain from knee OA is a key reason for seeking medical care and is an important antecedent to disability2. While pain from knee OA has long been considered a chronic condition, most people with symptomatic knee OA experience fluctuation in pain presence and severity3. The etiology for pain fluctuation from knee OA is not well understood. Over the last two decades, magnetic resonance imaging (MRI) has become an important tool in the evaluation and diagnosis of knee OA. Since MRI is able to visualize the subchondral bone marrow, synovial tissue, joint effusion and other abnormalities that cannot be seen with x-rays, several studies have examined the relation of the structural lesions assessed by MRI in or around the knee to knee pain4-13. Some studies found that bone marrow lesions (BMLs)5, 8, 10, 12, 13, effusions4, 9, 10 and synovitis4, 10, 11, were associated with knee pain, others, however, have failed to confirm the relation of BMLs to knee pain6, 7, 9. Some studies also demonstrated that an increase in BMLs was associated with pain onset12, 13 and that aggravating severity of synovitis was related to increasing pain severity11, nevertheless, such findings may be confounded by co-occurrence of worsening of other structural lesions. A few studies have suggested that cartilage defects may be associated with pain8, 10. There has been a paucity of information on changes in structural lesions in relation to fluctuation of knee pain over time, especially on whether reduction or complete resolution of these structural lesions is accompanied contemporaneously by a decrease in the presence of knee pain or pain severity. The study of improvement in lesions with pain change circumvents the problem of confounding by disease worsening. Further, the relation of reduction in these lesions to reduction in pain has treatment implications. The absence of longitudinal studies with repeat MRIs may reflect logistical and methodological challenges. First, obtaining and reading knee MRIs at multiple time points in participants in a longitudinal study is expensive. Second, pain is a subjective experience and biological, psychological, and social factors play important roles in a subject's response to pain stimuli14. However, in many studies of risk factors for knee pain, the majority of these risk factors were neither collected nor adjusted for. Since pain is a nociceptive phenomenon that requires sensory input, we hypothesize that nociceptive input must necessarily be related to some underlying structural lesions (i.e., biological origin). Such structural lesions are likely to be reversible in order to cause the fluctuation of knee pain. Therefore, we focused on three reversible structural lesions, i.e., BML's, synovitis and effusion and tested whether changes in these reversible structural lesions are associated with fluctuation of knee pain. To minimize the effect of time-invariant confounders for pain and to reduce the cost of reading knee MRIs, we conducted a self-matched case-control study15 focusing on persons with pain fluctuation to examine the relation of changes in BMLs, effusion, and synovitis to the fluctuation of knee pain among participants in the Multicenter Osteoarthritis Study (MOST).