ARTHRITIS & RHEUMATISM Vol. 56, No. 9, September 2007, pp 2986–2992 DOI 10.1002/art.22851 © 2007, American College of Rheumatology Correlation of the Development of Knee Pain With Enlarging Bone Marrow Lesions on Magnetic Resonance Imaging David T. Felson, 1 Jingbo Niu, 1 Ali Guermazi, 1 Frank Roemer, 2 Piran Aliabadi, 3 Margaret Clancy, 1 James Torner, 4 C. Elizabeth Lewis, 5 and Michael C. Nevitt 6 Objective. Results of cross-sectional studies have suggested that bone marrow lesions (BMLs) visualized on magnetic resonance imaging (MRI) are related to knee pain, but no longitudinal studies have been done. This study was undertaken to determine whether en- larging BMLs are associated with new knee pain. Methods. Subjects ages 50–79 years with knee osteoarthritis (OA) or at high risk of knee OA were asked twice at baseline about the presence of knee pain, aching, or stiffness (classified as frequent knee pain) on most days; absence of knee pain was the baseline eligibility criterion. At 15 months’ followup, subjects were again queried twice about frequent knee pain. A case knee was defined as absence of knee pain at baseline but presence of knee pain both times at fol- lowup. Controls were selected randomly from among knees with absence of pain at baseline. All MR images were scored for volume of BMLs in the medial, lateral, and patellofemoral compartments. We focused on the maximal change in BML score among the knee com- partments from baseline to 15 months. Multiple logistic regression, with adjustments for demographic and clin- ical variables, was used to assess whether an increased BML score is predictive of the development of knee pain. Results. Among case knees, 54 of 110 (49.1%) showed an increase in BML score within a compart- ment, whereas only 59 of 220 control knees (26.8%) showed an increase (P < 0.001 by chi-square test). A BML score increase of at least 2 units was much more common in case knees than in control knees (27.5% versus 8.6%; adjusted odds ratio 3.2, 95% confidence interval 1.5–6.8). Among case knees with increased BMLs, most already had BMLs at baseline, with enlarg- ing BMLs at followup, but among the subset of knees with no BMLs at baseline, new BMLs were more com- mon in case knees (11 [32.4%] of 34) than in control knees (9 [10.8%] of 83). Conclusion. Development of knee pain is associ- ated with an increase in BMLs as revealed on MRI. Approximately one-fourth of adults ages 55 years have frequent knee pain (1). Although many of these individuals have a diagnosis of knee osteoarthritis (OA), at least half do not. Furthermore, even in those subjects with knee OA, the source of the joint pain is unknown. Whereas cartilage is aneural, bone is richly inner- vated and the involvement of bone in the pathologic features of OA is well recognized (2–4). Because of this innervation, bone could be a source of pain in at least some subjects with knee OA. In a previous cross- sectional study, we compared the findings on magnetic resonance imaging (MRI) of the knee in subjects with pain-free knee OA with the findings in subjects with knee pain and radiographic knee OA (5). We found that the subjects with knee pain were much more likely to have bone marrow lesions (BMLs) (5). Subsequent studies of the association of BMLs with knee pain, all of which have been cross-sectional, have either corroborated our initial findings (6) or contradicted them (7,8). This has left uncertainty as to the relationship between BMLs and knee pain. The Supported by the NIH (grants U01-AG-18820, U01-AG- 18832, U01-AG-18947, U01-AG-19069, and AR-47785). 1 David T. Felson, MD, MPH, Jingbo Niu, DSc, Ali Guermazi, MD, Margaret Clancy, MPH: Boston University School of Medicine, Boston, Massachusetts; 2 Frank Roemer, MD: Klinikum Augsburg, Augsburg, Germany; 3 Piran Aliabadi, MD: Brigham and Women’s Hospital, Boston, Massachusetts; 4 James Torner, PhD: University of Iowa, Iowa City; 5 C. Elizabeth Lewis, MD: University of Alabama at Birmingham; 6 Michael C. Nevitt, PhD: University of California, San Francisco. Address correspondence and reprint requests to David T. Felson, MD, MPH, Boston University School of Medicine, Room A203, 650 Albany Street, Suite 200, Boston, MA 02118. E-mail: dfelson@bu.edu. Submitted for publication January 5, 2007; accepted in re- vised form May 18, 2007. 2986