Osteoarthritis, or OA, is the most common joint disease affecting middle-age and older people. It is characterized by progressive damage to the joint cartilage—the cushioning material at the end of long bones—and causes changes in the structures around the joint. These changes can include fluid accumulation, bony overgrowth, and loosening and weakness of muscles and tendons, all of which may limit movement and cause pain and swelling.
Knee osteoarthritis is a common form of osteoarthritis and is caused by cartilage breakdown in the knee joint. Factors that increase the risk of knee osteoarthritis — including being overweight, age, injury or stress to the joints, and family history — can increase the risk of knee osteoarthritis.
Sensitization refers to an alteration of the nervous system that results in heightened pain sensitivity, and may play an important role in knee OA pain. Because inflammation and/or tissue injury are thought to contribute to sensitization, U.S. researchers set out to learn whether this was the case in human knee OA. They specifically studied whether inflammation-related lesions in knee OA, such as synovitis or effusion, or mechanical load or remodeling due to non-inflammatory bone marrow lesions (a marker of tissue injury), are risk factors for increased sensitization in knee OA.
“It is widely recognized that the level of pain patients experience is not always what one would expect based upon what is seen on their X-rays,” said Tuhina Neogi, MD, PhD, FRCPC of Boston University School of Medicine and a lead author on the study. “In prior work, we have found that sensitization is associated with greater pain severity and may explain part of this discrepancy between pain levels and X-ray changes. However, we still did not understand why some people exhibit sensitization while others do not. If we could understand why sensitization occurs in some people with knee OA, then that could be a potential target for treatment that could ultimately reduce the severity of pain experienced by those individuals.”
Using data from the Multicenter Osteoarthritis (MOST) Study, researchers in the U.S. looked at test results obtained from 1,111 subjects with or at risk of knee OA, including X-rays, magnetic resonance imaging scans (MRI), and standardized somatosensory evaluations of two measures that give insights into the presence of sensitization: mechanical temporal summation and pressure pain thresholds (PPT). These measures were obtained at the knee at baseline and again two years later. The mean age of the subjects in the study was 66.9. The mean BMI was 29.7, and 62 percent were female.
The researchers looked at how synovitis, effusion and BMLs seen at the baseline assessment might be related to the new development of temporal summation in the same knee 2 years later among those who did not show signs of it at the baseline visit. They also assessed changes in PPT levels in the same knee between baseline and the visit two years later in all the subjects.
Of the 1,111 subjects studied, 22.6 percent developed incident temporal summation by the 2-year study visit. Between the baseline and two-year visit, changes in the PPT levels ranged from -7.35 to 7.15 kg/cm2. Synovitis was associated with significant decreases in PPT (i.e., more pain sensitive). Effusion was significantly associated with incident temporal summation. Bone marrow lesions presence or burden was not associated with temporal summation or change in PPT.
The study’s authors concluded that inflammation, such as that associated with synovitis or effusion, may drive sensitization in knee OA, while BMLs do not appear to do so. They suggested that early targeting of inflammation in knee OA may prevent sensitization and helping to reduce pain severity in people with knee OA.
“This is the first such study in knee OA to obtain sensitization measures at more than one time-point in such a large number of individuals, providing insights for the first time into how sensitization may develop or change over time in this disease,” said Dr. Neogi. “These results will help broaden understanding of how and why pain may evolve in people with knee OA and help identify potential treatment targets for pain in knee OA – a disease that affects millions of people, yet has very few effective treatment options.”
Funding sources for this study included the Rheumatology Research Foundation, National Institutes of Health, including NIAMS and NIA.
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The American College of Rheumatology is an international professional medical society that represents more than 9,500 rheumatologists and rheumatology health professionals around the world. Its mission is to Advance Rheumatology! The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit http://www.acrannualmeeting.org/ or join the conversation on Twitter by using the official #ACR14 hashtag. Paper Number: 2783
Effect of Synovitis, Effusion and Bone Marrow Lesions on Development of Sensitization in Knee OA: The Multicenter Osteoarthritis Study
Tuhina Neogi, Boston University School of Medicine, Boston, MA, Michael C. Nevitt, UCSF (University of California, San Francisco), San Francisco, CA, Joachim Scholz, Columbia University, New York, NY, Lars Arendt-Nielsen, Center for Sensory-Motor Interaction, Aalborg, Denmark, Clifford Woolf, Children's Hospital Boston, Boston, MA, Laurence A. Bradley, Univ of Alabama-Birmingham, Birmingham, AL, Emily K. Quinn, Boston University, Boston, MA and Laura Frey-Law, University of Iowa, Iowa City, IA
Background/Purpose: Alterations in the peripheral and central nervous systems including sensitization are thought to play an important role in the pain experience in knee OA. While sensitization could occur due to an underlying predisposition, it is hypothesized that joint inflammation and/or tissue injury in OA could provide sufficient peripheral nociceptive input to cause sensitization. We previously reported that radiographic knee OA severity or duration do not appear to be related to sensitization. However, whether specific MRI lesions related to inflammation (e.g., synovitis, effusion), or mechanical load or remodeling related to noninflammatory tissue injury (e.g., bone marrow lesions (BMLs)) are risk factors for development of sensitization is not yet known. Methods: The Multicenter Osteoarthritis (MOST) Study is a NIH-funded longitudinal cohort of persons with or at risk of knee OA. Subjects had x-rays and MRIs (1.0 T) of each knee obtained at each study visit, and a standardized somatosensory evaluation of mechanical temporal summation and pressure pain thresholds (PPT) at the patella at 60- and 84-months. Temporal summation was defined by increased pain during repeated mechanical stimulation (1 Hz x 30-sec) with a 60g monofilament. PPT was assessed with an algometer (1 cm2 tip, 0.5 Kg/sec) as the point at which the subject felt the pressure change to slight pain. Lower PPT indicates more sensitivity. Synovitis, effusion and BMLs on MRIs were scored using WORMS (one knee per person); these lesions were considered to be present if their score was ≥1 in any subregion. In sensitivity analyses, we assessed the sum of BML scores across all knee subregions as a measure of BML burden. We assessed the relation of presence of synovitis, effusion, and BMLs at 60-mo to incident temporal summation in the same knee at 84-mo among those who did not have temporal summation at 60-mo, and to change in PPT in the same knee between 60- and 84-mo in the whole sample using logistic and linear regression, respectively, adjusted for relevant potential confounders, including OA severity.
Results: There were 1111 subjects (mean age 66.9, mean BMI 29.7, 62% female) in the whole sample. 22.6% developed incident temporal summation at the 84-mo visit, and the range in change of PPT between the 60- and 84-mo visits was -7.35 to 7.15 kg/cm2. Presence of synovitis was associated with a significant decrease in PPT (i.e., more sensitized) over 24 mo, while effusion was significantly associated with incident temporal summation (Table). BML presence or burden were not associated with temporal summation or PPT.
Conclusion: Inflammation, as evidenced by synovitis or effusion, may drive the occurrence of sensitization in knee OA. In contrast, BMLs do not appear to contribute to sensitization in knee OA. Early targeting of inflammation in knee OA may be a reasonable strategy to test for its ability to prevent occurrence of sensitization, thereby reducing pain severity in knee OA.
Disclosures: T. Neogi, None.M. C. Nevitt, None.J. Scholz, None.L. Arendt-Nielsen, None.C. Woolf, None.L. A. Bradley, None.E. K. Quinn, None.L. Frey-Law, None.
Journal Link: American College of Rheumatology Annual Meeting
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