Knee OA is a leading cause of chronic disability in older Americans. Few strategies to prevent knee OA development, progression, or disability exist, due to limited knowledge of the responsible factors. There has been increasing recognition of the role of knee laxity and malalignment, two potentially modifiable factors that are the focus of the current application. These factors are being examined in the ongoing 300-subject MAK study (Mechanical Factors in Arthritis of the Knee) at Northwestern University, in which extensive experience has been gained with them, and evidence of their importance has accumulated. ? ? Now proposed is a comprehensive examination of the effect of laxity and malalignment in subjects with or at high risk to develop knee OA, as an ancillary study to the recently funded Multicenter OA Study (MOST). MOST is a study of 3000 men and women, with the primary goal of examining the effect of a panel of risk factors on OA outcomes over 3 years. MOST involves 4 sites: the Coordinating and MRI Reading Center (UCSF), Data Analysis and X-ray Reading Center (BU), and 2 Clinical Centers (UAB and UI). ? ? Hypotheses of this application focus on whether laxity and malalignment are each associated with: a higher risk of incident OA than non-lax knees and more neutrally aligned knees; a decline in physical function; risk of OA progression. Primary hypotheses focus on symptom and x-ray outcomes; MRI-based assessment of cartilage morphology is also proposed as a means of examining the compartment-specific effects of each of these factors in a subset of the MOST cohort. ? ? Support is requested: to replicate in MOST the measurement systems and protocols (for laxity and alignment) currently in use in the MAK study; to assess laxity and alignment at the baseline exam of MOST; in a subset of the cohort, to obtain MRI at baseline and at 3 year follow-up using a high-field scanner to examine change in cartilage volume and thickness as outcomes of laxity and malalignment; and to test the relationship of laxity and malalignment with risk of important OA outcomes.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD043500-05
Application #
7110919
Study Section
Special Emphasis Panel (ZRG1-EDC-3 (01))
Program Officer
Shinowara, Nancy
Project Start
2002-09-26
Project End
2009-08-31
Budget Start
2006-09-01
Budget End
2009-08-31
Support Year
5
Fiscal Year
2006
Total Cost
$223,989
Indirect Cost
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Felson, D T; Niu, J; Neogi, T et al. (2016) Synovitis and the risk of knee osteoarthritis: the MOST Study. Osteoarthritis Cartilage 24:458-64
Wise, Barton L; Niu, Jingbo; Felson, David T et al. (2015) Functional Impairment Is a Risk Factor for Knee Replacement in the Multicenter Osteoarthritis Study. Clin Orthop Relat Res 473:2505-13
Eckstein, F; Boudreau, R M; Wang, Z et al. (2014) Trajectory of cartilage loss within 4 years of knee replacement--a nested case-control study from the osteoarthritis initiative. Osteoarthritis Cartilage 22:1542-9
Felson, D T; Niu, J; Yang, T et al. (2013) Physical activity, alignment and knee osteoarthritis: data from MOST and the OAI. Osteoarthritis Cartilage 21:789-95
Sharma, Leena; Chmiel, Joan S; Almagor, Orit et al. (2013) The role of varus and valgus alignment in the initial development of knee cartilage damage by MRI: the MOST study. Ann Rheum Dis 72:235-40
Felson, David T; Niu, Jingbo; Gross, K Douglas et al. (2013) Valgus malalignment is a risk factor for lateral knee osteoarthritis incidence and progression: findings from the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative. Arthritis Rheum 65:355-62
Hayashi, D; Englund, M; Roemer, F W et al. (2012) Knee malalignment is associated with an increased risk for incident and enlarging bone marrow lesions in the more loaded compartments: the MOST study. Osteoarthritis Cartilage 20:1227-33
Wise, Barton L; Niu, Jingbo; Yang, Mei et al. (2012) Patterns of compartment involvement in tibiofemoral osteoarthritis in men and women and in whites and African Americans. Arthritis Care Res (Hoboken) 64:847-52
Gross, K Douglas; Niu, Jingbo; Stefanik, Joshua J et al. (2012) Breaking the Law of Valgus: the surprising and unexplained prevalence of medial patellofemoral cartilage damage. Ann Rheum Dis 71:1827-32
Sharma, Leena; Song, Jing; Dunlop, Dorothy et al. (2010) Varus and valgus alignment and incident and progressive knee osteoarthritis. Ann Rheum Dis 69:1940-5