MCRC Project 1, Some of Our Advances...

Varus Alignment and Risk of Incident and Progressive Radiographic Knee OA.  In 2001, we reported the compartment-specific effect of varus and valgus alignment (on medial and lateral tibiofemoral OA radiographic progression, respectively) (a), findings since replicated in several studies.  Alignment had a stronger effect in knees with moderate OA at baseline than in knees with mild OA, presumably relating to greater vulnerability of more diseased knees (b).  Within our MOST ancillary study, we reported that varus but not valgus alignment was associated with increased risk of incident radiographic tibiofemoral OA (c).  In knees with OA, varus and valgus alignment were each associated with increased risk of progression in the expected compartment.  As we recently reported in our MOST ancillary, in knees with normal cartilage morphology by MRI, varus was associated with incident cartilage damage in the medial compartment, and varus and valgus with a reduced risk of incident damage in the less loaded compartment (d).  

 

a. Sharma L, Song J, Felson DT, Cahue S, Shamiyeh E, Dunlop DD.  The role of knee alignment in disease progression and functional decline in knee osteoarthritis. JAMA 2001, 286:188-95.

 

b. Cerejo R, Dunlop DD, Cahue S, Song J, Sharma L. The influence of alignment on risk of knee osteoarthritis progression according to baseline stage of disease. Arthritis Rheum 2002;46:2632-6.

 

c. Sharma L, Song J, Dunlop D, Felson D, Lewis CE, Segal N, Torner J, Cooke TD, Hietpas J, Lynch J, Nevitt M.  Varus and valgus alignment and incident and progressive knee osteoarthritis.  Ann Rheum Dis 2010;69:1940-5.  Epub 2010 May 28.

 

d. Sharma L, Chmiel JS, Almagor O, Felson D, Guermazi A, Roemer F, Lewis CE, Segal N, Torner J, Cooke TDV, Hietpas J, Lynch J, Nevitt M.  The role of varus and valgus alignment in the initial development of knee cartilage damage by MRI: the MOST Study.  Ann Rheum Dis 2012 May 1. [Epub ahead of print]

    

Relationship of Meniscal Damage, Meniscal Extrusion, Malalignment, and Joint Laxity to Subsequent Cartilage Loss in Osteoarthritic Knees (e).  In analyses adjusting for age, gender, BMI, and (uniquely vs. prior studies) other local factors, medial meniscal damage predicted 2-year medial tibial cartilage loss, and tibial and femoral denuded bone increase, and varus malalignment predicted medial tibial cartilage loss, and tibial and femoral denuded bone increase.  Lateral meniscal damage predicted every lateral outcome.  

 

e. Sharma L, Eckstein F, Song J, Guermazi A, Prasad P, Kapoor D, et al.  The relationship of meniscal damage, meniscal extrusion, malalignment, and joint laxity to subsequent cartilage loss in osteoarthritic knees.  Arthritis Rheum 2008;58:1716-26.

 

Subregional Effects of Meniscal Tears on Cartilage Loss over Two Years in Knee OA (f).  To evaluate local impact of meniscal tears, we examined the association between a tear within a specific meniscal segment and subsequent 2-year cartilage loss by MRI in subregions that the torn segment overlies.  We found that the detrimental effect of meniscal tears is not spatially uniform across the tibial and femoral cartilage surfaces and that much of the effect is experienced locally.  

 

f. Chang A, Moisio K, Chmiel JS, Eckstein F, Guermazi A, Almagor O, Cahue S, Wirth W, Prasad P, Sharma L.  Subregional effects of meniscal tears on cartilage loss over 2 years in knee osteoarthritis.  Ann Rheum Dis 2011;70:74-9.  Epub 2010 Aug 12.

 

Within-subregion Relationship between Bone Marrow Lesions and Subsequent Cartilage Loss in Knee Osteoarthritis (g).  Analyzing 1953 subregions among 177 knees, 90% of subregions had no bone lesion at baseline.  Only 0-3% of subregions without cartilage lesions had bone lesions in the same subregion; in contrast, 5-33% of subregions without bone lesions had cartilage lesions.  Bone marrow lesions at baseline were associated with cartilage loss in the same subregion, adjusting for other types of bone lesions.  In persons with knee OA, bone marrow lesions were rare at early disease stages but predicted subregional cartilage loss after accounting for the presence of other types of bone lesions in the same subregion. 

    

g. Kothari A, Guermazi A, Chmiel JS, Song J, Almagor O, Dunlop D, Marshall M, Cahue S, Prasad P, Sharma L.  The within-subregion relationship between bone marrow lesions and subsequent cartilage loss in knee osteoarthritis.  Arthritis Care Res 2010;62:198-203.

 

Hip Abduction Moment and Protection against Medial Tibiofemoral OA Progression (h).  A previous MAK cycle included a gait study in a subset of 64 participants at Rush Medical Center (funded by a SCOR grant, Kuettner PI).  During gait, weakness of the stance limb hip abductor muscles causes excessive pelvic drop in the contralateral swing limb.  The resulting shift in body center of mass increases stance limb medial compartment forces.  We found that a greater internal hip abduction moment was associated with a reduced likelihood of radiographic medial OA progression, adjusting for age, gender, gait speed, knee pain, physical activity, varus malalignment, hip OA, and hip symptoms. 

 

h. Chang A, Hayes K, Dunlop D, Song J, Hurwitz D, Cahue S, Genge R, Sharma L.  The hip abduction moment and protection against medial tibiofemoral osteoarthritis progression.  Arthritis 

Rheum 2005;52:3515-9.

 

Relationship of Toe-out Angle during Gait with Medial Tibiofemoral OA Progression (i).  Walking with a greater toe-out angle shifts the ground reaction force vector laterally, creating a moment that counteracts the knee adduction moment.  We found that greater toe-out angle during gait at baseline was associated with a reduced likelihood of medial OA progression over the next 18 months, adjusting for pain, baseline disease severity, gait speed, and varus malalignment.  

 

i. Chang A, Hurwitz D, Dunlop D, Song J, Cahue S, Hayes K, Sharma L.  The relationship between toe-out angle during gait and progression of medial tibiofemoral osteoarthritis. Ann Rheum Dis 2007;66:1271-5. Epub 2007 Jan 31.

 

Physical Functioning over Three Years in Knee OA: Role of Psychosocial, Local Mechanical, and Neuromuscular Factors (j).  In persons with knee OA, factors associated with poor WOMAC physical function outcome were baseline laxity, BMI, and knee pain intensity.  Factors protecting against a poor WOMAC outcome were better mental health, self-efficacy, and social support, and more aerobic exercise.  Age and proprioceptive inaccuracy were associated with poor chair-stand outcome; self-efficacy, aerobic exercise, and quadriceps strength (attenuated by pain intensity or self-efficacy) reduced risk for poor outcome.  Of note, self-efficacy consistently predicted outcomes after adjusting for pain and strength. 

 

j. Sharma L, Cahue S, Song J, Hayes K, Pai Y-D, Dunlop D. Physical functioning over 3 years in knee osteoarthritis: role of psychosocial, local mechanical and neuromuscular factors. Arthritis Rheum 2003;48:3359-70. 

 

Basic Function, Advanced Function, and Role Performance by Disease Stage in Persons with Knee OA (k).  The LL-FI includes assessment of difficulty in completing specific physical actions [basic lower extremity (LE), advanced LE, and upper extremity (UE) function scores].  We found worse score by Kellgren/Lawrence radiographic disease severity group for advanced but not for basic LE function, UE function, or role score.  Among the advanced function items, substantial differences were found between K/L groups for: walking several blocks, walking a mile resting as needed, a brisk one mile walk, going up and down a flight of stairs outside without a handrail, running a short distance such as to catch a bus, and hiking a couple of miles on uneven surfaces.  Over two years, there was a trend towards greater loss of function as K/L worsened.  

    

k. Cahue S, Hayes K, Marshall M, Song J, Dunlop D, Kapoor D, Chang A, Sharma L.  Basic function, advanced function, and role performance by disease stage in persons with knee OA.  Arthritis Rheum 2006;54:S156.

 

Frailty and 3-Year Mobility Outcome in Persons With or at Higher Risk for Knee Osteoarthritis (l).  A simple frailty index, easily usable in a clinical setting, was independently associated with worse 3-year mobility outcome and SF12 physical component outcome in 4138 OAI participants, at high risk for or with knee OA.  At baseline, 14% of women and 11% of men were frail.  Frailty was associated with being African-American, having a lower education level, and poorer self-assessed health. 

 

l. Cahue S, Hayes KW, Song J, Dunlop DD, Chmiel JS, Hochberg MC, Colbert CJ, Sharma L.  Frailty and 3-year mobility outcome in persons with or at higher risk for knee osteoarthritis.  Arthritis Rheum 2010;62 (supplement):S78.

 

Function Outcome in the OAI.  In analyses of OAI cohort data, we found that worse knee confidence at baseline was independently associated with greater risk of poor function outcome by self-report measures, with evidence of a graded response; the relationship was not significant for the performance measures in the fully adjusted models (m). Factors independently associated with poor function outcome for all 4 outcome measures were depressive symptoms, comorbidity, BMI, and joint space narrowing (m).  Among OAI women with excess body weight, African-Americans were at greater risk than Caucasians for poor 4-year outcome (n).  Modifiable factors that helped to explain these findings in the OAI include comorbidity, depressive symptoms, and knee pain.  Targeting such factors, while supporting weight loss, may help to lessen the outcome disparity between African-American and Caucasian women.

 

m. Colbert CJ, Song J, Dunlop D, Chmiel JS, Hayes KW, Cahue S, Moisio KC, Chang AH, Sharma L. Knee confidence as it relates to physical function outcome in persons with or at higher risk for knee osteoarthritis in the Osteoarthritis Initiative.  Arthritis Rheum 2012;64:1437-46 PMC3319513

 

n. Colbert CJ, Almagor O, Chmiel JS, Song J, Dunlop D, Hayes KW, Sharma L.  Excess body weight and 4-year function outcomes:  Comparison of African-Americans and Caucasians in the Osteoarthritis Initiative.  Arthritis Care Res (Hoboken) 2012 Jul 25. [Epub ahead of print]

 

Denuded Subchondral Bone and Knee Pain in Persons with Knee OA (o).   How articular cartilage loss contributes to pain in persons with knee OA is unclear.  Full thickness cartilage defects expose the subchondral bone plate.  The relationship between denuded bone and pain has not been examined.  We studied whether %denuded bone is associated: with moderate-severe knee pain or frequent knee pain; and longitudinally with incident frequent knee pain two years after the baseline evaluation.  Cross-sectional analyses of 305 knees from 182 persons revealed that moderate-severe knee pain was associated with %denuded bone in the medial compartment (adjusted OR 3.90, 95% CI 1.33, 11.47), medial and patellar surfaces together, and lateral and patellar surfaces, adjusting for age, gender, BMI, and bone marrow lesions.  Frequent knee pain was associated with %denuded bone in the patellar surface, medial and patellar surfaces, and lateral and patellar surfaces.  Longitudinal analyses (in 168 knees without baseline frequent knee pain) revealed that denuded bone in medial and patellar surfaces was associated with incident frequent knee pain (adjusted OR 4.19, 95% CI 1.56, 11.22).  These results support a relationship between subchondral bone plate exposure and prevalent and incident knee pain in persons with knee OA.   

 

o. Moisio K, Eckstein F, Chmiel JS, Guermazi A, Prasad P, Almagor O, Song J, Dunlop D, Hudelmaier M, Kothari A, Sharma L.  Denuded subchondral bone and knee pain in persons with knee OA.  Arthritis Rheum 2009;60:3703-10.