Multicenter Osteoarthritis Study Cohort Research Articles

Knee Extensor and Flexor Torque Variability During Maximal Strength Testing and Change in Knee Pain and Physical Function at 60-Mo Follow-Up: The Multicenter Osteoarthritis Study (MOST).

As the population ages, there is a growing burden owing to musculoskeletal diseases, such as knee osteoarthritis, and subsequent functional decline. In the absence of a cure, there is a need to identify factors amenable to intervention to prevent or slow this process. The Multicenter Osteoarthritis Study cohort was developed for this purpose. In this study, associations between variability in peak knee flexor and extensor torque at baseline and worsening of pain and physical function over the subsequent 60 mos were assessed in a cohort of 2680 participants. The highest quartile of baseline knee flexor torque variability was found to be associated longitudinally with worsening pain (fourth quartile ß estimate, mean ± SE, 0.49 ± 0.19; P = 0.0115; with R2 = 0.28 and P for trend across quartiles = 0.0370) and physical function scores (fourth quartile ß estimate, mean ± SE, 1.39 ± 0.64; P = 0.0296; with R2 = 0.25 and P for trend across quartiles = 0.0371), after adjusting for baseline knee osteoarthritis and maximum knee flexor torque. There were no associations between baseline knee extensor torque and worsening pain or physical function by 60 mos. The presence of greater variability in maximum knee flexor strength may identify patients who may benefit from therapies aimed at preventing worsening knee pain and physical function.

Association of Visceral Adiposity With Pain but Not Structural Osteoarthritis.

Osteoarthritis (OA) and pain are both made more severe by low-grade inflammation. This study was undertaken to examine whether visceral fat, a major source of inflammatory cytokines and adipokines, is associated with an increased risk of knee OA or musculoskeletal pain. Subjects in the Multicenter Osteoarthritis Study cohort, who were age 50-79 years and had or were at high risk of knee OA, underwent whole-body dual x-ray absorptiometry (DXA) at baseline. At baseline, 30 months, and 60 months radiographs and magnetic resonance images (MRIs) of the knees were obtained, and patients were asked to score the severity of their knee pain and to identify sites of joint pain using a body homunculus. Baseline DXA scans were used to measure total body fat and visceral and subcutaneous fat in the torso. The association of fat depot size with structural outcomes (incident radiographic OA and cartilage loss and synovitis on MRI) and with pain outcomes (worsening knee pain, number of painful joints, and widespread pain) was assessed. Regression analyses were adjusted for age, sex, race, education level, smoking status, physical activity, body mass index (BMI), and depressive symptoms. Of the 2,961 participants at baseline, 60.7% were women. The mean age was 62.5 years and mean BMI was 30.5 kg/m2 . After adjustment for covariates, no fat measures were associated with any structural outcomes. However, total and visceral, but not subcutaneous, fat were positively associated with worsening knee pain (P = 0.0005 for total fat and P = 0.007 for visceral fat) and widespread pain (P = 0.001 for total fat and P = 0.02 for visceral fat), and the amount of visceral fat was associated with the number of painful joints (P = 0.07). Our findings indicate that visceral fat is associated with an increased risk of musculoskeletal and widespread pain.

Determinants of fatigue among individuals with symptomatic knee osteoarthritis: the multicenter osteoarthritis study

Purpose: Evidence regarding fatigue determinants in knee osteoarthritis (OA) is sparse. To gain greater understanding of fatigue aetiology in the OA population, more longitudinal studies with well-defined populations are warranted. The objective of the study was to identify sociodemographic, disease-related, physical and mental health-related determinants of generalised fatigue over a two-year follow-up among individuals with symptomatic knee osteoarthritis (OA). Methods: A longitudinal analysis of participants with symptomatic knee OA from the Multicenter Osteoarthritis Study (MOST) at the 60 months exam (here defined as baseline) was conducted to identify baseline predictors of fatigue at two-year follow-up. Symptomatic knee OA was defined as both the presence of radiographic whole knee OA and frequent knee pain at two different interviews at baseline. Only subjects with complete fatigue values at baseline and follow-up periods were included in the present study. Participants self-reported fatigue at baseline and at two-year follow-up using a 0-10 visual analogue scale. At baseline, questionnaires and/or examinations on sociodemographics (age, sex [men vs. women], race/ethnicity [white and caucasian vs. black and /or others], living situation [living alone vs. living with significant others], and monthly bill payment [no difficulty vs. difficulty/unable to pay monthly bills]), disease-related symptoms (sleep quality [poor vs. good], comorbidities, Western Ontario McMaster Universities Osteoarthritis index (WOMAC) pain, radiographic evidence of knee OA [KL score <2 vs. >2]), physical and mental health factors (Center for Epidemiologic Studies Depression Scale (CES-D), pain catastrophizing [<1 vs. >1], body mass index (BMI) and gait speed via 20 meter walk) were completed. Baseline fatigue was included as a predictor in the analysis. Data analysis was conducted using linear regressions with a backwards elimination approach. Results: Of the 2,330 individuals in the MOST cohort at baseline, 449 had symptomatic knee OA. The majority of participants included were women (64%) and white/caucasian (78%), had an average age of 66.27 [SD=7.85] years with baseline and follow-up fatigue scores of 3.91 [SD=2.45] and 3.70 [SD=2.37]. The final model showed that baseline fatigue (Unstandardized coefficient (B)=0.435; 95% confidence interval [CI] [0.348, 0.523]), slow gait speed (B=-1.124; 95% CI [-1.962, -0.285]), depressive symptoms (B=0.049; 95% CI [0.024, 0.075]) and higher numbers of comorbidities (B=0.242; 95% CI [0.045, 0.439]) were significant predictors of increased fatigue at follow-up. Conclusions: The result of this study indicated that higher pre-existing fatigue, lower physical function, higher depressive symptoms and increased comorbidities were determinants of fatigue longitudinally in those with symptomatic knee OA. Fatigue is strongly associated with modifiable physical and mental related health factors. In the light of these Results, combined targeted psychological and physical function rehabilitation might be modalities for generalised fatigue management in symptomatic knee OA.

Determinants of generalized fatigue in individuals with symptomatic knee osteoarthritis: The MOST Study.

The aim of the study was to identify sociodemographic, disease-related, physical and mental health-related determinants of fatigue at 2-year follow-up in individuals with symptomatic knee osteoarthritis (OA). A longitudinal analysis of participants with symptomatic knee OA from the Multicenter Osteoarthritis Study (MOST) was conducted to identify predictors of fatigue at 2-year follow-up. Participants self-reported fatigue at baseline for the first time in the MOST cohort and at follow-up using a 0-10 visual analog scale. At baseline, questionnaires on sociodemographics, disease-related symptoms, physical and mental health factors were completed. Data were analyzed using linear regressions with a backwards elimination approach. Of the 2330 individuals in the MOST cohort at baseline, 576 had symptomatic knee OA and of these, 449 with complete fatigue values at baseline and follow-up were included in this analysis. Minimally important fatigue change (ie, worsening [≥1.13], no change [<0.82 or <1.13] and improvement [≥-0.82]) from baseline to follow-up were unequal within the population (34.5%, 26.9%, 38.5%; χ2 [2, N=449]=9.32, P=.009). The multiple linear regression showed that baseline fatigue (unstandardized coefficient [Β]=0.435; 95% confidence interval [CI] 0.348-0.523, P<.001), slow gait speed (Β=-1.124; 95% CI -1.962 to -0.285, P=.009), depressive symptoms (Β=0.049; 95% CI 0.024-0.075, P<.001) and higher numbers of comorbidities (Β=0.242; 95% CI 0.045-0.439, P=.016) were significant predictors of greater fatigue at follow-up. Fatigue is strongly associated with physical- and mental-related health factors. Individualized treatments that include combined psychological and physical function rehabilitation might be modalities for fatigue management.

Impact of total knee replacement practice: cost effectiveness analysis of data from the Osteoarthritis Initiative

Objectives To evaluate the impact of total knee replacement on quality of life in people with knee osteoarthritis and to estimate associated differences in lifetime costs and quality adjusted life...

The value of total knee replacement revisited: A comparative analysis of its effectiveness and impact on healthcare costs using data from the osteoarthritis initiative

Purpose: Total knee replacement (TKR) utilization in the U.S. has more than doubled since 2000, primarily due to expanding eligibility to less symptomatic knee osteoarthritis (OA) patients. Yet the benefit and costs of TKR have not been evaluated for a contemporary U.S. patient population within a comparative analysis. We evaluated the impact of TKR on quality of life, lifetime costs and quality-adjusted life years (QALYs) while varying TKR utilization by preoperative functional status. Methods: Data for these analyses are from the Osteoarthritis Initiative (OAI) public use data set(s) and Multicenter Osteoarthritis Study (MOST). We estimated the effect of TKR on generic (Short Form [SF] 12 score), and OA-specific quality of life measures among 1,327 OAI participants with knee OA, aged 45 to 79 (median age 61), and 9 years of follow-up. Marginal structural models were used. Effects were validated in 965 knee OA patients in the MOST cohort. We subsequently modeled the virtual life courses of OAI patients until age 100 using microsimulation, tracking occurrence of primary TKR, revision TKR, and death. We calculated QALYs and costs from a U.S. health system perspective and compared scenarios ranging from current TKR practice, to TKR practice limited to those with severe functional status, to no TKR. Cost-effectiveness thresholds of $100,000 and $200,000 per QALY were considered for decision-making. We used 500 bootstrap equations 95% to calculate confidence intervals (CIs). Cost of TKR was varied in deterministic sensitivity analyses. Results: In both OAI and MOST, quality of life outcomes generally improved after TKR, with small effect sizes becoming larger with decreasing preoperative functional status. After adjustment for baseline and time-varying confounders, TKR had a marginal effect of 1.70 (95% CI 0.26 to 3.57) on the SF-12 PCS, and changed SF-12 MCS by −0.22 (95% CI -1.49 to 1.31). For OA-specific measures of quality-of-life, TKR improved WOMAC score by 10.69 (95% CI 8.01 to 13.39) and KOOS by 9.16 (95% CI 6.35 to 12.49) points. TKR reduced the odds of OA pain medication use, but this effect was uncertain: 0.81 (95% CI 0.55 to 1.12). In the scenario of current TKR practice, the lifetime risk of undergoing TKR, as predicted for OAI participants with knee OA, was 40.2% (95% CI 35.1 to 44.1). The average QALYs were 11.93 and the average costs were $24,982 per patient. None of the scenarios’ incremental cost-effectiveness ratios (ICERs) were below $100,000/QALY. Allocating TKR to patients with SF-12 PCS scores below 35 was the optimal scenario given a cost-effectiveness threshold of $200,000/QALY, gaining 0.0065 QALYs against $1,126 additional costs as compared to the previous best scenario resulting in an ICER of $172,338/QALY. The current TKR practice scenario was dominated (see Figure). TKR would become cost-effective when performed in patients with SF-12 PCS scores up to 40 if the hospitalization costs fell below $12,000. Conclusions: TKR practice in a contemporary U.S. knee OA patient population had minimal effects on quality-of-life and was economically unattractive. However, if TKR practice were restricted to patients with more severe functional status, effect size would rise and the procedure may be considered to be cost-effective.

The relationship between quadriceps muscle weakness and worsening of knee pain in the MOST cohort: a 5-year longitudinal study

To determine whether quadriceps weakness is associated with elevated risk of worsening knee pain over 5 years. The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of 50-79-year-old adults with knee osteoarthritis (OA) or known risk factors for knee OA. The predictor variable was baseline isokinetic quadriceps strength. Covariates included baseline body mass index (BMI), physical activity level, and history of knee surgery. The outcome was worsening pain reported on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale or knee replacement surgery between baseline and 5-year follow-up. Analyses were knee-based and used generalized estimating equations, stratified by sex to assess whether the lowest compared with the highest tertile of baseline quadriceps strength was associated with an increased risk of worsening knee pain at 5-year follow-up, controlling for age, BMI, history of knee surgery, and physical activity level as well as correlation between knees within participants. Analyses of worsening knee pain included 4,648 knees from 2,404 participants (61% female). Men with lower quadriceps strength did not have a higher risk of worsening knee pain (RR {95% CI}=1.01 {0.78-1.32}, P=0.9183). However, women in the lowest compared with the highest strength tertile had a 28% increased risk of worsening knee pain (RR {95% CI}=1.28 {1.08-1.52}, P=0.0052). Quadriceps weakness was associated with an increased risk of worsening of knee pain over 5 years in women, but not in men.

Participation Following Knee Replacement: The MOST Cohort Study

Participation is an important, yet seldom studied, outcome after total knee replacement (TKR). The purpose of this study was to investigate the extent and predictors of participation and participation restriction among people after TKR. This study investigated the changes in pain, function, and participation scores (measured using a subscale of the Late-Life Function and Disability Instrument) from pre-TKR to ≥1 year post-TKR among a subsample of participants from the Multicenter Osteoarthritis Study (MOST) longitudinal cohort (MOST is funded by the National Institutes of Health). The proportions of individuals with participation restriction pre-TKR and ≥1 and ≥2 years post-TKR were calculated for all participants and for important demographic subgroups. The association between demographic and clinical factors and participation was estimated using linear regression. The association between demographic and clinical factors and participation restriction was estimated using logistic regression. There were 292 individuals with outcome data ≥1 year post-TKR. Of these, 218 (75%) had data pre-TKR and ≥1 year post-TKR and 160 (55%) had data ≥2 years post-TKR. There were mean improvements in pain, function, and participation at ≥1 and 2 years. However, approximately 30% of the study sample had participation restriction pre-TKR and post-TKR, and the proportion decreased significantly only for those <65 years old. Non-whites had a higher proportion of participation restriction than any other subgroup (41% ≥1 year, 48% ≥2 years). Female sex and non-white race were associated with a worse participation score, and several demographic and modifiable factors were associated with participation restriction following TKR. The time between pre-TKR and post-TKR assessment varied across study participants, and data were not available on their rehabilitation utilization. Although there was a mean increase in participation ≥1 year following TKR, participation restriction was common. The likelihood of low participation was increased among women, non-whites, and those with depressive symptoms, severe pain in either knee, or worse pre-TKR function.

Medial Posterior Meniscal Root Tears Are Associated with Development or Worsening of Medial Tibiofemoral Cartilage Damage: The Multicenter Osteoarthritis Study

To assess the association of meniscal root tear with the development or worsening of tibiofemoral cartilage damage. Institutional review board approval and written informed consent from all subjects were obtained. A total of 596 knees with radiographically depicted osteoarthritis were randomly selected from the Multicenter Osteoarthritis study cohort. Cartilage damage was semiquantitatively assessed by using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system (grades 0-6). Subjects were separated into three groups: root tear only, meniscal tear without root tear, and neither meniscal nor root tear. A log-binomial regression model was used to calculate the relative risks for knees to develop incident or progressing cartilage damage in the root tear group and the meniscal tear group, with the no tear group serving as a reference. In the medial tibiofemoral joint, there were 37 knees with isolated medial posterior root tear, 294 with meniscal tear without root tear, and 264 without meniscal or root tear. There were only two lateral posterior root tears, and no anterior root tears were found. Thus, the focus was on the medial posterior root tear. The frequency of severe cartilage damage (WORMS ≥ 5) was higher in the group with root tear than in the group without root or meniscal tear (76.7% vs 19.7%, P < .0001) but not in the group with meniscal but no root tear (76.7% vs 65.2%, P = .055). Longitudinal analyses included 33 knees with isolated medial posterior root tear, 270 with meniscal tear, and 245 with no tear. Adjusted relative risk of cartilage loss was 2.03 (95% confidence interval [CI]: 1.18, 3.48) for the root tear group and 1.84 (95% CI: 1.32, 2.58) for the meniscal tear group. Isolated medial posterior meniscal root tear is associated with incident and progressive medial tibiofemoral cartilage loss.

Valgus malalignment is a risk factor for lateral knee osteoarthritis incidence and progression: Findings from the multicenter osteoarthritis study and the osteoarthritis initiative

To study the effect of valgus malalignment on knee osteoarthritis (OA) incidence and progression. We measured the mechanical axis from long limb radiographs from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) to define limbs with valgus malalignment (mechanical axis of ≥1.1° valgus) and examined the effect of valgus alignment versus neutral alignment (neither varus nor valgus) on OA structural outcomes. Posteroanterior radiographs and knee magnetic resonance (MR) images were obtained at the time of the long limb radiograph and at followup examinations. Lateral progression was defined as an increase in joint space narrowing (on a semiquantitative scale) in knees with OA, and incidence was defined as new lateral narrowing in knees without radiographic OA. We defined lateral cartilage damage and progressive meniscal damage as increases in cartilage or meniscus scores at followup on the Whole-Organ Magnetic Resonance Imaging Score scale (for the MOST) or the Boston Leeds Osteoarthritis Knee Score scale (for the OAI). We used logistic regression with adjustment for age, sex, body mass index, and Kellgren/Lawrence grade, as well as generalized estimating equations, to evaluate the effect of valgus alignment versus neutral alignment on disease outcomes. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs). We studied 5,053 knees (881 valgus) of subjects in the MOST cohort and 5,953 knees (1,358 valgus) of subjects in the OAI cohort. In both studies, all strata of valgus malalignment, including 1.1° to 3° valgus, were associated with an increased risk of lateral disease progression. In knees without radiographic OA, valgus alignment >3° was associated with incidence (e.g., in the MOST, adjusted OR 2.5 [95% CI 1.0-5.9]). Valgus alignment >3° was also associated with cartilage damage on MR imaging in knees without OA (e.g., in the OAI, adjusted OR 5.9 [95% CI 1.1-30.3]).We found a strong relationship of valgus malalignment with progressive lateral meniscal damage. Valgus malalignment increases the risk of knee OA radiographic progression and incidence as well as the risk of lateral cartilage damage. It may cause these effects, in part, by increasing the risk of meniscal damage.

Body mass index change after knee replacement in the multicenter osteoarthritis study cohort

Body mass index change after knee replacement in the multicenter osteoarthritis study cohort