Excess body weight and four-year function outcomes: Comparison of African Americans and whites in a prospective study of osteoarthritis

Authors


  • This manuscript was prepared using the Osteoarthritis Initiative (OAI) public use data set and does not necessarily reflect the opinions or views of the OAI Investigators, the NIH, or the private funding partners.

Abstract

Objective

We evaluated whether African Americans in the Osteoarthritis Initiative (OAI) have a greater risk (versus whites) of poor 4-year function outcome within strata defined by sex, body mass index (BMI), and waist circumference.

Methods

Using Western Ontario and McMaster Universities Osteoarthritis Index function, 20-meter walk, and chair stand performance, poor outcome was defined as moving into a worse function group or remaining in the 2 worst groups over 4 years. Logistic regression was used to evaluate the relationship between racial group and outcome within each stratum, adjusting for age, education, and income, and then further adjusting for BMI, comorbidity, depressive symptoms, physical activity, knee pain, and osteoarthritis (OA) severity.

Results

In 3,695 persons with or at higher risk for knee OA, higher BMI and large waist circumference were each associated with poor outcome. Among women with high BMI and among women with large waist circumference, African Americans were at greater risk for poor outcome by every measure, adjusting for age, education, and income. From fully adjusted models, potential explanatory factors included income, comorbidity, depressive symptoms, pain, and disease severity. Findings were less consistent for men, emerging only for the 20-meter walk or chair stand outcomes, and potentially explained by age and knee pain.

Conclusion

Among OAI women with excess body weight, African Americans are at greater risk than whites for poor 4-year outcome. Modifiable factors that may help 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 white women.

INTRODUCTION

Knee osteoarthritis (OA) is a common condition and a major source of chronic disability. In longitudinal studies of persons with knee OA, factors shown to be associated with greater function decline, a precursor to disability, include greater age, female sex, greater body mass index (BMI), knee pain, comorbid medical conditions, depressive symptoms, decreased knee confidence, varus–valgus laxity, malalignment, greater radiographic disease severity, and proprioceptive inaccuracy, while greater physical activity, aerobic exercise, strength, self-efficacy, and social support each have been associated with a reduced risk of function decline (1–12). Given the heterogeneity of the impact of knee OA among individuals, it is important to identify groups who are at higher risk for poor outcome. A better understanding of the underlying differences between risk groups may lead to development of more effective strategies to prevent or delay function decline and subsequent disability.

Elevated body weight is a strong risk factor for incident knee OA and is often present in persons with established knee OA. As recently demonstrated, the prevalence of knee pain and symptomatic knee OA rose substantially between 1974 and 1994, findings partially explained by obesity (13). It has been estimated that 66% of adults in the US are overweight or obese and that by 2015 this figure will rise to 75% (14). The prevalence of excess body weight differs by sex and race/ethnicity. In 1999–2002, the combined prevalence of overweight and obesity was 77.2% among non-Hispanic African American women versus 57.2% in non-Hispanic white women, with similar estimates for central obesity, 70.4% and 54.0%, respectively (14). Losina et al recently demonstrated substantial losses in quality-adjusted life years due to knee OA and obesity; African American and Hispanic women had disproportionately high losses (15). The impact of elevated body weight, i.e., above what is considered healthy, within racial groups on more proximal outcomes is not well understood.

We tested the hypothesis that African Americans have a greater risk (compared to whites) of poor baseline to 48-month physical function outcome with 4 strata, women with high BMI, women with large waist circumference, men with high BMI, and men with large waist circumference. The Osteoarthritis Initiative (OAI) cohort study, enriched with individuals above a healthy body weight, provided an ideal setting to evaluate this question.

Significance & Innovations

  • To our knowledge, this is the first demonstration that greater waist circumference is associated with a greater risk of poor long-term function outcome in persons with or at higher risk for knee osteoarthritis (OA).

  • To our knowledge, this is the first confirmation that, among overweight women with or at higher risk for knee OA, African Americans are at greater risk for poor long-term outcome than whites.

  • In addition to identifying this risk group, we report the results of exploration of potential explanatory factors. Ultimately, targeting such factors, while supporting weight loss, may improve strategies to prevent poor outcome.

PATIENTS AND METHODS

Sample.

The OAI is a prospective observational cohort study of men and women (ages 45–79 years) all with or at increased risk of developing symptomatic radiographic knee OA who were enrolled at 1 of 4 sites: Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island (http://www.oai.ucsf.edu/datarelease/About.asp). All racial/ethnic groups were eligible to enroll, and the recruitment goal was 23% of the cohort from racial/ethnic minority groups. To be eligible for the progression subcohort of the OAI, persons were required to have symptomatic radiographic knee OA, defined as the presence of both of the following in at least 1 native knee at baseline: pain, aching, or stiffness in or around the knee on most days for at least 1 month during the past 12 months, and a definite tibiofemoral osteophyte (osteophyte grade ≥1, using the Osteoarthritis Research Society International [OARSI] atlas [16]). Persons were eligible for the incidence subcohort of the OAI if they did not have symptomatic radiographic knee OA in either knee at baseline, but had characteristics that placed them at increased risk for developing it during the study. Age-specific criteria for determining increased risk were identified from within the following set of established risk factors: 1) knee symptoms in a native knee in the past 12 months, 2) overweight, defined using sex- and age-specific cut points for weight, 3) knee injury causing difficulty walking for at least a week, 4) history of any knee surgery, 5) family history of a total knee replacement for OA in a biologic parent or sibling, 6) Heberden's nodes, 7) repetitive knee bending at work or outside work, and 8) ages 70–79 years (see http://www.oai.ucsf.edu/datarelease/About.asp and Appendix B at that site for greater detail regarding the rationale and approach taken to derive the criteria).

Exclusion criteria were: 1) rheumatoid arthritis or inflammatory arthritis, 2) severe joint space narrowing in both knees on the baseline knee radiograph, or unilateral total knee replacement and severe joint space narrowing in the other knee, 3) bilateral total knee replacement or plans to have bilateral knee replacement in the next 3 years, 4) inability to undergo a 3.0T magnetic resonance imaging examination of the knee because of contraindications or inability to fit in the scanner or in the knee coil (including men weighing >285 pounds and women weighing >250 pounds), 5) positive pregnancy test, 6) inability to provide a blood sample for any reason, 7) use of ambulatory aides other than a single straight cane for >50% of the time in ambulation, 8) comorbid conditions that might interfere with the ability to participate in a 4-year study, and 9) current participation in a double-blind randomized trial.

Assessment of body weight, height, and waist circumference.

Body weight was measured in the OAI using a standard balance-beam scale, with the participant in lightweight clothes, without shoes or heavy jewelry, and with pockets emptied, and following a detailed protocol (http://oai.epi-ucsf.org/datarelease/operationsManuals/WeightV1_0p.pdf). Height was measured using a wall-mounted stadiometer, with the participant barefoot or wearing thin stockings or socks, following a detailed protocol (http://oai.epi-ucsf.org/datarelease/operationsManuals/HeightV1_0p.pdf).

BMI was calculated as the weight in kilograms divided by the height in meters squared. In analysis, BMI was categorized as high (above what is considered healthy) when ≥25.0 kg/m2. Waist circumference is an indicator of subcutaneous and deep adipose tissue, has been used to define central obesity, is well understood by the general public, and may better predict health outcomes (14). In the OAI, waist circumference was measured using a flexible, inelastic fiberglass tape following a detailed protocol (http://oai.epi-ucsf.org/datarelease/operationsManuals/Abdominal_circumferenceV1_0p.pdf). Waist circumference was classified as large when >102 cm in men and >88 cm in women (17).

Assessment of baseline to 4-year physical function outcome.

Physical function was assessed at baseline and at 48 months using: 1) the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function scale, 2) 20-meter walk performance, and 3) chair stand performance. To characterize the baseline to 4-year function experience of each participant, quintile grids were used, with poor outcome defined as remaining within the same low functioning group (the 2 worst quintile groups) or moving into a worse function quintile group (6, 11, 18).

The WOMAC is a self-report instrument with 17 questions comprising the physical function scale. It is extensively validated and widely recommended and used in studies of individuals with knee OA (19, 20). A higher score indicates worse function. Participants were categorized by WOMAC function score quintile derived from the OAI cohort at baseline, ranging from worst to best function as follows: first quintile (>20.19), second quintile (>10.00 and ≤20.19), third quintile (>3.40 and ≤10.00), fourth quintile (>0 and ≤3.40), and fifth quintile (0). The WOMAC outcome grid is shown in Table 1, with Xs representing a poor baseline to 4-year WOMAC function outcome.

Table 1. Definition of poor WOMAC function outcome*
WOMAC Q at baselineWOMAC quintile (Q) group at 48-month followup
Q1 (worst)Q2Q3Q4Q5 (best)
  • *

    Illustration of how poor outcome was defined in terms of the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) function measure. Quintile groups were defined by the cutoff values of the baseline WOMAC function score quintiles. The baseline to 48-month outcome was “poor” when a participant moved into a worse function group or remained within the same low functioning group (the 2 worst function groups).

Q1 (worst; >20.19)X    
Q2 (>10.00–≤20.19)XX   
Q3 (>3.40–≤10.00)XX   
Q4 (>0–≤3.40)XXX  
Q5 (best; 0)XXXX 

The 20-meter walk was evaluated as a rate (meters per minute). Participants were categorized by baseline walk rate quintile, ranging from worst to best function as follows: first quintile (≤68.65 or unable), second quintile (>68.65 and ≤76.09), third quintile (>76.09 and ≤82.48), fourth quintile (>82.48 and ≤89.55), and fifth quintile (>89.55). Chair stand test performance, i.e., time required for 5 repetitions of rising from a chair and sitting down (21), was evaluated as a rate (number of stands per minute calculated from the time required to complete 5 stands). Participants were categorized by baseline chair stand rate quintile, ranging from worst to best function as follows: first quintile (≤21.60 or unable), second quintile (>21.60 and ≤26.40), third quintile (>26.40 and ≤30.60), fourth quintile (>30.60 and ≤36.60), and fifth quintile (>36.60).

Assessment of covariates.

Education was assessed as response to, “What is the highest grade or year of school that you completed?” with possible responses being less than high school graduate, high school graduate, some college, college graduate, some graduate school, and graduate degree. Income was queried as personal family annual income of <$10,000, $10,000 to <$25,000, $25,000 to <$50,000, $50,000 to <$100,000, and ≥$100,000. Medical comorbidity was assessed using a questionnaire version of the Charlson Index (22). Depression was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) (23). Physical activity was assessed using the Physical Activity Scale for the Elderly (24). Pain was assessed using the WOMAC pain scale, adapted by the OAI to score pain separately for each knee; data from the worse knee were used in analysis. To assess OA radiographic disease severity within each tibiofemoral compartment, joint space was graded (0–3) in the medial and lateral compartments separately using the OARSI atlas (16). Bilateral isometric knee extensor strength was measured using the Good Strength isometric strength chair at a knee angle of 60° from full extension (Metitur) (25, 26). Details of this protocol may be found at http://oai.epi-ucsf.org/datarelease/operationsManuals/isometric_strengthv1_2p.pdf.

Statistical analyses.

Our analyses utilized the OAI public data release (clinical data V0.2.2 and V6.2.1 and radiographic data V0.5). All analyses were at the level of the person. Baseline characteristics are summarized using percentages for categorical variables and means ± SDs for continuous variables, overall and stratified by BMI, waist circumference, race, and sex. Descriptive statistics for outcomes are presented as percentages of persons with poor baseline to 48-month function outcome for each of the physical function measures. As described above, poor baseline to 48-month function outcome was defined as moving into a worse function group or remaining within the 2 lowest functioning groups.

To evaluate the hypothesis, the relationship between racial group and outcome was examined within each of 4 strata: women with high BMI, women with large waist circumference, men with high BMI, and men with large waist circumference. Using multiple logistic regression, unadjusted and adjusted odds ratios (ORs) and associated 95% confidence intervals (95% CIs) were calculated from a sequence of 3 nested models (based on prespecified groups of covariates), with covariates entered in the following sequence: 1) African American versus white (reference) race (unadjusted OR), 2) race (African American versus white), plus age, education, and income simultaneously in the model, and 3) previously listed variables plus BMI, comorbidity, depressive symptoms, physical activity, knee pain (worse score of 2 knees), and radiographic disease severity (worse of 2 knees). The socioeconomic factors are standard factors recognized to influence outcome in models evaluating race/ethnicity. Since these factors are not (or have limited ability to be) modifiable in older adults, it is informative to understand their influence separate from health-related factors. Health-related covariates were identified a priori as factors that may vary across the racial groups and potentially explain an association between racial group and outcome in the OAI population. Covariates were continuous except for race and depressive symptoms, which were categorized as high (CES-D score ≥16) or low.

The 95% CIs that exclude 1 indicate statistically significant associations with the outcome, based on the predetermined nominal 5% significance level for testing. Analyses were performed using SAS software, version 9.2. Additional sensitivity analyses further adjusted for extensor strength, excluded Hispanic participants (to confirm that results held in a non-Hispanic African American sample), and excluded persons who underwent total knee replacement during the study, a potential confounding factor; results were minimally altered.

RESULTS

Of 4,796 OAI participants, we excluded participants who had a knee replacement or did not belong to either the progression or incidence cohorts (n = 185), who were without baseline and 48-month WOMAC data (n = 587), and who were without baseline covariate data (n = 244). Of this group, we further excluded those who were neither African American nor white (n = 85), leaving 3,695 persons in the WOMAC outcome analysis sample. An additional 357 and 409 persons were missing 48-month chair stand and 20-meter walk time performance data, respectively, which yielded 3,338 persons in the chair stand outcome analysis sample and 3,286 in the 20-meter walk outcome analysis sample.

Characteristics of the overall WOMAC outcome analysis sample (16.1% African American) and strata based on BMI, race, and sex are shown in Table 2. Table 3 shows sample characteristics for strata based on waist circumference, race, and sex. The frequency of poor outcome by each function measure for the overall sample and within strata is shown in Table 4. In comparison with the overall sample, persons who were not included due to missing baseline or followup data were similar in age (mean ± SD 61.0 ± 9.5 years), BMI (mean ± SD 29.5 ± 5.2 kg/m2), waist circumference (mean ± SD 103.2 ± 13.3 cm), and disease severity (maximal joint space grade 0, 1, 2, and 3 of 41.5%, 27.6%, 24.0%, and 6.9%, respectively), but were on average less active (mean ± SD 147 ± 86.6), reported more pain (mean ± SD 4.8 ± 4.3), and had a higher frequency of African Americans (33.1%), college graduates (43.7%), income exceeding $50,000 (46.5%), comorbidity (34.1%), and depressive symptoms (16.0%).

Table 2. Baseline characteristics of sample for strata defined by sex and BMI*
VariablesOverall sample (n = 3,695)Women with low BMI (<25 kg/m2)Women with high BMI (≥25 kg/m2)Men with low BMI (<25 kg/m2)Men with high BMI (≥25 kg/m2)
African American (n = 43)White (n = 569)African American (n = 382)White (n = 1,149)African American (n = 11)White (n = 253)African American (n = 159)White (n = 1,129)
  • *

    Values are the percentage unless indicated otherwise. BMI = body mass index; CES-D = Center for Epidemiologic Studies Depression Scale; PASE = Physical Activity Scale for the Elderly; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

  • Worse of the 2 knees.

  • Highest (worst) joint space narrowing grade among the medial and lateral tibiofemoral compartments of both knees.

Age, mean ± SD years61.3 ± 9.160.7 ± 9.562.4 ± 9.159.2 ± 7.962.3 ± 8.959.0 ± 11.860.7 ± 9.959.2 ± 8.960.9 ± 9.3
BMI, mean ± SD kg/m228.5 ± 4.722.9 ± 1.622.5 ± 1.632.2 ± 4.230.3 ± 4.124.1 ± 1.023.4 ± 1.230.8 ± 3.829.8 ± 3.4
Waist circumference, mean ± SD cm102.5 ± 12.785.7 ± 10.589.4 ± 8.4105.3 ± 11.9107.5 ± 11.786.5 ± 6.589.9 ± 5.5105.2 ± 10.7106.2 ± 10.0
College graduate22.114.022.713.919.936.424.111.427.9
≥$50,000/year63.134.265.341.854.550.078.545.677.4
Comorbidity Index score >022.720.916.932.222.936.415.837.121.7
Depressive symptoms, CES-D score ≥169.014.08.616.28.618.26.715.16.4
Physical activity, mean ± SD PASE score163.5 ± 81.1150.5 ± 65.9160.2 ± 73.4139.9 ± 76.5152.9 ± 75.2205.2 ± 99.9188.0 ± 87.1175.2 ± 95.1176.9 ± 85.0
Mean ± SD WOMAC knee pain score3.3 ± 3.55.0 ± 3.82.2 ± 2.75.8 ± 4.53.3 ± 3.55.3 ± 4.92.0 ± 2.55.4 ± 4.32.9 ± 3.1
Joint space grade         
 045.962.861.040.644.054.656.940.939.6
 127.718.623.033.829.436.425.723.927.5
 219.711.612.521.221.39.112.327.722.1
 36.77.03.54.55.20.05.17.610.9
Table 3. Baseline characteristics of sample for strata defined by sex and waist circumference*
VariablesOverall sample (n = 3,695)Women with small waist circumference (≤88 cm)Women with large waist circumference (>88 cm)Men with small waist circumference (≤102 cm)Men with large waist circumference (>102 cm)
African American (n = 42)White (n = 279)African American (n = 383)White (n = 1,439)African American (n = 81)White (n = 656)African American (n = 89)White (n = 726)
  • *

    Values are the percentage unless indicated otherwise. BMI = body mass index; CES-D = Center for Epidemiologic Studies Depression Scale; PASE = Physical Activity Scale for the Elderly; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

  • Worse of the 2 knees.

  • Highest (worst) joint space narrowing grade among the medial and lateral tibiofemoral compartments of both knees.

Age, mean ± SD years61.3 ± 9.157.6 ± 8.459.4 ± 8.859.6 ± 8.162.9 ± 8.960.0 ± 9.660.0 ± 9.758.5 ± 8.761.7 ± 9.0
BMI, mean ± SD kg/m228.5 ± 4.724.5 ± 3.122.5 ± 2.432.0 ± 4.428.7 ± 4.827.8 ± 2.625.7 ± 2.432.8 ± 3.731.2 ± 3.3
Waist circumference, mean ± SD cm102.5 ± 12.780.7 ± 6.281.5 ± 5.3105.8 ± 11.2105.4 ± 11.294.7 ± 6.193.7 ± 5.7112.5 ± 8.2111.8 ± 7.7
College graduate22.111.922.914.120.412.425.613.628.7
≥$50,000/year63.142.570.340.955.750.079.442.076.1
Comorbidity Index score >022.721.414.332.122.232.116.241.624.7
Depressive symptoms, CES-D score ≥169.014.38.216.28.711.17.019.15.9
Physical activity, mean ± SD PASE score163.5 ± 81.1174.2 ± 67.3176.3 ± 78.2137.3 ± 75.6151.2 ± 73.3178.3 ± 97.1186.7 ± 83.5176.2 ± 94.4171.9 ± 84.8
Mean ± SD WOMAC knee pain score3.3 ± 3.55.2 ± 4.42.3 ± 3.15.8 ± 4.53.0 ± 3.35.0 ± 4.22.3 ± 2.95.7 ± 4.53.1 ± 3.1
Joint space grade         
 045.971.464.539.746.840.748.242.737.9
 127.714.319.734.228.825.927.423.626.9
 219.711.911.521.219.723.516.329.223.8
 36.72.44.35.04.79.98.14.511.4
Table 4. Frequency of poor outcome in the overall sample and in strata based on race, sex, BMI, and waist circumference*
 Poor WOMAC outcomePoor 20-meter walk outcomePoor chair stand outcome
  • *

    Values are the number/total number (percentage with poor outcome). High and low body mass index (BMI) were defined as ≥25 kg/m2 and <25 kg/m2, respectively. High and low waist circumference were defined as >88 cm and ≤88 cm, respectively, for women, and >102 cm and ≤102 cm, respectively, for men. WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

Overall sample1,446/3,695 (39.1)1,556/3,286 (47.4)1,339/3,338 (40.1)
Women   
 African American   
  Low BMI15/43 (34.9)21/34 (61.8)12/35 (34.3)
  High BMI206/382 (53.9)206/327 (63.0)185/332 (55.7)
  Small waist18/42 (42.9)18/33 (54.6)7/34 (20.6)
  Large waist203/383 (53.0)209/328 (63.7)190/333 (57.1)
 White   
  Low BMI181/569 (31.8)190/493 (38.5)164/503 (32.6)
  High BMI461/1,149 (40.1)571/1,022 (55.9)439/1,036 (42.4)
  Small waist81/279 (29.0)78/244 (32.0)58/247 (23.5)
  Large waist561/1,439 (39.0)683/1,271 (53.7)545/1,292 (42.2)
Men   
 African American   
  Low BMI4/11 (36.4)3/10 (30.0)3/10 (30.0)
  High BMI77/159 (48.4)86/154 (55.8)77/155 (49.7)
  Small waist30/81 (37.0)36/76 (47.4)37/77 (48.1)
  Large waist51/89 (57.3)53/88 (60.2)43/88 (48.9)
 White   
  Low BMI74/253 (29.3)75/228 (32.9)62/237 (26.2)
  High BMI428/1,129 (37.9)404/1,018 (39.7)397/1,030 (38.5)
  Small waist197/656 (30.0)191/599 (31.9)172/610 (28.2)
  Large waist305/726 (42.0)288/647 (44.5)287/657 (43.7)

In the full analysis sample (n = 3,695 for WOMAC outcome), high BMI (versus BMI <25 kg/m2 as reference) was associated with an increased risk of poor WOMAC outcome by 48 months, adjusting for age, race, sex, education, income, comorbidity, depressive symptoms, physical activity, knee pain, and disease severity (adjusted OR 1.27, 95% CI 1.06–1.52). This was also the case when BMI was evaluated as a continuous variable (adjusted OR 1.04/1 kg/m2, 95% CI 1.02–1.06). Results were similar with the 20-meter walk outcome for high BMI (adjusted OR 1.57, 95% CI 1.30–1.90) and for BMI as a continuous variable (adjusted OR 1.06/1 kg/m2, 95% CI 1.04–1.07), as well as with the chair stand outcome for high BMI (adjusted OR 1.57, 95% CI 1.30–1.90) and for BMI as a continuous variable (adjusted OR 1.05/1 kg/m2, 95% CI 1.04–1.07). Similarly, large waist circumference (defined by sex-specific cut points noted above, versus low waist circumference as reference) was associated with an increased risk of poor 4-year WOMAC outcome (adjusted OR 1.49, 95% CI 1.25–1.77), 20-meter walk outcome (adjusted OR 1.60, 95% CI 1.34–1.93), and chair stand outcome (adjusted OR 1.82, 95% CI 1.51–2.19).

To test our hypotheses, we focused first on individuals with high BMI and second on individuals with large waist circumference. Tables 5 and 6 present the results for women and men, respectively, as unadjusted, adjusted for age, education, and income, and fully adjusted. For all models, the covariates significantly associated with the outcome are provided in the table footnotes. As shown in Table 5, among African American and white women with high BMI in the OAI cohort, being African American was associated with an elevated OR for every outcome measure, adjusting for age, education, and income; in the fully adjusted models, the association remained significant for chair stand outcome and was borderline for WOMAC and 20-meter walk outcomes. The pattern of findings was similar to this for the association between race and outcome (but differed slightly for the covariates) among women with large waist circumference (Table 5).

Table 5. Odds of poor outcome associated with race among women with high BMI and among women with large waist circumference*
 Women with high BMI (≥25 kg/m2)Women with large waist circumference (>88 cm)
Poor WOMAC outcomePoor 20-meter walk outcomePoor chair stand outcomePoor WOMAC outcomePoor 20-meter walk outcomePoor chair stand outcome
  • *

    Unless indicated otherwise, values are the odds ratio (OR; 95% confidence interval [95% CI]) associated with being African American (vs. white) for poor baseline to 4-year function outcome (dependent variable). The crude ORs are shown first, followed by the ORs adjusted for age, education, and income, followed by the ORs from fully adjusted models (adjusted for age, education, income, body mass index [BMI], comorbidity, depressive symptoms, physical activity, knee pain, and disease severity). WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

  • Covariates significantly associated with outcome: pain OR 1.06, 95% CI 1.03–1.10; disease severity OR 1.24, 95% CI 1.09–1.41; depressive symptoms OR 1.65, 95% CI 1.13–2.40; and income OR 0.87, 95% CI 0.77–0.99.

  • Covariates significantly associated with outcome: age OR 1.06, 95% CI 1.05–1.08; disease severity OR 1.18, 95% CI 1.02–1.36; comorbidity OR 1.29, 95% CI 1.07–1.55; and income OR 0.86, 95% CI 0.75–0.99.

  • §

    Covariates significantly associated with outcome: age OR 1.04, 95% CI 1.02–1.05; income OR 0.86, 95% CI 0.75–0.98; and BMI OR 1.04, 95% CI 1.01–1.08.

  • Covariates significantly associated with outcome: pain OR 1.07, 95% CI 1.03–1.10; disease severity OR 1.29, 95% CI 1.15–1.46; depressive symptoms OR 1.54, 95% CI 1.10–2.18; and comorbidity OR 1.18, 95% CI 1.01–1.37.

  • #

    Covariates significantly associated with outcome: age OR 1.06, 95% CI 1.04–1.07; disease severity OR 1.20, 95% CI 1.05–1.37; comorbidity OR 1.22, 95% CI 1.02–1.46; income OR 0.83, 95% CI 0.73–0.95; and BMI OR 1.05, 95% CI 1.02–1.08.

  • **

    Covariates significantly associated with outcome: age OR 1.04, 95% CI 1.02–1.05 and BMI OR 1.04, 95% CI 1.01–1.06.

No./total no. (% with poor outcome)      
 African American206/382 (53.9)206/327 (63.0)185/332 (55.7)203/383 (53.0)209/328 (63.7)190/333 (57.1)
 White461/1,149 (40.1)571/1,022 (55.9)439/1,036 (42.4)561/1,439 (39.0)683/1,271 (53.7)545/1,292 (42.2)
African American vs. white (unadjusted)1.75 (1.38–2.21)1.35 (1.04–1.74)1.71 (1.33–2.20)1.77 (1.41–2.22)1.51 (1.18–1.94)1.82 (1.43–2.32)
African American vs. white (adjusted for  age, education, income)1.54 (1.19–1.98)1.43 (1.07–1.91)1.81 (1.37–2.39)1.55 (1.21–1.99)1.57 (1.18–2.07)2.02 (1.54–2.65)
African American vs. white (fully adjusted)1.29 (0.99–1.68)1.29 (0.96–1.75)1.63 (1.22–2.17)§1.22 (0.94–1.60)1.35 (1.00–1.81)#1.68 (1.26–2.24)**
Table 6. Odds of poor outcome associated with race among men with high BMI and with large waist circumference*
 Men with high BMI (≥25 kg/m2)Men with large waist (>102 cm)
Poor WOMAC outcomePoor 20-meter walk outcomePoor chair stand outcomePoor WOMAC outcomePoor 20-meter walk outcomePoor chair stand outcome
  • *

    Unless indicated otherwise, values are the odds ratio (OR; 95% confidence interval [95% CI]) associated with being African American (vs. white) for poor baseline to 4-year function outcome (dependent variable). The crude ORs are shown first, followed by the ORs adjusted for age, education, and income, then followed by the ORs from fully adjusted models (adjusted for age, education, income, body mass index [BMI], comorbidity, depressive symptoms, physical activity, knee pain, and disease severity). WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

  • Covariates significantly associated with outcome: pain OR 1.08, 95% CI 1.04–1.12; disease severity OR 1.23, 95% CI 1.09–1.39; comorbidity OR 1.26, 95% CI 1.07–1.48; income OR 0.84, 95% CI 0.73–0.96; and BMI OR 1.08, 95% CI 1.04–1.12.

  • Covariates significantly associated with outcome: age OR 1.06, 95% CI 1.04–1.07; income OR 0.80, 95% CI 0.69–0.93; and BMI OR 1.06, 95% CI 1.02–1.10.

  • §

    Covariates significantly associated with outcome: age OR 1.04, 95% CI 1.02–1.05 and pain OR 1.09, 95% CI 1.05–1.14.

  • Covariates significantly associated with outcome: pain OR 1.10, 95% CI 1.05–1.16; disease severity OR 1.32, 95% CI 1.13–1.54; comorbidities OR 1.30, 95% CI 1.07–1.58; and BMI OR 1.07, 95% CI 1.02–1.12.

  • #

    Covariates significantly associated with outcome: age OR 1.07, 95% CI 1.04–1.09 and income OR 0.77, 95% CI 0.63–0.92.

  • **

    Covariates significantly associated with outcome: age OR 1.05, 95% CI 1.02–1.07 and pain OR 1.10, 95% CI 1.04–1.16.

No./total no. (% with poor outcome)      
 African American77/159 (48.4)86/154 (55.8)77/155 (49.7)51/89 (57.3)53/88 (60.2)43/88 (48.9)
 White428/1,129 (37.9)404/1,018 (39.7)397/1,030 (38.5)305/726 (42.0)288/647 (44.5)287/657 (43.7)
African American vs. white (unadjusted)1.54 (1.10–2.15)1.92 (1.37–2.71)1.57 (1.12–2.21)1.85 (1.19–2.89)1.89 (1.20–2.97)1.23 (0.79–1.92)
African American vs. white (adjusted for  age, education, income)1.26 (0.87–1.81)1.94 (1.31–2.87)1.56 (1.07–2.28)1.53 (0.93–2.52)2.24 (1.30–3.85)1.34 (0.80–2.23)
African American vs. white (fully adjusted)0.99 (0.67–1.45)1.66 (1.11–2.48)1.25 (0.84–1.85)§1.23 (0.73–2.09)1.91 (1.09–3.34)#1.10 (0.65–1.86)**

As shown in Table 6, among African American and white men with high BMI, being African American was associated with poor outcome by 20-meter walk and chair stand outcomes after adjusting for age, education, and income; in the fully adjusted models, the association remained significant for 20-meter walk outcome. The pattern of findings was similar to this for the association between race and WOMAC and 20-meter walk outcomes (but differed slightly for the covariates) among men with large waist circumference (see Table 6).

Results of models shown in Tables 5 and 6 were minimally altered by the addition of extensor strength as a covariate, and strength itself was not associated with outcome (data not shown). In sensitivity analyses, we excluded individuals from our analysis sample who reported that they were “Hispanic or Latino” (n = 23) or who underwent knee replacement during the study (n = 93) and then re-ran the models of Tables 5 and 6. Results were minimally altered (data not shown).

DISCUSSION

In women and men with or at elevated risk for symptomatic radiographic knee OA, greater BMI and large waist circumference were each associated with an increased risk of poor 4-year function outcome. Among women with high BMI and among women with large waist circumference, African Americans were at greater risk than whites for poor 4-year function outcome by each measure evaluated in analyses adjusting for age, education, and income. From the fully adjusted models, factors that may in part explain these findings in women include income, comorbidity, depressive symptoms, knee pain, and disease severity for WOMAC and 20-meter walk outcomes; the factors we analyzed did not explain the chair stand outcome in women. The findings were less consistent for men, emerging (in analyses adjusting for age, education, and income) among men with high BMI only for the 20-meter walk and chair stand outcomes and among men with large waist circumference only for the 20-meter walk outcome. Factors that may partially explain these findings in men include age and knee pain for chair stand outcome; the factors we analyzed did not explain the 20-meter walk outcome in men.

Although there is abundant literature dealing with body weight and function in OA, we were unable to identify a prior report evaluating the effect of race within elevated BMI or waist circumference strata in persons with or at high risk for knee OA. However, several lines of research are relevant to the focus of this report. In persons with any arthritis in the Health and Retirement Study, Song et al found a significantly greater demographic-adjusted activities of daily living disability hazard ratio (HR) in African Americans compared with whites (27). Adjustment for health factors (comorbid chronic conditions, depressive symptoms, function limitations, and health behaviors) reduced estimated excess HRs by 55%, with a 12% further reduction by additional control for education, wealth, income, and health insurance. Cross-sectional studies of knee OA have shown worse function in African Americans than whites (28–31). In the Johnston County Osteoarthritis Project, this finding was explained by pain, female sex, BMI, and depressive symptoms (28). Using baseline data from a trial of phone-based self-management in veterans with knee OA, Allen et al found that worse function scores in African Americans were explained by self-efficacy, affect, emotion-focused coping, pain, and self-rated health (29). Notably, in a merged sample of older adults with knee OA from the Fitness Arthritis in Seniors Trial and the Arthritis, Diet, and Activity Promotion Trial, race was associated with performance-based and self-reported function in adjusted analyses, but this finding was not significant after 18 months of exercise therapy, suggesting a role for physical activity in reducing health disparities (32).

Measurement of function outcome over time in studies of knee OA is necessary to better understand the impact of the disease. However, the best way to evaluate this outcome in knee OA has not been established. As we previously described (6), a focus on change ignores those with persistently high or low function, effectively placing them into the same group, and reducing the ability to detect the effects of factors responsible for an individual's state of function. In a disease that is slow to evolve, such as knee OA, factors related to persistent low- or high-function states are particularly important. We (6, 11) and others (18) have used the outcome approach of the current manuscript to address this issue. It is possible that the outcome definition may have led to classification of some persons with a small decline in function (who started near a cut point) as having poor outcome, when the observed decline was solely or partially due to measurement variability/error. Misclassification resulting from use of the quintile approach may have reduced our ability to identify only clinically meaningful changes in function. Given this, it is possible that our findings underestimate the true situation. However, we believe the strengths of the outcome definition outweigh this limitation in our study. We evaluated both self-reported and performance-based function outcome. While objective, performance measures may not mirror activities considered important to individuals or the range of activities experienced during daily life (33). Self-report measures may better capture wider aspects of functioning and better define change in function over time at the individual level (33).

The OAI provided an excellent setting in which to examine the questions we posed. The OAI sample is effectively enriched for elevated body weight, provided both self-report and performance measures of function, provided not only body weight and height but also waist circumference, and the opportunity to evaluate outcome over 4 years. This study has limitations that must be acknowledged. We were unable to undertake evaluation of other ethnic groups or of subgroups with BMI <25 kg/m2 due to their small numbers in the OAI. The findings cannot be generalized to groups who had been excluded from the OAI, i.e., persons with bilateral, severe knee OA, men weighing over 285 pounds and women weighing over 250 pounds, persons using certain ambulatory aids more than 50% of the time, or comorbidity that would preclude participation in a study. Persons who were not included in the analysis sample (but would have been eligible) differed in a number of ways from the analysis sample and it is unclear how their inclusion would have affected the findings. The mean BMI differed between some subgroups of interest; we sought to address this by adjusting for BMI in multivariable analyses. Self-reported estimates of physical activity may not be accurate, and a better understanding of the role of physical activity may require objective measures.

The current findings identify subsets of individuals who are at greater risk for poor outcome, which is of value in both clinical and public health settings. Our findings suggest some explanatory factors; future studies should delve further into the factors contributing to this finding. Such factors include not only those we identified and are particularly relevant to knee OA but also individual socioeconomic status measures, other lifestyle factors, and social and physical environments.

In conclusion, in persons with or at higher risk for knee OA, greater BMI and large waist circumference were each associated with an increased risk of poor 4-year function outcome. Among women with high BMI and among women with large waist circumference, African Americans were at greater risk than whites for poor 4-year function outcome by each measure evaluated, adjusting for age, education, and income. Modifiable factors that may in part explain these findings in women 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 white women.

AUTHOR CONTRIBUTIONS

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Sharma had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Colbert, Chmiel, Hayes, Sharma.

Acquisition of data. Almagor, Song, Dunlop.

Analysis and interpretation of data. Colbert, Almagor, Chmiel, Song, Dunlop, Hayes, Sharma.

ROLE OF THE STUDY SPONSOR

Merck Research Laboratories, Novartis Pharmaceuticals, GlaxoSmithKline, and Pfizer played no role in the study design, data collection, data analysis, writing of the manuscript, or approval of the submitted manuscript, nor was publication contingent upon approval by Merck Research Laboratories, Novartis Pharmaceuticals, GlaxoSmithKline, and Pfizer.

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