Body Weight Changes and Corresponding Changes in Pain and Function in Persons With Symptomatic Knee Osteoarthritis: A Cohort Study
Body Weight Changes and Corresponding Changes in Pain and Function in Persons With Symptomatic Knee Osteoarthritis: A Cohort Study
Body Weight Changes and Corresponding Changes in Pain and Function in Persons With Symptomatic Knee Osteoarthritis: A Cohort Study
AND
PAUL W. STRATFORD2
Objective. To determine if a dose-response relationship exists between percentage changes in body weight in persons
with symptomatic knee osteoarthritis (OA) and self-reported pain and function.
Methods. Data from persons in the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis (MOST) study data
sets (n 1,410) with symptomatic function-limiting knee OA were studied. For the OAI, we used baseline and 3-year
followup data, while for the MOST study, baseline and 30-month data were used. Key outcome variables were Western
Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function and pain change scores. In addition
to covariates, the predictor variable of interest was the extent of weight change over the study period divided into 5
categories representing different percentages of body weight change.
Results. A signicant dose-response relationship (P < 0.003) was found between the extent of percentage change in body
weight and the extent of change in WOMAC physical function and WOMAC pain scores. For example, persons who gained
>10% of body weight had WOMAC physical function score changes of 5.4 (95% condence interval 8.7, 2.00) points,
indicating worsening physical function relative to the reference group of persons with weight changes between <5%
weight gain and <5% weight reduction.
Conclusion. Our data suggest a dose-response relationship exists between changes in body weight and corresponding
changes in pain and function. The threshold for this response gradient appears to be body weight shifts of >10%. Weight
changes of >10% have the potential to lead to important changes in pain and function for patient groups as well as
individual patients.
INTRODUCTION
Osteoarthritis (OA) of the knee has multiple causes, but
one of the more powerful risk factors for OA onset and
progression is excessive body weight (1,2). The Framingham study, for example, reported that women who lost at
least 5 kg had a 50% reduction in the odds of developing
symptomatic knee OA (3). Given the high costs and high
prevalence of knee OA, many researchers have focused on
This article was prepared using Multicenter Osteoarthritis study data and does not necessarily reect the opinions
or views of the Multicenter Osteoarthritis study investigators. This article was prepared using an Osteoarthritis Initiative public use data set and does not necessarily reect
the opinions or views of the Osteoarthritis Initiative investigators, the NIH, or the private funding partners.
The Multicenter Osteoarthritis (MOST) study is comprised of 4 cooperative grants (AG18820, AG18832,
AG18947, AG19069) funded by the NIH, a branch of the
Department of Health and Human Services, and conducted
by the MOST study investigators. The Osteoarthritis Initiative (OAI) is a public-private partnership comprised of 5
contracts (N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260,
N01-AR-2-2261, N01-AR-2-2262) funded by the NIH, a
branch of the Department of Health and Human Services,
and conducted by the OAI study investigators. Private funding partners include Merck, Novartis, GlaxoSmithKline,
and Pzer. Private sector funding for the OAI is managed by
the Foundation for the NIH.
1
Daniel L. Riddle, PT, PhD: Departments of Physical Therapy and Orthopaedic Surgery, Virginia Commonwealth
University, Richmond; 2Paul W. Stratford, PT, MSc: McMaster University, Hamilton, Ontario, Canada.
Dr. Riddle has received consultancy fees, speaking fees,
and/or honoraria (less than $10,000) from the Physical Therapy Editorial Board.
Address correspondence to Daniel L. Riddle, PT, PhD,
Virginia Commonwealth University Department of Physical Therapy, PO Box 980224, Richmond, VA 23298-0224.
E-mail: dlriddle@vcu.edu.
Submitted for publication October 18, 2011; accepted in
revised form March 26, 2012.
15
16
It is also unknown whether persons who gain weight actually experience worse pain and function and whether
this pain and functional loss is proportional to the amount
of weight gained. Knowing whether persons in the community report proportionate reductions (or increases) in
pain and function following changes in body weight
would equip clinicians with additional evidence-based
information to aid in the management of knee OA. The
purpose of our longitudinal cohort study was to determine
if a dose-response relationship exists between the extent of
weight changes (including both weight reduction and
weight gain) and the extent of changes in self-reported
function-related pain and functional status.
We analyzed data from 2 public use data sets. The Osteoarthritis Initiative (OAI) is a publicly and privately funded
prospective longitudinal cohort study with 4 years of followup. A primary objective of the OAI was to develop
diverse cohorts of persons for the study of the natural
history, risk factors, onset, and progression of tibiofemoral
knee OA. The Multicenter Osteoarthritis (MOST) study is
also a publically funded prospective longitudinal cohort
study. The overall aims of the MOST study were to identify novel and modiable biomechanical factors, bone and
joint structural factors, and nutritional factors that affect
the occurrence and progression of knee OA. All centers in
both studies required all subjects to read and sign institutional review boardapproved consent forms prior to participation.
OAI and MOST study samples. In the OAI, subjects
between the ages of 45 and 79 years with or at high risk for
developing knee OA were recruited from communities in
and around 4 clinical sites: the University of Maryland
School of Medicine in Baltimore, Maryland, the Ohio State
University in Columbus, Ohio, the University of Pittsburgh in Pittsburgh, Pennsylvania, and the Memorial Hospital of Rhode Island in Pawtucket, Rhode Island. Persons
recruited for the MOST study also had or were at high risk
for developing knee OA and were ages 50 79 years. The
MOST subjects were recruited from communities in and
around 2 clinical sites: the University of Iowa in Iowa City,
Iowa, and the University of Alabama, Birmingham in Birmingham, Alabama. Details of the study populations from
both cohorts have been described in detail elsewhere
(15,16).
Persons from both the OAI and MOST study had to have
the following features to be recruited for our study: 1)
radiographic tibiofemoral knee OA, dened as denite
osteophytes (Osteoarthritis Research Society International
atlas grade 13 [17] in the OAI or Kellgren/Lawrence grade
2 or higher [18] in the MOST study) as measured on a
standardized xed-exion radiograph (19,20), 2) a
WOMAC pain scale score of 4 or higher, 3) a WOMAC
physical function score of 9 or higher, and 4) no knee
replacement surgery during the followup period. We intended to study a sample of persons who had radiologically conrmed knee OA and function-limiting pain.
Minimal detectable clinical improvement estimates for
17
Statistical analysis. We used chi-square tests for categorical baseline variables and t-tests for continuous variables to compare persons who had followup weight data
and those whose followup weight data were missing. The
subsequent analyses were performed for the dependent
variables of changes in WOMAC function score and
changes in WOMAC pain score. We investigated our primary question by rst performing 2 regression analyses
that included WOMAC function score and WOMAC pain
score as dependent variables and weight changes categorized into 5 groups (10% reduction, 59.9% reduction,
4.9% reduction to 4.9% gain, 59.9% gain, and 10%
gain) as the independent variable. These analyses tested
whether function or pain differed among the weight reduction or gain categories compared to the reference category
(4.9% reduction to 4.9% gain). Next, we repeated these
analyses adjusting for the following covariates: baseline
scores for the dependent variable of interest (i.e., either
WOMAC function or pain scores), sex (2 levels: female,
male) (38), depression (2 levels: depressed, not depressed)
(39), and number of comorbidities (40). Our regression
model was as follows: changes in WOMAC function or
pain constant b1(10% weight reduction) b2(5
9.9% weight reduction) b3(59.9% weight gain)
b4(10% weight gain) b5(baseline function or pain)
b6(number of comorbidities) b7(sex) b8(depression).
We applied the following dummy variable coding
scheme: 1 if the weight category applies, 0 if otherwise; 1
if female, 0 if male; and 1 if depressed, 0 if not depressed.
Applying this coding scheme, the reference weight category was the 4.9% weight reduction to 4.9% weight gain
category (i.e., b1 b2 b3 b4 0). We performed a
trend analysis to assess whether the results were consistent with a dose-response relationship. Specically, we
examined the extent to which linear, quadratic, cubic, and
quartic trends were evident.
Prior to initiating the analyses, we examined the distributional properties of the variables and checked for heterogeneity of dependent variable variances among the 5
weight change categories. For all analyses, we applied
2-tailed tests and an effect was considered statistically
signicant if a P value was less than 0.05. Analyses were
conducted using Stata, version 10.1.
RESULTS
The characteristics of the sample are shown in Table 1.
There were some demographic differences between the 2
data sets. For example, persons from the OAI data set were
generally younger, had a higher education level, and
weighed less than the persons in the MOST study data set.
18
Table 1. Characteristics of the samples at baseline and those with complete versus missing data*
Age, years
Women, %
African American, %
Marital status, %
Married
Widowed
Divorced
Separated
Never married
Education, %
Less than high school
diploma
High school diploma
At least some college
Comorbidity
Weight, kg
Current smoker, %
CES-D, % depressed
WOMAC pain score
WOMAC physical function
score
OAI
baseline
(n 976)
MOST
baseline
(n 809)
Combined
baseline
(n 1,785)
Complete
weight data
at baseline
and followup
(n 1,410)
61.72 9.25
62.2
33.5
63.74 8.09
64.5
22.9
62.63 8.79
63.2
28.7
62.73 8.62
62.5
25.5
62.26 9.38
66.1
40.8
58.7
10.7
17.2
3.1
10.4
68.8
12.9
13.0
0.9
4.5
62.6
11.5
15.1
2.1
7.6
65.5
10.7
14.9
1.9
7.0
54.9
15.1
16.8
3.0
10.3
6.7
7.8
7.2
6.2
11.1
Missing
weight data
at followup
(n 375)
Comparing complete
and missing data,
2 or t-test (P)
0.94 (0.35)
1.70 (0.19)
34.07 ( 0.001)
16.4 (0.002)
15.0 (0.001)
18.9
30.2
24.0
23.2
23.7
74.4
62.1
68.8
70.6
61.7
0.55 0.95
0.64 1.01
0.59 0.98
0.57 0.95
0.67 1.07
86.63 16.50 93.55 20.98 89.80 19.98 89.62 18.6 90.32 20.25
8.6
13.1
9.8
9.0
12.6
17.9
19.2
18.5
17.7
21.6
7.96 3.20
8.15 3.11
8.05 3.17
7.83 3.06
8.85 3.42
25.23 10.76 26.73 10.29 25.91 10.57 25.12 10.14 28.88 11.63
1.80 (0.07)
0.63 (0.53)
3.58 (0.06)
3.03 (0.08)
5.57 ( 0.001)
6.17 ( 0.001)
* Values are the mean SD unless otherwise indicated. OAI Osteoarthritis Initiative; MOST Multicenter Osteoarthritis study; CES-D Center
for Epidemiologic Studies Depression Scale; WOMAC Western Ontario and McMaster Universities Osteoarthritis Index.
In addition, there was evidence of selective loss to followup when comparing persons who had followup weight
data (n 1,410) to persons whose followup weight data
were missing (n 375). For example, persons with missing followup weight measures had a lower level of education, were more frequently African American, and had
higher levels of pain and worse function. The distribution
of persons in each of the 5 weight change categories were
n 82 in the 10% weight reduction group, n 176 in
the 59.9% weight reduction group, n 953 in the 4.9%
weight reduction to 4.9% weight gain group, n 148 in
the 59.9% weight gain group, and n 51 in the 10%
weight gain group.
The distributions of the dependent variables approximated a normal distribution, and for each dependent variable, the variances among the 5 weight categories did not
Weight change
group
10% reduction
59.9% reduction
4.9% reduction to
4.9% gain
59.9% gain
10% gain
WOMAC
physical function,
mean SD change
WOMAC
physical function
change score of >9 points,
no./total (%)
WOMAC pain,
mean SD change
7.50 13.24
3.34 12.62
2.78 11.82
37/82 (45.1)
50/171 (29.2)
269/940 (28.6)
2.05 4.60
0.99 4.34
1.09 3.86
31/82 (37.8)
33/171 (19.3)
233/951 (24.5)
3.23 12.34
1.67 13.6
41/145 (28.3)
10/48 (20.8)
1.40 3.99
0.06 3.93
42/148 (28.4)
8/51 (15.7)
19
Table 3. Comparison of weight change groups with the 4.9% reduction to 4.9% gain reference group*
Unadjusted analysis
WOMAC function
regression coefcient
(95% CI), P
Weight change category
10% reduction
4.71 (1.97, 7.45), 0.001
59.9% reduction
0.55 (1.42, 2.53), 0.582
4.9% reduction to
Ref.
4.9% gain
59.9% gain
0.44 (1.68, 2.57), 0.682
10% gain
4.45 (7.98, 0.93), 0.013
Baseline dependent
N/A
Female
N/A
Comorbidity (number)
N/A
Depressed (yes)
N/A
Constant
2.78 (2.01, 3.56), 0.001
Adjusted analysis
WOMAC pain
regression coefcient
(95% CI), P
WOMAC function
regression coefcient
(95% CI), P
WOMAC pain
regression coefcient
(95% CI), P
* WOMAC Western Ontario and McMaster Universities Osteoarthritis Index; 95% CI 95% condence interval; N/A not applicable.
and 10% weight gain differed from the reference category. The dose-response relationship for weight changes
and the WOMAC physical function scale is shown in
Figure 1, while Figure 2 shows the dose-response relationship for the WOMAC pain scale. The trend analyses identied statistically signicant linear and cubic trends for
both the WOMAC physical function (linear: F[1,1362]
16.47, P 0.001 and cubic: F[1,1362] 12.11, P 0.001)
and pain (linear: F[1,1381] 8.77, P 0.003 and cubic:
F[1,1381] 13.79, P 0.001) measures. The linear trend
explains the extent to which there was a steady decline in
the scores of the outcome measures across the weight
change categories, while the cubic trend supports that
there was a attening or similarity in the scores of the
outcome measures for the middle 3 weight change categories.
DISCUSSION
Our study shows that there was a dose-response relationship between body weight changes and changes in selfreported pain and functional status. Such a study would at
a minimum require a large sample of persons followed up
over an extended period of time; well-dened methods for
quantifying arthritis, pain, and functional status; a high
rate of followup; and a sufcient number of persons who
either lost or gained weight during the followup period.
We found that persons who lost 10% of their body
weight over an approximately 3-year period reported signicantly lower function-related pain and improved functional status relative to the reference category. In contrast,
persons who gained 10% of their baseline body weight
had signicantly worse function-related pain and function
than persons in the reference category. The dose-response
relationship between weight changes and pain and func-
20
tional status changes was highly signicant (P 0.003)
both for linear and cubic trends.
We found no other evidence that quantied the potential
impact of body weight gain on subsequent pain and functional status. Our study suggests that body weight gains of
10% body weight have signicant effects particularly on
self-reported function, but also on pain. After adjusting for
covariates, mean WOMAC physical function scores worsened (increased) by 5.4 points (95% condence interval
[95% CI] 2.0, 8.7 points), while WOMAC pain scores worsened (increased) by 1.6 points (95% CI 0.5, 2.6 points)
relative to scores in the reference group. While these differences are approximately half the amount of difference
required to infer change at the level of the individual
patient (2126), for group-level changes, these estimates
approximate the magnitude of changes reported in successful weight loss (6 8) and knee exercise (41) trials.
When interpreting the meaningfulness of these group-level
changes, it is necessary to distinguish between an important within-patient change and an important betweengroup difference. Goldsmith and colleagues have shown
that an important within-patient change is substantially
greater than an important between-group difference (42).
For example, randomized trials of rheumatoid arthritis
patients have found an important within-patient change in
pain to be 36% of the baseline scores compared to 20% of
the baseline scores for a between-group difference. Similarly, Goldsmith et al identied an important within-patient change in disability to be 49% of the baseline scores
compared to 16% of the baseline scores for a betweengroup difference (42). Applying the percentage difference
estimates reported by Goldsmith et al to the 9-point
WOMAC physical function (26) and 4-point WOMAC pain
(25) minimal detectable change estimates used in our
study yields important between-group differences of 2.2
and 2.9 WOMAC pain and function points, respectively.
Referring to Table 3, the mean disability change scores of
the 10% weight reduction and 10% weight gain groups
differ signicantly from the reference group. For pain, all
between-group comparisons with the reference group are
less than 2.2 points.
Table 2 delineates the percentages of patients who met
or exceeded the minimum clinically important thresholds
for important within-person change. For example, 45.1%
of the patients who lost 10% of body weight reported
changes that met or exceeded the criterion of 9 WOMAC
physical function points, while 29.2% of persons who lost
between 5% and 9.9% of body weight met the WOMAC
physical function change threshold. Similar estimates
were reported for the WOMAC pain scale. These data
suggest that weight changes of 10% appear to be important thresholds for individual patient pain and function
changes.
Most of the studies examining the effects of body weight
changes on pain and function have been directed toward
weight loss. Trials have consistently shown that a 5% or
greater weight loss resulted in signicantly reduced pain
or improved function. For example, Messier and colleagues examined the efcacy of a diet and exercise intervention on obese persons with symptomatic knee OA (8).
The authors found that a mean 5.7% weight loss was
21
AUTHOR CONTRIBUTIONS
All authors were involved in drafting the article or revising it
critically for important intellectual content, and all authors approved the nal version to be published. Dr. Riddle 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. Riddle, Stratford.
Acquisition of data. Riddle.
Analysis and interpretation of data. Riddle, Stratford.
REFERENCES
1. Blagojevic M, Jinks C, Jeffery A, Jordan KP. Risk factors for
onset of osteoarthritis of the knee in older adults: a systematic
review and meta-analysis. Osteoarthritis Cartilage 2010;18:
24 33.
2. Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Rheum
Dis Clin North Am 2008;34:51529.
3. Felson DT, Zhang Y, Anthony JM, Naimark A, Anderson JJ.
Weight loss reduces the risk for symptomatic knee osteoarthritis in women: the Framingham Study. Ann Intern Med
1992;116:5359.
4. Bliddal H, Leeds AR, Stigsgaard L, Astrup A, Christensen R.
Weight loss as treatment for knee osteoarthritis symptoms in
obese patients: 1-year results from a randomised controlled
trial. Ann Rheum Dis 2011;70:1798 803.
5. Christensen R, Astrup A, Bliddal H. Weight loss: the treatment of choice for knee osteoarthritis? A randomized trial.
Osteoarthritis Cartilage 2005;13:20 7.
6. Christensen R, Bartels EM, Astrup A, Bliddal H. Effect of
weight reduction in obese patients diagnosed with knee
osteoarthritis: a systematic review and meta-analysis. Ann
Rheum Dis 2007;66:4339.
7. Gudbergsen H, Boesen M, Christensen R, Astrup A, Bliddal H.
Radiographs and low eld MRI (0.2T) as predictors of efcacy
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
22
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
on the development of the AUSCAN Hand Osteoarthritis Indices. Clin Exp Rheumatol 2005;23:S148 53.
Stratford PW, Kennedy DM, Hanna SE. Condition-specic
Western Ontario McMaster Osteoarthritis Index was not superior to region-specic Lower Extremity Functional Scale at
detecting change. J Clin Epidemiol 2004;57:102532.
Baron G, Tubach F, Ravaud P, Logeart I, Dougados M. Validation of a short form of the Western Ontario and McMaster
Universities Osteoarthritis Index function subscale in hip and
knee osteoarthritis. Arthritis Rheum 2007;57:633 8.
Martinson ML, Teitler JO, Reichman NE. Health across the life
span in the United States and England. Am J Epidemiol 2011;
173:858 65.
Zhao G, Ford ES, Li C, Tsai J, Dhingra S, Balluz LS. Waist
circumference, abdominal obesity, and depression among
overweight and obese U.S. adults: National Health and Nutrition Examination Survey 2005-2006. BMC Psychiatry 2011;
11:130.
Losina E, Walensky RP, Reichmann WM, Holt HL, Gerlovin
H, Solomon DH, et al. Impact of obesity and knee osteoarthritis on morbidity and mortality in older Americans. Ann Intern
Med 2011;154:21726.
Jenkinson CM, Doherty M, Avery AJ, Read A, Taylor MA,
Sach TH, et al. Effects of dietary intervention and quadriceps
strengthening exercises on pain and function in overweight
people with knee pain: randomised controlled trial. BMJ
2009;339:b3170.
Goldsmith CH, Boers M, Bombardier C, Tugwell P, for the
OMERACT Committee. Criteria for clinically important
changes in outcomes: development, scoring and evaluation of
rheumatoid arthritis patient and trial proles. J Rheumatol
1993;20:5615.
Hunt JR, White E. Retaining and tracking cohort study members. Epidemiol Rev 1998;20:5770.