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University of Southern California Dissertations and Theses

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Associations between physical activities with bone mineral density in postmenopausal women

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Associations between physical activities with bone mineral density in postmenopausal women

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Content ASSOCIATIONS BETWEEN PHYSICAL ACTIVITIES WITH BONE
MINERAL DENSITY IN POSTMENOPAUSAL WOMEN
By
Chuan Qin

A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
MASTER OF SCIENCE
(APPLIED BIOSTATISTICS AND EPIDEMIOLOGY)
August 2015

Chuan Qin

I

Table of Contents
Abstract II
Introduction 1
Methods 4
Subjects 4
Assessment of Physical Activity 5
Assessment of Bone Mineral Density 6
Statistical Analysis 6

Results 9
Baseline characteristics 9
Baseline associations with bone density 9
Longitudinal associations with bone density 10

Discussion 12

Conclusions 15

Tables
Table 1: Baseline Characteristics of WISH Participants 16
Table 2: Associations with Baseline Bone Density 19
Table 3: Average Annual Rate of Change in BMD 25
Table 4: Longitudinal Associations with Bone Density 26
Table 5: Longitudinal Associations with Bone Density 35
In Early Menopausal Women

References 44
II

Abstract
Objective: The role of physical activity on bone mineral density (BMD) in
postmenopausal women remains unclear. This study aimed to investigate the
association between level of physical activity and 2.5-year longitudinal change in
BMD in postmenopausal women.
Methods: The WISH trial was a randomized, placebo-controlled trial testing the
effects of isoflavone soy protein supplementation on health outcomes. Subjects
were 350 healthy postmenopausal women. Physical activity was assessed by the
Stanford Seven-Day Physical Activity self-report recall questionnaire which was
completed at baseline and every 6 months throughout the trial. Bone mineral
density (BMD) of the lumbar spine, femoral neck and total hip were measured by
Dual-energy x-ray absorptiometry (DXA) at baseline, 12- and 30-months post-
randomization. Linear mixed effects models were used to analyze the association
of physical activity with annual rate of change in BMD.
Results: The average annual rate of change in BMD significantly declined over 2.5
years in the femoral neck and total hip (p<0.0001). There were no significant
associations between rates of change in BMD at any of the three bone sites with
the baseline or trial averaged total weekly metabolic equivalents (MET) hours,
III

weekly vigorous activity hours, weekly moderate +vigorous activity hours and
weekly hours in weight bearing activities (all p>0.05).
Conclusions: In this population of healthy postmenopausal women, annual rates
of change in BMD of lumbar spine, femoral neck and total hip were not
significantly associated with self-reported physical activity.

1

Introduction
Osteoporosis is an age-related bone disease characterized by a decrease in
bone density and mass which increases the risk of fracture.
1
Osteoporosis is
defined as a T-score lower than -2.5, while low bone mass is defined as a T-score
between -1.0 and -2.5. The T-score represents the number of standard deviation
units above or below the mean bone mineral density of normal young adults.
2

Osteoporosis is usually a silent disease that is associated with serious
complications including fractures, loss of height, and kyphosis, especially in older
individuals.
3
Around 54 million Americans have osteoporosis or low bone mass.
Experts predict that osteoporosis is responsible for approximately three million
fractures and $25.3 billion in costs each year by 2025.
3
In 2005-2008, nine percent
of the non-institutionalized U.S. population aged 50 years and older had
osteoporosis at either the neck of the femur or lumbar spine; roughly one-half of
these persons had low bone mass at either the femur neck or lumbar spine.
4
In a
sample of older women and men, all low-trauma fractures were associated with
increased mortality risk for 5 to 10 years; subsequent fracture was associated
with increased mortality risk for an additional 5 years.
28

2

Postmenopausal-related changes in the hormonal milieu are related to many
menopause-associated disease risks, such as osteoporosis, breast cancer and
cardiovascular disease.
5, 6
The menopause transition is related to accelerated
bone density loss.
7, 8
Estrogen therapy in postmenopausal women can increase
bone mineral density (BMD) and reduce risk of fracture.
9, 10, 11

Physical activity is associated with sex hormone levels in postmenopausal
women.
12
In a 3-year longitudinal clinical trial in early postmenopausal (1-8 years)
women, a low-volume/high-intensity exercise program lasting 38 months
maintained bone mineral density at the spine, hip and calcaneus, compared to
participants in the control group who were asked to continue their normal
lifestyle.
13
While observational studies have investigated the association between
different types of physical activity with BMD, the findings of these studies are
inconsistent.
14, 15
Thus, the role of physical activity on BMD in postmenopausal
women remains unclear.
This study used data from the Women’s Isoflavone Soy Health (WISH) trial, a
randomized, double-blind, placebo-controlled trial. As one of the trial outcomes,
BMD was measured by dual-energy x-ray absorptiometry (DXA) bone scans at
baseline, 12- and 30-months post-randomization. Physical activity was assessed
3

throughout the trial at 6-month intervals. The present study aimed to use the
WISH data to investigate the association between level of physical activity and
longitudinal change in BMD in postmenopausal women.

4

Methods
The WISH was a randomized, double-blind, placebo-controlled trial designed
to test the effects of high-dose isoflavone-rich soy protein (ISP) supplementation
on progression of subclinical atherosclerosis in 350 healthy postmenopausal
women without pre-existing CVD. The trial was conducted from April 12, 2004 to
March 19, 2009. A secondary outcome of the WISH trial was change in BMD and
markers of bone metabolism.
Subjects
Participants were recruited from the Greater Los Angeles area, over a 2-year
recruitment period. Eligible subjects were postmenopausal women without
vaginal bleeding for 1 year and a serum estradiol level <20 pg/ml. Exclusion
criteria included: clinical signs, symptoms or personal history of cardiovascular
disease; diabetes mellitus or fasting serum blood glucose>126 mg/dl; fasting
triglyceride levels>500 mg/dl; serum creatinine>2.0 mg/dL; uncontrolled
hypertension (systolic blood pressure>160 mmHg and/or diastolic blood
pressure>110 mmHg); untreated thyroid disease; life threatening disease with
prognosis<5 years; alcohol intake>5 drinks per day or substance abuse; taking
menopausal replacement hormones or soy, nut or related food allergies.
5

A total of 350 women were randomized in a 1:1 allocation to the ISP
group or to the daily total milk protein matched placebo (0 isoflavones) group.
Subjects were followed every month for the first 6 months and every other month
thereafter for 2.5-3 years.
Assessment of Physical Activity
Physical activity was assessed with the Stanford Seven-Day Physical Activity
self-report recall questionnaire which was completed at baseline and every 6
months throughout the trial.
27
In the Stanford structured questionnaire, subjects
self-reported the specific activities and duration of moderate, hard and very hard
activities engaged in over the prior week; total sleep hours were also reported.
Activity was coded for its metabolic equivalents (METs) using the coding scheme
developed by Ainsworth et al.
16
Activities coded as three to six METs were
categorized as moderate activity and activities coded as more than six METs were
categorized as vigorous physical activity. Activities coded as less than three METs
were considered as light physical activity. Total duration of light activity was
calculated as subtracting the sum of the time spent in sleep and in doing
moderate and vigorous activity from the total 168 weekly hours. The time spent
per week in sleep, light activity, moderate activity, vigorous activity and weight-
6

bearing activity were computed. In addition, a variable of total MET-hours was
computed as the sum of each reported activity’s MET multiply by hours spent in
sleep and in doing light, moderate, and vigorous activities. Sleep was coded as 1
MET and light activities were coded as 1.5 MET.
Assessment of Bone Mineral Density
Dual-energy x-ray absorptiometry (DXA) bone scans were performed at
baseline, 12- and 30-months post-randomization. The bone mineral density of the
lumbar spine, femoral neck and total hip were measured by DXA using a Hologic
Bone Densitometer reported in g/cm
2
.
Statistical Analysis
Analysis included 349 subjects who had data available for both bone mineral
density and physical activity. One subject was excluded due to missing BMD at all
visits. Education was categorized as high school or less, some college and college
graduate. Total weekly MET-hours and weekly hours in weight bearing activities
were modeled as categorical variables defined by quartiles. Hours per week spent
in vigorous physical activity was categorized into three levels, including women
reporting no vigorous activity; the higher two levels were categorized using a
median split of weekly hours of vigorous activity (among women who reported at
7

least some vigorous activities). The sum of weekly hours spent in moderate and
vigorous activity (i.e., moderate and higher level physical activity) was also
categorized by the quartile distribution. We modeled these variables as
categorical variable since we were interested as to whether change in BMD
differed by levels of each reported physical activity.
Bone mineral density dependent variables included the three sites (lumbar
spine, femoral neck and total hip) modeled as continuous dependent variables.
We first assessed the cross-sectional baseline associations of bone density of
these three sites with physical activity using linear regression. Univariate
associations of age, BMI, race and education with BMD were analyzed for
inclusion as possible confounders in physical activity-BMD associations. Physical
activity associations with BMD were adjusted for age, race and education since
we found these variables are more likely related to bone density through the
spearman correlation test.
To model longitudinal associations of physical activity with bone density, we
used mixed linear regression models to test whether the annual rate of change in
BMD of the lumbar spine, femoral neck and total hip differed by physical activity
or other variables. A time variable of years since first scan was calculated as
8

(scan_date – baseline_date ) / 365.25. Independent variables included age, BMI,
race, education and baseline measures of physical activity including total weekly
MET-hours, sum of moderate and vigorous activity hours per week, weekly
vigorous activity hours, total weekly sleep hours and weekly hours in weight
bearing activities. We also computed and analyzed the average value of each
physical activity variable for each subject assessed every 6 months through trial
follow up. For each physical activity variable (each modeled separately), the
model included independent variables of the physical activity variable, years and
the interaction term of years-by-physical activity. All mixed effects models for the
physical activity variables were adjusted for age, race and education. The
interaction term tested whether the annual rate of change in BMD differed by
physical activity. We additionally analyzed these longitudinal association models
in a sub-sample of women who were within 2 years of menopause since within 2
years of menopause is the most rapid time of bone loss for women and in a sub-
sample of women who were within 8 years of menopause since some studies
found significant associations between physical activities with change in BMD of
women who were within 8 years of menopause.
13, 18
Two-sided p-values < 0.05
were considered statistically significant.

9

Results
Baseline characteristics
Baseline characteristics of 349 participants included in the analysis are
summarized in Table 1. Women in this sample were on average (SD) 60.6 (7.1)
years old with an average BMI of 26.6 (5.2) kg/m
2
. Women were primarily (64%)
of non-Hispanic white race/ethnicity and 59% were college graduates. The
average (SD) bone mineral density at baseline on the lumbar spine, femoral neck
and total hip was 0.9 (0.1), 0.7 (0.1) and 0.9 (0.1) g/cm
2
respectively; these values
were slight higher than other studies for a similar sample of women.
13, 14, 19

Median weekly physical activity was approximately 240 MET hours with 4.3 hours
in moderate or higher intensity physical activity. Women primarily (84%) spent no
time in vigorous physical activity.
Baseline associations with bone density
The associations with bone density measured at baseline are shown in Table 2.
Age was significantly negatively associated with BMD in the femoral neck
(p=0.001) and total hip (p=0.035), but was not significantly associated with
lumbar spine BMD (p=0.39). BMI was in contrast significantly positively associated
with BMD of all three sites (p<0.0001). Compared to non-Hispanic White women,
10

Hispanic, Asian and other race groups had lower BMD of the lumbar spine; Black
women had higher BMD of the lumbar spine (p=0.04). In the femoral neck and
total hip, only Asian women had lower BMD; all other race groups had higher
BMD compared to non-Hispanic White women. Physical activity variables include
total weekly sleep hours were not significantly associated with BMD of the three
sites (lumbar spine, femoral neck and total hip), with all physical activity
associations adjusted for age, race and education (p>0.05).
Longitudinal associations with bone density
Estimates of annual rates of change in BMD in the total sample are shown in
Table 3. The average annual rate of change in BMD significantly declined in the
femoral neck and total hip (p<0.0001). The annual rate of change in BMD in the
lumbar spine was not significantly different from zero (p=0.15).
Table 4 shows longitudinal associations of BMD of the lumbar spine, femoral
neck and total hip. The average annual rate of change in BMD of the lumbar spine
was positively associated with age (p=0.001); age was not associated with
longitudinal change of BMD in the femoral neck or total hip. Rates of change in
BMD were not significantly associated with BMI, race or education; however,
11

there was a marginally positive association of BMI with rate of change in BMD of
the lumbar spine (p=0.059).
All mixed effects models for physical activity variables were adjusted for age,
race and education. No associations between physical activity variables include
total weekly sleep hours with average annual rate of change in BMD were
statistically significant. Consistent results were seen in all the trial-averaged
physical activity variables, in that the average annual rate of change in BMD of all
three sites had no significant associations with average total MET hours/w,
moderate + vigorous hours/w and vigorous hours/w (p>0.05).
In analyses confined to earlier postmenopausal women (≤8 years since
menopause), we found no significant associations between physical activity
variables with change in BMD of the lumbar spine, femoral neck or total hip in
early menopausal women (Table 5). Consistent results were seen in analyses
confined to earlier postmenopausal women (≤2 years since menopause).
However, there was a significant positive association of BMI with rate of change
in BMD of the lumbar spine in these two sub-sample analyses. (p=0.04).

12

Discussion
We investigated the association between level of physical activity and
longitudinal change in BMD in postmenopausal women. We did not detect any
significant cross-sectional (at baseline) or longitudinal (annual rates of change)
associations of BMD of the lumbar spine, femoral neck and total hip with levels of
physical activity.
Other studies have similarly shown no significant associations between
physical activity with BMD.
14,16,17
A 5-year cohort study reported that none of the
physical activities (housework, farm work, and moderate leisure-time physical
activity within the previous week) predicted BMD changes of the femoral neck
and vertebrae.
14
A 24-month randomized trial showed that increases in BMD of
the femoral neck, total hip, spine, and total radius in weight training exercises
plus medication (1,200 mg of calcium and 400 IU of vitamin D daily and 35 mg of
risedronate weekly) group were not significantly different from a medication only
group.
16

However, some intervention trials have reported significant associations
between different levels of physical activity with change in BMD.
13, 18-20, 22, 23
A 12-
month randomized controlled study observed that block-periodized exercise
13

training positively affected BMD at the lumbar spine in early post-menopausal (1-
3 years) women; however the intervention was not effective in modifying BMD at
the total hip compared to a control group (low-volume/low-intensity exercise).
18

A randomized trial investigated the association between different types of
physical activity with change of BMD; compared to strength training (4 s
(concentric)/4 s (eccentric)), power training (explosive/4 s) showed significantly
superior effects on maintaining BMD of the lumbar spine in postmenopausal
women.
19
In a 6-month randomized controlled study, postmenopausal women
with osteopenia in a high-impact exercise training group had a significant increase
in BMD of the lumbar spine and femoral neck compared to strength exercise
training and no exercise groups.
20

Observational studies also showed significant positive associations between
physical activity with change in BMD.
15, 21, 24-26
A population-based cohort study
identified significant interactions between physical activity with calcium intake in
BMD of the lumbar spine, right hip and left hip in Scottish postmenopausal
women; at low, medium and high calcium intakes, left hip BMD was higher in the
highest tertile of physical activity compared to the lowest tertile of physical
activity.
26
A cross-sectional study concluded that normal and brisk gait speed,
normal step length, brisk step length and timed 1-leg stance are positively
14

significantly associated with BMD in several skeletal sites in postmenopausal
women.
15
Habitual activity including heavy housework, walking (faster pace),
sports/recreational activities and low-impact physical activity were also beneficial
for bone in older women.
21

Inconsistent results in associations between physical activities with BMD may
be due to different study designs, sample size, characteristics of populations and
duration of intervention. Also BMD was measured at different bone sites in
different studies. The WISH trial had a large sample size but was nonetheless
limited on the assessment of physical activity. Since the Stanford Seven-Day that
we used to assess physical activity was a self-report questionnaire, subjects may
have over- or under-reported their activities and duration, thereby decreasing the
reliability of the physical activity data. Additionally, subjects recalled activities
engaged in over the prior week, this may create some inaccurate information due
to limitations in human memory.

15

Conclusions
The average annual rate of change in BMD was significantly positively
associated with age in the lumbar spine (p=0.001). However, we found no
significant associations between physical activity with change in BMD of lumbar
spine, femoral neck and total hip. Based on the null findings of this analysis, it is of
great interest as to how bone metabolism markers associate with physical activity.
Additional study is needed.

16

Table 1: Baseline characteristics of WISH participants (n=349)
Variable N Mean (SD) or n (%)
Age(Years) 349 60.6(7.1)
Years since menopause
<= 8 years 171(49%)
> 8 years 178(51%)
BMI(kg/m
2
) 349 26.6(5.2)
Race/ethnicity
White, Non-Hispanic 223(63.9%)
Black 20(5.7%)
Hispanic 55(15.8%)
Asian 38(10.9%)
Other 13(3.7%)
Education
High school or less 19(5.7%)
Some College 122(34.9%)
College graduate 208(59.4%)
Bone density(g/cm
2
)
Lumbar spine 347 0.937(0.137)
17

Femoral neck 348 0.730(0.114)
Total hip 348 0.898(0.122)
7-Day Physical Activity
Sleep hours/w 349 48.4(8.1)
Total MET hours/w
210-232.75 MET-hours 90(25.8%)
232.75-240.24 MET-hours 87(24.9%)
240.33-251.0 MET-hours 83(23.8%)
251.25-402.0 MET-hours 89(25.5%)
Vigorous hours/w
0 hours 292(83.7%)
0.08-1.0 hours 30(8.6%)
1.25-15.5 hours 27(7.7%)
Moderate+ Vigorous hours/w
0-2.0 hours 93(26.7%)
2.08-4.33 hours 86(24.6%)
4.34-7.59 hours 78(22.4%)
7.75-54.0 hours 92(26.4%)
Hours in weight bearing activities/w
0-0.05 hours 83(23.8%)
18

0.25-1.83 hours 80(22.9%)
2.0-3.92 hours 100(28.7%)
4.0-30.0 hours 86(24.6%)
MET: metabolic equivalents (1 MET=1 kcal/kg/hour)

19

Table 2a: Associations with Baseline Bone Density (N=349)
Site N β ( S E ) *1 0
-3
P-value
Lumbar spine
Age(Years) 347 0.9(1) 0.39
BMI(kg/m
2
) 347 9.1(1.3) <0.0001
Race 0.036
White, Non-Hispanic 221 ___ ___
Black 20 58.4 （31.8 ）
Hispanic 55 -25.0 （20.5 ）
Asian 38 -52.4 （23.9 ）
Other 13 -9.6 （38.8 ）
Education 0.74
High school or less 19 24.6(33.0)
Some College 121 5.4(15.7)
College graduate 207 ___ ___
Sleep hours/w 347 0.8(0.9) 0.38
Total MET hours/w 0.54
210-232.75 MET-hours 89 ___ ___
232.75-240.24 MET-hours 86 -11.3(20.8)
20

Table 2a: Associations with Baseline Bone Density (N=349) (Continued)
240.33-251.0 MET-hours 83 0.9(21.0)
251.25-402.0 MET-hours 89 -26.2(20.6)
Vigorous hours/w 0.30
0 hours 290 ___ ___
0.08-1.0 hours 30 40.3(26.3)
1.25-15.5 hours 27 -11.7(27.6)
Moderate+ Vigorous hours/w 0.80
0-2.0 hours 92 ___ ___
2.08-4.33 hours 85 -8.1(20.7)
4.34-7.59 hours 78 -12.5(21.2)
7.75-54.0 hours 92 -19.9(20.3)
Hours in weight bearing activities/w 0.68
0-0.05 hours 82 ___ ___
0.25-1.83 hours 80 21.5(21.8)
2.0-3.92 hours 99 4.8(20.6)
4.0-30.0 hours 86 -2.8(21.3)

21

Table 2b: Associations with Baseline Bone Density (N=349)
Femoral neck N β ( S E ) *10
-3
P-value
Age(Years) 348 -2.9(0.9) 0.0010
BMI(kg/m
2
) 348 9.8(1.1) <0.0001
Race 0.0002
White, Non-Hispanic 222 ___ ___
Black 20 116.4(26.0)
Hispanic 55 10.2(16.8)
Asian 38 -17.7(19.5)
Other 13 32.5(31.8)
Education 0.31
High school or less 19 15.1(27.4)
Some College 122 19.6(13.0)
College graduate 207 ___ ___
Sleep hours/w 348 -0.2(0.8) 0.76
Total MET hours/w 0.47
210-232.75 MET-hours 90 ___ ___
232.75-240.24 MET-hours 87 17.5(17.2)
240.33-251.0 MET-hours 82 -6.0(17.5)
251.25-402.0 MET-hours 89 10.3(17.1)
22

Table 2b: Associations with Baseline Bone Density (N=349) (Continued)
Vigorous hours/w 0.29
0 hours 292 ___ ___
0.08-1.0 hours 30 8.7(21.9)
1.25-15.5 hours 26 -35.4(23.4)
Moderate+ Vigorous hours/w 0.79
0-2.0 hours 93 ___ ___
2.08-4.33 hours 86 -2.0(17.1)
4.34-7.59 hours 77 -11.6(17.7)
7.75-54.0 hours 92 6.8(16.9)
Hours in weight bearing activities/w 0.49
0-0.05 hours 83 ___ ___
0.25-1.83 hours 79 23.0(17.9)
2.0-3.92 hours 100 2.7(16.8)
4.0-30.0 hours 86 17.0(17.4)

23

Table 2c: Associations with Baseline Bone Density (N=349)
Total hip N β ( S E ) *10
-3
P-value
Age(Years) 348 -1.9(0.9) 0.035
BMI(kg/m
2
) 348 11.4(1.1) <0.0001
Race 0.012
White, Non-Hispanic 222 ___ ___
Black 20 78.0(28.0)
Hispanic 55 10.3(18.1)
Asian 38 -40.6(21.1)
Other 13 4.3(34.2)
Education 0.16
High school or less 19 29.7(29.1)
Some College 122 24.6(13.8)
College graduate 207 ___ ___
Sleep hours/w 347 -0.4(0.8) 0.63
Total MET hours/w 0.52
210-232.75 MET-hours 90 ___ ___
232.75-240.24 MET-hours 87 26.3(18.3)
240.33-251.0 MET-hours 82 7.9(18.6)
251.25-402.0 MET-hours 89 17.4(18.2)
24

Table 2c: Associations with Baseline Bone Density (N=349) (Continued)
Vigorous hours/w 0.37
0 hours 292 ___ ___
0.08-1.0 hours 30 26.4(23.3)
1.25-15.5 hours 26 -20.7(24.9)
Moderate+ Vigorous hours/w 0.96
0-2.0 hours 93 ___ ___
2.08-4.33 hours 86 3.8(18.3)
4.34-7.59 hours 77 -1.7(18.8)
7.75-54.0 hours 92 8.9(17.9)
Hours in weight bearing activities/w 0.55
0-0.05 hours 83 ___ ___
0.25-1.83 hours 79 17.8(19.1)
2.0-3.92 hours 100 25.3(18.0)
4.0-30.0 hours 86 19.2(18.6)
2 subjects had a missing value of the baseline lumbar spine; 1 subject had a
missing value of the baseline femoral neck and total hip
Beta(SE) obtained by linear regression
Univariate associations are reported for age, race and education. Physical
activity associations are adjusted for age, race and education
25

Table 3: Average Annual Rate of Change in BMD (N=349)
Site β ( S E ) *1 0
-3
(g/cm
2
/year) 95%CI*10
-3
p-value
Lumbar spine 1.350(0.939) -0.50,3.199 0.15
Femoral neck -3.72(0.651) -5.0 ，-2.44 <0.0001
Total hip -2.94(0.612) -4.14 ，-1.74 <0.0001
P-values from linear mixed effects model

26

Table 4a: Longitudinal Associations with Bone Density (N=349)
Lumbar Spine N Estimated Annual Rate- 95%CI*10
-3
p-value
of Change (SE)*10
-3

Age*Years 349 0.5(0.1) 0.186,0.723 0.001
BMI*Years 349 0.3(0.1) -0.01,0.693 0.059
Race*Years 0.14
White, Non-Hispanic 223 2.3(1.2) -0.06,4.571
Black 20 5.0(3.8) -2.49,12.57
Hispanic 55 1.0(2.4) -3.72,5.728
Asian 38 -4.9(2.7) -10.22,0.427
Other 13 2.0(4.8) -7.51,11.55
Education*Years 0.23
High school or less 19 2.6(3.8) -4.94,10.11
Some College 122 3.5(1.6) 0.284,6.629
College graduate 208 0.04(1.2) -2.34,2.421
BL Sleep hours/w*years 349 0.07(0.1) -0.17,0.31 0.55
BL Total MET hours/w*years 0.83
210-232.75MET-hours 90 1.4(1.9) -2.34,5.180
232.75-240.24MET-hours 87 2.6(1.9) -1.20,6.417
240.33-251.0MET-hours 83 1.3(1.9) -2.33,5.018
27

Table 4a: Longitudinal Associations with Bone Density (N=349) (Continued)
251.25-402.0MET-hours 89 0.03(1.9) -3.78,3.852
BL Vigorous hours/w*years 0.54
0 hours 292 1.8(1.0) -0.22,3.779
0.08-1.0 hours 30 0.3(3.6) -6.93,7.432
1.25-15.5 hours 27 -2.4(3.8) -9.92,5.060
BL Moderate+ Vigorous hours/w*years 0.83
0-2.0 hours 93 1.3(1.9) -2.33,4.975
2.08-4.33 hours 86 2.8(2.0) -1.04,6.736
4.34-7.59 hours 78 0.9(1.9) -2.89,4.632
7.75-54.0 hours 92 0.4(2.0) -3.46,4.235
BL Hours in weight bearing activities/w*years 0.06
0-0.05 hours 83 4.7(1.9) 0.991,8.339
0.25-1.83 hours 80 -0.9(2.0) -4.82,3.102
2.0-3.92 hours 100 2.5(1.8) -1.12,6.115
4.0-30.0 hours 86 -1.9(1.9) -5.69,1.868
Average Total MET hours/w*years 0.08
200.58-235.06 hours 91 2.3(1.9) -1.45,6.003
235.09-241.0 hours 85 3.0(1.8) -0.64,6.598
241.05-249.75 hours 86 3.0(1.9) -0.62,6.693
249.79-333.62 hours 87 -2.8(1.9) -6.45,0.877
28

Table 4a: Longitudinal Associations with Bone Density (N=349) (Continued)
Average Moderate+ Vigorous hours/w*years 0.1
0-2.85 hours 95 5.2(1.9) 1.477,9.02
2.86-4.46 hours 83 0.7(1.8) -2.90,4.339
4.46-6.87 hours 81 1.1(1.8) -2.46,4.746
6.93-24.0 hours 90 -1.3(1.8) -4.98,2.388
Average Vigorous hours/w*years 0.2
0 hours 210 1.7(1.2) -0.69,4.211
0.01-0.4 hours 72 3.0(1.9) -0.72,6.715
0.42-11.0 hours 67 -1.9(2.1) -6.14,2.286

29

Table 4b: Longitudinal Associations with Bone Density (N=349)
Femoral Neck N Estimated Annual Rate- 95%CI*10
-3
p-value
of Change (SE)*10
-3

Age*Years 349 0.014(0.095) -0.17,0.2 0.89
BMI*Years 349 -0.02(0.1) -0.27,0.237 0.90
Race*Years 0.90
White, Non-Hispanic 223 -4.1(0.8) -5.75,-2.51
Black 20 -3.1(2.7) -8.31,2.176
Hispanic 55 -2.4(1.7) -5.69,0.909
Asian 38 -3.9(1.9) -7.69,-0.17
Other 13 -2.6(3.4) -9.16,4.035
Education*Years 0.73
High school or less 19 -3.9(2.7) -9.35,1.454
Some College 122 -3.0(1.1) -5.19,-0.80
College graduate 208 -4.1(0.8) -5.76,-2.44
BL Sleep hours/w*years 349 0.1(0.1) -0.08,0.25 0.32
BL Total MET hours/w*years 0.28
210-232.75MET-hours 90 -2.9(1.4) -5.56,-0.22
232.75-240.24MET-hours 87 -6.1(1.4) -8.84,-3.38
240.33-251.0MET-hours 83 -2.7(1.3) -5.35,-0.06
30

Table 4b: Longitudinal Associations with Bone Density (N=349) (Continued)
251.25-402.0MET-hours 89 -3.2(1.3) -5.90,-0.53
BL Vigorous hours/w*years 0.56
0 hours 292 -3.9(0.7) -5.30,-2.52
0.08-1.0 hours 30 -1.2(2.6) -6.32,3.908
1.25-15.5 hours 27 -4.9(2.7) -10.25,0.505
BL Moderate+ Vigorous hours/w*years 0.89
0-2.0 hours 93 -4.5(1.3) -7.11,-1.84
2.08-4.33 hours 86 -3.7(1.4) -6.45,-0.96
4.34-7.59 hours 78 -3.8(1.4) -6.49,-1.08
7.75-54.0 hours 92 -3.0(1.4) -5.69,-0.23
BL Hours in weight bearing activities/w*years 0.20
0-0.05 hours 83 -2.7(1.4) -5.42,-0.03
0.25-1.83 hours 80 -6.2(1.5) -9.09,-3.28
2.0-3.92 hours 100 -2.2(1.3) -4.79,0.391
4.0-30.0 hours 86 -4.4(1.4) -7.05,-1.65
Average Total MET hours/w*years 0.45
200.58-235.06 hours 91 -5.4(1.3) -8.03,-2.83
235.09-241.0 hours 85 -2.9(1.3) -5.45,-0.40
241.05-249.75 hours 86 -2.7(1.3) -5.32,-0.15
249.79-333.62 hours 87 -3.8(1.3) -6.36,-1.26
31

Table 4b: Longitudinal Associations with Bone Density (N=349) (Continued)
Average Moderate+ Vigorous hours/w*years 0.19
0-2.85 hours 95 -5.9(1.3) -8.47 ，-3.22
2.86-4.46 hours 83 -2.0 （1.3 ） -4.55 ，0.535
4.46-6.87 hours 81 -2.9 （1.2 ） -5.41 ，-0.41
6.93-24.0 hours 90 -4.2 （1.3 ） -6.74 ，-1.64
Average Vigorous hours/w*years 0.25
0 hours 210 -4.0 （0.9 ） -5.70 ，-2.31
0.01-0.4 hours 72 -2.0 （1.3 ） -4.56 ，0.633
0.42-11.0 hours 67 -5.1 （1.5 ） -8.05 ，-2.16

32

Table 4c: Longitudinal Associations with Bone Density (N=349)
Total Hip N Estimated Annual Rate- 95%CI*10
-3
p-value
of Change (SE)*10
-3

Age*Years 349 0.09(0.09) -0.09,0.266 0.32
BMI*Years 349 -0.09(0.1) -0.33,0.149 0.46
Race*Years 0.82
White, Non-Hispanic 223 -2.8(0.8) -4.27,-1.22
Black 20 -1.0(2.5) -5.95,3.921
Hispanic 55 -3.0(1.6) -6.11,0.077
Asian 38 -4.2(1.8) -7.69,-0.63
Other 13 -4.9(3.2) -11.18,1.303
Education*Years 0.79
High school or less 19 -1.6(2.6) -6.63,3.477
Some College 122 -2.7(1.0) -4.74,-0.61
College graduate 208 -3.2(0.8) -4.77,-1.66
BL Sleep hours/w*years 349 0.04(0.1) -0.11,0.199 0.57
BL Total MET hours/w*years 0.32
210-232.75MET-hours 90 -1.6(1.2) -4.03,0.862
232.75-240.24MET-hours 87 -2.8(1.3) -5.25,-0.29
240.33-251.0MET-hours 83 -2.6(1.2) -5.01,-0.20
33

Table 4c: Longitudinal Associations with Bone Density (N=349) (Continued)
251.25-402.0MET-hours 89 -4.8(1.3) -7.31,-2.36
BL Vigorous hours/w*years 0.93
0 hours 292 -3.0(0.7) -4.34,-1.73
0.08-1.0 hours 30 -2.4(2.4) -7.05,2.257
1.25-15.5 hours 27 -2.3(2.5) -7.17,2.666
BL Moderate+ Vigorous hours/w*years 0.21
0-2.0 hours 93 -1.4(1.2) -3.84,0.954
2.08-4.33 hours 86 -1.8(1.3) -4.32,0.675
4.34-7.59 hours 78 -3.8(1.2) -6.27,-1.38
7.75-54.0 hours 92 -4.6(1.3) -7.11,-2.13
BL Hours in weight bearing activities/w*years 0.24
0-0.05 hours 83 -3.2(1.2) -5.67,-0.81
0.25-1.83 hours 80 -3.3(1.3) -5.93,-0.69
2.0-3.92 hours 100 -1.0(1.2) -3.39,1.314
4.0-30.0 hours 86 -4.5(1.3) -6.99,-2.04
Average Total MET hours/w*years 0.58
200.58-235.06 hours 91 -2.0 （1.2) -4.44 ，0.459
235.09-241.0 hours 85 -3.4 （1.2 ） -5.80 ，-1.06
241.05-249.75 hours 86 -2.2 （1.2 ） -4.60 ，0.256
249.79-333.62 hours 87 -4.0 （1.2 ） -6.44 ，-1.65
34

Table 4c: Longitudinal Associations with Bone Density (N=349) (Continued)
Average Moderate+ Vigorous hours/w*years 0.34
0-2.85 hours 95 -3.2 （1.3 ） -5.66 ，-0.71
2.86-4.46 hours 83 -1.6 （1.2 ） -4.02 ，0.767
4.46-6.87 hours 81 -2.3 （1.2 ） -4.65 ，0.054
6.93-24.0 hours 90 -4.6 （1.2 ） -7.02 ，-2.21
Average Vigorous hours/w*years 0.79
0 hours 210 -2.8 （0.8 ） -4.36 ，-1.16
0.01-0.4 hours 72 -2.6 （1.2 ） -5.09 ，-0.19
0.42-11.0 hours 67 -3.8 （1.4 ） -6.57 ，-1.01
BL: Baseline
P-value from linear mixed effects models;
1 per unit of continues variable, otherwise mean rate in each category.
Each variable has different mixed effects model, all mixed effects models for
physical activity variables are adjusted for age, race and education.

35

Table 5a: Longitudinal Associations with Bone Density in Early Menopausal Women (Years
since Menopause <= 8 years) (N=171)
Lumbar Spine N Estimated Annual Rate- 95%CI*10
-3
p-value
of Change (SE)*10
-3

Age*Years 171 0.4(0.2) -0.09,0.82 0.11
BMI*Years 171 0.5(0.2) 0.02,0.96 0.04
Race*Years 0.12
White, Non-Hispanic 100 0.3(1.6) -2.86,3.55
Black 13 5.3(4.4) -3.34,13.89
Hispanic 29 -2.3(3.0) -8.19,3.56
Asian 23 -6.9(3.1) -13.12,-0.67
Other 6 5.6(6.2) -6.56,17.85
Education*Years 0.18
High school or less 7 -4.9(5.8) -16.3,6.51
Some College 61 2.3(2.0) -1.74,6.34
College graduate 103 -2.1(1.6) -5.23,1.07
BL Total MET hours/w*years 0.32
210-232.75MET-hours 47 2.3(2.5) -2.59,7.14
232.75-240.24MET-hours 36 -0.8(2.8) -6.32,4.82

36

Table 5a: Longitudinal Associations with Bone Density in Early Menopausal Women(Years since
Menopause <= 8 years) (N=171) (Continued)
240.33-251.0MET-hours 36 0.3(2.5) -4.58,5.23
251.25-402.0MET-hours 52 -4.0(2.3) -8.59,0.67
BL Vigorous hours/w*years 0.80
0 hours 141 -0.6(1.3) -3.31,7.49
0.08-1.0 hours 18 2.2(4.6) -6.90,11.2
1.25-15.5 hours 12 -2.1(4.8) -11.65,7.49
BL Moderate+ Vigorous hours/w*years 0.18
0-2.0 hours 50 1.7(2.4) -3.16,6.52
2.08-4.33 hours 35 -0.4(2.7) -5.69,4.93
4.34-7.59 hours 36 1.6(2.5) -3.26,6.55
7.75-54.0 hours 50 -5.0(2.4) -9.78,-0.23
BL Hours in weight bearing activities/w*years 0.21
0-0.05 hours 41 2.2(2.4) -2.61,7.08
0.25-1.83 hours 40 0.1(2.6) -5.15,5.27
2.0-3.92 hours 47 -0.1(2.5) -5.0,4.91
4.0-30.0 hours 43 -5.0(2.4) -9.79,-0.11
Average Total MET hours/w*years 0.38
200.58-235.06 hours 54 0.8(2.3) -3.81,5.42
235.09-241.0 hours 32 1.0(2.7) -4.32,6.27
37

Table 5a: Longitudinal Associations with Bone Density in Early Menopausal Women(Years since
Menopause <= 8 years) (N=171) (Continued)
241.05-249.75 hours 38 0.7(2.6) -4.48,5.92
249.79-333.62 hours 47 -3.9(2.3) -8.46,0.57
Average Moderate+ Vigorous hours/w*years 0.11
0-2.85 hours 50 4.5(2.5) -0.4,9.50
2.86-4.46 hours 40 -0.7(2.4) -5.38,4.08
4.46-6.87 hours 35 -3.2(2.5) -8.24,1.78
6.93-24.0 hours 46 -2.7(2.3) -7.30,1.97
Average Vigorous hours/w*years 0.36
0 hours 99 -1.4(1.7) -4.71,1.91
0.01-0.4 hours 32 2.8(2.6) -2.42,7.94
0.42-11.0 hours 40 -1.7(2.5) -6.69,3.23

38

Table 5b: Longitudinal Associations with Bone Density in Early Menopausal Women (Years
since Menopause <= 8 years) (N=171)
Femoral Neck N Estimated Annual Rate- 95%CI*10
-3
p-value
of Change (SE)*10
-3

Age*Years 171 0.02(0.17) -0.31,0.35 0.89
BMI*Years 171 -0.3(0.2) -0.06,0.62 0.10
Race*Years 0.84
White, Non-Hispanic 100 -3.5(1.2) -5.79,-1.10
Black 13 -1.0(3.2) -7.29,5.31
Hispanic 29 -2.3(2.2) -6.58,2.03
Asian 23 -4.8(2.3) -9.43,-0.13
Other 6 -0.9(4.5) -9.75,8.05
Education*Years 0.13
High school or less 7 -6.7(4.1) -14.82,1.43
Some College 61 -0.9(1.5) -3.75,2.01
College graduate 103 -4.3(1.1) -6.55,-2.04
BL Total MET hours/w*years 0.55
210-232.75MET-hours 47 -2.5(1.8) -6.11,1.07
232.75-240.24MET-hours 36 -5.6(2.1) -9.64,-1.45
240.33-251.0MET-hours 36 -1.6(1.8) -5.21,1.20
39

Table 5b: Longitudinal Associations with Bone Density in Early Menopausal Women(Years since
Menopause <= 8 years) (N=171) (Continued)
251.25-402.0MET-hours 52 -3.4(1.7) -6.82,-0.05
BL Vigorous hours/w*years 0.79
0 hours 141 -3.1(1.0) -5.05,-1.2
0.08-1.0 hours 18 2.2(3.4) -8.80,4.47
1.25-15.5 hours 12 -5.4(3.6) -12.4,1.70
BL Moderate+ Vigorous hours/w*years 0.73
0-2.0 hours 50 -3.1(1.8) -6.69,0.51
2.08-4.33 hours 35 -5.1(2.0) -9.01,-1.13
4.34-7.59 hours 36 -2.3(1.8) -5.9,1.4
7.75-54.0 hours 50 -2.5(1.8) -5.99,1.08
BL Hours in weight bearing activities/w*years 0.48
0-0.05 hours 41 -1.4(1.8) -5.01,2.27
0.25-1.83 hours 40 -5.1(2.0) -8.98,1.19
2.0-3.92 hours 47 -2.1(1.9) -5.76,1.65
4.0-30.0 hours 43 -4.2(1.8) -7.76,-0.54
Average Total MET hours/w*years 0.53
200.58-235.06 hours 54 -5.1(1.7) -8.43,-1.70
235.09-241.0 hours 32 -1.7(1.9) -5.47,2.15
241.05-249.75 hours 38 -2.0(1.9) -5.80,1.71
40

Table 5b: Longitudinal Associations with Bone Density in Early Menopausal Women(Years since
Menopause <= 8 years) (N=171) (Continued)
249.79-333.62 hours 47 -3.3(1.6) -6.54,-0.02
Average Moderate+ Vigorous hours/w*years 0.92
0-2.85 hours 50 -3.7(1.8) -7.31,-0.05
2.86-4.46 hours 40 -3.7(1.8) -7.18,-0.19
4.46-6.87 hours 35 -2.1(1.9) -5.78,1.55
6.93-24.0 hours 46 -3.1(1.7) -6.48,0.3
Average Vigorous hours/w*years 0.72
0 hours 99 -2.9(1.2) -5.27,-0.46
0.01-0.4 hours 32 2.4(1.9) -6.15,1.32
0.42-11.0 hours 40 -4.4(1.8) -7.96,-0.80

41

Table 5c: Longitudinal Associations with Bone Density in Early Menopausal Women (Years
since Menopause <= 8 years) (N=171)
Total Hip N Estimated Annual Rate- 95%CI*10
-3
p-value
of Change (SE)*10
-3

Age*Years 171 0.2(0.2) -0.13,0.53 0.22
BMI*Years 171 -0.08(0.2) -0.33,0.35 0.96
Race*Years 0.82
White, Non-Hispanic 100 -2.8(1.2) -5.13,-0.44
Black 13 -0.5(3.2) -6.76,5.83
Hispanic 29 -5.0(2.2) -9.29,-0.72
Asian 23 -2.8(2.3) -7.35,1.86
Other 6 -2.5(4.5) -11.42,6.50
Education*Years 0.93
High school or less 7 -2.1(4.2) -10.34,6.19
Some College 61 -2.7(1.5) -5.59,0.25
College graduate 103 -3.2(1.2) -5.52,-0.95
BL Total MET hours/w*years 0.08
210-232.75MET-hours 47 -1.0(1.7) -4.44,2.42
232.75-240.24MET-hour 36 -0.7(2.0) -4.54,3.21
240.33-251.0MET-hours 36 -2.9(1.7) -6.28,0.55
42

Table 5c: Longitudinal Associations with Bone Density in Early Menopausal Women(Years since
Menopause <= 8 years) (N=171) (Continued)
251.25-402.0MET-hours 52 -6.3(1.6) -9.55,-3.06
BL Vigorous hours/w*years 0.39
0 hours 141 -2.7(1.0) -4.63,-0.81
0.08-1.0 hours 18 -7.0(3.2) -13.29,-0.62
1.25-15.5 hours 12 -1.2(3.4) -4.63,-0.81
BL Moderate+ Vigorous hours/w*years 0.07
0-2.0 hours 50 -0.4(1.7) -3.86,3.0
2.08-4.33 hours 35 -1.6(1.9) -5.30,2.12
4.34-7.59 hours 36 -2.4(1.7) -5.83,1.0
7.75-54.0 hours 50 -6.6(1.7) -9.9,-3.21
BL Hours in weight bearing activities/w*years 0.10
0-0.05 hours 41 -3.8(1.7) -7.19,0.4
0.25-1.83 hours 40 -1.1(1.8) -4.78,2.50
2.0-3.92 hours 47 -0.5(1.7) -3.93,2.97
4.0-30.0 hours 43 -6.0(1.7) -9.38,-2.59
Average Total MET hours/w*years 0.43
200.58-235.06 hours 54 -1.0(1.7) -4.35,2.32
235.09-241.0 hours 32 -2.4(1.9) -6.19,1.38
241.05-249.75 hours 38 -3.5(1.9) -7.17,0.26
43

Table 5c: Longitudinal Associations with Bone Density in Early Menopausal Women(Years since
Menopause <= 8 years) (N=171) (Continued)
249.79-333.62 hours 47 -4.8(1.6) -8.05,-1.59
Average Moderate+ Vigorous hours/w*years 0.18
0-2.85 hours 50 -1.7(1.8) -5.21,1.89
2.86-4.46 hours 40 -2.9(1.7) -6.33,0.51
4.46-6.87 hours 35 -0.9(1.8) -4.51,2.64
6.93-24.0 hours 46 -5.9(1.7) -9.26,-2.61
Average Vigorous hours/w*years 0.35
0 hours 99 -1.9(1.2) -4.23,5.22
0.01-0.4 hours 32 -3.4(1.9) -7.12,0.28
0.42-11.0 hours 40 -4.9(1.8) -8.47,-1.39
BL: Baseline
P-value from linear mixed effects models;
1 per unit of continues variable, otherwise mean rate in each category.
Each variable has different mixed effects model, all mixed effects models for
physical activity variables are adjusted for age, race and education.

44

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Abstract (if available)

Abstract Objective: The role of physical activity on bone mineral density (BMD) in postmenopausal women remains unclear. This study aimed to investigate the association between level of physical activity and 2.5‐year longitudinal change in BMD in postmenopausal women. ❧ Methods: The WISH trial was a randomized, placebo‐controlled trial testing the effects of isoflavone soy protein supplementation on health outcomes. Subjects were 350 healthy postmenopausal women. Physical activity was assessed by the Stanford Seven‐Day Physical Activity self‐report recall questionnaire which was completed at baseline and every 6 months throughout the trial. Bone mineral density (BMD) of the lumbar spine, femoral neck and total hip were measured by Dual‐energy X‐ray absorptiometry (DXA) at baseline, 12‐ and 30‐months post‐randomization. Linear mixed effects models were used to analyze the association of physical activity with annual rate of change in BMD. ❧ Results: The average annual rate of change in BMD significantly declined over 2.5 years in the femoral neck and total hip (p<0.0001). There were no significant associations between rates of change in BMD at any of the three bone sites with the baseline or trial averaged total weekly metabolic equivalents (MET) hours, weekly vigorous activity hours, weekly moderate + vigorous activity hours and weekly hours in weight bearing activities (all p>0.05). ❧ Conclusions: In this population of healthy postmenopausal women, annual rates of change in BMD of lumbar spine, femoral neck and total hip were not significantly associated with self‐reported physical activity.

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