Relationship
of menopause
John
M McGowan,
F Aloia,
Denise
ABSTRACT body
Cross-sectional
composition
determine of body
with
the relationship fat to bone mass.
curvilinear
component
ligible
rates
of loss
ments
also
indicated
Ashok
and
age were
N Vaswani,
longitudinal
examined
changes
in
women
to
in white
to loss oftotal
body
menopause.
a relationship
potassium
a
neg-
measure-
the
proximity
KEY WORDS mass,
Menopause,
bone
mass,
bone
composition,
body
density,
body
cell
aging,
mass,
mus-
adiposity
Changes in body composition with aging have been associated with increased morbidity and mortality, perhaps best exemplified loss
of skeletal
mass,
which
predisposes
to osteoporotic
mass and skeletal mass decline with increasing age whereas there is a tendency towards an increase in fat mass (1). A variety of hypotheses have been put forward concerning the interrelationships between the various body compartments. Skeletal mass and muscle mass are believed to decline with aging as a result of reduced mechanical stress from an increasingly sedentary lifestyle whereas fat mass increases as a result ofthe reduced energy expenditure. It is widely believed that a reduction in muscle mass leads to reduced skeletal mass. Adiposity has also been postulated to be related to skeletal mass (with an increased fat-cell mass protecting fractures.
Cross-sectional
against
osteoporosis)
vation
reported
a variety
analysis
suggest
that
muscle
(2).
We previously by using
studies
on aging changes
of methods
in body in vivo
composition neutron-acti-
Involutional changes in skeletal because there is an increased rate of loss of skeletal mass associated with menopause (1). Although gonadal-hormone deficiency might be expected to result in a loss of fat-free tissue as well as skeletal tissue, cross-sectional studies suggested that a linear model adequately describes the decline in fat-free mass with aging (4). Because we have collected extensive cross-sectional and longitudinal cell
data mass)
pathogenesis amine
these
acceleration
1378
and
including
on total in white
whole-body counting (3-10). mass differ in women and men
body women
and prevention to answer
data
ofloss
ofTBK
potassium
(TBK,
a measure
of body
of an ongoing study of the of osteoporosis, we decided to cxthe following questions: Is there an as part
associated
with
estrogen
withdrawal
Am J C/in Nutr
Stanton
H Cohn relationship
ofTBK
and
total
body
Subjects
l991;53:l378-83.
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1378/4732432 by Washington University in St. Louis user on 11 June 2018
and methods
Subjects
Infroduction
by the
and
at menopause? What is the fat (TBF) to bone mass?
to
menopause and the rate of loss of potassium. Total body potassium was significantly related to total body calcium and bone density of the spine, radius, and femoral neck. Total body fat was not related to any of these measurements. We found no evidence that adiposity plays a major role in protecting against boneloss. AmJClinNutr l99l;53:l378-83.
dc
Ross,
mass13
and for
with
Longitudinal between
and muscle
Patrick
cell mass to menopause was statistical evidence
ofbody There
before
to skeletal
Bone
mineral
made
on
and
healthy
recruited
from
history
TBK
with
spine
chronic
illness, bone
press.
No
or any
disease.
to exclude
the presence of diuretic
disease.
Menstrual
was normal
for
12 mo
in women
of an
hormone
(>
aged
50 U/L).
45 y and
>
appropriate
level
A history
mass.
Each
subject
had
count, blood chemistry phosphorus, potassium, fasting
and
glucose,
free
who
and
No subject
and postmeno-
was
confirmed
was an exclu-
ofprolonged medication values
immobilization thought to affect for complete
measurements (including alkaline phosphatase, urea
thyroxine,
serum
by the
follicle-stimulating
ofoophorectomy
normal
had
lumbar
therapy at any of menstruation
of serum
sion factor. No subject had a history or was an athlete. No subject took
a is
or gastrointestinal
women did not take estrogen-replacement Menopause was defined by the absence
presence
y,
had that
deformity.
pausal time.
bone
subject
subject
hypertension,
history
20-80
abnormality
Each
ofvertebral use,
were
aged
also had an x ray of the thoracic
a history
or renal
volunteers, in the
metabolic
measured
measurements
Caucasian
announcements
of fractures,
associated
had
total-body-potassium
female
protein
blood
calcium, nitrogen,
electrophoresis),
urinalysis.
Excess body weight was not an exclusion charStanding height was measured with a wall stadiometer. written consent was obtained from each subject. The
acteristic.
Informed procedures board
followed
were
approved
of Winthrop-University
by the
institutional
review
Hospital.
The data reported in this paper include both cross-sectional and longitudinal observations. Cross-sectional data were available for total body calcium (TBCa; n = 304), TBK (n = 304), bone mineral density of the radius (BD1; n = 288), and bone mineral
(n for
=
density 93).
For
of the TBK
18 1 women.
from
1
2 to
From
1 1 with
and
The
lumbar
number
a mean
the Department
spine
TBCa,
(BD1;
longitudinal
of annual of 4.46
of Medicine,
n
=
198)
data
were
measurements
± 2.0 1 (SD).
The
Winthrop-University
and
femur
available
varied length
of
Hospital,
Mineola, NY; the Brookhaven National Laboratory, Upton, NY; and the Health Science Center, SUNY, Stony Brook, NY. 2 Supported by the National Institutes of Health grant AR37520-03. 3 Address reprint requests to JF Aloia, Department of Medicine, Winthrop-University Hospital, 259 First Street, Mineola, NY I 1501. Received April 10, 1990. Accepted for publication August 8, 1990. Printed
in USA. © 1991 American
Society for Clinical
Nutrition
MENOPAUSE, time
in the
± 26.5 were
study
(SD). reported
±2-3%
1 38 mo,
with
a mean
on bone-mineral
‘
data
single-photon
WI) The
absorptiomctry
absorptiometer
at the
reproducibility
of this
femoral measurements on a Lunar Radiation
a ‘53Gd source. L2-L4. women
The region
Reproducibility without crush
on
8-cm
a
site
by
measurement
is
trochanteric region (BDJ. band 1 .5 cm wide across
were made by dual-photon DP3 (Madison, WI) with
of interest
of the fractures
for measuring
lumbar-spine is ±2-3%.
for bone density were automatically the femoral neck (BD5), Ward’s
The
BD5 was
measurement in Regions of interest
selected on femur triangle (BD), and
femoral
the neck
neck
ofthc
scans for the inter-
is defined
femur
as that
perpendicular
to the neutral axis with the lowest density. Ward’s triangle region of interest (which may not coincide exactly with the anatomic location of Ward’s triangle) is defined as a square (‘- 1.5 X 1.5 cm)
with
the
trochanteric was
lowest
changed
in the
is lateral
proximal
femur.
to the femoral
annually.
All
available
software
commercially
source
density
region
scans
were that
The
neck.
whole-body
analyzed corrects
by for the
counting
inter-
Serial
data
available
tissue and LBM for were then averaged number and spacing equations were tested The rates of loss were intercept
measurement
using
the
effects
analysis Laboratory
in an
LBM where TBK is expressed culated as the difference mass:
=
0.442
of and (14).
anthropomorphic
TBK
in g and LBM in kg (8). TBF was calbetween body weight and lean body
wt (kg)
=
LBM
-
of each
were
available
in the study, varied
among
for many
of the
although
the amount
participants.
Routine
of lin-
were used to estimate yearly rates of site and individual rates of boss of fat
each woman. These individual loss rates by weighting each proportionately to the of the observations. The linear-regression for the presence ofa quadratic component. calculated as the percent change from the
individual’s
slope
with
the
y-axis
at the
time
of the first measurement. Separate calculations were made for age groups corresponding to pre-, peri-, and postmenopausal ages. A multiple-range test was used to determine the statistical significance
between
detailed
analysis
the rates
was
done
ofloss
based
in each on actual
age group.
A more
menopausal
status,
with a separate calculation of rates for postmenopausal women who were within 3 y of menopause and 6 y postmenopausal. All analyses were done with the Statistical Package for Social Sciences (SPSS 21. SPSS Inc, Chicago).
Results
TBK was measured by counting the isotope “#{176}K in the Brookhaven whole-body counter. Lean body mass (LBM; fat-free mass, fat-free body cell mass) was calculated as follows:
TBF
data.
who participated
currently
Mean (±SD) height and weight for premenopausal women were 1.64 ± 0.06 m and 64.7 ± 12.7 kg, respectively, as compared with
by using neutron-activation at Brookhaven National
The precision of this phantom is ± 1.1%.
1379
The source
decay.
TBCa was measured
MASS
Longitudinal
women
(13).
Spinal and absorptiometry
MUSCLE
ear-regression procedures bone loss at each skeletal by
Atkinson, source.
251
AND
of 46.8
measurements
( 1 1 , 12).
measured
(Ft an
as
measurements
was
Norland using
as high
of the data
previously
Bone-mineral BDr
was
Some
BONE,
1.62 ± 0.056
m and
66 ± 9.7 kg for postmenopausal
women.
There
was no difference from zero when height was regressed against age for premenopausal women and a low correlation when either postmenopausal (r -0. 1 14, P < 0.05) or all (r = -0. 1 59, P < 0.05) women were included. There was evidence for a curvilinear component to loss of TBK (Z quadratic, = 1.95, P = 0.05). When the data were analyzed by calculating separate linear regressions against age for pre- and postmenopausal women, the relationship developed is as described in Figure 1 and Table 1. Significant relationships (which persisted after adjustment for height, age, and weight) with TBK were noted for TBCa(r = 0.51, P < 0.001, n = 304), BD1 (r = 0.30, P < 0.001, n = 198), BD (r = 0.28, P < 0.001, n = 190), and BD (r = 0.20, P < 0.05, n
(kg)
where wt is body weight and LBM is calculated from TBK (9). The precision of the TBK measurement is ±2%. Body mass index (BMI) was calculated as wt/ht2 expressed as kg/m2.
3.8
3.6
8)
Statisticalanalysis
3.3
For each skeletal site the data from all women in the study, both pre- and postmcnopausal, were cornbined to calculate a single linear-regression equation to determine
3.1
E
Cross-sectional
yearly study
data.
rates ofbone loss. Because was to determine the extent
a primary to which
thrust rates
ofthc ofloss
current of TBK
and TBF change at different ages, a quadratic form was added to the linear equation and tested for significance. Finally, data were analyzed separately for premenopausal and postmenopausal women by separate regression analyses based on menopausal status,
and
the differences
between
rates
ofloss
-
U)
2.8 0.
2.6
>-
0 0
2.3
::
for the two groups 1.6
of women
were
tested
for
significance.
Correlations
were
cal-
culated between TBK, TBF, and the various bone mineral measurements. Women were also classified by adiposity (normal, overweight,
among ducted
and
obese)
and
bone
mineral
values
the different groups. Separate analyses for pre- and postmenopausal women.
were
were
compared also
con-
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1378/4732432 by Washington University in St. Louis user on 11 June 2018
t._____ 20
I 30
I 40
AGE
t
I
50
60
,_I.
_-._-
70
(years)
FIG 1. Total body potassium regressed against (0) and postmenopausab women (#{149}).
age for premenopausal
80
1380
ALOIA
TABLE Changes status
1 in total body
ET
AL
3.3
(TBK) with age by menopausal
potassium
3.1
.
S
‘I)
Age
TBK
b*
8)
rt
Fdiff
S
0
6
mmol
V
mmoltl’
2.8 .
E
S S
Overall (n
=
304)
2167
±
279
-5.6
± 8.8
2085
± 281
-0.2
-0.005
± 6.4
2131
±
261
-8.4
-0.211
51.1
±
40.5 56.6
lO.8f
3.84*
U) U) U)
-0.221
Premenopausal
S
0
= 108)
(0
2.6
a. 2.3
Postmenopausal (n = 96)
0
2.1 S
*
Slope.
0
t Correlation
t
regression
of the
against
1.8
age. 1.5
§P
6 y postsignificant
3.3 S
S
3.1
U)
U) 8) 0
E
S S
E
S
S
S
S.
55 #{149}5
(I) U) U)
S
S
0 0.
S.
2.3
S
S
S
S.
S >.
S
V 0
S
S
2. 1 U)
U) 0
S S
.55
S
S
I 0
.
E E
S
S
S.
U) U) U) 0 Q.
a, 0
S
2.8
0
1.8
1.5
12.5
15.0
17.5
20.0
Total
22.5
Body
FIG 2. The relationship between calcium (r = 0.51, P
19, 24, 30.
24.
30.
Obese
(n
104)
=
34)
=
27
±
1.5
33
± 2.6
45 2174
±
5. 1
52
±
± 256
± 2719 0.687 ± 0.078 1.116 ± 0.172 52±9
20309
expressed
of the distal radius; BD,, bone density
compartment compart-
Overweightf
166)
=
37 ± 2098 ± 20334 ± 0.680 ± 1.087 ± 50±9
SD. BMI, body
±
density
body
nitrogen
(BMI)
4.9
2379
± 358
19785 0.692
± 2719 ±
0.070
1.179 ± 0.169
as kg/m2;
of the lumbar
52±9 BDr,
spine.
bone
1382
ALOIA
ET
AL
fat and fat-free mass at these sites. Studies using techniques with the capacity to perform measurements on a narrow field, such as magnetic-resonance imaging, may provide the answer to this
compared
question
potassium
in the
future.
Osteoporosis
obese
is believed
women.
ofobesity
Several
to bone
density
of the
obese
density.
hip
Lid
body
Obesity
weight
increased
et al (19)
found
but
the
women
(n
in this study
as determined
Life Insurance
(20).
of the
not =
as
obese
spine,
than
the bone
2 1 black
1983 tables
The
lumbar
in lean
in
the relationship radius,
was defined
by the
Company
density
common
examined
spine,
and
premenopausal
women).
to be more
investigators
mineral
is higher
ofthe
in
Metropolitan
white
women
trochanter,
and
had an
by
that
obesity
producing
DiSimone pausal
Again, and
degree Ribot
increase
bone
mechanical
et al (2) later
women.
measurements the
may
increased
reported
similar
correlations weight
of adiposity
(cg,
et al (2 1) studied
were
but
formation,
strain
no
on
findings found
attempt
was
by correlating obesity
and
skeleton.
in postmeno-
with
bone made
with
mineral to assess
BMI).
its influence
in peri-
and
postmenopausal women. Obesity in their study was defined as a weight in excess of> 10% as calculated by Lorenty’s equation. Bone density of the spine was measured by dual-photon absorptiometry. They found a higher bone density in postmenopausal obese women (7.7%) but not in perimenopausal women. In addition, they noted a higher alkaline phosphatase and lower osteocalcin
concentrations.
difference
Interestingly,
in estradiol
concentrations
they
did
between
not
obese
find and
any non-
obese postmenopausal women. In another study Bevier et al (22) measured fat mass in women aged > 60 y by using bioelectrical impedence and skinfoldthickness
measurements.
Bone
mineral
density
of the
lumbar
spine and midradius were measured using dual- and single-photon absorptiometry, respectively. Aerobic capacity and muscle strength were also determined. LBM was calculated by subtracting fat mass from body weight. Weight, fat mass, and LBM did not correlate with radius density. However, spinal density did correlate with fat mass and LBM as determined by either technique.
These
authors
also
observed
a clear
correlation
between
findings
are discordant
with
Pocock
et al (23)
who
found
a significant correlation between BMI and bone density of the radius, femur, and spine in 78 Australian women. Because the BMI values for these women were not reported, it is not known if this
whether increases
could
study,
to the
difference
from
our
findings
bone neither
that loss, BMI
if adiposity it must nor
plays
at best TBF
was
a protective
be a minor
role.
positively
related
role
in invo-
In the present to the
lower
The
values
assumes
has a fixed
ignored
do other
methods
the other age. The
measures measurement
fat is anhydrous However,
The calculation when muscle with
age,
result
present
gives
values
that
because it appears of body fat by
and that fat-free
study,
is also
TBK
body
hydration
elevated
not
gives Thus,
mass
ofthe
fat-
mineral
problems.
value
as muscle
mass
of fat-cell
However,
to bone
without
a higher
calculation
were constant. of TBF
with yields
to 0.73. In addition, as water, which has of fat from body water. The use
is reduced.
a falsely
ifweight
TBN
varies from 0.67 12-15% of weight
of fat from mass
and
the actual
in the calculation
as in the
TBK,
and measurement
with with
that
group
methods:
measurement,
than
hydration.
Brookhaven
different
skinfold-thickness
free body compartment adipose tissue contains been
The
by
when values
from
mass
we examined
in younger
fat
declines
would the
women,
we still failed to observe a significant relationship. It is likely that the use of more sophisticated methods for the measurement offat (such as the measurement oftotal body carbon, along with TBK, TBN, and total body water) will confirm our hypothesis that it is the higher muscle mass or simply increased body weight that may result in a slightly higher bone mass in obesity. In the current study there was no statistically significant difference by analyses of variance in bone mineral measurements when women were classified by BMI (Table 3). This allows rcasonabbe confidence that in the average population, adiposity is not a major determinant of bone mass. However, it is possible that women who are obese (as opposed to overweight) should be considered have compared
as a separate group. Indeed, most previous studies lean women with obese women. The small
number of obese patients in our study may have resulted in a lack ofability to detect differences that are statistically significant. Moreover, there seems to be a trend for higher bone mineral values, especially in the spine in the obese women. (There was a positive correlation of BMI with BD in the obese group). The lower value for TBCa in the obese patients may be due to technical error in the moderation of neutrons by excess fat and we believe that the current Brookhaven technique for TBCa must be modified to accurately measure TBCa in obese patients.
In
summary,
analysis ofTBK
of cross-sectional in white
women
in white
women
except
longitudinal that
there
is an
with menopause. Body or regional bone mineral
accelerated loss ofmuscbe mass associated fat does not appear to be related to total measurements
and suggests
for a relationship
between
weight and BD5. On the other hand, TBK is significantly related to TBCa, BD5, BDr, and BD . Muscle mass is related to bone mineral concentrations and is increased in obesity. It is likely that adiposity influences bone density ofthe spine simply body
by the
effects
of increased
weight
bearing.
El
or
there are population differences. The fact that adiposity after menopause whereas skeletal tissue declines beads
us to speculate butional
contribute
(24).
measurements
fat mass and lean mass. When they used stepwise multiple regression, they found that only the lean mass contributed significantly to the prediction of spinal density. Thus, these investigators called attention to the fact that fat mass is not a predictor of bone mass. These
much
water
of adiposity. of TBF
skinfold-thickness
relationship
perhaps
the
water,
body
measure
measurement
of TBK,
femoral
neck of 6%, 19%, and 9%, respectively. Height and BMI were not given for these women, but the weight of the obese group was 34% higher than that of the nonobese group. These investigators also found that serum osteocalcin is higher in obesity, suggesting
is a gross
are not consonant to be inconsistent
and 2 1 white 30% above ideal
>
BMI
bone
mineral measurements except for a relationship between BMI and BD5 . The correlation observed was less than that between BD and weight and BD5 and TBK.
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1378/4732432 by Washington University in St. Louis user on 11 June 2018
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MENOPAUSE,
BONE,
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of menopause
John
M McGowan,
F Aloia,
Denise
ABSTRACT body
Cross-sectional
composition
determine of body
with
the relationship fat to bone mass.
curvilinear
component
ligible
rates
of loss
ments
also
indicated
Ashok
and
age were
N Vaswani,
longitudinal
examined
changes
in
women
to
in white
to loss oftotal
body
menopause.
a relationship
potassium
a
neg-
measure-
the
proximity
KEY WORDS mass,
Menopause,
bone
mass,
bone
composition,
body
density,
body
cell
aging,
mass,
mus-
adiposity
Changes in body composition with aging have been associated with increased morbidity and mortality, perhaps best exemplified loss
of skeletal
mass,
which
predisposes
to osteoporotic
mass and skeletal mass decline with increasing age whereas there is a tendency towards an increase in fat mass (1). A variety of hypotheses have been put forward concerning the interrelationships between the various body compartments. Skeletal mass and muscle mass are believed to decline with aging as a result of reduced mechanical stress from an increasingly sedentary lifestyle whereas fat mass increases as a result ofthe reduced energy expenditure. It is widely believed that a reduction in muscle mass leads to reduced skeletal mass. Adiposity has also been postulated to be related to skeletal mass (with an increased fat-cell mass protecting fractures.
Cross-sectional
against
osteoporosis)
vation
reported
a variety
analysis
suggest
that
muscle
(2).
We previously by using
studies
on aging changes
of methods
in body in vivo
composition neutron-acti-
Involutional changes in skeletal because there is an increased rate of loss of skeletal mass associated with menopause (1). Although gonadal-hormone deficiency might be expected to result in a loss of fat-free tissue as well as skeletal tissue, cross-sectional studies suggested that a linear model adequately describes the decline in fat-free mass with aging (4). Because we have collected extensive cross-sectional and longitudinal cell
data mass)
pathogenesis amine
these
acceleration
1378
and
including
on total in white
whole-body counting (3-10). mass differ in women and men
body women
and prevention to answer
data
ofloss
ofTBK
potassium
(TBK,
a measure
of body
of an ongoing study of the of osteoporosis, we decided to cxthe following questions: Is there an as part
associated
with
estrogen
withdrawal
Am J C/in Nutr
Stanton
H Cohn relationship
ofTBK
and
total
body
Subjects
l991;53:l378-83.
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1378/4732432 by Washington University in St. Louis user on 11 June 2018
and methods
Subjects
Infroduction
by the
and
at menopause? What is the fat (TBF) to bone mass?
to
menopause and the rate of loss of potassium. Total body potassium was significantly related to total body calcium and bone density of the spine, radius, and femoral neck. Total body fat was not related to any of these measurements. We found no evidence that adiposity plays a major role in protecting against boneloss. AmJClinNutr l99l;53:l378-83.
dc
Ross,
mass13
and for
with
Longitudinal between
and muscle
Patrick
cell mass to menopause was statistical evidence
ofbody There
before
to skeletal
Bone
mineral
made
on
and
healthy
recruited
from
history
TBK
with
spine
chronic
illness, bone
press.
No
or any
disease.
to exclude
the presence of diuretic
disease.
Menstrual
was normal
for
12 mo
in women
of an
hormone
(>
aged
50 U/L).
45 y and
>
appropriate
level
A history
mass.
Each
subject
had
count, blood chemistry phosphorus, potassium, fasting
and
glucose,
free
who
and
No subject
and postmeno-
was
confirmed
was an exclu-
ofprolonged medication values
immobilization thought to affect for complete
measurements (including alkaline phosphatase, urea
thyroxine,
serum
by the
follicle-stimulating
ofoophorectomy
normal
had
lumbar
therapy at any of menstruation
of serum
sion factor. No subject had a history or was an athlete. No subject took
a is
or gastrointestinal
women did not take estrogen-replacement Menopause was defined by the absence
presence
y,
had that
deformity.
pausal time.
bone
subject
subject
hypertension,
history
20-80
abnormality
Each
ofvertebral use,
were
aged
also had an x ray of the thoracic
a history
or renal
volunteers, in the
metabolic
measured
measurements
Caucasian
announcements
of fractures,
associated
had
total-body-potassium
female
protein
blood
calcium, nitrogen,
electrophoresis),
urinalysis.
Excess body weight was not an exclusion charStanding height was measured with a wall stadiometer. written consent was obtained from each subject. The
acteristic.
Informed procedures board
followed
were
approved
of Winthrop-University
by the
institutional
review
Hospital.
The data reported in this paper include both cross-sectional and longitudinal observations. Cross-sectional data were available for total body calcium (TBCa; n = 304), TBK (n = 304), bone mineral density of the radius (BD1; n = 288), and bone mineral
(n for
=
density 93).
For
of the TBK
18 1 women.
from
1
2 to
From
1 1 with
and
The
lumbar
number
a mean
the Department
spine
TBCa,
(BD1;
longitudinal
of annual of 4.46
of Medicine,
n
=
198)
data
were
measurements
± 2.0 1 (SD).
The
Winthrop-University
and
femur
available
varied length
of
Hospital,
Mineola, NY; the Brookhaven National Laboratory, Upton, NY; and the Health Science Center, SUNY, Stony Brook, NY. 2 Supported by the National Institutes of Health grant AR37520-03. 3 Address reprint requests to JF Aloia, Department of Medicine, Winthrop-University Hospital, 259 First Street, Mineola, NY I 1501. Received April 10, 1990. Accepted for publication August 8, 1990. Printed
in USA. © 1991 American
Society for Clinical
Nutrition
MENOPAUSE, time
in the
± 26.5 were
study
(SD). reported
±2-3%
1 38 mo,
with
a mean
on bone-mineral
‘
data
single-photon
WI) The
absorptiomctry
absorptiometer
at the
reproducibility
of this
femoral measurements on a Lunar Radiation
a ‘53Gd source. L2-L4. women
The region
Reproducibility without crush
on
8-cm
a
site
by
measurement
is
trochanteric region (BDJ. band 1 .5 cm wide across
were made by dual-photon DP3 (Madison, WI) with
of interest
of the fractures
for measuring
lumbar-spine is ±2-3%.
for bone density were automatically the femoral neck (BD5), Ward’s
The
BD5 was
measurement in Regions of interest
selected on femur triangle (BD), and
femoral
the neck
neck
ofthc
scans for the inter-
is defined
femur
as that
perpendicular
to the neutral axis with the lowest density. Ward’s triangle region of interest (which may not coincide exactly with the anatomic location of Ward’s triangle) is defined as a square (‘- 1.5 X 1.5 cm)
with
the
trochanteric was
lowest
changed
in the
is lateral
proximal
femur.
to the femoral
annually.
All
available
software
commercially
source
density
region
scans
were that
The
neck.
whole-body
analyzed corrects
by for the
counting
inter-
Serial
data
available
tissue and LBM for were then averaged number and spacing equations were tested The rates of loss were intercept
measurement
using
the
effects
analysis Laboratory
in an
LBM where TBK is expressed culated as the difference mass:
=
0.442
of and (14).
anthropomorphic
TBK
in g and LBM in kg (8). TBF was calbetween body weight and lean body
wt (kg)
=
LBM
-
of each
were
available
in the study, varied
among
for many
of the
although
the amount
participants.
Routine
of lin-
were used to estimate yearly rates of site and individual rates of boss of fat
each woman. These individual loss rates by weighting each proportionately to the of the observations. The linear-regression for the presence ofa quadratic component. calculated as the percent change from the
individual’s
slope
with
the
y-axis
at the
time
of the first measurement. Separate calculations were made for age groups corresponding to pre-, peri-, and postmenopausal ages. A multiple-range test was used to determine the statistical significance
between
detailed
analysis
the rates
was
done
ofloss
based
in each on actual
age group.
A more
menopausal
status,
with a separate calculation of rates for postmenopausal women who were within 3 y of menopause and 6 y postmenopausal. All analyses were done with the Statistical Package for Social Sciences (SPSS 21. SPSS Inc, Chicago).
Results
TBK was measured by counting the isotope “#{176}K in the Brookhaven whole-body counter. Lean body mass (LBM; fat-free mass, fat-free body cell mass) was calculated as follows:
TBF
data.
who participated
currently
Mean (±SD) height and weight for premenopausal women were 1.64 ± 0.06 m and 64.7 ± 12.7 kg, respectively, as compared with
by using neutron-activation at Brookhaven National
The precision of this phantom is ± 1.1%.
1379
The source
decay.
TBCa was measured
MASS
Longitudinal
women
(13).
Spinal and absorptiometry
MUSCLE
ear-regression procedures bone loss at each skeletal by
Atkinson, source.
251
AND
of 46.8
measurements
( 1 1 , 12).
measured
(Ft an
as
measurements
was
Norland using
as high
of the data
previously
Bone-mineral BDr
was
Some
BONE,
1.62 ± 0.056
m and
66 ± 9.7 kg for postmenopausal
women.
There
was no difference from zero when height was regressed against age for premenopausal women and a low correlation when either postmenopausal (r -0. 1 14, P < 0.05) or all (r = -0. 1 59, P < 0.05) women were included. There was evidence for a curvilinear component to loss of TBK (Z quadratic, = 1.95, P = 0.05). When the data were analyzed by calculating separate linear regressions against age for pre- and postmenopausal women, the relationship developed is as described in Figure 1 and Table 1. Significant relationships (which persisted after adjustment for height, age, and weight) with TBK were noted for TBCa(r = 0.51, P < 0.001, n = 304), BD1 (r = 0.30, P < 0.001, n = 198), BD (r = 0.28, P < 0.001, n = 190), and BD (r = 0.20, P < 0.05, n
(kg)
where wt is body weight and LBM is calculated from TBK (9). The precision of the TBK measurement is ±2%. Body mass index (BMI) was calculated as wt/ht2 expressed as kg/m2.
3.8
3.6
8)
Statisticalanalysis
3.3
For each skeletal site the data from all women in the study, both pre- and postmcnopausal, were cornbined to calculate a single linear-regression equation to determine
3.1
E
Cross-sectional
yearly study
data.
rates ofbone loss. Because was to determine the extent
a primary to which
thrust rates
ofthc ofloss
current of TBK
and TBF change at different ages, a quadratic form was added to the linear equation and tested for significance. Finally, data were analyzed separately for premenopausal and postmenopausal women by separate regression analyses based on menopausal status,
and
the differences
between
rates
ofloss
-
U)
2.8 0.
2.6
>-
0 0
2.3
::
for the two groups 1.6
of women
were
tested
for
significance.
Correlations
were
cal-
culated between TBK, TBF, and the various bone mineral measurements. Women were also classified by adiposity (normal, overweight,
among ducted
and
obese)
and
bone
mineral
values
the different groups. Separate analyses for pre- and postmenopausal women.
were
were
compared also
con-
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1378/4732432 by Washington University in St. Louis user on 11 June 2018
t._____ 20
I 30
I 40
AGE
t
I
50
60
,_I.
_-._-
70
(years)
FIG 1. Total body potassium regressed against (0) and postmenopausab women (#{149}).
age for premenopausal
80
1380
ALOIA
TABLE Changes status
1 in total body
ET
AL
3.3
(TBK) with age by menopausal
potassium
3.1
.
S
‘I)
Age
TBK
b*
8)
rt
Fdiff
S
0
6
mmol
V
mmoltl’
2.8 .
E
S S
Overall (n
=
304)
2167
±
279
-5.6
± 8.8
2085
± 281
-0.2
-0.005
± 6.4
2131
±
261
-8.4
-0.211
51.1
±
40.5 56.6
lO.8f
3.84*
U) U) U)
-0.221
Premenopausal
S
0
= 108)
(0
2.6
a. 2.3
Postmenopausal (n = 96)
0
2.1 S
*
Slope.
0
t Correlation
t
regression
of the
against
1.8
age. 1.5
§P
6 y postsignificant
3.3 S
S
3.1
U)
U) 8) 0
E
S S
E
S
S
S
S.
55 #{149}5
(I) U) U)
S
S
0 0.
S.
2.3
S
S
S
S.
S >.
S
V 0
S
S
2. 1 U)
U) 0
S S
.55
S
S
I 0
.
E E
S
S
S.
U) U) U) 0 Q.
a, 0
S
2.8
0
1.8
1.5
12.5
15.0
17.5
20.0
Total
22.5
Body
FIG 2. The relationship between calcium (r = 0.51, P
19, 24, 30.
24.
30.
Obese
(n
104)
=
34)
=
27
±
1.5
33
± 2.6
45 2174
±
5. 1
52
±
± 256
± 2719 0.687 ± 0.078 1.116 ± 0.172 52±9
20309
expressed
of the distal radius; BD,, bone density
compartment compart-
Overweightf
166)
=
37 ± 2098 ± 20334 ± 0.680 ± 1.087 ± 50±9
SD. BMI, body
±
density
body
nitrogen
(BMI)
4.9
2379
± 358
19785 0.692
± 2719 ±
0.070
1.179 ± 0.169
as kg/m2;
of the lumbar
52±9 BDr,
spine.
bone
1382
ALOIA
ET
AL
fat and fat-free mass at these sites. Studies using techniques with the capacity to perform measurements on a narrow field, such as magnetic-resonance imaging, may provide the answer to this
compared
question
potassium
in the
future.
Osteoporosis
obese
is believed
women.
ofobesity
Several
to bone
density
of the
obese
density.
hip
Lid
body
Obesity
weight
increased
et al (19)
found
but
the
women
(n
in this study
as determined
Life Insurance
(20).
of the
not =
as
obese
spine,
than
the bone
2 1 black
1983 tables
The
lumbar
in lean
in
the relationship radius,
was defined
by the
Company
density
common
examined
spine,
and
premenopausal
women).
to be more
investigators
mineral
is higher
ofthe
in
Metropolitan
white
women
trochanter,
and
had an
by
that
obesity
producing
DiSimone pausal
Again, and
degree Ribot
increase
bone
mechanical
et al (2) later
women.
measurements the
may
increased
reported
similar
correlations weight
of adiposity
(cg,
et al (2 1) studied
were
but
formation,
strain
no
on
findings found
attempt
was
by correlating obesity
and
skeleton.
in postmeno-
with
bone made
with
mineral to assess
BMI).
its influence
in peri-
and
postmenopausal women. Obesity in their study was defined as a weight in excess of> 10% as calculated by Lorenty’s equation. Bone density of the spine was measured by dual-photon absorptiometry. They found a higher bone density in postmenopausal obese women (7.7%) but not in perimenopausal women. In addition, they noted a higher alkaline phosphatase and lower osteocalcin
concentrations.
difference
Interestingly,
in estradiol
concentrations
they
did
between
not
obese
find and
any non-
obese postmenopausal women. In another study Bevier et al (22) measured fat mass in women aged > 60 y by using bioelectrical impedence and skinfoldthickness
measurements.
Bone
mineral
density
of the
lumbar
spine and midradius were measured using dual- and single-photon absorptiometry, respectively. Aerobic capacity and muscle strength were also determined. LBM was calculated by subtracting fat mass from body weight. Weight, fat mass, and LBM did not correlate with radius density. However, spinal density did correlate with fat mass and LBM as determined by either technique.
These
authors
also
observed
a clear
correlation
between
findings
are discordant
with
Pocock
et al (23)
who
found
a significant correlation between BMI and bone density of the radius, femur, and spine in 78 Australian women. Because the BMI values for these women were not reported, it is not known if this
whether increases
could
study,
to the
difference
from
our
findings
bone neither
that loss, BMI
if adiposity it must nor
plays
at best TBF
was
a protective
be a minor
role.
positively
related
role
in invo-
In the present to the
lower
The
values
assumes
has a fixed
ignored
do other
methods
the other age. The
measures measurement
fat is anhydrous However,
The calculation when muscle with
age,
result
present
gives
values
that
because it appears of body fat by
and that fat-free
study,
is also
TBK
body
hydration
elevated
not
gives Thus,
mass
ofthe
fat-
mineral
problems.
value
as muscle
mass
of fat-cell
However,
to bone
without
a higher
calculation
were constant. of TBF
with yields
to 0.73. In addition, as water, which has of fat from body water. The use
is reduced.
a falsely
ifweight
TBN
varies from 0.67 12-15% of weight
of fat from mass
and
the actual
in the calculation
as in the
TBK,
and measurement
with with
that
group
methods:
measurement,
than
hydration.
Brookhaven
different
skinfold-thickness
free body compartment adipose tissue contains been
The
by
when values
from
mass
we examined
in younger
fat
declines
would the
women,
we still failed to observe a significant relationship. It is likely that the use of more sophisticated methods for the measurement offat (such as the measurement oftotal body carbon, along with TBK, TBN, and total body water) will confirm our hypothesis that it is the higher muscle mass or simply increased body weight that may result in a slightly higher bone mass in obesity. In the current study there was no statistically significant difference by analyses of variance in bone mineral measurements when women were classified by BMI (Table 3). This allows rcasonabbe confidence that in the average population, adiposity is not a major determinant of bone mass. However, it is possible that women who are obese (as opposed to overweight) should be considered have compared
as a separate group. Indeed, most previous studies lean women with obese women. The small
number of obese patients in our study may have resulted in a lack ofability to detect differences that are statistically significant. Moreover, there seems to be a trend for higher bone mineral values, especially in the spine in the obese women. (There was a positive correlation of BMI with BD in the obese group). The lower value for TBCa in the obese patients may be due to technical error in the moderation of neutrons by excess fat and we believe that the current Brookhaven technique for TBCa must be modified to accurately measure TBCa in obese patients.
In
summary,
analysis ofTBK
of cross-sectional in white
women
in white
women
except
longitudinal that
there
is an
with menopause. Body or regional bone mineral
accelerated loss ofmuscbe mass associated fat does not appear to be related to total measurements
and suggests
for a relationship
between
weight and BD5. On the other hand, TBK is significantly related to TBCa, BD5, BDr, and BD . Muscle mass is related to bone mineral concentrations and is increased in obesity. It is likely that adiposity influences bone density ofthe spine simply body
by the
effects
of increased
weight
bearing.
El
or
there are population differences. The fact that adiposity after menopause whereas skeletal tissue declines beads
us to speculate butional
contribute
(24).
measurements
fat mass and lean mass. When they used stepwise multiple regression, they found that only the lean mass contributed significantly to the prediction of spinal density. Thus, these investigators called attention to the fact that fat mass is not a predictor of bone mass. These
much
water
of adiposity. of TBF
skinfold-thickness
relationship
perhaps
the
water,
body
measure
measurement
of TBK,
femoral
neck of 6%, 19%, and 9%, respectively. Height and BMI were not given for these women, but the weight of the obese group was 34% higher than that of the nonobese group. These investigators also found that serum osteocalcin is higher in obesity, suggesting
is a gross
are not consonant to be inconsistent
and 2 1 white 30% above ideal
>
BMI
bone
mineral measurements except for a relationship between BMI and BD5 . The correlation observed was less than that between BD and weight and BD5 and TBK.
Downloaded from https://academic.oup.com/ajcn/article-abstract/53/6/1378/4732432 by Washington University in St. Louis user on 11 June 2018
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MENOPAUSE,
BONE,
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