Caffeine, moderate alcohol intake,

the hip and forearm in middle-aged

ABSTRACT

In

Graham
A Colditz,
C Willeit

Walter

1 980,

84 484

US

women

Meir

aged

J Stampfer,

34-59

Bernard

y
and

curred

time

in association

a positive
not

forearm

with

increased

After

a dose-response

relation.

consuming
4.57) for hip

25 g alcohol/d
fractures
and

fractures

potential

consumption

risk

hip

We observed

and

risk of hip but

factors
(95%

CI

forearm

with

had an RR of2.33
an RR of 1.38 (95%

fractures.
These prospective
consumption
both increase

represent

associated

arm

with

important

cause

of morbidity

Lifetime

risk

for a 50-y-old

woman

(2.8%)

is equal

due

a major

to breast

women

lected

(95% CI = 1.18CI = 1.09-1.74)

cancer

(largely

data

of death
to the

(1 5). Alcohol

from

and

1976

Health

to study
diet

intake

cortical
bone)

and cancer

between

In this report

alcohol

reflecting

the Nurses

hormones

relations

concern.
and

trabecular

since

female

health

caffeine

reflecting

followed
the

public

between

fractures

(largely

data suggest that caffeine

the risk of osteoporotic
Am J Clin Nutr 199 1;54:

women.

an

States.

risk ofdeath

the relation

nondrinkers,

are

United

due
life-

caffeine

are consumed
regularly
by the majority
ofadults
(16, 17). Thus
any effect ofeither
on the risk ofosteoporosis
or fractures
would

in the top

and

in the

fracture

1.18-7.38,

fractures

fractures

mortality

to hip

controlled

was independently
and

Compared

in middle-aged

were

for women

was 2.95

intake

trauma.

intake

of hip fracture

0.003).
Alcohol
risk of both

for forearm
and alcohol

to moderate

caffeine

risk (RR)

ofcaffeine

P, trend

mild

between

fracture.

for the relative

quintile

with

relation

Rosner,

Osteoporotic

completed
an independently
validated
dietary
questionnaire.
During
the ensuing
6 y, 593 forearm
and 65 hip fractures
oc-

of

bone)

by using
Study.

we assess

and
and

risk of forehip

fractures

prospectively
This

cohort

colhas been

the relation
between
exogenous
and was expanded
in 1980 to study

and

major

illnesses.

Methods

157-63.

The
KEY

WORDS

Women,

diet,

caffeine,

alcohol,

when

fractures,

Nurses

states,

incidence

their

responded

medical

scribed

Introduction

items

Dietary

caffeine

increased

urinary

loss

and

coffee

of caffeine

ciation

induces

was noted

of caffeine

was

ported

an increase

ever,

intake
neither

(9) reported
women
unit,

studies
in others

association

from

of tea

the
0.5

Holbrook

(18 cases)

caffeine/d
had

perwith

( I 5 cases);

significant.

Framingham

unit)

effect

et al (8) re-

in women

in men

statistically

2 units

an adverse

(6; M Hernandez-Avila,

relation

was

No asso-

Study

Kid

cup

of coffee

a relative

risk

of 1.69

et al

that
1
(95%

CI 1.49-1.92).
but

Alcohol
abuse
is strongly
the effects of moderate

olism,
studied.

osteoporosis,
In some

but

combined

we were

Am J C/in Nutr

not

to the risk
of alcohol

of fractures
(10)
on bone metab-

or fracture
risk have not been
reports,
medium
to high alcohol

associated
with an increased
14). We previously
reported
fractures

related
amounts

to examine

l99l;54:l57-63.

extensively
intake
was

risk of osteoporotic
fractures
( 1 1an increased
risk ofhip
and forearm

in women
able

consuming
these

Printed

>

1 5 g alcohol/d

fracture

sites

in USA.

1991

(13),

separately.

American

weight,

and

events.

1980

and

requesting

lifestyle
(18,

variables.

19). The

menopausal
cigarette

information

This

status,
Every

sent

to update

information

to obtain

data

on newly

diagnosed

follow-up

questionnaire

include
a 6 1-item
semiquantitative
naire; this was returned
by 98 462

is de-

included

postmenopausal

have been
the

on

study

questionnaires

smoking.

in 1976,
from
11

2 y, follow-up
on potential
major

was

food-frequency
participants.

medical

expanded

to

question-

high
how-

showing

(one

risk factors

and

elsewhere

height,
therapy,

In

cohort
was established
nurses
30-55
y ofage,

to a questionnaire

questionnaires

the influence

Study
registered

history

in detail
on

hormone

through

is limited.

whereas

Recently,

an inverse

>

balance
about

mass

(3-5)

in hip fracture
and

data
cup

on bone

1990).

consuming
one

intake

observed

communication,

calcium

2) but information

(1,

in some

sonal
caffeine

a negative

Health

12 1 700 female

Society

I From
the Channing
Laboratory,
the Department
of Medicine,
Brigham
and Womens
Hospital
and Harvard
Medical School, and the
Departments
of Epidemiology,
Biostatistics,
and Nutrition,
Harvard
School of Public Health, Boston.
2 The contents
ofthis publication
do not necessarily
reflect the views
or policies
of the US Department
of Agriculture,
nor does mention
of
trade names, commercial
products,
or organizations
imply endorsement
by the US Government.
3 Supported
by research grant CA 90356 from the National
Institutes
ofHealth
and in part by the US Department
ofAgriculture,
Agricultural
Research
Service, under contract
53 3K06-5-10.
4 Address
reprint requests
to GA Colditz,
180 Longwood
Avenue,
Boston, MA 021 15-5899.

24,

1990.

Received

July

Accepted

for publication

for Clinical

Nutrition

November

28, 1990.

157

Downloaded from ajcn.nutrition.org at UNAM Instituto de Investigaciones Biomedicas on January 26, 2015

Mauricio
Hernandez-Avila,
Frank
E Speizer,
and

and risk of fractures

women14

HERNANDEZ-AVILA

158

The semiquantitativefood-frequency
A detailed
ofits

description

reproducibility

questionnaire

ofthe
and

questionnaire

validity

were

agnosis

published

elsewhere

(19-

we identified
a list of 6 1 foods and beverages
[incoffee (not decaffeinated),
carbonated
cola beverages,

beer,

wine,

and

liquor]

that

gave

maximal

discrimination

intake of 1 8 nutrients.
For each food a commonly
portion
size was specified,
and participants
were
their average
frequency
of use over the preceding
possible

responses

or more

times

were

provided,

ranging

as 13.2

g per

ofwine

(120

a glass

intakes

from

never

to six

bottle

or can

mL),

and

were computed

of beer
15.1

(360

g for

mL),

a drink

10.8

of hard

liquor (45 mL). Caffeine

intake was estimated
from average use
over the past year for coffee, not decaffeinated
(cups; 136 mg/
cup), tea (cups; 64 mg/cup),
and cola drinks (glasses; 46 mg/
bottle or can). Following
this general approach,
we also calculated
calcium
intake from responses
to the food-frequency
questionnaire.
The validity and reproducibility
of the food-frequency
questionnaire
to assess caffeine,
alcohol,
and calcium
intake
was
evaluated
in a random
sample
of 194 members
of the cohort
living

in the

study

were

greater

Boston

instructed

area.

Participants

in weighing

and

in the

measuring

all food

and

period.
Four l-wk
diet records
were completed
at 3-mo intervals
during
the year
after the completion
ofthe food-frequency
questionnaire.
At the
end ofeither
the third or the fourth week ofrecording,
a second
dietary questionnaire,
identical
to the first, was completed.
The
beverages

that

assessment
reproducible

they

consumed

ofcaffeine,

during

alcohol,

and

a 7-d

calcium

intake

were

highly

over the l-y interval (Spearman

r = 0.90 for alcohol,
0.80 for caffeine,
and 0.56 for calcium).
Individual
beverages
were also highly correlated
with measurements
made during the
4-wk of diet recording
(Spearman
r = 0.78 for coffee, 0.93 for
tea, 0.84 for cola drink, 0.94 for beer, 0.90 for wine, and 0.84
for liquor)
(24). The Pearson
correlations
for the nutrients
of
interest
in this study were small; for intake of energy-adjusted
nutrients
in 1980, r = 0.06 for caffeine
and alcohol,
0.03 for
caffeine and calcium,
and -0. 13 for alcohol and calcium.
Hence,
there was likely to be little or no influence
of the effect of one
of these nutrients
on the others.
Nondietary

exposure

Weight

and

height

variables
were

reported

on the

1976

posity.

Menopausal

status

were

updated

Population

for

analysis

Four

percent

food-frequency
items were

plausibly

left

and

every

current

use

blank,

of postmenopausal

2 y.

and

2.7%

were

high or low total

food

scores.

returned
because

excluded

Women

the

because

reporting

nonmelanoma

skin

1980

10 food
of im-

a di-

cancer),

cor-

offractures

The 1982, 1984, and 1986 follow-up

questionnaires
inquired
about the occurrence
of hip or forearm
fractures.
Women
were
asked for the date of occurrence
and a description
of the cucumstance
in which the injury occurred.
Women
who reported
a forearm
or hip fracture
but did not provide
the additional
information
on circumstances
were mailed
a supplementary
questionnaire

inquiring

about

these

details.

The validity of self-reported

fractures
was documented
elsewhere (25). Briefly, we sought permission
to review medical
records among a random
sample of 50 women who reported
fractures on the 1982 questionnaire.
Forty-three
women
responded
and confirmed
their previous
self-report
and 33 gave permission
to review medical
records,
which confirmed
the self-reported
diagnosis
in all cases.
For this analysis we defined osteoporotic
fractures
as fractures
of the proximal
femur (hip fractures)
or fractures
of the distal
radius (Colles fractures)
that occurred
in association
with lowimpact
trauma,
predominantly
about the house, during
recreational
activities,
or after falls while on the level. Such trauma
would not usually be expected
to result in a fracture.
Fractures
associated
with higher-impact
trauma
were excluded
from the
(mainly

or recreational
cycling).
These

those

associated

with

motor

vehicle

accidents

activities
such as skiing, roller skating,
and bicriteria were developed
and applied
before any

analysis
of the data. For the fractured
wrists the most common
causes were slip, trip, or stumble
on a flat surface,
29.4%; slip

on ice, 22.0%; slip or trip on a slippery or wet surface,

10.6%;
and fall from standing
on a chair,
9.3%. The most frequent
causes
oflow-trauma
hip fractures
included
in the analysis were
slip, trip, or stumble
on a flat surface,
22 (32.4%);
slip or
trip on a slippery
or wet surface,
14 (20.6%);
slip on ice, 9
( 1 3.2%); fall from a standing
position,
7 ( 10.3%);
stress
fracture, 5 (7.4%); and fall down two steps or more,
5 (7.4%).
Analysis

The primary analysis was based on incidence

rates with personmonths
of follow-up
used as the denominator.
For each participant, person-months
were allocated
according
to the 1980 cxposure variables
and for nondietary
variables
they were updated
according
to information
on subsequent
follow-up
questionnaires. For women
reporting
a fracture
or who died, follow-up
terminated
with the fracture
or death. Women
who reported
a

tionnaire

were

excluded

from

subsequent

skin

cancer),

cor-

1982 or 1984 quesfollow-up.

Thus

the

population
was free from major illness that would likely modify
risk of fracture
or diet. If no questionnaire
was returned
for a
follow-up
cycle, the most recently recorded
covariate
data were
used for the subsequent
follow-up
interval.
Person-time

of the 98 462 women

who
questionnaire
were excluded

than

diagnosis
ofcancer
(other
than nonmelanoma
onary
heart disease,
or osteoporosis
on the

questionnaire

and weight was updated

every 2 y. We calculated
body
mass
index (weight divided
by height squared)
as a measure
of adiestrogens

(other

disease,

Identification

analyses

validation

of cancer
heart

for

each

covariate

was

accumulated

and

new

fractures
were allocated
to the status of each variable
at the beginning
of each follow-up
interval.
Age-specific
incidence
rates
(using 5-y age intervals)
were calculated
by dividing
the number
of fractures
by the person-time
of follow-up.
We used relative

Downloaded from ajcn.nutrition.org at UNAM Instituto de Investigaciones Biomedicas on January 26, 2015

for

Nutrient

used unit or
asked about
year. Nine

by multiplying
the frequency
of consumption
of each unit of food by
the nutrient
content
of the specified
food. Alcohol
intake was
recorded
as the average
frequency
of intake of each beverage
over the preceding
year: beer (bottles
or cans), wine (glasses),
and liquor-whiskey,
gin, etc (drinks).
The alcohol content
was
estimated

a day.

for

AL

or osteoporosis
at any time in the past or a
fracture
in the 4 y before
1980 were also excluded,
leaving a
total of 84 484 women
who were included
in the analyses.
onary

and documentation

23). Briefly,
cluding

ET

ALCOHOL,

CAFFEINE,
risk

as a measure

fractures

of association,

in women

cidence

in women

defined

as the

who

consumed

caffeine

who

consumed

<

alcoholic

beverages

never

or almost

analyses
were carried
out
and to explore the possibility
might
linear

and

risk

factors

never.

and

other

pers

Incidence/iC

in(this

stratified

risk factors
and alcohol

used the Mantel

test for
relations
between
caf-

alcohol

and

models

to adjust

and

to examine

sources

159

FRACTURES

risk

(26).

for multiple

the

of caffeine

offractures
effects

risk

of specific

and alcohol

were con-

Colles

and

65 femur)

documented

during

Results
Six hundred
caused
482

fifty-eight

by mild
347

person-years

rose sharply
in women

aged

were

of follow-up.

The

y to 19.4 per

y for Colles

fractures

for hip

incidence
1 .5 per 1000

from

35-39

person-years

Caffeine

(593

trauma

with age, increasing

aged

60-64

fractures

to moderate

fractures

1000

person-years

and from

(Fig

of fractures
person-years

quintile

who

all these

consumed

192 mg caffeine!

<

with an intake of 192-359.9

mgJd had an age-adjusted
relative risk ofhip fractures
that was 2.38 (95% CI
0.94-6.03)
and those who consumed
8 1 7 mg/d
had an age-adjusted
relative risk of2.96 (95% CI = 1.21-7.24).
The test for linear trend
d, those

relating

caffeine

intake

with

the

risk

of hip

fracture

was

of bor-

P = 0.07).
Ofthe dietary sources ofcaffeine
(coffee, tea, and cola drinks)
the only significant
predictor
ofthe risk ofhip fracture was coffee
(Table 1). When compared
with women
who almost never consumed
coffee, women
with a high consumption
(> 4 cups/d)
had a threefold
increase
in the risk ofhip fractures
(age-adjusted
relative risk 3.62; 95% CI = 1.60-8.18). We observed
a significant
trend
of increasing
risk of hip fractures
with increasing
coffee
consumption
x
2.90, P = 0.004).
Tea was not significantly
associated
with the risk of hip fractures
(x =
1.18, P = 0.24).
The consumption
ofcola drinks was not associated
with risk of
hip fractures
except for nonsignificant
elevation
among women
consuming
4 glasses/d
(relative
risk for
4 glasses/d
=
1.57;
derline

statistical

significant

(x

1.84,

95%

CI

Adjustment
menopausal
in stratified
caffeine

for body
analyses

consumption

mass

index,

use, calcium
did

not

and

menopausal
status, postintake,
and cigarette
smoking

materially
hip fractures.

alter

the relation

When

incidence

50-54

rates ofhip

between

we controlled

for

potential

risk

factors

as well

follow-up
cycle simultaneously
the relative
risks remained

largely

caffeine

associated

(U)

55-59
and forearm

60-64
(0) fractures

consumption

were

as alcohol

intake,

in a proportional-hazards

unchanged.
with

age,

All categories
an increased

and

model,
risk

of
of

hip fractures
compared
with women
who consumed
< 1 92 mg
caffeine/d
(Table
1). The multivariate-adjusted
relative risk for
women
who consumed
817 mg/d
was 2.95 (95% CI 1.187.38).
The test for linear
trend
was significant
(X = 2.97,
P
= 0.003).

In a second
simultaneously

model we included
coffee, tea, and cola drinks
and observed
similar results: coffee was significantly associated
with risk ofhip fractures,
tea had no association,
and the highest levels of intake of cola drinks were related to a
nonsignificant
elevation
in risk (Table
I).
We observed
no association
between
caffeine
intake and the
risk offorearm
fracture (Table 1). Similar null associations
were
observed
when we examined
separately
coffee, tea, or cola drinks.
For all categories,
the age-adjusted
and multivariate-adjusted
relative risks were close to the null value of 1.0.
Akohol

intake

We observed
an increase
in the risk of both hip and forearm
fractures
in women
who reported
moderate
alcohol
intake (524 g/d; Table 2). As compared
with women who did not consume
alcohol, the age-adjusted
relative risk ofhip fracture
for women
who consumed
25.0 g/d was 2.35 (95% CI
1 .02-5.4
1). After
multivariate
adjustment
for potential
confounding
variables
including
caffeine
2.33 (95% CI

icant

intake,
this relative
1 . 18-4.57).
The test

risk decreased
slightly
to
for trend
remained
signif-

P = 0.04). We also observed

positive but smaller
for forearm
fractures;
the multivariate-adjusted
relrisk was 1.38 (95% CI = 1.09-1.74)
for women
who con-

(X

2.07,

associations

ative

0.49-4.98).
hormone

FIG 1. Age-specific
in 84 484 US women.

45-49

1000

1).

intake

in the lowest

40-44

in women

0. 1 to 2.5 per

Of the participants
75% were coffee drinkers
and 68% were
tea drinkers;
44.8% ofwomen
reported
drinking
carbonated
cola
beverages
at least once per month.
The median
reported
daily
intake
for coffee drinkers was 2-3 cups/d and among tea drinkers
was 5-6 cups/wk.
Caffeine
consumption
in this population
ranged from a minimum
intake ofO mg/d to a maximum
intake
of 1439 mg/d; median
intake was 404 mg/d.
We observed
a strong positive
association
between
caffeine
consumption
and the risk of hip fractures.
Compared
with
women

35-39

sumed

>

25 g/d.

The

test

for a trend

relating

alcohol

intake

to

risk offorearm
fracture was slightly reduced
(x = 1 .73, P = 0.08).
We next examined
the separate
effects of alcohol
from beer,
wine, and liquor. We observed
a significant
trend relating beer

Downloaded from ajcn.nutrition.org at UNAM Instituto de Investigaciones Biomedicas on January 26, 2015

beverages
while
trolled for (27).

OF

of alcohol
drinking

Additional

hazards

simultaneously

caffeine/d

to control
for potential
that the effect ofcaffeine

offractures

We used proportional

mg

RISK

of

by the

For analyses
who reported

be modified
by these factors.
We
trend to examine
the dose-response

feine

incidence

divided

I 92

level defines the lowest quintile ofintake).

intake, the reference
group was women

AND

160

HERNANDEZ-AVILA

TABLE

Relative

risk of hip and forearm

fractures

according

to intake

of caffeine,

ET
coffee,

AL

cola drinks,

tea, and alcohol

in a cohort

Hip fractures

Variable

years

Caffeine (mg/d)
0- 19 1.9
192-359.9

94 778
97 415

360-499.9
500-816.9

94 002
99 037

8l7

97 1 15

fractures

Forearm

Relative risk
Observed
cases

Person-

of 88 484 US women

CI)

(95%

Relative

risk (95% CI)

Observed
Age adjusted

6
14
15
13
17

Testfortrend

Multivariatet

Reference
2.30 (0.89-5.95)
2.22 (1.15-5.67)
0.80 (0.68-4.72)
2.95 (1.18-7.38)

x= l.84,P=0.07

x=2.97,P=0.003

Reference
0.57 (0.08-4.25)
2.65 (1.08-6.53)
1.87 (0.80-4.36)
3.62(1.60-8.18)

Reference
0.58 (0.07-4.76)
2.66 (0.99-7.17)
1.77 (0.71-4.45)
3.35(1.32-8.49)

x=2.90,P=0.004

x=2.26,P=0.02

I 20
1 13
98
139
123

Age

adjusted

Multivariatet

Reference
0.94 (0.73-1.22)
0.79 (0.60-1.03)
1.08 (0.85-1.38)
1.03 (0.80-1.32)

Reference
0.93 (0.72-1.21)
0.77 (0.58-1.00)
1.05 (0.82-1.35)
1.05 (0.82-1.35)

x=0.70,P=0.48

x=

Reference
1.08 (0.74-1.57)

Reference
1.01 (0.69-1.49)

1.09 (0.82-1.43)

0.97 (0.73-1.30)

1.05 (0.83-1.31)
1.13(0.87-1.46)

0.98 (0.78-1.24)
1.10(0.85-1.44)

x=0.70,P=0.48

x0.44,P=0.66

l.26,P=0.21

Coffee(cups)
Almost
1-3/mo
5-6/wk
2-3/d

never
to 2-4/wk
to 1/d

I 11
29
64
157

385
154
573
355
80 135

4/d

7
1
12
20
19

Testfortrend

Tea

124
84
84
197

104

(cups)

never
to 2-4/wk
to l/d

Almost

1-3/mo
5-6/wk

143 158
136 902
98 700
98 716

2/d

18

Reference

Reference

184

Reference

Reference

26

1.58 (0.88-2.87)

1.38 (0.75-2.56)

0.94 (0.76-1.16)

0.97 (0.77-1.21)

12
7

0.97 (0.47-2.02)
0.60 (0.25-1.44)

0.83 (0.39-1.77)
0.71 (0.29-1.73)

160
140
104

1.1 1 (0.89-1.38)

1.13 (0.89-1.43)
1.01 (0.78-1.29)

x=-1.18,P=0.24

x=-l.23,P=0.22

Testfortrend

Cola drinks (glasses)

Almost never
1-3/mo to 2-4/wk
5-6/wk
2-3/d
4/d

269 357
68 317

to 1/d

46
5
6
5

85 980
48 600
10 091

Testfortrend

Number

of cases do not always

Adjusted

for

intake

Reference
0.60 (0.23-1.52)
0.66 (0.28-1.58)
1.53 (0.64-3.67)
1.88 (0.58-6.1
1)
x0.04,P0.97

350
82
95
54
12

= 2.51, P = 0.01) and liquor (x = 2.39, P = 0.02) but not

wine (X = -0.53
P = 0.60) to the risk of hip fracture
(Table 3).
Few women in the cohort
were heavy consumers
ofwine,
which
limited
the possibility
of examining
the relation
between
wine
and risk of fracture.
We observed
similar
results
for forearm
fractures;
however,
liquor
was the only beverage
with statistically

TABLE

Relative

risk of hip and forearm

fracture

according

to alcohol

intake

significant

data

(X = 2.24,

attenuated

after

multivariate

Reference

1.06 (0.84-1.72)
1.09 (0.87-1.37)
1.18 (0.88-1.59)
0.85 (0.48-1.51)

1.03 (0.80-1.34)
1.13 (0.83-1.54)
0.93 (0.52-1.66)

x0.79,P0.43

x0.44,P0.66

1.09 (0.86-1.38)

Relative
Variable:

Person-

alcohol

years

None
g/d
5.0-14.9
g/d
15.0-24.9
g/d
25.0 gJd
Testfortrend

0.1-4.9

Adjusted
intake,

Observed
cases

153
162
97
33

721
943
143
740
34 800

for age (seven

and caffeine

14
21
12

10
8

categories),
intake

therapy,

P = 0.03),
adjustment

calcium

an association
(see Table

intake,

and

that

was

3).

Discussion
In this study we observed
that risk of hip fracture
was significantly higher in women who consumed
greater amounts
of caf-

in a cohort

of 84 484 US women

Hip fractures

Reference

age (seven

(x

calcium

x-0.51,P=0.61

add up to 65 because of missing information

for specific beverages.
categories), Quetelet Index (five categories),
menopause
status (before, after, or uncertain),
estrogen-replacement
(five categories). Multivariate
results
for specific beverages also had other caffeinated beverages controlled for.

alcohol

Reference
0.54 (0.22-1.32)
0.57 (0.24-1.35)
0.94 (0.35-2.53)
1.57 (0.49-4.98)
x=-0.44,P=0.66

0.88 (0.69-1.12)
x-0.43,P0.66

Forearm
risk (95% CI)

fractures

Relative

risk (95% CI)

Observed

Age adjusted
Reference
1.57 (0.80-3.06)
1.41 (0.65-3.04)
3.04 (1.40-6.60)
2.35 (1.02-5.41)
x=2.49,P=0.Ol
Quetelet

(five categories).

Index

ca

Multivariate
Reference
0.94 (0.35-2.68)
1.99 (0.97-4.07)
1.15 (0.51-2.61)
2.33 (1.18-4.57)

(five categories),

171
190
123
60
49

Reference
1.12 (0.91-1.38)
1.16 (0.92-1.47)
1.50 (1.12-2.01)
1.18 (0.86-1.62)

x2.l1,P0.03

x2.07,P0.04

menopause

Age adjusted

status

(before,

after, or uncertain),

Multivariate*
Reference
1.18 (0.91-1.52)
1.21 (0.94-1.54)
1.22 (0.95-1.57)
1.38 (1.09-1.74)
X
1.73,P0.08

estrogen-replacement

therapy,

Downloaded from ajcn.nutrition.org at UNAM Instituto de Investigaciones Biomedicas on January 26, 2015

Reference
2.38 (0.94-6.03)
2.42 (0.97-6.03)
2.00 (0.77-5.19)
2.96 (1.21-7.24)

cases

CAFFEINE,
TABLE

Relative

risk of hip and forearm

fractures

ALCOHOL,

according

to beer,

wine,

AND

RISK

and liquor

intake

OF

161

FRACTURES

in a cohort

of 84 484 US women
Forearm

Hip fractures
Relative

Relative

risk (95% CI)*

risk (95% CI)*

Observed

Observed

Variable

fractures

cases

Age adjusted

Multivariate

cases

Age adjusted

Multivariate

Beer (drinks)

Almost

never

1-3/mo
5-6/wk
2-3/d

to 2-4/wk
to l/d

43

4/d

6
7
9

Reference

Reference

1.26 (0.54-2.94)
1.66 (0.76-3.62)
4.13 (2.12-8.03)

1.45 (0.60-3.51)
1.68 (0.69-4.08)
4.20 (1.87-9.43)

48
52
27
14

x=2.51,P=0.01

x=2.42,P=0.02

Reference

Reference

0.93
1.10
1.16
1.40

0.83
0.99
1.06
1.30
X

(0.69-1.25)
(0.83-1.47)
(0.79-1.71)
(0.82-2.38)
l.31,P=0.l9

(0.60-1.14)
(0.72-1.30)
(0.70-1.59)
(0.72-2.36)
0.80,P=0.42

Wine (drinks)
Almost

never

26

Reference

Reference

238

Reference

Reference

1-3/mo
5-6/wk
2-3/d

to 2-4/wk
to l/d

21
14
4

1.65 (0.94-2.90)
1.18 (0.62-2.25)
0.62 (0.22-1.76)

1.83 (0.86-3.89)
1.15 (0.50-2.64)
0.52 (0.16-1.70)

147
122
80
6

1.23 (1.00-1.51)
1.1 1 (0.89-1.38)
1.34 (1.04-1.72)
0.99 (0.44-2.21)
X
1.91,P0.06

1.27
1.09
1.30
0.74
X

4/d

Testfortrend
Liquor (drinks)

x=-0.53,P=0.60

x-0.04,P=0.97

(0.98-1.04)
(0.83-1.45)
(0.95-1.76)
(0.30- 1.82)
1.76,P0.08

Almost

never

27

Reference

Reference

302

Reference

Reference

1-3/mo
5-6/wk
2-3/d

to 2-4/wk
to l/d

12
13
11
2

1.43
1.65
1.94
3.27

1.72
2.16
2.32
6.99

98
111
72
10

1.02
1.26
1.19
1.51
x =

0.94
1.21
1.06
1.28
x =

4/d
Test fortrend

(0.73-2.80)
(0.85-3.17)
(0.97-3.90)
(0.84-12.7)
2.39, P = 0.02

(0.71-4.17)
(0.91-5.1
1)
(0.97-5.55)
(1.55-31.60)
2.41, P = 0.02

S Adjusted
for age (seven categories), Quetelet Index (five categories), menopause
calcium
intake, and caffeine intake (five categories), and other alcohol-containing

consuming

higher

The
sibility

(before,

after,

Reference

or uncertain),

category

(0.69-1.29)
(0.89-1.64)
(0.76-1.47)
(0.60-2.71)
1.56, P = 0.12

estrogen-replacement

for multivariate

therapy,

analyses

is women

no alcohol.

feine compared
with those women
who drank little or none.
This association
was most evident
for coffee consumption,
the
major source of caffeine
intake
in this population.
Moderate
alcohol
intake was associated
with increased
risk of both hip
and forearm
fractures.
The strong association
observed
for coffee
consumption
but not for tea is possibly
explained
by the less
frequent

status

beverages.

(0.81-1.28)
(1.01-1.56)
(0.92-1.53)
(0.81-2.82)
2.24, P= 0.03

consumption

fluoride

of tea,

its lower

caffeine

content,

and

its

content.

prospective
design of this study greatly reduces the posof bias due to reporting
dietary or other risk factors for
fractures.
In a validation
study of a sample of Boston-area
participants,
caffeine,
alcohol,
and the individual
beverages
were
reported
with a high degree of validity.
The positive
association
between
alcohol intake and breast cancer in this cohort (28) and
the protective
association
with coronary
heart disease
(29), which
agree with findings
in other studies,
also lend support
to the
accuracy of self-report,
because
inaccurate
self-reporting
would
tend to obscure
associations
with all end points.
A spurious
association
between
alcohol or caffeine intake and
fracture
risk could arise ifwomen
who consumed
these beverages
and sustained
fractures
were more likely to respond
to followup questionnaires
or more likely to report fractures
if they had
occurred.
However,
this is unlikely
because
the response
rates
were almost identical
across levels ofalcohol
and caffeine intake.
Forexample,
90.3% ofnondrinkers
responded
in 1986 and 89.8%
of women
drinking
25 g alcohol/d
responded.
For caffeine
intake the response
was 90.2% for women
in the lowest quintile

and 90.3% for women in the highest quintile.

A positive
could also arise ifwomen
who drank coffee or alcohol
were at a higher risk ofsustaining
accidents,
that is, ifthey were
more active or engaged
in more high-risk
activities
during the
follow-up
period. However,
such an association
for caffeine seems
unlikely.
Considerable
evidence
supports
a biological
mechanism
for
the effect of caffeine on bone density.
Caffeine
has a calciuretic
effect in some studies
(30-32),
and high urinary
excretion
of
calcium
could promote
a negative
calcium
balance.
A randomized trial of 16 women
showed
a 4% decrease
in net calcium
balance
that failed to attain statistical
significance
(33). However,
even such a modest
shift in calcium
balance,
if sustained
over
a prolonged
period, could produce
a biologically
significant
calofintake

association

cium
depletion.
inverse
association

Heaney
and Reeker
between
calcium

(1)

observed

a significant

balance and caffeine intake

in healthy premenopausal
women. The relation between
caffeine
intake and bone density
has been evaluated
in several epidemiologic
studies.
Daniell (34) reported
a high caffeine intake in
osteoporotic
women
as compared
with age-matched
control
subjects.
Yano et al (6) reported
an inverse correlation
between
caffeine intake and bone density. Kid et al (9) reported
that men
and women
consuming
> 2 units
caffeine/d
were at increased
risk of hip fractures
compared
with those consuming
< 2 units/
d. However,
other investigators
have failed to find a significant
inverse
association
between
caffeine (or coffee) intake and osteoporosis
(3-5). A recent
14-y follow-up
study that included

Downloaded from ajcn.nutrition.org at UNAM Instituto de Investigaciones Biomedicas on January 26, 2015

Testfortrend

452

HERNANDEZ-AVILA

162
33 hip

fractures

reported

with

associated
ciation

only

caffeine

for males

a borderline

consumption

(8). These

data

increase

in the

for females

relating

and

caffeine

risk

no asso-

to bone

The

relation

evaluated

between

alcohol

in case-control

and

(1 1) reported

that

alcoholism

an

risk

of fractures

increased

and

cohort

fractures

with

studies.

increasing

number

et al

associated

with

women.

trend

of shots

in the

of liquor

Parisk

per

of

8 shots/wk
had a relative
who never drink
liquor.
In

Women

aged

31-95

y drinking

210

mL

alcohol/wk

had a relative risk of 1.54, although

this did not attain statistical
significance.
However,
when analyses were restricted
to ages 3165 y, a strong association
was observed
between
alcohol
intake
and

the

risk

of hip

The association
explained

cohol.

fractures.

between

alcohol

by a combination

The increased

in part,

intake

of acute

prevalence

to intoxication,

and fractures

and

chronic

offractures

which

may be

effects

in alcoholics

is associated

with

an

of al-

is due,
increased

risk of trauma.
A marked
reduction
in bone remodeling
mdcpendent
of hormonal
factors suggests that the consumption
of
alcohol
may also directly
relate to the development
of osteoporosis

(40).

Alcohol
in this

intake

is inversely

population

sociated with bone density

(42).

Therefore,

body

obesity

alcohol

between

mass

decreased,

(41)

only

the

with

and

cause

slightly.

risk ofhip fractures

positive
association

a spurious

risk. Indeed,

relation

between

body mass index

is positively
as-

obesity

and with a reduced

may

and fracture

index,
but

correlated

of women

after

alcohol

Adjustment

we adjusted
and

for other

for

fracture

risk

potential

risk

factors, including
menopause,
estrogen-replacement
therapy, and
calcium
intake did not appreciably
alter the relation
between
alcohol and risk of fracture.
From these prospective
data we conclude
that caffeine
and
alcohol
may both contribute
to the etiology
of osteoporotic
fractures
of the hip in middle-aged
women.
Moderate
alcohol
intake was also associated
with increased
risk of forearm
fractures, although
this association
was not evident
for caffeine intake.
a
We thank the registered

nurses who made this study possible.

also grateful to Gary Chase, Susan Wu, Steven

Cynthia
Morrow,
Lori Egan, Marion McPhee,
assisted in the research.

Stuart,

Karen

We are
Corsano,

and Chris Pappas,

who

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