Download Association Between Low Bone Density and Stroke

940
Association Between Low Bone Density
and Stroke in Elderly Women
The Study of Osteoporotic Fractures
Warren S. Browner, MD, MPH; Alice R. Pressman, MS; Michael C. Nevitt, PhD;
Jane A. Cauley, DrPH; Steven R. Cummings, MD;
for the Study of Osteoporotic Fractures Research Group
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Background and Purpose: To determine whether women with low bone mineral density are at increased
risk of stroke, the present study was conducted.
Methods: We studied 4024 ambulatory women aged 65 years or older participating in the prospective
Study of Osteoporotic Fractures. Bone mineral density was measured at baseline using single photon
absorptiometry; strokes were ascertained using a computerized Medicare data base and death certificates.
Results: During a mean of 1.98 years of follow-up, 83 women suffered first strokes (five fatal). Osteopenia
was associated with an increased stroke risk Each SD decrease in bone mineral density at the calcaneus
(0.09 g/cm2) was associated with a 1.31-fold increase in stroke (95% confidence interval, 1.03-1.65),
adjusted for age, follow-up time, and several potential confounders, including diabetes, systolic blood
pressure, use of alcohol, cigarettes or postmenopausal estrogens, cognitive ability, grip strength, and
functional ability. The observed relation between bone density and stroke was strongest for intracerebral
hemorrhages and occlusions.
Conclusions: Most likely, low bone density does not cause stroke; some other process probably results in
both osteopenia and cerebrovascular disease. (Stroke 1993;24:940-946)
KEY WoRDs * bone diseases, metabolic * osteoporosis * risk factors * women
W e previously reported that osteopenia (low
bone density) was associated with increased
mortality among elderly women.1 This
somewhat surprising relation was strongest for the 25
deaths due to stroke: a 74% increase in mortality per
SD (0.09 g/cm') decrease in calcaneus bone density. We
speculated that low bone density may be a marker for
another factor or factors that are related to fatal
strokes.
To confirm these findings and to determine whether
bone density is associated with incident strokes, both
fatal and nonfatal, we followed more than 4000 ambulatory women aged >65 years in the prospective Study
of Osteoporotic Fractures who had at least one Medicare claim filed between 1986 and 1989. We compared
bone density measured at baseline in women who
Received December 7, 1992; final revision received January 28,
1993; accepted March 24, 1993.
From the Department of Epidemiology and Biostatistics
(W.S.B., A.R.P., M.C.N., S.R.C.), the General Internal Medicine
Section, Department of Medicine, Veterans Affairs Medical Center (W.S.B.), and the Division of General Internal Medicine,
Department of Medicine (S.R.C.), University of California, San
Francisco; and the Department of Epidemiology, Graduate School
of Public Health, University of Pittsburgh, Pittsburgh, Pa (J.A.C.).
A complete list of the investigators in the Study of Osteoporotic
Fractures Research Group appears at the end of this article.
Correspondence to Study of Osteoporotic Fractures, 74 New
Montgomery, Suite 600, San Francisco, CA 94105 (Dr Browner).
suffered a stroke during that time with those who did
not and adjusted for potential confounding variables.
Subjects and Methods
Ambulatory women 65 years of age or older who had
not previously had bilateral hip fractures were recruited
from September 1986 to October 1988 at four clinical
centers: The Kaiser-Permanente Center for Health
Research, Portland, Oregon; The University of Minnesota in Minneapolis; the University of Maryland in
Baltimore; and the University of Pittsburgh.2 Men and
black women were excluded because of their relatively
low incidence of osteoporotic fractures. Subjects in
Portland and in Minneapolis were recruited primarily
from health maintenance organizations. Many of these
women did not file Medicare claims during follow-up,
and thus women from these two clinics were excluded.
Subjects in Baltimore (n=2424) were recruited from
holders of driver's licenses and identification cards
within Baltimore County, whereas those in the Monongahela Valley, Pennsylvania (n=2401) were recruited
from 1985 voter registration lists. A total of 4134 women
(2097 in Baltimore and 2037 in Pittsburgh) filed at least
one Medicare claim, including inpatient and outpatient
services, during the follow-up period from the time of
enrollment until December 31, 1989. Women with a
history of previous stroke (n=110), in whom 12 subsequent strokes occurred, were excluded from analysis,
leaving the cohort of 4024 women who were followed for
Browner et al Bone Density and Stroke
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a mean of 1.98 years. (There were no significant differences in bone density in the women with Medicare
claims and those without such claims during the follow-up period.)
Participants completed a questionnaire that was reviewed by an interviewer during the 3-hour baseline
examination. The questionnaire asked about use of
alcohol and cigarettes, health status compared with
other women of similar age (very poor/poor/fair versus
good/excellent), previous stroke, diabetes mellitus, hypertension (on diuretic medications or with measured
blood pressure >160/90 mm Hg), current and past use
of steroids and postmenopausal estrogens, ability to
perform six activities of daily living (with one point for
each activity that could not be performed or was
performed with difficulty), and physical activity as average number of times per week exercised. Weight,
body-mass index, and the waist-to-hip ratio were measured with standard techniques.3 Grip strength was
measured in both hands with a hand-held dynamometer; in these analyses, we used whichever side was
stronger. Hip abduction strength was measured in the
dominant leg using a hand-held isometric dynamometer. A modified version of the Mini-Mental State Examination4 with a maximum score of 26 was administered.
Bone mineral density (g/cm2) was measured at three
sites-the distal radius, the proximal radius and the
calcaneus-using single photon absorptiometry (OsteoAnalyzer, Siemens-Osteon, Wahiawa, Hawaii). Coefficients of variation at these sites were 1.5%, 2.0%,
and 1.3%, respectively. Aspirin use was not ascertained
at baseline but was measured at the second annual visit,
approximately 2 years later.
Many women in the University of Pittsburgh cohort
(n=1361) had serum cholesterol levels measured at
baseline using a Kodak DT-60 portable chemistry analyzer. Quality control standards were run with each
assay; the coefficient of variation was 1.8% for the low
standard and 1.1% for the high standard.
We used the Health Care Finance Administration's
Medicare Automated Data Retrieval System (MADRS)
to obtain medical records for our study group. We
matched our cohort to MADRS data by social security
number, sex (the same number can apply to both husband
and wife), and date of birth, and searched for hospitalizations with ICD-9-CM codes for stroke (431, 432.9, 433,
434, 436, 437, 437.1, 437.9) as one of the first five diagnoses. We also reviewed death certificates on all women
who died during follow-up. Strokes were classified as
intracerebral hemorrhage or occlusion (431 or 432.9 or
434), occlusion of precerebral arteries (433), or nonspecific cerebrovascular disease (all other categories).
For women with more than one reported claim for
stroke, the first event was used. Fatal strokes were those
that resulted in death within 30 days of the incident
event. Follow-up began on January 1 of the year of the
first Medicare claim or at the time of enrollment into
the Study of Osteoporotic Fractures, whichever came
last. Follow-up ended on December 31 of the year of the
last claim, at the time of a stroke, or at the woman's
death, whichever came first.
Proportional hazards (Cox) models were used to
determine the age-adjusted relations between predictors and incident stroke.5 Age-adjusted hazard ratios
941
(RR) with 95% confidence intervals (CI) and two-sided
P values are reported; unless otherwise specified, these
are reported per SD change in a continuous predictor
variable. We examined the effects of potential confounders by adding them to models containing bone
mineral density and age and assessing the effect on the
coefficients for bone mineral density and mortality. All
analyses were performed using SAS software (SAS Institute, Inc, Cary, NC).
Results
Participants in the study were generally healthy women
(Table 1). During a mean of 1.98 years of follow-up, 83
women suffered fatal (5) or nonfatal (78) strokes. Of
these, 29 women had intracerebral hemorrhage or occlusion, 26 had occlusion of precerebral arteries, and 28 had
nonspecific cerebrovascular disease.
Age-adjusted associations are reported in Table 1.
Women with osteopenia were at increased risk of
stroke: Each 0.09 g/cm2 (1 SD) decrease in bone density
at the calcaneus was associated with a 30% increase in
stroke rate. Among women in the lowest quartile of
age-adjusted calcaneus bone density, 26 suffered
strokes during follow-up compared with 13 strokes
among those in the upper quartile (Figure). This relation between bone density and stroke was similar for
measurements made at the proximal radius but was not
statistically significant at the distal radius.
Higher systolic blood pressure was associated with an
increased stroke rate, as was diabetes mellitus. We
found no relation between serum cholesterol level and
stroke in the Pittsburgh cohort. There was only one
hemorrhagic stroke in the Pittsburgh cohort so we could
not look at the relation between serum cholesterol and
these events.
Women who currently drank alcohol had a 50% lower
rate of stroke. To test the possibility that women who
abstain from alcohol do so because of unmeasured
health problems that placed them at higher risk of
stroke, we compared women who reported alcohol
consumption in the past 12 months with those who were
lifelong teetotalers. In this analysis, current drinkers
remained at a substantially reduced risk (RR=0.48;
95% CI, 0.30-0.79).
Diminished cognitive function, lower grip strength,
and reduced functional status were also associated with
increased stroke risk. Women with modified Mini-Mental State Examination scores of 23 or less were more
than twice as likely to suffer incident strokes as those
with higher scores. Reduced grip strength and difficulties in performing activities of daily living were both
associated with an increased stroke rate.
The association between low bone density and stroke
remained significant in models that included these
potential confounders (Table 2). We report models that
included cognitive function, grip strength, and functional status separately because these variables measure
related attributes. The bone density-stroke association
also was not confounded by smoking, use of aspirin or
postmenopausal estrogens, weight at age 50 years, current weight, body-mass index, or hip abduction strength.
Similar multivariable results were seen when bone
density was measured at the proximal radius.
Stroke Vol 24, No 7 July 1993
942
TABLE 1. Characteristics of 4024 Women Aged 65 Years and Older From the Study of Osteoporotic Fractures
Clinics in Baltimore and Pittsburgh Who Had at Least One Medicare Report During Follow-up and Associations
With Stroke*
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Characteristic
n (%)t
Hazard ratio
95% CI
Associated with increased risk of stroke*
40 (1)
History of diabetes
4.2
1.3-13
Systolic blood pressure (mm Hg)
139+18
1.21
0.99-1.48
Mini-mental state examination score .23
722 (18)
2.15
1.35-3.43
No. of functional disabilities§
0.9+1.4
1.27
1.11-1.43
Calcaneus bone density (g/cm2)
0.41+0.09
1.31
1.03-1.65
Proximal radius bone density (g/cm2)
0.64±0.10
1.26
1.00-1.58
Associated with decreased risk of stroke*
Current use of alcohol
2710 (67)
0.50
0.32-0.76
Grip strength (kg)
22.3±4.3
0.73
0.59-0.91
No statistically significant association with stroket
History of hypertension
1347 (33)
1.23
0.79-1.91
Current cigarette smoking
426 (11)
1.56
0.84-2.89
Current use of thiazide diuretics
1047 (26)
0.88
0.54-1.45
Current use of estrogens
405 (10)
1.21
0.60-2.43
Use of aspirin
1331 (36)
1.39
0.86-2.24
Body weight (kg)
67.2+12.7
0.88
0.69-1.11
Body weight at age 50 (kg)
62.5±9.3
1.06
0.86-1.33
Body-mass index (kg/m2)
26.7±4.8
0.93
0.74-1.16
Hip strength (kg)
10.7±3.4
1.02
0.81-1.27
Serum cholesterol (mg/dL)
247+42
1.01
0.73-1.41
Distal radius bone density (g/cm2)
0.36±0.08
1.09
0.87-1.37
CI, confidence interval.
*Current users of alcohol, cigarettes, or medications are compared with current nonusers. Use of aspirin was based
on second visit data, available in 3760 women. Serum cholesterol levels were available in 1321 women in Pittsburgh
clinic.
tValues are mean+SD. Age-adjusted hazard ratios are reported per unit (yes/no) for binary variables and per one
unit increase in SD for all continuous variables, except per one unit decrease in SD for bone density measurements.
tStatistical significance set at P<.10 (two sided) in age-adjusted analysis.
§Hazard ratio reported per activity (of six) that was not performed or was performed with difficulty.
In a post hoc analysis, the relation between bone
density and stroke appeared stronger for intracerebral
hemorrhages or occlusions than for the other types of
strokes (Table 3). This relation was not changed by
lo -
c 14-
12100
S-.
86
l
U)
I
It
Quartile
llt
IV
ot Age-Adjusted BMD
Stroke rate per 1000 woman-years by age-adjusted quartile of
calcaneus bone density, from lowest (I) to highest (IV).
Numbers of women by
were 992, 1009, 1011, and
1006, respectively. Calcaneus bone density data were missing
for six women.
quartile
adjustment for diabetes, alcohol use, systolic blood
pressure, functional status, grip strength, and cognitive
function.
When we repeated our analysis for incident strokes
using the entire cohort of women (not just those with
Medicare records) from Baltimore and Pittsburgh who
were free of stroke at baseline (n=4646 with the same
83 strokes), we found nearly identical results. For
example, the age-adjusted hazard ratio (per SD of bone
density at the calcaneus) was 1.31 (95% CI, 1.03-1.65).
Discussion
These results confirm that women with low bone
density are at an increased risk of stroke. The magnitude of the increase (a relative risk of about 1.3 per SD)
is substantial (a woman with a bone density that is 1 SD
below the mean for her age is at a 70% increase in
stroke risk compared with a woman whose bone density
is 1 SD above the mean) and comparable with that
observed for the relation between systolic blood pressure and stroke in the elderly.6
However, unlike the cause-effect relation between
blood pressure and stroke, we do not believe that low
bone density causes stroke. Besides cause-effect, there
are four other explanations for any epidemiologic asso-
Browner et al Bone Density and Stroke
943
TABLE 2. Multivariable Models of Age-Adjusted Association Between Bone Density and
Incident Stroke
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Variable (unit)
Hazard ratio
Model 1
Calcaneus BMD (-0.09 g/cm2)
1.29
Systolic BP (+18 mm Hg)
1.20
Current alcohol use
0.54
Diabetes mellitus
3.6
Model 2
Calcaneus BMD (-0.09 g/cm2)
1.36
Systolic BP (+18 mm Hg)
1.21
Current alcohol use
0.58
Diabetes mellitus
3.5
Mini-mental state examination score .23
1.88
Model 3
Calcaneus BMD (-0.09 g/cm2)
1.36
Systolic BP (+18 mm Hg)
1.21
Current alcohol use
0.57
Diabetes mellitus
3.3
Functional disability (per activity)*
1.20
Model 4
Calcaneus BMD (-0.09 g/cm2)
1.31
1.22
Systolic BP (+18 mm Hg)
Current alcohol use
0.58
Diabetes mellitus
3.4
1.23
Grip strength (-4.3 kg)
BMD, bone mineral density; BP, blood pressure; CI, confidence interval.
*Per activity unable to perform or performed with difficulty.
ciation: effect-cause, effect-effect (also known as confounding), chance, and bias. An effect-cause type of
association implies that stroke causes low bone density.
This could have occurred if there were substantial
numbers of women with undetected or unreported
strokes at baseline who were at increased risk of subsequent strokes for which they were hospitalized.7 If
95% CI
P
1.03-1.62
0.97-1.49
0.35-0.84
1.1-11
.03
.1
.006
.03
1.08-1.72
0.99-1.47
0.37-0.90
1.1-11
1.16-3.04
.01
.06
.02
.03
.01
1.08-1.70
0.99-1.48
0.37-0.90
.009
.06
.02
.05
.006
1.0-10.6
1.05-1.37
1.03-1.67
1.00-1.49
0.37-0.91
1.0-10.9
0.99-1.54
.03
.05
.02
.04
.06
women with subclinical strokes had reduced their activity levels or were otherwise in frail health, they also may
have had lower bone density. We attempted to reduce
the possibility of effect-cause (as much as possible given
the inherent limitations in measuring these factors) by
adjusting for strength (hip abduction, triceps extension,
and grip), physical activity, mental status, general
TABLE 3. Age-Adjusted Associations* Between Measurements of Bone Density at Various Sites and
Type of Incident Stroket
Hazard ratio
P
Type of stroke
95% CI
Calcaneus bone density
1.83
Cerebral hemorrhage/occlusion
1.21-2.78
.004
Precerebral occlusion
1.44
0.95-2.19
.09
0.88
0.61-1.29
Nonspecific cerebrovascular disease
.52
Proximal radius bone density
Cerebral hemorrhage/occlusion
1.84
1.25-2.71
.002
Precerebral occlusion
1.52
1.02-2.26
.04
.11
0.73
0.49-1.07
Nonspecific cerebrovascular disease
Distal radius bone density
1.35
0.89-2.03
.15
Cerebral hemorrhage/occlusion
1.36
0.90-2.06
Precerebral occlusion
.15
0.74
0.51-1.09
.13
Nonspecific cerebrovascular disease
CI, confidence interval.
*As the hazard ratio per decrease of SD.
tThere were 29 women with cerebral hemorrhage or occlusion (10 in Baltimore), 26 women with
precerebral occlusion (4 in Baltimore), and 28 women with nonspecific cerebrovascular disease (15 in
Baltimore). SD of bone density was 0.09 g/cm2 at the calcaneus, 0.10 g/cm2 at the proximal radius, and
0.08 g/cm2 at the distal radius.
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Stroke Vol 24, No 7 July 1993
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health, and functional status at baseline. Adjustment for
these variables did not affect the relation between bone
density and stroke.
Another possibility is that of effect-effect, namely that
both low bone density and stroke are the effects of some
other process. Low bone density may be a marker for ill
health or other comorbidities, and these conditions may
be nonspecifically associated with an increased risk of
stroke. There are also several more specific explanations
for a link between osteopenia and cerebrovascular
disease. Recent work has found that aortic calcification
is more common among women with osteoporotic vertebral fractures.8 Diffuse atherosclerotic disease may
cause unfavorable patterns of calcitropic hormones, in
particular low levels of vitamin D and its metabolites,
high levels of parathormone, or both perhaps as a result
of decreased renal function, and thus indirectly have
detrimental effects on bone. Effects of calcitropic hormones on vascular reactivity and on the risk of myocardial infarction have been described.9-11
Both atherosclerosis and osteoporosis may result
from estrogen deficiency. Exogenous estrogens reduce
perimenopausal bone loss and prevent fractures.12
Some but not all studies have found that estrogen users
have lower rates of stroke.'2 Estrogens also could reduce the risk of thrombosis by altering clotting factors
and other vascular mediators.13 Perhaps endogenous
estrogens have similar effects.
Elevated serum levels of homocysteine seen in persons who are heterozygous for cystathionine (3-synthase
deficiency have been associated with stroke.14 Homozygotes (persons with homocystinuria) have premature
osteoporosis.15 We previously compared homocysteine
levels in 23 women randomly selected from participants
in our study whose bone density was in the highest
decile for age with 23 age-matched participants whose
bone density was in the lowest decile for age. Although
we did not find a relation between homocysteine levels
and bone density in these women,16 that does not
eliminate the possibility that hyperhomocysteinemia
may be associated with osteopenia and stroke. Importantly, this condition can be reversed with supplemental
folate.17
Several dietary factors may be responsible for the
association between bone density and stroke. Low levels
of consumption of potassium-rich foods (such as fruits)
have been associated with an increased risk of stroke.18
If such diets also contain more acid residues (ie, have
higher protein loads), they also may result in loss of
bone calcium as seen in long-standing metabolic acidoSiS.19-21 Finally, dietary ascorbic acid is essential for the
synthesis of collagen in bone matrix; decreased intake
also has been associated with cardiovascular disease.22
The only way to distinguish between effect-cause and
effect-effect as explanations for the bone density-stroke
association would be to establish a clear temporal
sequence by determining whether subclinical strokes
preceded changes in bone density. This would require
making those measurements and performing a detailed
neurologic examination, including imaging of the central nervous system, on all participants at baseline so
subclinical events could be detected. Those with normal
examinations then would be followed for the occurrence
of clinically evident strokes.
The remaining possibilities are that the association
between bone density and stroke is due to chance or bias.
Chance is an unlikely explanation, given the statistical
significance of these results and those we previously
reported for fatal strokes. Finally, most forms of bias also
seem unlikely: Bone density was measured before the
occurrence of stroke, and stroke ascertainment was done
without knowledge of a woman's bone density. We cannot
eliminate the possibility that frail women with a limited
physiologic reserve (and low bone density) were more
likely to be hospitalized if they suffered a stroke and thus
be detected by our outcome ascertainment system. This
form of detection bias, however, could not explain the
association between low bone density and fatal strokes
that we previously reported.'
The biologic plausibility of a bone density-stroke
relation is supported by the recent finding that the
stroke-prone spontaneously hypertensive rat develops
osteoporosis.23 In this study, Yamori et al noted that the
skulls of these animals seemed abnormally weak; this
qualitative impression was supported by the finding
that, when compared with control rats, bones from rats
who were stroke-prone had lower mineral content and
torsion strength. Also, several intriguing studies in cell
biology suggest links between the vascular system, blood
coagulation, and calcium metabolism. In response to
low concentrations of calcium, for example, the parathyroid gland appears to secrete parathyroid hormone
and tissue plasminogen activator in parallel.24 Osteoblasts respond to parathyroid hormone with increased
production of plasminogen activator.25-27 Pang and associates have suggested a role for so-called parathyroid
hypertensive factor in the etiology of hypertension in
both humans and animals, including the spontaneously
hypertensive rat,2829 probably by increasing calcium
uptake in smooth muscle cells. Moreover, endothelins,
which are extremely potent systemic vasoconstrictors
and whose levels are increased in persons with myocardial infarction,30 are likely to have a role in bone:
Endothelin-1 increases bone perfusion pressure31 and
affects bone resorption and collagen production in
tissue culture.32,33 Perhaps the local effects of plasminogen activators and endothelins on bone and their
systemic effects, including hypertension, atherosclerosis, and changes in blood coagulability, are associated.
There also may be links mediated through vitamin
K-dependent proteins, which are important both in
coagulation and bone formation.34
We cannot explain why a relation between bone
density and stroke was seen when bone density was
measured at the calcaneus and at the proximal radius
but not at the distal radius. One explanation, of course,
is that this represents a chance occurrence; the confidence intervals around the risk estimates do overlap.
The observation also is consistent with the heterogenous nature of bone at different sites. The associations
between bone density and fracture risk, for example,
vary by site of measurement as well as site of fracture.35
Given the small numbers of types of strokes, the post
hoc observation that bone density was a stronger predictor of strokes ascribed to intracerebral causes might
be a chance finding. Conversely, any misclassification of
stroke etiology recorded in Medicare records would
make it hard to find true associations. Thus, if this
Browner et al Bone Density and Stroke
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finding is real, the actual relation may be even stronger.
Perhaps the factor that links bone mineral density with
stroke is more closely related to the integrity of the
intracerebral vasculature than to the development of
precerebral atherosclerotic plaques.
Our results confirm those of several other studies of
risk factors for stroke in elderly women. As expected,
diabetes and an elevated systolic blood pressure were
both independent predictors of stroke.36,37 We also
found that women who drank alcohol were at a 50%
lower risk of stroke. Most women in the Study of
Osteoporotic Fractures cohort who used alcohol, however, did so in moderation: The average weekly consumption (among drinkers) was less than 1 ounce.
These results are consistent with another study that
found small amounts of alcohol consumption were
associated with a reduced risk of stroke.38 Consistent
with other findings,6,35 we found no relation between
cholesterol level and stroke. Cognitive ability,39 physical
function,40 and strength were all related to stroke risk,
perhaps because they are markers for subclinical events.
There are several limitations to this study. We enrolled only ambulatory women over the age of 65 years,
nearly all of whom were white. Thus, our results may not
apply to men, nonwhite women, or less healthy women.
We did not have any data on atrial fibrillation, valvular
heart disease, or ventricular aneurysms, although it
seems unlikely that any of these conditions would be
strongly related to bone density. Finally, because we
used Medicare records to ascertain the occurrence of
stroke, we may have misclassified some women as
having a stroke who did not, and vice versa; thus, our
estimates of the relative risks are probably biased
toward the null.
If the association between bone density and stroke is
due to an underlying common cause, this may suggest a
new field of inquiry in stroke research and prevention.
Many of the possible links between osteopenia and
cerebrovascular events, such as estrogen deficiency and
hyperhomocysteinemia, are treatable. Alternatively, low
bone density may be a consequence of subclinical
strokes in some women. In this case, the true burden of
atherosclerotic cerebrovascular disease on age-related
frailty may be greater than we currently recognize.
Acknowledgments
Supported by Public Health Service grants AG-05394, AG05407, AR-35582, AR-35583, and AR-35584.
Investigators in the Study of Osteoporotic Fractures Research Group include the following: University of California,
San Francisco (coordinating center): S. Cummings (principal
investigator), M. Nevitt (project director), C. Arnaud, D.
Black, W. Browner, C. Fox, H. Genant, S. Harvey, S. Hulley,
L. Palermo, A. Pressman, D. Seeley; University ofMaryland: R.
Sherwin (principal investigator), J. Scott, K. Fox, J. Lewis;
University of Minnesota: R. Grimm Jr. (principal investigator),
K. Ensrud (coprincipal investigator), C. Bell, E. Mitson;
University of Pittsburgh: J. Cauley (principal investigator), L.
Kuller (coprincipal investigator), L. Harper, M. Nasim; and
The Kaiser-Permanente Center for Health Research, Portland,
Oregon: T. Vogt (principal investigator), W. Vollmer, E.
Orwoll, J. Blank, B. Packer.
945
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Association between low bone density and stroke in elderly women. The study of
osteoporotic fractures.
W S Browner, A R Pressman, M C Nevitt, J A Cauley and S R Cummings
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Stroke. 1993;24:940-946
doi: 10.1161/01.STR.24.7.940
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