Error bars indicate 95% confidence intervals.
Cauley JA, Lui L, Ensrud KE, Zmuda JM, Stone KL, Hochberg MC, Cummings SR. Bone Mineral Density and the Risk of Incident Nonspinal Fractures in Black and White Women. JAMA. 2005;293(17):2102-2108. doi:10.1001/jama.293.17.2102
Author Affiliations: Department of Epidemiology,
University of Pittsburgh, Pittsburgh, Pa (Drs Cauley and Zmuda); Department
of Medicine, Univeristy of California, San Francisco (Ms Lui and Dr Stone);
VA Medical Center and Department of Medicine and Epidemiology, University
of Minnesota, Minneapolis (Dr Ensrud); Departments of Medicine, Epidemiology,
and Preventive Medicine, University of Maryland, Baltimore (Dr Hochberg);
and California Pacific Medical Center, San Francisco (Dr Cummings).
Context Black women have a lower rate of fracture than white women, but whether
bone mineral density (BMD) predicts fracture risk as well in black women as
it does in white women is not established.
Objective To examine the association between BMD and incident nonspinal fractures
in older black and white women.
Design, Setting, and Participants Prospective cohort study of baseline data collected from 1986 through
1990 (7334 white women aged 67-99 years) and from 1996 through 1998 (636 black
women aged 65-94 years) at 4 US clinical centers in the Study of Osteoporotic
Fractures; mean (SD) follow-up of 6.1 (1.5) years until October 1, 2004.
Main Outcome Measures Incident nonspinal fractures were confirmed by radiograpic report. Total
hip and femoral neck BMD and bone mineral content were measured by dual energy
Results A total of 58 black women had a combined total of 61 fractures and 1606
white women had a combined total of 1712 fractures. In age-adjusted proportional
hazard models, a 1-SD decrease in femoral neck BMD was associated with a 37%
increased risk of fracture in black women (relative risk [RR], 1.37; 95% confidence
interval [CI], 1.08-1.74) and a 49% increase in fracture in white women (RR,
1.49; 95% CI, 1.40-1.58). Adjustment for body weight and other risk factors
for fracture weakened the association between BMD and fracture, especially
among black women (multivariable adjusted RR per 1-SD decrease in femoral
neck BMD for black vs white women: RR, 1.20 [95% CI, 0.93-1.55] vs RR, 1.42
[95% CI, 1.32-1.52]). The absolute incidence of fracture across the pooled
BMD distribution was 30% to 40% lower among black women at every BMD tertile.
The lower risk of fracture among black compared with white women was independent
of BMD and other risk factors (RR, 0.48; 95% CI, 0.36-0.64).
Conclusions Decreased total hip and femoral neck BMD is associated with an increased
risk of fracture in both older black and white women, but this relationship
was largely explained by other risk factors in black women. Black women have
a lower fracture risk than white women at every level of BMD. Race-specific
normative databases may be appropriate for the densitometric definition of
The recently released US surgeon general’s report on bone health
and osteoporosis noted that 1 in 2 individuals older than 50 years will be
at risk for fractures from osteoporosis.1 Although
fracture rates are lower among black women,2 the
report emphasizes that osteoporosis is a real risk for any aging man or woman.
The identification of individuals at risk for osteoporotic fracture is essential
for prevention. Low bone mineral density (BMD) has been shown to be an important
predictor of increased fracture risk.3- 6 However,
these data are primarily based on studies of North American and European white
women. Two case-control studies of fracture in black women reported a higher
risk of fracture with low body mass index (BMI), low physical activity, and
poor neuromuscular function,7,8 but
neither of these studies measured BMD. Low heel, forearm, or finger BMD was
associated with an increased 1-year risk of fracture in black women.9 It is not known whether BMD in the axial skeleton,
which is the criterion standard for assessing risk of osteoporosis, is related
to fractures in older black women.
In the current study, we examined the relationship between BMD measured
by dual-energy x-ray absorptiometry (DXA) and incident nonspinal fractures
in 636 black and 7334 white women enrolled in the Study of Osteoporotic Fractures
(SOF). We tested 3 hypotheses: low BMD will predict fracture risk in black
women; the magnitude of this association will be similar to that observed
in white women; and the absolute risk of fracture in black and white women
at a given BMD level will be similar.
We enrolled 9704 white women into the SOF from 1986 to 1988 using population-based
listings in Baltimore, Md; Minneapolis, Minn; Portland, Ore; and the Monongahela
Valley near Pittsburgh, Pa. To be eligible to participate, women had to be
aged 65 years or older and ambulatory. We excluded women who reported a bilateral
hip replacement. Details of the cohort study have been published.10 In the current study we analyzed 7334 white women
who had a technically adequate hip BMD measurement at the second examination
Black women were originally excluded from the SOF because of their low
incidence of hip fractures. At a sixth SOF examination conducted between 1996
and 1998, we enrolled 662 black women aged 65 years or older. Race was self-declared
and only women designating themselves as black were enrolled. Because the
black women were recruited later in the SOF, we targeted black women aged
70 years or older. Of these, 636 women had technically adequate BMD measurements
and follow-up information. Other inclusion and exclusion criteria were the
same for both races. The protocol and consent forms were approved by the institutional
review boards at all of the participating institutions. All women provided
written informed consent.
Bone mineral content (BMC) was defined as the amount of bone mineral
in grams in the region of interest. Bone mineral density was defined as the
amount in grams of BMC divided by the region of interest in centimeters squared.
The BMC and BMD of the total hip and the femoral neck were measured by DXA
using Hologic QDR 1000 and 2000 scanners (Bedford, Mass). Details of the measurement
and densitometry quality-control procedures have been published elsewhere.11,12 In brief, a random sample of scans
was reviewed by technicians at a quality-control center. In addition, all
scans flagged by the technicians for certain problems (such as difficulty
defining bone edges) were reviewed at the quality-control center. To assess
longitudinal performance of the scanners, an anthropometric spine phantom
was scanned daily and a hip phantom was scanned once per week at each clinic.
Areal BMD measurements are based on bone length and width. Because they
do not include bone depth, the measurements only partially adjust for bone
size. To test whether a volumetric measurement of BMD is a better predictor
of fracture occurrence, we also calculated the femoral neck bone mineral apparent
density (BMAD) using the formula13 BMC/area2 reported as g/cm3.
Body weight was measured using a balance beam scale and height was measured
using the Harpenden stadiometer (Holtain Ltd, Crymych, United Kingdom). The
BMI was calculated as the weight in kilograms divided by the square of height
in meters. Participants were asked to stand up from a chair without using
their arms and this was coded as able or unable. The participants also completed
a questionnaire and interview that collected information on demographics,
lifestyle (current smoking, alcohol use in the past 30 days), and medical
and family history. Information was obtained on whether participants walked
as a form of exercise. The number of blocks walked per day (assuming 12 blocks =
1.6 km) as part of their normal routine and as part of an exercise routine
was estimated. Kilocalorie expenditure from walking was calculated by assigning
8 kcal per 1 block walked.14 Participants were
asked to bring all prescription and over-the-counter medications to the clinic
for verification of use. Dietary calcium intake was estimated using the Block
food frequency questionnaire15 and expressed
in milligrams per day.
After the initial enrollment visit, all women were contacted by either
letter or telephone every 4 months to ask if they had sustained a fracture;
these contacts were 99% complete. Women who reported a fracture were interviewed
by telephone about the circumstances under which the fracture occurred. We
excluded fractures that occurred because of a major trauma, eg, motor vehicle
crash. Women could report having more than 1 fracture. The time to the first
fracture was calculated as time from the baseline BMD measure to the event.
All fractures were confirmed by radiographic report. We truncated the follow-up
in the white women so that the average follow-up of 6.1 years would be the
same in both racial groups.
The characteristics of black and white women who had a fracture were
compared with women who did not have a fracture using t tests for continuous variables and χ2 tests for categorical
variables. We used Cox proportional hazards models to estimate the relative
risk (RR) of fracture and the 95% confidence interval (CI) for each SD decrease
in BMC, BMD, or BMAD. The SD for each site was determined from the combined
cohort of women. To compare the predictive value of various measurements,
we analyzed the areas under receiver operating characteristic curves in the
age-adjusted models.16,17 We initially
adjusted for age. Because of the major effect of body weight on BMD,18 we adjusted separately for age and body weight. In
the full multivariable model, we adjusted for age, body weight, height, fracture
since age 50 years, walking as a form of exercise, current calcium supplement
use, current hormone use, alcohol consumption in the past 30 days, history
of osteoarthritis or chronic obstructive pulmonary disease, falling 2 or more
times in past year, using arms to stand up from a chair, and current smoking.
To compare the absolute rate of fracture at a given bone density level
in black and white women, we calculated incidence rates of fracture per 1000
person-years across tertiles of BMC, BMD, and BMAD. The combined distribution
of BMC, BMD, and BMAD in both black and white women were used to identify
the cut points for the tertiles. To test whether BMD or BMAD and other risk
factors account for the lower fracture rate among black women, we calculated
the adjusted RR (95% CI) of fracture among black compared with white women. P<.05 was considered significant. All analyses were
performed using SAS version 8.2 (SAS Institute Inc, Cary, NC).
Black women were older, had a greater body weight and BMI, and were
less likely than white women to report a fracture since age 50 years, a maternal
history of fracture, walking for exercise, and current use of calcium supplements
(Table 1). Dietary calcium intake was
lower among black women. Use of thiazide diuretics and hormone therapy did
not differ by race. Few black women reported bisphosphonate use. A greater
proportion of white women reported consuming alcohol. Compared with white
women, osteoarthritis, chronic obstructive pulmonary disease, diabetes, and
hypertension were more common among black women. A similar proportion of both
races reported a history of fall (25.6% of black women and 28.9% of white
women aged 65-69 years, 26.4% and 30.8% for women aged 70-74 years, 28.0%
and 29.7% for women aged 75-79 years, and 32.6% and 33.9% for women aged ≥80
years, respectively). Compared with white women, a higher proportion of black
women were not able to stand from a chair without using their arms.
As of October 1, 2004, after a mean (SD) follow-up of 6.1 (1.5) years,
58 black women had a combined total of 61 fractures and 1606 white women had
a combined total of 1712 fractures. The specific fractures by site in black
and white women, respectively, were hip or pelvis, 12 (19.7%) and 347 (20.3%);
rib, 8 (13.1%) and 141 (8.2%); wrist, 7 (11.5%) and 306 (17.9%); finger or
hand, 6 (9.9%) and 90 (5.3%); toes or feet, 11 (18%) and 241 (14.1%); arm,
shoulder, or elbow, 5 (8.2%) and 247 (14.4%); leg, ankle, or knee, 12 (19.6%)
and 248 (14.5%); and other, 0 and 92 (5.4%). Compared
with black women who did not have a fracture, black women who had a fracture
were slightly older and had a lower body weight and BMI; were less likely
to report walking as a form of exercise; and were more likely to report osteoarthritis,
a history of falling 2 or more times in the past year, and use of arms to
stand up from a chair (Table 1).
Compared with white women who did not have a fracture, white women who
had a fracture were older; had a lower height, weight, and BMI; were more
likely to report a past and maternal history of fracture; were more likely
to report calcium supplement use, a history of chronic obstructive pulmonary
disease, a history of falls in the past year, and use of arms to stand up
from a chair; and were less likely to report hormone therapy use and alcohol
Compared with white women, black women had a 9% higher baseline total
hip BMD, a 15% higher femoral neck BMD, and a 17% higher femoral neck BMAD
(Table 2). In both groups, BMD at the
total hip and femoral neck was lower among women who had a fracture compared
with women who did not have a fracture (Table 2). A higher percentage of both
black and white women who had a fracture had a femoral neck T score of −2.5
or less. Use of a black referent database for the calculations of T scores
resulted in a higher prevalence of black women with osteoporosis.
In black and white women, respectively, after adjusting for age, the
RR of fracture per 1-SD decrease in BMD was 1.44 (95% CI, 1.12-1.86) and 1.47
(95% CI, 1.39-1.56) for the total hip and 1.37 (95% CI, 1.08-1.74) and 1.49
(95% CI, 1.40-1.58) for the femoral neck (Table
3); all increases were statistically significant. Total hip and
femoral neck BMC were related to the risk of nonspinal fractures, but the
magnitude of the association was weaker. A 1-SD decrease in BMAD was associated
with an RR of fracture of 1.59 (95% CI, 1.16-2.18) and 1.34 (95% CI, 1.26-1.43)
in black and white women, respectively. For the areas under receiver operating
characteristic curves, BMD in the total hip and femoral neck were better predictors
of subsequent fractures than were BMC measures (P<.05)
in black but not white women (Table 3).
Additional adjustment for body weight decreased the magnitude of the
RR of fracture in black women (Table 3). The additional adjustment had little
effect on the RR of fracture in white women. In the full multivariable model,
a 1-SD decrease in total hip BMD was associated with a 42% increased risk
of fracture in white women independent of other covariates (RR, 1.42; 95%
CI, 1.33-1.52). Among black women, the multivariable-adjusted RR of fracture
per 1-SD decrease in total hip BMD was 1.23 (95% CI, 0.92-1.65). Similar associations
were found with femoral neck BMD. The BMC was not related to fracture occurrence
in black women in the multivariable models. The association between volumetric
BMAD and subsequent fracture was of borderline significance in black women.
The incidence rate of nonspinal fracture by tertile of femoral neck
BMC, BMD, and BMAD in black and white women is shown in the Figure. Within each racial group, fracture rates were highest among
women with the lowest BMC, BMD, or BMAD. Nevertheless, within each tertile,
fracture rates were 30% to 40% lower among black compared with white women.
In age-adjusted models, black women had a 64% lower risk of fracture than
white women (Table 4). Adjusting for
BMD and other risk factors, the RR of fracture was 0.48 (95% CI, 0.36-0.64)
in black compared with white women.
We have demonstrated that reduced BMD of the hip and femoral neck is
associated with an increased risk of all nonspinal fractures in older black
women in age-adjusted models—a relationship largely mitigated by other
risk factors. The strength of the association between BMD and all nonspinal
fractures in black women after age adjustment appears to be similar to that
observed for white women in the SOF19 and other
cohorts.20 Total hip and femoral neck BMD were
somewhat better predictors of fracture than BMC, perhaps because BMC makes
no correction for bone size. Among white women in the SOF, we also found that
BMC was a poorer predictor of hip fracture than either BMD or BMAD.3
We hypothesized that if BMAD provides a more accurate estimate of volumetric
BMD of the femoral neck, then it may be a stronger predictor of fracture than
areal BMD alone. There was some suggestion that estimated femoral neck volumetric
BMD had a stronger relationship to fractures than areal BMD for the prediction
of fractures in black women, but the areas under receiver operating characteristic
curves were not significantly different for BMD and BMAD, which is consistent
with our observations in white women.21 Our
results are also consistent with a recent study9 of
peripheral BMD and fractures in a multiethnic cohort in which each 1-SD decrease
in peripheral BMD T score was associated with a 1.54-fold increased risk of
fracture. However, the follow-up period was only 1 year. Moreover, the World
Health Organization recommendations and the other guidelines for using BMD
and interpreting BMD results for diagnosis are based on central DXA.1,22
An important implication of the improved life expectancy among black
women23 is that the overall impact of osteoporosis,
a disease that is more prevalent among older individuals, will increase in
blacks. About 24% of the black women who had a fracture had a T score of −2.5
or less if a black referent database was used compared with 19% when a white
referent database was used. However, despite the association between BMD and
nonspinal fracture risk in black women, fracture incidence was 30% to 40%
lower among black women compared with white women at every BMD level. This
was true for both areal BMD and estimated volumetric BMD of the femoral neck.
The current clinical recommendation is to diagnose osteoporosis among nonwhites
at or below a T score threshold of −2.5 using the uniform normative
database for whites.24 Our results suggest
that low BMD is useful to identify blacks at risk of experiencing an osteoporotic
fracture and those who may benefit from therapy and other preventive measures.
Our results also suggest that race-specific databases for black women may
The lower fracture rate among black women may reflect both skeletal
and other factors. In models adjusting for BMD or BMAD, the differential fracture
risk by race was attenuated somewhat; nevertheless, the lower RR of fracture
among black women was independent of BMD and other covariates, suggesting
that other factors account for their lower risk. Slower rates of bone loss25 among black women, possibly due to lower bone turnover,
has been observed in some26 but not all studies27 and could contribute to their lower rate of fracture.
Microarchitectural and geometric differences may contribute. Calcaneal quantitative
ultrasound measurements were higher28 and hip
axis lengths were shorter in black29 compared
with white women. Other factors could include lifestyle and anthropometric
factors, although we adjusted for these covariates in our model. Differences
in sex-steroid and growth hormones and metabolism also may contribute. Lower
fall rates among black women have been reported in some studies,30 but
we adjusted for falls in our analyses.
Osteoporosis and fracture occurrence appear to be strongly correlated
with genetics.31 A maternal history of fracture
confers a 2-fold increased risk of fracture that is independent of BMD.10 There has been rapid progress in identifying genes
and alleles that determine BMD, but little progress in identifying genetic
determinants of fracture, and in identifying genes that contribute to racial
differences in fracture occurrence.
Among black women, the relationship between BMD and fracture was attenuated
in the fully adjusted model. This was somewhat surprising because the overall
variation in BMD explained by individual characteristics has been shown to
be similar in blacks32 and whites.18 Nevertheless, these results suggest that lifestyle
and medical and family history may be important determinants of BMD in black
women and could account for the association between BMD and fracture.
The prospective design of our study avoids many of the potential biases
inherent in case-control studies of BMD and fracture. We studied 2 well-characterized
cohorts of community-dwelling black and white women. We used state-of-the-art
measurements of BMD and controlled for a number of important covariates. However,
our participants were likely to be healthier than average because they were
volunteers and because we excluded women who were unable to walk without assistance.
Race was self-declared. Estimated European admixture among blacks ranges
from 11.6% to 22.5% in the United States with considerably less in a Jamaican
population (6.8%).33 In our study, we had no
information on admixture. Other factors that we did not measure include genetic
and cultural factors. Future studies may consider assigning race based on
the race and/or ethnicity of paternal and maternal grandparents, as well as
measuring genetic and/or cultural factors.
Our estimated volumetric BMD may underestimate true volumetric BMD,
but this is proportional in participants who had a fracture and controls and
therefore would not alter our conclusions.34,35 The
BMAD only partially adjusts for bone size; direct measures of volumetric BMD
are needed to confirm our findings. Finally, we studied a smaller number of
black women and our estimates of fracture incidence may be less precise.
In conclusion, decreased hip BMD is associated with an increased risk
of fracture in older black women when adjusting for age but not other factors.
The lower fracture rate in black compared with white women was independent
of BMD and other risk factors. Our results suggest that race-specific normative
databases may be appropriate for the densitometric definition of osteoporosis.
Corresponding Author: Jane A. Cauley, DrPH,
University of Pittsburgh, 130 DeSoto St, Crabtree Hall A543, Pittsburgh, PA
Author Contributions: Ms Lui had full access
to all of the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Study concept and design: Cauley, Stone, Cummings.
Acquisition of data: Cauley, Ensrud, Stone,
Analysis and interpretation of data: Cauley,
Lui, Ensrud, Zmuda, Stone, Hochberg.
Drafting of the manuscript: Cauley.
Critical revision of the manuscript for important
intellectual content: Lui, Ensrud, Zmuda, Stone, Hochberg, Cummings.
Statistical analysis: Lui, Stone.
Obtained funding: Cauley, Ensrud, Stone, Hochberg,
Administrative, technical, or material support:
Study supervision: Stone, Cummings.
Financial Disclosures: Dr Cauley has received
honoraria from Eli Lilly & Co, Merck & Co, and Novartis and has served
on the speaker’s bureau for Eli Lilly & Co and Merck & Co. No
other authors reported financial disclosures.
Funding/Support: Supported in part by Public
Health Service research grants AR35582, AR35583, AR35584, AR44811, and AG05407
from the National Institutes of Health.
Role of the Sponsors: The funding agencies
had no direct role in the conduct of the study, the collection, management,
statistical analyses, and interpretation of the data, preparation, or approval
of the manuscript.