Osteoporos Int (2009) 20:363370

DOI 10.1007/s00198-008-0688-x

ORIGINAL ARTICLE

Weight and body mass index predict bone mineral density

and fractures in women aged 40 to 59 years
S. Morin & J. F. Tsang & W. D. Leslie

Received: 13 March 2008 / Accepted: 29 May 2008 / Published online: 17 July 2008
# International Osteoporosis Foundation and National Osteoporosis Foundation 2008

Abstract
Summary Weight and body mass index are associated with
low bone mineral density and fractures in older women.
This retrospective cohort study confirms a similar relationship in women aged 40 to 59 years.
Introduction Risk factors for the prediction of osteoporosis
and fractures have been less thoroughly studied in younger
women. We evaluated the associations between weight,
body mass index (BMI), the Osteoporosis Self-Assessment
Tool (OST), bone mineral density (BMD) and fracture risk
in women aged 40 to 59 years.
Methods Using administrative health management databases, we conducted a retrospective cohort study in 8,254
women aged 4059 years who had baseline BMD testing.
Linear regression and Cox proportional multivariate models
were created to examine the associations with weight, BMI,
OST, BMD, and subsequent fractures throughout a 3.3-year
follow-up.
Results Body weight, BMI, and OST had a similar overall
performance in their ability to classify women with femoral
neck T-score 2.5. Throughout 27,256 person years of
On behalf of the Manitoba Bone Density Program.
S. Morin
Department of Medicine, McGill University,
Montreal, Canada
J. F. Tsang : W. D. Leslie
Faculty of Medicine, University of Manitoba,
Winnipeg, Canada
S. Morin (*)
Division of General Internal Medicine,
McGill University Health Center (MUHC),
1650 Cedar Avenue, Room B2118,
Montreal, QC H3G 1A4, Canada
e-mail: suzanne.morin@mcgill.ca

observation, 225 women experienced one or more fractures.

After adjustment for age, prevalent fractures, and use of
corticosteroids, each standard deviation decrease in weight
was associated with a 19% increase in the risk of incident
fracture (95% CI: 1.011.35). Femoral neck BMD and the
presence of prevalent fractures were also associated with
the risk of incident fractures.
Conclusions Low weight and BMI predict osteoporosis and
are associated with increased fracture risk in younger
women. The negative impact of low body weight on bone
health should be more widely recognized.
Keywords Body mass index . Body weight .
Bone mineral density . Osteoporosis fractures .
Younger women

Introduction
Osteoporosis is characterized by low bone mass and an
increased risk of fracture [1]. Fractures most commonly
associated with osteoporosis are those of the hip, the
vertebrae, and the wrist, and these are responsible for
morbidity and excess mortality. Many clinical guidelines
recommend risk factor assessment and measurement of
bone mineral density (BMD) through dual energy X-ray
absorptiometry (DXA) to identify individuals at high risk of
fracture [24]. Risk factors have been extensively characterized in women over the age of 65 years and are used in
practice, often in combination, to predict fractures [58].
However, the application of these algorithms in younger
women has not been well studied.
Body weight is positively associated with BMD, from
childhood through adulthood (with correlations to the order
of 0.3 to 0.6) [9]. This relationship is known to be stronger

364

in older women in whom both weight and body mass index

(BMI) have been shown to explain an large proportion of
the variance in BMD (8.919.8% of total variance) [9, 10].
There are currently insufficient data on the predictive value
of body weight and BMI in younger women.
Low weight and low BMI are also related to an
increased fracture risk. In a large meta-analysis of 12 prospective population-based cohorts, De Laet et al. documented that the age-adjusted risk of a hip fracture was
increased 2-fold in older individuals with a BMI of 20 kg/m2
compared with a BMI of 25 kg/m2 [11]. In the Study of
Osteoporosis Fractures (SOF), women aged 65 years and
older in the lowest quartile for weight had twice as many
hip fractures as those in the other quartiles [5]. Similar data
exist for the risk of vertebral and forearm fractures in older
women [1214].
The purpose of this study was to investigate the associations between body weight, BMI, BMD and subsequent
fractures in women aged 40 to 59 years to guide clinicians
in the evaluation of fracture risk in this population.

Osteoporos Int (2009) 20:363370

contacts. A province-wide pharmacy database provides

information on all prescription medications dispensed to
out-patients. The Manitoba Bone Density Program database
can be linked with these provincial computerized health
databases through an anonymous personal identifier. The
accuracy of these databases has been well validated [17, 18].
We identified all women aged 40 to 59 years with a first
bone density measurement. Women were required to have
results for the lumbar spine (L1L4) and proximal femur
(total hip, femoral neck and trochanter sites) prior to 31
October 2002 and medical coverage from Manitoba Health
during the observation period ending 31 March 2004. As
earlier software versions did not provide total hip measurements, records prior to May 1998 were not used in the
analysis. For women with more than one eligible set of
measurements, only the first record was included.
The study was approved by the Research Ethics Board
for the University of Manitoba and the Health Information
Privacy committee of Manitoba Health.
Body weight measurements

Materials and methods

Study design and population
Using comprehensive health care databases of the Province
of Manitoba in Canada (population 1.2 million in 2004), we
designed a retrospective historical cohort study of women
aged 40 to 59 years who underwent clinical BMD testing in
the province for evaluation of fracture risk. Citizens of the
province of Manitoba have universal access to publicly
funded medical care including BMD testing. The Manitoba
Bone Density Program is a unique, integrated program that
has managed all clinical DXA testing of the province since
1997 [15]. Criteria for testing are consistent with most
published guidelines and, include female sex, age 65 years
or older, premature ovarian failure, prior fragility fracture,
X-ray evidence of osteopenia, prolonged corticosteroid use,
and other pertinent clinical risk factors (www.gov.mb.ca/
health/programs/mbd). DXA testing rates for this program
have been published and the programs database has been
shown to be over 99% complete and accurate [15, 16].
The hospital discharge summary database provides
information on hospital admissions for the entire province.
The physician claims database provides information on all
in- and out-patient therapeutic procedures and physician
visits. Hospital discharge abstracts provide up to 16 diagnoses and up to four procedure codes using the International Classification of Disease-9-Clinical Modification
(ICD-9-CM) system and physician billing claims provide
one ICD-9-CM diagnosis code and one or more procedure
codes for all in-patient, out-patient, and office-based

Height and weight were by self-report prior to 2000 and

were measured by a wall-mounted stadiometer and bathroom scale from 2000 onward. BMI was calculated as
weight in kilograms divided by height squared in meters.
Although weight is used in many osteoporosis risk
assessment strategies, we also evaluated BMI as it has
been selected by the World Health Organization (WHO) as
one of several fracture risk assessment parameters for
inclusion in an absolute fracture risk prediction tool [11].
Bone density measurements
Prior to 2000, DXA measurements were performed using a
pencil-beam instrument (Lunar DPX; GE Lunar, Madison,
WI, USA) and after this date a fan-beam instrument was
used (Lunar Prodigy; GE Lunar, Madison, WI, USA).
Instruments were cross-calibrated using 59 volunteers and
anthropomorphic phantoms. No clinically significant differences were identified (T-score differences < 0.2). Therefore,
all analyses are based upon the unadjusted numerical results
provided by the instrument. Densitometers showed stable
long-term performance (coefficient of variation [CV]
<0.5%) and satisfactory in vivo precision (CV 1.7% for
L1L4 and 1.1% for the total hip) [19].
Dual-energy X-ray absorptiometry scans were performed
and analyzed in accordance with the manufacturers recommendations. Lumbar spine T-scores (number of standard
deviations [SD] above or below young adult mean BMD)
and Z-scores (number of SDs above or below age-matched
mean BMD) were calculated using the manufacturers USA
white female reference values based upon the revised

Osteoporos Int (2009) 20:363370

NHANES III reference data (Prodigy version 8.8) [20].

Vertebral levels affected by artifacts were excluded by
experienced physicians using conventional criteria [21]. A
T-score of 2.5 or lower was considered to be osteoporotic
based upon the WHO classification [2].
Osteoporosis Self-Assessment Tool
Because BMD measurements are not widely available in
certain communities, several risk assessment tools have been
developed to target women at higher risk of osteoporosis for
BMD testing [22]. The Osteoporosis Self-Assessment Tool
(OST) uses self-reported data and is derived by score = 0.2
(weight in kg age), truncated to an integer with a lower
score, identifying women at higher risk of osteoporosis at the
femoral neck [23]. OST has been reported to have a
sensitivity of 89.2% and a specificity of 45.0% (using a
cut-off point of 1) for identifying osteoporosis in
postmenopausal women aged 45 to 64 years [24].
Fracture ascertainment
Each participants longitudinal health service record was
assessed from the date of the BMD testing to 31 March 2004
for the presence of ICD-9-CM fracture codes that were not
associated with trauma codes (ICD-9-CM E800-E879 and
E890-E999). Specific fracture sites of interest were the hip
(ICD-9-CM 820821), the spine (ICD-9-CM 805), forearm
(ICD-9-CM 813), and proximal humerus (ICD-9-CM 812)
[25]. As vertebral fractures are frequently asymptomatic,
we were only able to ascertain those that necessitated
medical attention. In addition, we required that hip fractures
and forearm fractures be accompanied by a site-specific
fracture reduction, fixation or casting code. Hip, spine,
forearm, and proximal humerus fractures defined in this
way were collectively designated osteoporotic fractures.
Using these fracture definitions, we have previously shown
that BMD measurements predict fractures in our clinical
cohort as well as those reported in large meta-analyses [26].

365

province or the end of the observation period (31 March

2004).
Statistical analysis
Descriptive statistics were tabulated for the study cohort.
Linear regression was performed to evaluate the relationship between weight or BMI and BMD after adjustment for
age. We divided the cohort into quartiles of weight, BMI,
and OST, and computed the proportions of individuals with
low BMD scores and incident fractures in each stratum. A
Chi-squared test with CochraneArmitage linear trend analysis was performed to test for a difference across quartiles.
Receiver operating characteristic (ROC) curves were
plotted for weight, BMI, and OST using femoral neck Tscore 2.5, T-score 2.5 at any site, or incident osteoporotic fractures as the reference variables. We compared
the areas under the ROC curves for the three variables for
all women and within predefined subgroups: age group
(4049 years and 5059 years), and in women with no
prevalent fractures or use of systemic corticosteroids.
Diagnostic accuracy measures were considered using
different thresholds of weight, BMI, and OST score.
Using multivariate Cox proportional hazard models, the
association between weight, BMI and OST and incident
osteoporotic fractures was evaluated, in turn, with and
without including baseline femoral neck BMD. The models
each included age (in years), presence of a prevalent
fracture (as a binary variable) and use of systemic corticosteroids (as a binary variable) as covariates, which were all
entered into the models simultaneously.
Receiver operating characteristic curves were compared
using the non-parametric method of DeLong et al. [27],
which allows for efficient comparison of the highly
correlated curves originating from a common population
(AccuROC 2.5; Accumetric, Montreal, QC, Canada). All
other analyses were performed using Statistica (Version 6.1,
StatSoft, Tulsa, OK, USA). A p value of less than 0.05 was
considered statistically significant for all analyses.

Covariates
Results
The presence of a prevalent non-craniofacial fracture (any
ICD-9-CM 805829 code between 1987 and the date of
BMD testing) and use of systemic corticosteroids in the
year prior to BMD testing (3 months or more at a mean
daily equivalent dose of at least 7.5 mg of prednisone) were
documented.
Clinical endpoints
Women were followed until the first one of these events:
occurrence of a fracture, death, relocation out of the

We identified 8,254 women aged 40 to 59 years who

fulfilled the study criteria. The mean age and weight of the
study cohort were 52.7 (SD 4.9) years and 69.2 (15.0) kg
respectively; 589 (7.1%) had a prevalent fracture and 1,226
(14.9%) had a BMD measurement consistent with osteoporosis (Table 1). The mean OST score was 2.9 (SD 3.0,
range 10 to 18); 3,149 (38.2%) had an OST of 1.
Women aged 4049 years had higher T-scores and more
frequent use of systemic corticosteroids than women aged
5059 years.

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Osteoporos Int (2009) 20:363370

Table 1 Baseline characteristics of women in the entire cohort and by age groups

Age (SD), years

Weight (SD), kg
Height (SD), kg
BMI (SD), kg/m2
OST score (SD)
OST score 1, n (%)
Prevalent fracture, n (%)
Systemic corticosteroid use, n (%)
Lumbar spine T-score
Femoral neck T-score
Total hip T-score
Femoral neck T-score 2.5, n (%)
T-score -2.5 at any site, n (%)

All women
(4059 years),
N=8,254

Women
4049 years,
n=2,262

Women
5059 years,
n=5,992

P younger
vs older

52.7 (4.9)
69.2 (15.0)
162.1 (6.5)
26.3 (5.6)
2.9 (3.0)
3,149 (38.2)
589 (7.1)
434 (5.3)
0.8 (1.4)
1.1 (0.9)
0.6 (1.1)
377 (4.6)
1,226 (14.9)

46.1 (2.7)
68.6 (16.2)
162.5 (6.8)
26.0 (6.0)
4.0 (3.3)
516 (22.8)
150 (6.6)
184 (8.1)
0.5 (1.3)
0.9 (0.9)
0.5 (1.1)
58 (2.6)
234 (10.3)

55.1 (2.8)
69.4 (14.5)
161.9 (6.4)
26.5 (5.4)
2.5 (2.8)
2,633 (43.9)
439 (7.3)
250 (4.2)
0.9 (1.3)
1.1 (0.9)
0.6 (1.1)
319 (5.3)
992 (16.6)

< 0.0001
0.0307
< 0.0001
< 0.0001
< 0.0001
< 0.0001
0.2738
< 0.0001
< 0.0001
< 0.0001
< 0.0001
< 0.0001
< 0.0001

Osteoporosis Self-Assessment Tool; lower score indicates a greater number of osteoporotic factors (OST=0.2 (weight in kg age))

Over 27,256 person years of observation (mean 3.3 years

per individual), 225 (2.7%) experienced one or more
incident fractures (19 hip, 56 spine, 59 humerus, and 97
wrist). The proportion with incident fractures was similar in
women aged 5059 years (158, [2.6%]) and women aged
4049 years (67 [3.0%]). The prevalence of osteoporosis
and of incident fractures increased with decreasing weight,
BMI, and OST quartile (Table 2). The proportion of
incident fractures increased from 2.1% in the highest BMI
quartile (BMI > 29 kg/m2) to 3.4% in the lowest quartile
(BMI < 22 kg/m2; p=0.0094).
The area under the ROC curves revealed that weight,
BMI, and OST predicted low BMD in the whole cohort, in
both age subgroups (40 to 49 years and 50 to 59 years) and
in women without prior fracture or corticosteroid therapy

(Table 3). These variables were less discriminatory, however, when it came to predicting incident fractures, particularly in the younger age group.
The performance characteristics of various thresholds of
each of the clinical variables are shown in Table 4. Body
weight of 57 kg or less was found to have a sensitivity of
50.9% and a specificity of 80.9% for predicting a T-score of
2.5 at the femoral neck, and of 24.9% and 79.6%
respectively, for prediction of incident fractures. At a cut-off
point of 70 kg, the sensitivity was 89.4% and the specificity
42.4% to identify women with osteoporosis at the femoral
neck. BMI below 20 kg/m2 had specificity of 93.5%, but very
low sensitivity (24.9%) in detecting femoral neck osteoporosis; at a cut-off of 26 kg/m2, the sensitivity rose to 82.5%,
but the specificity decreased to 45.6%. OST, at a threshold of

Table 2 Prevalence (%) of osteoporosis by BMD criteria and incident fractures in relation to weight, BMI, and OST quartiles
Criteria/fractures
Weight (kg)
Femoral neck T-score 2.5
T-score 2.5 at any site
Any incident fracture
BMI (kg/m2)
Femoral neck T-score 2.5
T-score 2.5 at any site
Any incident fracture
OST
Femoral neck T-score 2.5
T-score 2.5 at any site
Any incident fracture

P for trend
Q1 (n=2,032)
weight < 59
221 (10.9)
559 (27.5)
66 (3.2)
Q1(n=2,062)
BMI < 22
199 (9.7)
532 (25.8)
71 (3.4)
Q1 (n=1,900)
Score < 0
227 (11.9)
574 (30.2)
66 (3.5)

Q2 (n=2,135)
weight 59 to 67
94 (4.4)
337 (15.8)
64 (3.0)
Q2 (n=2,065)
BMI 22 to 25
101 (4.9)
310 (15.0)
54 (2.6)
Q2 (n=2,456)
Score 02
98 (4.0)
367 (14.9)
74 (3.0)

Q3 (n=1,982)
weight 68 to 77
48 (2.4)
216 (10.9)
48 (2.4)
Q3 (n=2,064)
BMI 26 to 29
46 (2.2)
251 (12.2)
57 (2.8)
Q3 (n=1,919)
Score 34
42 (2.2)
193 (10.1)
40 (2.1)

Q4 (n=2,105)
weight > 77
14 (0.7)
114 (5.4)
47 (2.2)
Q4 (n=2,063)
BMI > 29
31 (1.5)
133 (6.4)
43 (2.1)
Q4 (n=1,979)
Score > 4
10 (0.5)
92 (4.6)
45 (2.3)

< 0.0001
< 0.0001
0.0215

< 0.0001
< 0.0001
0.0094

< 0.0001
< 0.0001
< 0.0001

Osteoporos Int (2009) 20:363370

367

Table 3 Area under the receiver operating characteristic curves (95% CI) for osteoporotic BMD or incident osteoporotic fracture
Femoral neck
T-score 2.5
All (N=8,254)
Weight
0.76 (0.730.78)
BMI
0.72 (0.700.75)*
0.77 (0.750.79) **,***
OSTa
Without prior fracture or corticosteroids (n=7,270)
Weight
0.77 (0.740.79)
BMI
0.73 (0.710.76)*
0.77 (0.750.80)***
OSTa
Age 4049 years (n=2,262)
Weight
0.73 (0.670.79)
BMI
0.69 (0.6200.76)
0.73 (0.660.79)
OSTa
Age 5059 years (n=5,992)
Weight
0.77 (0.740.79)
BMI
0.73 (0.710.76)*
0.77 (0.740.79)***
OSTa

T-score 2.5
at any site

Incident fracture

0.69 (0.680.71)
0.67 (0.650.69)*
0.71 (0.690.72)*,***

0.55 (0.510.59)
0.55 (0.510.59)
0.56 (0.520.60)

0.70 (0.680.72)
0.68 (0.660.70)*
0.72 (0.700.73)*,***

0.55 (0.510.60)
0.56 (0.510.60)
0.56 (0.520.60)

0.71 (0.680.75)
0.69 (0.660.73)
0.71 (0.680.75)

0.50 (0.430.57)
0.48 (0.410.55)
0.50 (0.430.58)

0.69 (0.680.71)
0.67 (0.650.79)*
0.70 (0.680.72)***

0.57 (0.530.61)
0.58 (0.530.62)
0.58 (0.540.63)

*p<0.001 or ** p<0.05 for BMI versus weight, ***p<0.001 for OST versus BMI;
OST was transformed to (OST) to construct ROC curves

1, had a sensitivity of 46.8% and a specificity of 81.8% for

identifying women with a low T-score at the femoral neck.
In univariate analysis, each standard deviation decrease
in weight (15 kg) was associated with a 17% increase in the
risk of incident fracture (95% CI; 1.011.35), and each
standard deviation decrease in BMI (5.6 kg/m2) and OST
[3] with a similar risk increase (Table 5). These remained
constant after adjustment for age, prevalent fracture, and
use of systemic corticosteroids. The addition of femoral
neck BMD to the model caused the association between
weight, BMI and OST and fractures to lessen. Femoral neck
BMD and the presence of osteoporotic fractures at baseline
were independently associated with the risk of incident

fracture in all three multivariate models (HR 1.6, 95% CI

1.41.9 and HR 2.7, 95% CI 1.93.8 respectively).

Discussion
Women at high risk of osteoporosis-related fractures can be
targeted in clinical practice with specific interventions.
Younger women with risk factors such as low body weight
and BMI may also be at higher risk of fractures. The results
from our large cohort study support the previously documented associations between weight, BMI, and BMD.
Body weight has been identified in previous reports as a

Table 4 Discriminatory performance of weight, BMI and OST for the prediction of T-score 2.5 or any incident fracture
Femoral neck T-score 2.5

T-score 2.5 at any site

Incident fracture

Sensitivity %
(95% CI)

Specificity %
(95% CI)

Sensitivity %
(95% CI)

Specificity %
(95% CI)

Sensitivity %
(95% CI)

Specificity %
(95% CI)

(49.852.0)
(57.659.7)
(88.790.1)

80.9 (80.181.8)
77.0 (76.177.9)
42.4 (41.343.4)

39.6 (38.540.6)
45.6 (44.546.7)
80.0 (79.280.9)

82.8 (82.083.6)
79.0 (78.279.9)
44.6 (43.545.7)

24.9 (24.025.8)
29.3 (28.430.3)
65.3 (64.366.4)

79.6 (78.780.4)
75.5 (74.676.4)
41.1 (40.042.2)

(24.025.9)
(46.148.3)
(81.783.3)

93.5 (93.094.0)
80.3 (79.481.1)
45.6 (44.546.7)

19.8 (19.020.7)
38.2 (37.139.2)
74.1 (73.275.1)

94.8 (94.395.3)
82.0 (81.282.8)
47.6 (46.548.6)

11.1 (10.411.8)
27.6 (26.628.5)
60.4 (59.461.5)

92.8 (92.293.3)
79.2 (78.380.1)
44.5 (43.445.5)

(59.261.3)
(75.577.3)
(85.587.0)

78.8 (77.979.6)
63.7 (62.664.7)
48.8 (47.749.9)

46.8 (45.747.9)
63.8 (62.764.8)
76.8 (75.877.7)

81.1 (80.382.0)
66.3 (65.367.3)
51.4 (50.352.5)

29.3 (28.430.3)
45.8 (44.746.9)
62.2 (61.263.3)

77.2 (76.378.1)
62.1 (61.063.1)
47.5 (46.448.6)

Weight (kg)
57
50.9
59
58.6
70
89.4
BMI (kg/m2)
20
24.9
22
47.2
26
82.5
OST
1
60.2
2
76.4
3
86.2

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Osteoporos Int (2009) 20:363370

Table 5 Risk of developing any incident osteoporotic fracture without and with adjustment for age, prior fracture history, systemic corticosteroid
use and femoral neck BMD

Model 1
Weight per SD decrease
Age per decade increase
Prevalent osteoporotic fracture
Systemic corticosteroid use
Femoral neck BMD per SD decrease
Model 2
BMI per SD decrease
Age per decade increase
Prevalent osteoporotic fracture
Systemic corticosteroid use
Femoral neck BMD per SD decrease
Model 3
OST per SD decrease
Prevalent osteoporotic fracture
Systemic corticosteroid use
Femoral neck BMD per SD decrease

Univariate HR
(95% CI)

Multivariate HR (95% CI)

without BMD

Multivariate HR (95% CI)

with BMD

1.17 (1.011.35)

1.19
1.07
3.28
1.24

(1.031.37)
(0.941.22)
(2.364.57)
(0.752.04)

0.97
0.98
2.68
0.97
1.61

(0.841.14)
(0.851.12)
(1.913.76)
(0.591.61)
(1.371.89)

1.17 (1.011.35)

1.18
1.07
3.26
1.25

(1.021.37)
(0.941.22)
(2.354.54)
(0.762.06)

1.00
0.98
2.70
0.98
1.59

(0.861.17)
(0.861.12)
(1.933.78)
(0.591.63)
(1.361.86)

1.19 (1.031.38)

1.20 (1.041.39)
3.29 (2.364.57)
1.24 (0.752.03)

0.98
2.68
0.97
1.60

(0.831.14)
(1.913.75)
(0.591.62)
(1.371.88)

predictor of peak bone mass in pre-menopausal women and

a predictor of BMD in women aged 45 to 64 years and in
older women [5, 22, 28]. We have shown that osteoporosis,
as defined by a T-score of 2.5 at the femoral neck or a Tscore 2.5 at any site is associated with weight, BMI, and
OST in the entire cohort and also in the subgroups of
women aged 4049 years and women aged 5059 years.
The area under the curve for all clinical parameters was
consistent with better identification of osteoporosis at the
femoral neck than at any other site. This may be important
as prospective studies have demonstrated that proximal
femur BMD has a gradient for fracture risk as high as or
higher than that of other sites [29, 30].
To evaluate the prognostic performance of weight, BMI,
and OST, we tested thresholds found to be predictive in
previous studies, mostly performed in post-menopausal
women. In a cohort of Canadian women aged 45 years and
over, weight below 70 kg had a sensitivity of 87% and a
specificity of 48% in identifying osteoporosis at the femoral
neck (40% of the cohort was below the age of 65 years)
[22]. We documented a sensitivity of 89.4% and a
specificity of 42.4% at a weight threshold of 70 kg for
predicting a femoral neck T-score of 2.5 or less. Body
weight below 58 kg has found to be predictive of hip
fractures in post-menopausal women in the Study of
Osteoporotic Fractures [5].
A BMI of 25 kg/m2 has been identified as the reference
point below which the risk of hip and any osteoporotic
fracture starts to increase [11]. Similar conclusions were
reached in the Study of Osteoporotic Fractures using a BMI
of 26.2 kg/m2 [5]. With a BMI cut-off point of 26 kg/m2,

we found that the diagnostic accuracy for classifying

women as osteoporotic or as having an incident fracture
was similar to using a weight criterion of 70 kg.
OST of >1 has traditionally been used to determine low
risk designation in post-menopausal women [31]; in a
cohort of post-menopausal women aged 4565 years, the
accuracy of OST for femoral neck T-score 2.5 at a cutoff value 1 was 89.2% and 45.0% for sensitivity and
specificity respectively [24]. With our data, the cut-off
value that produced a sensitivity of 86% and a specificity of
49% was 3. Our findings are in close agreement with a
recent report from the Study of Osteoporotic Fractures that
compared several fracture risk assessment tools (including
OST) to identify low hip and lumbar spine BMD in 7,779
US women aged 67 years and older. OST had the greatest
area under the ROC curve (AUC 0.76, 95% CI 0.740.77).
Using published cut-off points, the risk tools had sensitivities of 85% and specificities of 48% [32].
Recently, the World Health Organization has proposed a
10-year fracture prediction tool, validated in multiple
cohorts of men and women over 40 years of age, which
incorporates a number of clinical parameters (including
BMI) and BMD at the femoral neck [33]. Prediction tables
have been created to estimate risk, based on BMI in the
absence of BMD measurement, which could be of use in
regions where DXA is unavailable.
The positive predictive values of these anthropometric
markers at cut-off points of high sensitivity were low (data
not shown); this is in keeping with the low prevalence of
osteoporosis and fractures in this young population and the
low specificity of the tests.

Osteoporos Int (2009) 20:363370

An important finding of our study is the association

between lower weight or BMI and an increased risk of
osteoporosis-related fractures in this younger population.
With each standard deviation decrease in weight or in BMI,
the age-adjusted risk for fractures increased by approximately 18%. Results were comparable with OST. We were
unable to show an independent effect of weight or BMI on
the risk of osteoporotic fracture after integration of femoral
neck BMD into the models. De Laet came to similar
conclusions in a meta-analysis in which the age-adjusted
risk for any fracture increased with lower BMI; after
adjusting for BMD, BMI was not found to be predictive
of fracture risk except for hip fracture [11]. This suggests
that BMD may be an important intermediate in the causal
pathway.
The presence of fractures was associated with an almost
three-fold increase in the risk of fractures, as documented in
other populations [33, 34]. This association was independent of BMD and underlines the importance of identifying
women with this strong clinical marker for recurrent
fractures.
The determination of thresholds for high or low risk of
outcomes depends on the clinical context and varies with
expected benefits and costs associated with further testing,
high risk designation and availabilities of effective interventions [35]. Pharmacological interventions have proven
successful in reducing the risk of fractures in women
selected mostly on the basis of low BMD and/or the
presence of fragility fractures [1].
Interventions specifically aimed at clinical risk factors
have been not been extensively studied and have not been
shown to reduce fracture risk. Behavioral changes and
multi-faceted approaches are necessary for long-term
beneficial impact on body weight [36]. Preservation of
proper weight should be encouraged as weight loss has also
been related to further reduction in bone strength and
fractures [37].
Our study has multiple strengths; this is the largest study
to evaluate the association between weight, BMD, and
fractures in women aged 40 to 59 years. We have used two
statistical approaches to assessing the strength of association between the variables and the outcomes of osteoporosis
and fracture. First, the discriminatory performance of
weight, BMI, was evaluated with measures of sensitivity
and specificity and receiver operating characteristic curves,
and second, the risk of fractures as function of weight and
BMI and other baseline predictors was modeled in a
multivariate regression. Both techniques yielded comparable results that are consistent with data documented in
observational studies and clinical trials performed in older
women.
Because of the observational study design and the lack
of information on clinical variables in the database, we

369

were unable to control for menopausal status, family history

of fracture, alcohol and tobacco use, and history of
rheumatoid arthritis, which have all been shown in metaanalyses to predict fractures in older women [8]. Nonetheless, we were able to adjust for age, BMD, systemic
corticosteroid use and the presence of prior fractures; these
variables have been selected for being highly predictive of
incident fractures in clinical prediction tools and have
proven to reflect a higher risk of fracture in our population
as well [38]. Our cohort consisted of women referred for
BMD testing, and perhaps at higher risk of fractures than
the general population of similar age, and this limits the
generalizibility of our study. We have documented incident
fractures in 2.7% of all women during the study period. In
women with no prevalent fracture or use of corticosteroids,
this proportion was slightly lower at 2.3%. Referral bias
had little effect on mean Z-scores for our cohort, as documented by the fact that those scores were in close agreement with manufacturer reference data (within 0.2 SD of
the expected value).
In summary, we have shown that low weight and BMI at
specific thresholds of 70 kg and 26 kg/m 2 predict
osteoporosis as determined by BMD with good sensitivity,
but low specificity in women aged 4059 years. We have
also demonstrated the importance of prevalent fractures in
predicting future fractures in that age group. In multivariate
analysis, BMI and weight were found to be associated with
fracture risk independent of prevalent fracture and use of
corticosteroids, but were dependent on BMD. We conclude
that the measurement of simple clinical variables such as age,
fracture history, and weight (or BMI) in areas where BMD
testing is not readily accessible or limited facilitates the
identification of middle-aged women at risk of osteoporosis
and related fractures. The negative impact of low body
weight on bone health should be more widely recognized.
Acknowledgements We are indebted to Manitoba Health for
providing data. The authors had full access to all of the data in the
study and take responsibility for the integrity of the data and the
accuracy of the data analysis. The results and conclusions are those of
the authors, and no official endorsement by Manitoba Health is
intended or should be inferred. This article has been reviewed and
approved by the members of the Manitoba Bone Density Program
Committee. This study was supported in part by an unrestricted
educational grant from the CHAR/GE Healthcare Development
Awards Programme.
Conflicts of interest S. Morin: honoraria for lecture and advisory
board membership from Merck Frosst, Procter & Gamble, sanofiaventis, Novartis, E. Lilly, Servier, and Amgen.
W.D. Leslie: honoraria for lectures in the past year: Merck Frosst
Canada.
Unrestricted educational and research grants: Merck Frosst Canada,
The Alliance for Better Bone Health - sanofi-aventis and Procter &
Gamble Pharmaceuticals Canada, Novartis Pharmaceuticals Canada.
James T. Tsang: No conflicts.

370

Osteoporos Int (2009) 20:363370

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