Full text of DOI:10.1359/jbmr.2001.16.1.120

JOURNAL OF BONE AND MINERAL RESEARCH
Volume 16, Number 1, 2001
©
2001 American Society for Bone and Mineral Research
Fracture Site-Specific Deficits in Bone Size and Volumetric
Density in Men with Spine or Hip Fractures
1
1
1,2
1
EGO SEEMAN, YUNBO DUAN, CHRISTOPHER FONG, and JAN EDMONDS
ABSTRACT
To study the structural basis of bone fragility in men, we compared bone size and volumetric bone mineral
density (vBMD) of the third lumbar vertebra and femoral neck in 95 men with spine fractures, 127 men with
hip fractures, and 395 healthy controls using dual-energy X-ray absorptiometry (DXA). The results were
expressed in absolute terms and age-specific SD scores (mean ؎ SEM). In controls, vertebral body and femoral
neck width increased across age, being 0.46 ؎ 0.11 SD and 0.91 ؎ 0.08 SD higher in elderly men than in young
men, respectively (both, p < 0.001). Men with spine fractures had reduced vertebral body width (؊0.45 ؎ 0.10
SD; p < 0.01) but not femoral neck width (؊0.15 ؎ 0.10 SD, NS). Men with hip fractures had reduced femoral
neck width (؊0.45 ؎ 0.11 SD; p < 0.01) and vertebral body width (؊0.25 ؎ 0.10 SD; p < 0.05). The deficits
in bone volume (BV) exaggerated the deficits in bone mineral content (BMC) by 40% at the vertebrae in men
with spine fractures and by 9% at the femoral neck in men with hip fractures. vBMD deficits were greater at
the vertebrae in men with spine fractures than in men with hip fractures (؊1.37 ؎ 0.08 SD vs.؊0.70 ؎ 0.10
SD, respectively; p < 0.01) but were similar at the femoral neck (؊0.93 ؎ 0.10 SD and ؊0.76 ؎ 0.11 SD,
respectively, NS), despite the men with spine fracture being 10 years younger. Bone fragility leading to spine
or hip fractures in men may be the result of fracture site–specific deficits in bone size and vBMD that have
their origins in growth, aging, or both. (J Bone Miner Res 2001;16:120–127)
Key words: bone size, volumetric bone mineral density, spine fracture, hip fracture, men
INTRODUCTION
will be either obscured or underestimated leading to the
erroneous conclusion that neither reduced accrual nor ex-
cessive bone loss occurred.
N
THE study of the pathogenesis of bone fragility of
Thus, the failure to recognize influence of bone size on
the BMC and aBMD measurement leads to (1) failure to
consider the independent contribution of bone size to bone
I
women or men, patients are grouped together because
they have “one or more nontraumatic” spine fractures or a
hip fracture “sustained in a fall from no greater than the
standing position.” The patients are consistently reported to fragility; (2) failure to consider the potential contribution of
have deficits in bone mineral content (BMC) or areal bone reduced periosteal expansion during growth, aging, or both
mineral density (aBMD) usually attributed to excessive to any deficit in bone size in old age; and (3) flawed
(1)
bone loss.
conclusions regarding the existence or magnitude of re-
Because neither BMC nor aBMD fully account for bone duced accrual and bone loss to the deficit in volumetric
(
2,3)
(3,4,9)
size,
reduced bone size and fractures will be exaggerated.
any deficit in BMC or aBMD in patients with BMD (vBMD).
(
4–8)
In
Women with spine fractures may have reduced vertebral
(4–7)
patients with larger bones, any deficit in BMC or aBMD body size.
This deficit in bone size overestimates the
1
Department of Endocrinology, Austin and Repatriation Medical Center, University of Melbourne, Melbourne, Victoria, Australia.
Present Address: Caulfield General Medical Center, Caulfield, Victoria, Australia.
2
1
20

BONE MASS, SIZE, AND VOLUMETRIC BMD IN MEN WITH FRACTURES
121
(4)
deficit in BMC by 48% and aBMD by 16%. Men with
spine fractures also may have reduced vertebral size, but the
contribution of the reduced bone size to the deficit in BMC
(8)
or aBMD has not been quantified. There have been no
studies examining the deficit in vBMD in men with spine
fractures and none examining bone size and vBMD in men
with hip fractures.
To address these issues and gain insight into the patho-
genesis of bone fragility in men with fractures, we com-
pared bone size, BMC, aBMD, and vBMD in men with
spine or hip fractures with age-matched controls. We asked
the following questions. (1) Does bone size increase with
advancing age in healthy men? (2) Do men with spine or hip
fractures have reduced bone size at the fracture site? (3) Are
there differences in bone size, BMC, aBMD, and vBMD of
the vertebrae and the femoral neck that distinguish men with
spine or hip fractures?
MATERIALS AND METHODS
FIG. 1. Diagram showing the geometric measurements of
Subjects
FNAL and femoral neck (FN) width as described in the text.
We studied 95 men aged 45–90 years with one or more
nontraumatic spine fractures. The patients were recruited
from the Metabolic Bone Clinic of Austin & Repatriation lumbar vertebra obtained by posteroanterior (PA) scan-
(2)
(10)
Medical Centre. All the patients had symptomatic spine ning. This measurement overestimates
but correlates
fractures confirmed radiologically by a reduction in verte- with volume determined in vitro by submersion (r ϭ 0.80;
3
bral body height by greater than 20%. We excluded patients p Ͻ 0.001; standard error of estimate (SEE) ϭ 6.2 cm ;
with secondary osteoporosis because of thyroid diseases, Tabensky and Seeman, unpublished data, 1996). Vertebral
primary hyperparathyroidism, multiple myeloma, cortico- vBMD ϭ total BMC (of the vertebral body plus posterior
steroid therapy, and chronic liver or renal disease. We processes)/V. Vertebral body width and height were ob-
excluded patients taking medication known to affect bone tained from the PA scan. The CV ranged from 1.1% to 1.7%
and patients with fractures of the third lumbar vertebra (the for these measurements.
site of measurement of bone size and vBMD).
Femoral neck volume was determined assuming the re-
We also studied 127 men aged 45–95 years with hip gion was cylindrical; V ϭ ␲ ϫ (W/2) ϫ h, where W is
fractures (58 cervical, 59 trochanteric, and 10 unspecified femoral neck width at the middle point of the femoral neck
fractures) sustained after a fall from no greater than the axis length (FNAL) using the DXA ruler option (Fig. 1),
standing position. Hip fractures caused by severe trauma and h is the height of the scanned region of the femoral
(motor vehicle accident) or local pathology were excluded. neck. As h is held constant (1.5 cm), femoral neck volume
About 80% of patients were recruited within 12 months of is determined by width only. FNAL was the distance be-
hip fracture; 20% were recruited within 1–3 years of frac- tween the cortical rim of the femoral head to the periosteal
ture. We excluded patients taking medication or having surface of the greater trochanter. All manual analyses of
illness known to affect bone.
FNAL and width were made by one investigator (Y.D.).
Three hundred and ninety-five healthy male controls aged Measurements were performed on the unfractured femoral
7–91 years with no history of spine and hip fractures were neck. The CV was 1.0% for FNAL and 1.6% for femoral
1
recruited from the local community by advertisement as part neck width based on scanning 10 subjects twice within 3
of the ongoing research in this department. Subjects taking months. The CV ranged from 2.6% to 3.1% for BMC,
medication or having illness known to affect bone were volume, aBMD, and vBMD at the femoral neck.
excluded. All cases and controls were whites. Informed
consent was obtained from all the participants. The study
was approved by the Human Research Ethics Committee of
Statistical analysis
the Austin and Repatriation Medical Center.
The data were expressed in absolute terms and as the
number of SD scores above or below the young normal or
age-matched normal mean (T or Z score, respectively).
Multiple linear regression analysis was used to adjust for the
Measurement of BMC, size, aBMD, and vBMD
(11)
BMC, aBMD, and bone size of the third lumbar vertebra confounding factors of body height and weight.
One-
and femoral neck were measured by dual-energy X-ray sample t-tests were used to determine whether the T or Z
absorptiometry (DXA; DPX-L, Version 1.3z; Lunar Corp., scores differed from zero. Two-sample t-tests were used to
Madison, WI, USA). Vertebral body volume (V) was esti- determine the significance of any difference comparing
3
/2
mated as V ϭ A , where A is the projected area of the third fracture cases with controls or spine with hip fracture cases.

1
22
SEEMAN ET AL.
FIG. 2. Vertebral body
(
(
VB) and femoral neck
FN) width plotted against
age in healthy men (E) and
men with spine or hip frac-
tures (F).
Bonferroni correction of multiple comparisons was carried and clarity, the following results are presented as group
(12)
out.
Results were regarded as statistically significant at means only; SEMs and p values are provided for data not
the 5% level (two-tailed).
shown in the tables.
BMC depends on bone size. To derive the volume-
adjusted BMC or aBMD in patients and age-matched con-
trols, we regressed BMC or aBMD on volume in men aged
Vertebral and femoral neck size in healthy controls
and patients with fractures
1
8–43 years assuming that BMC and bone size are stable
(4)
As shown in Fig. 2 and Table 1, vertebral body and
femoral neck width increased across age in healthy men
(r ϭ 0.17 and r ϭ 0.40, respectively; both, p Ͻ 0.001),
being 0.46 SD and 0.91 SD higher in the elderly men than
in the young men, respectively. Vertebral body volume was
independent of age (r ϭ Ϫ0.01, NS) because vertebral body
width increased (r ϭ 0.17) while vertebral body height
decreased across age (r ϭ Ϫ0.17; p Ͻ 0.001). Men with
spine fractures had reduced vertebral body volume (Ϫ0.73
SD) because of reduced vertebral body width (Ϫ0.45 SD)
and height (Ϫ0.35 SD) but no deficit in femoral neck width
(Ϫ0.15 SD). The deficit in vertebral body width was greater
than the deficit in femoral neck width in men with spine
fractures (p Ͻ 0.02). Vertebral body volume remained
lower after adjusting for body height and weight (Ϫ0.21 Ϯ
during these years. Volume-adjusted BMC ϭ observed
BMC ϩ (mean volume Ϫ observed volume) ϫ slope. Mean
vertebral body volume (cm ) and slope (g/cm ) used in the
formula to derive the volume-adjusted BMC were 69 cm
and 0.34 g/cm , respectively. The corresponding values for
mean femoral neck volume and slope were 14 cm and 0.15
g/cm , respectively. Similarly, volume-adjusted aBMD ϭ
observed aBMD ϩ (mean volume Ϫ observed volume) ϫ
slope. Mean vertebral body volume (cm ) and slope (g/cm
per cm ) used in the formula to derive the volume-adjusted
aBMD were 69 cm and 0.0077 g/cm per cm and mean
femoral neck volume and slope were 14 cm and 0.00015
g/cm per cm , respectively. The deficit in BMC or aBMD
in patients with fractures before size adjustment is caused
by smaller bone size and/or less bone in the bone; the deficit
after size adjustment reflects reduced accrual, excessive
bone loss, or both (ignoring bone loss after the fracture); the
difference between the two is the BMC or aBMD difference
attributable to the difference in bone size.
3
3
3
3
3
3
3
2
3
3
2
3
3
2
3
0
.13 SD; p ϭ 0.10), while femoral neck volume remained
no different from controls.
Men with hip fractures had reduced femoral neck width
(Ϫ0.45 SD) and vertebral body width (Ϫ0.25 SD) relative
to age-matched controls. Femoral neck and vertebral body
volume also were reduced (Ϫ0.42 SD and Ϫ0.37 SD, re-
spectively). After adjusting for body height and weight,
femoral neck volume remained significantly reduced
RESULTS
Results (mean Ϯ SEM; p values) are presented in abso- (Ϫ0.37 Ϯ 0.12 SD; p Ͻ 0.004) while vertebral body volume
lute terms, T scores, and Z scores in the tables. For brevity was no different from age-matched controls (Ϫ0.05 Ϯ 0.12

BONE MASS, SIZE, AND VOLUMETRIC BMD IN MEN WITH FRACTURES
123
TABLE 1. AGE, HEIGHT, WEIGHT, BMI, L3 VERTEBRAL BODY WIDTH, HEIGHT, VOLUME, BMC, ABMD, AND VBMD;
FNAL, WIDTH, VOLUME, BMC, ABMD, AND VBMD IN YOUNG MEN, MEN WITH SPINE OR HIP FRACTURES, AND THEIR
RESPECTIVE AGE-MATCHED CONTROLS
Men with spine
fractures
Age-matched
controls
Men with hip
fractures
Age-matched
controls
Young men
Variables
Age (year)
(n ϭ 104)
(n ϭ 95)
(n ϭ 166)
(n ϭ 127)
(n ϭ 134)
29.3 Ϯ 0.7
178.1 Ϯ 0.7
77.9 Ϯ 1.2
24.5 Ϯ 0.3
66.5 Ϯ 1.2
167.5 Ϯ 0.7*
71.8 Ϯ 1.3*
25.6 Ϯ 0.4*
66.4 Ϯ 0.8
172.7 Ϯ 0.5
79.9 Ϯ 0.8
26.8 Ϯ 0.3
75.5 Ϯ 0.9
169.8 Ϯ 0.7*
68.0 Ϯ 1.1*
72.0 Ϯ 0.7
172.3 Ϯ 0.6
79.0 Ϯ 0.9
26.6 Ϯ 0.3
§
‡
Height (cm)
Weight (kg)
§
§
2
§
§
BMI (kg/m )
23.6 Ϯ 0.3*
L3 vertebra
Body width (cm)
T score
Z score
Body height (cm)
T score
‡
4.55 Ϯ 0.04
4.50 Ϯ 0.05
4.72 Ϯ 0.04
0.42 Ϯ 0.10
—
3.59 Ϯ 0.03
Ϫ0.28 Ϯ 0.08
—
69.12 Ϯ 0.86
0.05 Ϯ 0.08
—
21.23 Ϯ 0.32
Ϫ0.03 Ϯ 0.07
—
1.262 Ϯ 0.015
Ϫ0.04 Ϯ 0.08
—
0.309 Ϯ 0.004
Ϫ0.05 Ϯ 0.09
—
4.65 Ϯ 0.05
0.25 Ϯ 0.14࿣
Ϫ0.25 Ϯ 0.10
3.50 Ϯ 0.04*
Ϫ0.52 Ϯ 0.12
Ϫ0.10 Ϯ 0.11
4.73 Ϯ 0.04
0.46 Ϯ 0.11
—
3.56 Ϯ 0.04
Ϫ0.35 Ϯ 0.10
—
68.60 Ϯ 0.87
Ϫ0.01 Ϯ 0.08
—
21.37 Ϯ 0.36
Ϫ0.01 Ϯ 0.07
—
1.277 Ϯ 0.019
0.04 Ϯ 0.10
—
0.313 Ϯ 0.005
0.05 Ϯ 0.11
—
‡
—
—
Ϫ0.13 Ϯ 0.13
#
Ϫ0.45 Ϯ 0.10
§
3.68 Ϯ 0.03
3.45 Ϯ 0.04*
§
—
—
Ϫ0.67 Ϯ 0.11
#
Z score
Volume (cm )
Ϫ0.35 Ϯ 0.10
3
§
†
68.60 Ϯ 1.13
61.24 Ϯ 1.08*
65.02 Ϯ 1.23*
§
†
T score
Z score
BMC (g)
T score
—
—
Ϫ0.64 Ϯ 0.09
Ϫ0.31 Ϯ 0.11
#
¶
Ϫ0.73 Ϯ 0.10
Ϫ0.37 Ϯ 0.11
§
§
21.38 Ϯ 0.48
14.68 Ϯ 0.35*
18.02 Ϯ 0.50*
§
§
—
—
Ϫ1.37 Ϯ 0.07
Ϫ0.70 Ϯ 0.10
#
#
Z score
aBMD (g/cm )
Ϫ1.53 Ϯ 0.08
Ϫ0.78 Ϯ 0.11
2
§
§
§
1.269 Ϯ 0.019
0.943 Ϯ 0.018*
1.108 Ϯ 0.023*
§
§
T score
Z score
vBMD (g/cm )
—
—
Ϫ1.65 Ϯ 0.09
Ϫ0.82 Ϯ 0.11
#
#
Ϫ1.57 Ϯ 0.08
Ϫ0.81 Ϯ 0.10
3
§
0.311 Ϯ 0.004
0.241 Ϯ 0.004*
0.277 Ϯ 0.005*
§
§
T score
Z score
—
—
Ϫ1.62 Ϯ 0.10
Ϫ0.79 Ϯ 0.12
#
#
Ϫ1.37 Ϯ 0.08
Ϫ0.70 Ϯ 0.10
Femoral neck
FNAL (cm)
T score
Z score
Width (cm)
T score
10.51 Ϯ 0.06
10.58 Ϯ 0.05
0.09 Ϯ 0.15
Ϫ0.04 Ϯ 0.13
3.63 Ϯ 0.03*
0.69 Ϯ 0.09
Ϫ0.15 Ϯ 0.10
15.63 Ϯ 0.26*
0.70 Ϯ 0.10
10.56 Ϯ 0.08
0.12 Ϯ 0.09
—
3.69 Ϯ 0.02
0.86 Ϯ 0.07
—
16.11 Ϯ 0.21
0.89 Ϯ 0.008
—
5.42 Ϯ 0.006
Ϫ0.58 Ϯ 0.05
—
0.956 Ϯ 0.010
Ϫ0.93 Ϯ 0.06
—
0.344 Ϯ 0.006
Ϫ1.05 Ϯ 0.05
—
10.71 Ϯ 0.06
0.35 Ϯ 0.12
0.18 Ϯ 0.10
10.58 Ϯ 0.06
0.11 Ϯ 0.11
—
3.71 Ϯ 0.03
0.91 Ϯ 0.08
—
16.25 Ϯ 0.22
0.95 Ϯ 0.09
—
5.38 Ϯ 0.07
Ϫ0.62 Ϯ 0.06
—
0.943 Ϯ 0.011
Ϫ0.95 Ϯ 0.06
—
0.339 Ϯ 0.006
Ϫ1.10 Ϯ 0.06
—
—
—
†
3.41 Ϯ 0.03
3.61 Ϯ 0.04*
†
—
—
0.61 Ϯ 0.11
#
Z score
Volume (cm )
Ϫ0.45 Ϯ 0.11
3
†
13.81 Ϯ 0.26
15.48 Ϯ 0.30*
†
T score
Z score
BMC (g)
T score
—
—
0.64 Ϯ 0.12
#
Ϫ0.15 Ϯ 0.10
Ϫ0.42 Ϯ 0.11
§
§
6.14 Ϯ 0.12
4.31 Ϯ 0.08*
4.07 Ϯ 0.10*
§
§
—
—
Ϫ1.48 Ϯ 0.07
Ϫ1.68 Ϯ 0.08
#
#
Z score
aBMD (g/cm )
Ϫ1.38 Ϯ 0.10
Ϫ1.55 Ϯ 0.12
2
§
§
§
§
1.121 Ϯ 0.017
0.784 Ϯ 0.014*
0.722 Ϯ 0.014*
§
§
T score
Z score
vBMD (g/cm )
—
—
Ϫ1.90 Ϯ 0.08
Ϫ2.20 Ϯ 0.08
#
#
Ϫ1.35 Ϯ 0.10
Ϫ1.59 Ϯ 0.10
3
0.451 Ϯ 0.010
0.281 Ϯ 0.007*
0.273 Ϯ 0.008*
§
§
T score
Z score
—
—
Ϫ1.67 Ϯ 0.06
Ϫ1.74 Ϯ 0.08
#
#
Ϫ0.93 Ϯ 0.10
Ϫ0.76 Ϯ 0.11
Results are expressed as mean Ϯ SEM. Z scores were adjusted for age only.
All p values remain significant except for femoral neck width and volume ( p ϭ 0.07, 0.08) in hip fracture cases after Bonferroni
adjustments.
BMI, body mass index; L3, third lumbar.
†
‡
§
࿣
*
p Յ 0.01, compared with young men; p Ͻ 0.05, p Ͻ 0.01, p Ͻ 0.001, compared with age matched controls; p Ͻ 0.05,
¶
#
p Յ 0.01, p Ͻ 0.001, compared with zero.
SD, NS). There was no significant difference of age, height,
Comparing the deficits in men with spine and hip frac-
and weight or in the size of the deficits in femoral neck and tures, the deficit in vertebral body volume in men with spine
vertebral size in patients with cervical and trochanteric fractures was greater than the deficit in vertebral body
fractures.
volume in men with hip fractures (p Ͻ 0.01); there was no

1
24
SEEMAN ET AL.
2
TABLE 2. THE OBSERVED AND VOLUME-ADJUSTED VALUES FOR BMC (g) AND ABMD (g/cm ) AT THE L3 VERTEBRA IN
MEN WITH SPINE FRACTURES AND AT THE FN IN MEN WITH HIP FRACTURES
Men with spine fractures
Patients
Controls
Differences
Observed L3 BMC (g)
Volume-adjusted L3 BMC (g)
Observed L3 aBMD (g/cm )
Volume-adjusted L3 aBMD (g/cm )
14.68 Ϯ 0.35
17.29 Ϯ 0.31
0.943 Ϯ 0.018
1.003 Ϯ 0.018
21.23 Ϯ 0.32
21.19 Ϯ 0.29
1.262 Ϯ 0.015
1.261 Ϯ 0.016
Ϫ6.55 Ϯ 0.35
Ϫ3.90 Ϯ 0.31
Ϫ0.319 Ϯ 0.018
Ϫ0.258 Ϯ 0.018
2
2
Men with hip fractures
Controls
Patients
Differences
Observed FN BMC (g)
Volume-adjusted FN BMC (g)
Observed FN aBMD (g/cm )
Volume-adjusted FN aBMD (g/cm )
4.07 Ϯ 0.10
3.85 Ϯ 0.10
0.722 Ϯ 0.014
0.722 Ϯ 0.014
5.38 Ϯ 0.07
5.04 Ϯ 0.07
0.943 Ϯ 0.011
0.942 Ϯ 0.011
Ϫ1.31 Ϯ 0.10
Ϫ1.19 Ϯ 0.10
Ϫ0.221 Ϯ 0.014
Ϫ0.220 Ϯ 0.014
2
2
Results are expressed as mean Ϯ SEM.
L3, third lumbar vertebra; FN, femoral neck.
difference in femoral neck volume in men with spine or hip
fractures. However, the deficit in vertebral body volume in
men with spine fractures was greater than the deficit in
DISCUSSION
We report that (1) advancing age was associated with
femoral neck volume in men with hip fractures (Ϫ0.73 SD increased vertebral body and femoral neck width in healthy
vs. Ϫ0.42 SD; p Ͻ 0.01).
men. Relative to age-matched controls, men with spine
As shown in Table 2, reduced vertebral size was respon- fractures had reduced vertebral body size and men with hip
sible for about 40% of the deficit in vertebral BMC in men fractures had reduced femoral neck size. Deficits in verte-
with spine fractures but only 9% of the deficit in femoral bral body size were greater in men with spine fractures than
neck BMC in men with hip fractures. Similarly, about 19% in men with hip fractures while deficits in femoral neck size
of the deficit in spinal aBMD in men with spine fractures occurred in men with hip fractures only. (2) The smaller
was accounted for by the smaller vertebra. However, there bone size overestimated the deficit in BMC. There was more
was no contribution of the reduced femoral neck size to the contribution of bone size to the deficit in BMC in men with
deficit in femoral neck aBMD in patients with hip fractures. spine fractures than in men with hip fractures. (3) The
FNAL was unchanged with age in healthy men (r ϭ 0.05, smaller bones also had reduced vBMD. (4) Despite a 10-
NS), and was not reduced in men with spine (Ϫ0.04 SD) or year difference in age, men with spine fractures had greater
hip fractures (0.18 SD; Table 1).
vertebral vBMD deficits and similar femoral neck vBMD
deficits compared with men with hip fractures. This site
specificity of the deficits in vBMD persisted after matching
spine and hip fracture cases by age.
vBMD in patients with spine fractures versus hip
fractures
Bone size is an independent determinant of bone
(5,10,13–16)
strength.
We confirmed several cross-sectional
As shown in Table 1 and Fig. 3, vertebral and femoral and longitudinal studies of increasing bone size in vertebral
(17–23)
neck vBMD was reduced in men with either fracture. How- body and femur in men with advancing age.
ever, the deficit in vertebral vBMD in men with spine increase in bone size offsets the fall of bone strength con-
This
(20,23)
fractures was greater than in men with hip fractures 10 years ferred by bone loss.
Vertebral body width increased by
more advanced in age. Femoral neck vBMD was similar in 0.5 SD while femoral neck width increased by 0.9 SD,
men with spine and hip fractures, despite this age differ- increments that are likely to be conservative as secular
ence. Matching men with spine and hip fractures by age changes in bone size underestimate the age-related increase.
(
between 65 to 75 years) did not affect the results (vertebral
The importance of bone size has been underestimated.
vBMD, 0.24 Ϯ 0.01 g/cm vs. 0.29 Ϯ 0.01 g/cm and p Ͻ For example, gender differences in vertebral body compres-
3
3
3
0
0
.01; femoral neck vBMD, 0.28 Ϯ 0.01 g/cm vs. 0.28 Ϯ sive strength disappear after accounting for gender differ-
3
(24)
.01 g/cm , NS). There were no significant differences in ences in bone size. BMD plus the cross-sectional area of
vBMD or bone size in younger men versus older men with bone is a better predictor of bone strength than BMD alone
(
13,14,16)
spine fractures, or younger men versus older men with hip at the spine and hip.
Reduced vertebral size is found
(5,8)
fractures (data not shown). There were no differences in in men and women with spine fractures ; about half of the
vertebral or femoral neck vBMD in men with cervical and deficit in vertebral BMC in women with spine fractures was
(4)
trochanteric fractures.
explained by the difference in bone size. We found that

BONE MASS, SIZE, AND VOLUMETRIC BMD IN MEN WITH FRACTURES
125
FIG. 3. Third lumbar ver-
tebral (L3) and femoral
neck (FN) vBMD plotted
against age in healthy men
(E) and men with spine or
hip fractures (F).
vertebral size was reduced in men with spine fractures, and
The site specificity of the deficits in bone size in patients
femoral neck size was reduced in men with hip fractures with fracture may be related to the normally disparate
relative to age-matched controls, but the deficit in femoral patterns of growth of the axial and appendicular skeleton.
neck size in men with hip fractures was less than the deficit Leg growth proceeds more rapidly than trunk growth before
in vertebral size in men with spine fractures. Moreover, puberty and then decelerates during puberty as trunk growth
(
28)
femoral neck size did not differ in men with spine or hip accelerates.
fractures. before puberty may affect the legs; exposure to illness or
About 40% of the deficit in vertebral BMC in spine risk factors delaying pubertal growth may affect the
Thus, exposure to disease or risk factors
(28,29)
fractures was because of the smaller vertebra, while the spine.
contribution of the smaller femoral neck size to the deficit in vBMD was reduced relative to the age-predicted mean at
femoral neck BMC is less (9%). Increased femoral neck all sites in both types of fracture. However, the deficits in
width has been reported in one study of men with hip vBMD also were site-specific; men with spine fracture had
(25)
fractures. We suggest that the greater deficits in vertebral greater deficits at the spine than men with hip fractures
size may be more important in the pathogenesis of spine while deficits at the femoral neck were similar (despite the
fractures than femoral neck size in hip fractures because age difference). Matching cases with spine and hip fractures
vertebral size disperses loads so stress (load per unit area) by age did not affect the site specificity of the deficits in
diminishes with age in men. Bone size still may be impor- vertebral vBMD. A greater deficit in aBMD of the femoral
tant in hip fracture pathogenesis, but relatively less so than neck than of the spine in women with hip fractures has been
(30–33)
bone size in spine fracture pathogenesis because the trauma reported by several investigators.
is critical in hip fractures. icits are growth or age related is uncertain but, again,
Whether these def-
Whether the reduced bone size in men with spine or hip finding reduced aBMD in offspring and relatives of men and
fractures is caused by reduced attainment of peak bone size women with spine fractures is also consistent with the
or by failed periosteal expansion during advancing age is possibility that the deficits are, at least in part, growth
unclear. We suggest that these size deficits are likely to be related.
growth-related rather than age-related because (1) failed
periosteal expansion should produce greater deficits in older tive of fracture risk and bone strength,
Although BMC, aBMD, and vBMD are equally predic-
(10,34)
the problems
fracture cases than younger fracture cases but this was not produced by the expressions of bone mass such as BMC and
observed, and (2) the offspring and relatives of patients with aBMD should not be ignored. The failure to account for
spine fractures have reduced aBMD, which may be, in part, bone size obscures the structural diversity in patients with
caused by reduced bone size and reduced mineral accru- fractures, overestimates the deficit attributable to reduced
(9,26,27)
al.
accrual or excess bone loss in patients with smaller bones,

1
26
SEEMAN ET AL.
and obscures any deficit in patients with larger bones. The ulate bone size and volumetric density and recognition of
(3)
failure to account for bone size also obstructs progress in the the limitations of bone densitometry.
study of the growth-related or age-related mechanisms re-
sponsible for producing reduced bone size, an independent
determinant of bone strength.
ACKNOWLEDGMENTS
Longer hip axis length has been suggested to be an
independent determinant of risk of hip fracture in women in
We thank senior technologists Ms. Vanessa De Luca and
Patricia D’Sousa for technical assistance during this study.
(35–37)
(25,38)
some,
but not all,
studies. There also is evidence
to suggest that women with hip fractures have greater hip
(37)
axis length than women with spine fractures.
We found
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Trabecular mineral content of the spine in women with hip Received in original form March 28, 2000; in revised form July 27,
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