Title: Vertebral fracture assessment in healthy men: prevalence and risk factors.
Authors: A. El Maghraoui, A. Mounach, S. Gassim, M. Ghazi.
Address: Rheumatology and physical Rehabilitation Department, Military Hospital
Mohammed V, Rabat, Morocco.
1
Abstract
Introduction: vertebral fracture assessment (VFA) is a technology than can reliably and
accurately diagnose vertebral fractures with greater patient convenience, less radiation
exposure, and lower cost than standard spine radiography.
Objective: to study prevalence and risk factors of vertebral fractures using VFA in healthy
men.
Methods: the study cohort consists of a population of 216 healthy men aged between 50 and
79 (mean age, weight and BMI of 63.8 years, 73.3 Kgs and 25.7 kg/m2, respectively). Lateral
VFA images and scans of the lumbar spine and proximal femur were obtained by two
technologists using a GE Healthcare Lunar Prodigy densitometer. Vertebral fractures were
defined using a combination of Genant semiquantitative (SQ) approach and morphometry.
Results: ninety-three percent of vertebrae from T4–L4 and 98% from T8–L4 were adequately
visualized on VFA. Vertebral fractures were detected in 29.6% (64/216) of these men: 34/216
(15.7%) had grade 1 and 30/216 (13.8%) had grade 2 or 3. Twenty one of men with VFAidentified fracture (32.8%) had only a single vertebral fracture, while the other 67.2% had two
or more. Fractures were most common in the mid-thoracic spine and at the thoraco-lumbar
junction. As would be expected, the prevalence of VFA-detected fractures increased with age
and as BMD declined. This group of men had a statistically significant lower weight, height,
calcium consumption and T-score than those without a VFA-identified vertebral fracture.
Regression analysis showed that presence of vertebral fracture was mainly related to the
osteoporotic status (OR: 9.0; 95% CI: 3.5 – 22.8).
Conclusion: VFA allows evaluation of the majority of vertebral bodies in men. Vertebral
fractures are common in healthy men and are related to low BMD.
2
Vertebral fracture is one of the most common consequences of osteoporosis, a major public
health burden worldwide characterized by decreased bone mass and by increased
susceptibility to fractures. Men account for 33–50% of all vertebral fractures, 20–35% of all
femoral fractures and 15% of all distal forearm fractures1. Vertebral fractures are important to
detect because they have been associated with reduced quality of life, increased morbidity and
mortality, and increased risk of future vertebral and non-vertebral fractures2, 3.
The standard method to assess vertebral fracture is radiography of the thoraco-lumbar spine.
However, there is no gold standard for the definition of osteoporotic vertebral fracture4. A
number of methods have been developed for interpretation of spinal X-rays, including the
Genant semi-quantitative method, which has been used as a surrogate gold standard in a
number of key osteoporosis studies5. This approach is more objective and reproducible than
other qualitative methods6. Vertebral morphometry using dual-energy X-ray absorptiometry
(DXA) also known as VFA is a fast, low-radiation technique which produces images that are
of sufficient quality to be used to diagnose the presence of vertebral deformity consistent with
fracture7. VFA has demonstrated utility for vertebral visualization and thus is an important
tool for fracture detection in women and men8, 9. VFA offers “point of service” convenience
for the patient when it is done at the same visit as for BMD measurement by DXA, with far
less radiation than standard radiography10. The effective radiation dose for VFA is about 3050 micro Sieverts (μSv) vs. 1800-2000 μSv for a lateral thoracic and lumber spine X-ray. By
comparison, typical background radiation at sea level in the USA is about 7 μSv per day11.
Clinical risk factors associated with vertebral fractures have been well studied in women12-15.
In contrast, few studies of prevalence and risk factors for vertebral fractures in men exist
especially in healthy and asymptomatic populations.
3
We aimed in the present study to evaluate the prevalence, risk factors and clinical
characteristics associated with vertebral fractures in a cohort of healthy men aged over 50
who had a VFA examination during their bone mineral density (BMD) testing.
Material and methods
Subjects
A total of 216 healthy Caucasian men (age range: 5079 yr) living in the Rabat area
participated in the present study. Rabat is the capital of Morocco with a diverse population
representing most Moroccans. Morocco has a population of 29,891,708 (2004 population
Census), most of whom are Caucasians, and Rabat is a modern city of 627,932 inhabitants
(49.8% male). The subjects were extracted from a database of healthy volunteers aged
between 20 and 79 years which served to establish the normal reference curve of BMD in
Moroccan men. The recruitment was made in part among hospital staff, university students
and lay people contacted by word of mouth. Though the sample was not a true probability
sample, care was taken to ensure representativeness of the general population, enrolling
nearly ten subjects per year of age and with a particular regard to the inclusion of a wide
range of body sizes and activities.
The BMD of the lumbar spine and proximal right femur of these male volunteers with no
previous history of bone disease was measured after they gave informed consent. The study
was approved by the local Ethics Committee. All subjects were fully ambulatory. Screening
was done by physical examination and questionnaires. Men using medications affecting
calcium metabolism and those with medical conditions known to affect bone metabolism or
with a history of any fracture or major systemic disorder were excluded. Thus, we excluded
subjects with non-Caucasian origin, gastrectomy, intestinal resection, recent hyperthyroidism
or hyperparathyroidism, treatment with corticosteroids for more than 6 months, or recent
severe immobilization (last two years). We did not exclude individuals using inhalation
4
steroids or with certain lifestyle habits, such as heavy smoking, being sedentary, being
athletic, or having a high or low calcium intake, which are examples of voluntary factors that
may have some impact on bone metabolism.
Each subject completed a standardized questionnaire designed to document putative risk
factors of osteoporosis. The questionnaire collected information on life style, smoking habits,
and level of physical activity in leisure time, along with calcium consumption and the use of
vitamins and medications. Height and weight were measured in our centre before DXA
measurement with light indoor clothes on, but without shoes. Body mass index (BMI) was
calculated by dividing weight in kilograms by height in meters squared. Lifestyle (alcohol
consumption, gymnastics or jogging/walking, smoking) and diet (milk, yogurt, cheese, coffee,
soda) habits were also recorded. The men were asked whether they usually drank milk, coffee,
soda or alcohol, if they ate cheese or yogurt, if they did gymnastics or jogging/walking, and if
they smoked tobacco. If the answer was positive, they were asked to quantify their average
current consumption (evaluated on the 7 days prior to the interview) of milk or yogurt (mL/d),
cheese (g/d), and wine and/or spirits (mL/d). Tobacco smoking was quantified as average
number of cigarets (smoked/d) multiplied by the number of years of smoking, gymnastics
(defined as a sport involving performance of exercises requiring physical strength, agility and
coordination) as minutes per week, or jogging/walking as minutes per day. Finally, patients
were categorized as never smokers, ex-smokers and current smokers; high, normal and low
calcium intake (more than 1500 mg/d, between 800 and 1500/d and below 800 mg/d
respectively); high, moderate and low coffee intake (more than 3 cups/d, between 1 and 3
cups/d and below 1 cup/d respectively); high, moderate and low soda intake (more than 500
mL/d, between 100 and 500 mL/d and less than 100 mL/d respectively); high, moderate and
low physical activity (more than 3 h/week, 2-3 h/week and below 1h/week respectively).
5
In total, 678 men were screened. Among them 186 individuals were excluded from the study
according to predetermined exclusion criteria, whereas 592 met all inclusion criteria and were
invited to participate in the BMD measurement. Men aged over 50 had a VFA at the same
time of BMD measurement.
BMD Measurement
Bone mineral density was determined by a Lunar Prodigy Vision DXA system (Lunar Corp.,
Madison, WI). The DXA scans were obtained by standard procedures supplied by the
manufacturer for scanning and analysis. All BMD measurements were carried out by 2
experienced technicians. Daily quality control was carried out by measurement of a Lunar
phantom. At the time of the study, phantom measurements showed stable results. The
phantom precision expressed as the coefficient of variation percentage was 0.08. Moreover,
reproducibility has been assessed recently in clinical practice and showed a smallest
detectable difference of 0.04 g/cm2 (spine) and 0.02 (hips)16, 17. Patient BMD was measured at
the lumbar spine (anteroposterior projection at L1-L4) and at the femurs (i.e., femoral neck,
trochanter, and total hip). The World Health Organization (WHO) classification system was
applied, defining osteoporosis as T-score ≤−2.5 and osteopenia as −2.5<T-score<−1. Study
participants were categorized by the lowest T-score of the L1–4 lumbar spine, femur neck, or
total femur. The Moroccan male normative database was used for T-score calculation: the
mean (SD) values for young normal adults in the Moroccan male normative database were
1.205 g/cm2 (0.15) for lumbar spine, 1.147 g/cm2 (0.16) for femoral neck, and 1.161 g/cm2
(0.16) for total hip.
VFA was classified using a combination of Genant semiquantitative (SQ) approach and
morphometry in the following manner: each VFA image was inspected visually by two
clinicians (MG and AM who had a previous training session in VFA) to decide whether it
contained a fracture in any of the visualized vertebrae. Each vertebra that was judged as
6
fractured by visual inspection by any of the investigators was measured using built-in
morphometry and assigned a grade based on Genant SQ scale5, where grade 1 (mild) fracture
is a reduction in vertebral height of 20-25%, grade 2 (moderate) a reduction of 26-40%, and
grade 3 (severe) a reduction of over 40%. Subjects with no fractures were included in the nonfracture group, whereas those with grade 1 or higher fractures were included in the fracture
group. However, as many studies rarely report mild deformities as “fractures”, and to realize
comparisons with the literature, we performed a double analysis including and excluding
grade 1 fractures from the fracture group.
Statistical Analysis
Results are presented as means (SD) and categorical variables are expressed as frequencies.
To compare patients with and without vertebral fractures, chi-square test and analysis of
variance ANOVA were used firstly. Potential risk factors were entered to a stepwise
conditional binary regression analysis and the resulted odds ratios with 95% confidence
intervals were reported. The level for significance was taken as p  0.05. Excel 2007 and
SPSS 15.0 were used for statistical analysis.
Results
Patient demographics
In this cohort of 216 men, the mean ± SD (range) age, weight and BMI were 63.8 ± 8.2 (50 to
79) years, 73.3 ± 12.3 (40 to 106) and 25.7 ± 3.9 (17.0 to 37.5) kg/m2, respectively. All
patients were Caucasian. Vertebral fractures were identified using VFA in 64 (29.6%); this
group of men had a statistically significant lower weight, height, calcium consumption and
lumbar spine and total hip BMD and T-scores than those without a VFA-identified vertebral
fracture (Table 1).
Vertebral visualization and fracture identification on VFA
7
In these 216 men, 93% of vertebrae from T4–L4 and 98% from T8–L4 were adequately
visualized on VFA (Figure 1). The percentage of vertebrae not visualized at T4, T5, and T6
levels was 42.1%, 26.9, and 13.0% respectively. Vertebral fractures were detected in 29.6%
(64/216) of these men: 34 (53.1%) had grade 1 and 30 (46.8%) had grade 2 or 3. Twenty one
of men with VFA-identified fracture (32.8%) had only a single vertebral fracture, while the
other 67.2% had two or more. Fractures were most common in the mid-thoracic spine and at
the thoraco-lumbar junction (Figure 2).
As would be expected, the prevalence of VFA-detected fractures globally increased with age
and as BMD declined (Figure 3). In this study population, 25% (n=55) had normal BMD,
62% (n=135) were osteopenic and 12% (n=26) osteoporotic. Though numerically more VFAidentified fractures occurred in men with osteopenia, the fracture prevalence was higher
(p<0.0001) in men with lower BMD (Figure 4). Interestingly, a fracture was identified on
VFA in 21.8% of men with normal BMD. Stepwise regression analysis showed that presence
of vertebral fracture was mainly related to the osteoporotic status (OR: 9.0; 95% CI: 3.5 –
22.8).
Discussion
About 30% of asymptomatic healthy men over 50 had a previously undiagnosed vertebral
deformity. Sub-analysis of patients by grade of deformity revealed that 30 (13.8%) of the
patients had vertebral deformities of Grade 2 and Grade 3. This prevalence of vertebral
fractures in our population is similar to figures reported in western Caucasian populations as
reported in a recent review18 where prevalence of vertebral fracture (grade 2 and 3) is between
18% and 26%. This is also similar to the reported prevalence of vertebral fractures estimated
at 12% in a sample of 150 healthy Lebanese men over 64 years19.
The spine is a key fracture site20; however, it has been estimated that only 30% of vertebral
fractures receive clinical attention (which means that the majority of patients with vertebral
8
fractures remain undetected)21,
22
. It appears that only those patients with the most severe
vertebral fractures come to clinical attention (it is likely that this is due to higher levels of
back pain and disability). Moreover, even vertebral fractures that are visible on X-rays are
commonly not reported by radiologists23. Under-diagnosis of vertebral fractures on spine Xrays has been observed worldwide, with false negative interpretation rates of about 45% in
North America, 46% in Latin America, and 29% in Europe/South Africa/Australia24. As many
vertebral fractures are clinically unappreciated, but convey increased risk for future fracture,
knowledge of existing fracture status is necessary for the optimal assessment of fracture risk25,
26
.
Although spine radiographs are considered the gold standard for vertebral fracture detection,
Vertebral Fracture Assessment (VFA) offers advantages including patient convenience, lower
radiation exposure, cost effectiveness and ease of directly integrating knowledge of bone
density and fracture status into prediction of future fracture probability, and thus in the
therapeutic decision11, 27-29. The main limiting factor in utilizing VFA is the legibility of the
vertebrae. The difficulty is mostly seen in the upper thoracic vertebrae. However, so few
osteoporotic fractures occur at this level8. Our work reports the ability to visualize a greater
percentage of vertebral bodies than others in the field. This may be explained by two factors:
1.our technicians had been trained before for a long time in the performance of VFA, and 2.
our study population is composed of “healthy” men.
This study is the first large descriptive evaluation of VFA in a population of asymptomatic
healthy men and documents that vertebral fractures are common when searched
systematically and that these fractures are directly related to low BMD. In fact, as could be
expected, the prevalence of vertebral fractures in this cohort of men was higher in those of
older age and with lower BMD. However, similar to prior reports, numerically more fractures
were observed in men with osteopenia. Importantly, approximately 14% of these men (with
9
osteopenia) and 9% of men with normal BMD who otherwise may not have been identified as
being at greater fracture risk were found to have unappreciated evident vertebral fracture
(grade 2 and 3). It is well known in postmenopausal women that about half of fractures occur
in patients without densitometric osteoporosis and that other factors than BMD may play a
role30. In this case, recognition of vertebral fractures by imaging of the spine change the
patient’s diagnostic classification, estimation of fracture risk, and threshold for
pharmacological intervention as treatment of patients with prevalent vertebral fractures
reduces the risk of future fractures even when the baseline T-score is above the osteoporosis
diagnostic cutpoint of -2.5. Thus, these data suggest that T-score (i.e., osteopenia) by DXA
should receive consideration as an indication for performance of VFA in elderly men as it is
now recommended by the ISCD31.
The assessment of prevalent mild vertebral fractures is problematic, as although they
represent a large proportion of the vertebral fractures32, such deformities are sometimes
considered as an expected effect of aging. Indeed, some of grade 1 fractures may be missed
because physicians consider that there is only an expected effect of age, and because their
clinical significance has been a subject of controversy. Actually this point is raised when such
deformities are used to discriminate patients with or without osteoporosis33. However, in our
study, excluding patients with Genant grade 1 did not change the results when comparing
patients with and without vertebral fractures. Moreover, Mild vertebral fractures (grade 1)
have been shown recently to be a risk factor for subsequent vertebral and non-vertebral
fracture in postmenopausal women with osteoporosis34.
Vertebral deformities can be due to developmental abnormalities, Scheuermann’s disease
sequelae, and degenerative changes. Attention must be paid on osteoporotic depressions of the
central end plates of the vertebrae, as osteoarthritic changes occur only on the anterior part of
the vertebrae. The main difficulties are related to isolated short anterior vertebral heights at
10
the mid-thoracic spine. The interpretation of such deformities must take into account
degenerative changes of adjacent discs, and the presence of deformities of similar appearances
on contiguous vertebrae, both signs being more in favor of a non-osteoporotic origin of the
deformity. Vertebral fractures are unlikely to have identical aspect and occur more frequently
to non-contiguous vertebrae, although these signs are not specific of osteoporosis35. Thus, as
we did in our study, the use of the semi quantitative method for fractures assessment needs a
first step of visual identification of nonfracture deformities or normal variants, otherwise the
method may be less specific than the quantitative approach.
Fractures of the spine are associated with reduced pulmonary function, chronic back pain, loss
of height, kyphosis, loss of self-esteem, abdominal discomfort, disability, loss of
independence, and death36. The mortality rate five years after a clinical vertebral fracture is
about 20% greater than expected, with mortality rates higher for men than women. Mortality
rates increase with the number of vertebral fractures37. New vertebral fractures, even those
that are not recognized clinically (i.e., morphometric fractures), are associated with substantial
increases in back pain and functional limitations38. The presence of a vertebral fracture
increases the relative risk of future vertebral fractures by about 4.4-fold, and increases the risk
of fragility fractures at other skeletal sites as well39, 40. The presence of a vertebral fracture is a
risk factor for future fracture that is independent of BMD41. Thus, many societies interested in
osteoporosis management recommend that patients with a prior vertebral fracture receive drug
therapy regardless of BMD T-score42.
Our study has strengths and limitations. The assessment of fracture was carefully conducted
using standard procedures of acquisition, and standard reading of all VFA. All the
morphometric assessments were made by two experienced investigators after training sessions
and after a previous global visualization. Before diagnosis of fracture, a non-osteoporotic
origin was considered for each deformity. However, even history of trauma was inquired, we
11
cannot exclude that some subjects did not report remote traumas. The main limitation lies in
the procedures used to select subjects, who were all volunteers and ambulatory, and
presumably healthier than the general population. The Rabat population may not be
adequately representative of the whole population. However, since the population living in the
area of Rabat is a balanced mixture of the various regions constitutive of the country, we
believe the impact on prevalence estimate is limited.
In summary, VFA is a technology than can reliably and accurately diagnose vertebral
fractures with greater patient convenience, less radiation exposure, and lower cost than
standard spine radiography. Our results support the recommendation to perform VFA in
elderly men referred for DXA measurement especially for whom the diagnosis of vertebral
fracture is likely to influence clinical management and when BMD is low.
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14
Table 1: comparison between patients with and without vertebral fractures.
Patients without
vertebral fractures
N=152
Age: yrs
63.2 (8.1)
Weight: Kgs
74.4 (11.9)
Height: m
1.69 (0.06)
BMI: m/Kg2
25.9 (3.8)
Current tobacco consumption
63 (41.2)
Low calcium consumption
106 (69.7)
High coffee consumption
42 (27.5)
High soda consumption
80 (52.3)
Low physical activity
117 (76.5)
Lumbar spine BMD: g/cm2
1.120 (0.15)
Lumbar spine T-score
-0.5 (1.0)
Total hip BMD: g/cm2
0.905 (0.14)
Total hip T-score
-1.3 (0.7)
Data as mean (SD) or number (percent)
Patients with
Patients with
grade 1 vertebral
grade 2 or 3
fractures
vertebral fractures
N=34
N=30
66.3 (9.3)
64.4 (7.7)
72.4 (11.5)
68.8 (14.2)
1.67 (0.05)
1.66 (0.06)
25.9 (4.1)
24.6 (4.0)
1 (3.0)
6 (20.0)
28 (82.4)
25 (83.3)
9 (26.5)
10 (33.3)
12 (35.3)
16 (53.3)
9 (26.5)
8 (26.7)
1.033 (0.19)
1.031 (0.15)
-1.0 (1.3)
-1.1 (0.9)
0.845 (0.12)
0.706 (0.65)
-1.7 (0.9)
-1.7 (0.8)
P
NS
0.028
NS
NS
NS
0.047
NS
NS
NS
0.026
0.028
0.001
0.005
Figure 1: Vertebral visualization using VFA.
15
Figure 2: VFA-identified fracture distribution.
Figure 3: Vertebral fracture prevalence by age and by Genant grade.
16
Figure 4: Vertebral fracture prevalence by BMD diagnostic category and Genant grade.
17