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382
Review
J Clin Med Res. 2017;9(5):382-387
ress
Elmer
Gender Disparities in Osteoporosis
Khaled A. Alswat
Abstract
Osteoporosis is a growing health concern worldwide and its compli-
cations are as prevalent as other common chronic disease complica-
tions such as hypertension and diabetes. In this review, we will dis-
cuss the role of gender in osteoporosis, especially related to peak bone
mass and maturation, rate of annual bone loss, screening, prevalence
of osteoporosis and its related fractures, mortality after osteoporosis-
related fracture, fracture risk predication using different technologies
and the impact of gender on osteoporosis management.
Keywords: Osteoporosis; Men; Fracture and dual energy X-ray ab-
sorptiometry
Introduction
Osteoporosis is dened as a decrease in bone density that re-
sults in micro-architecture deterioration, which predisposes
affected patients to fractures. It is recognized as the most com-
mon form of metabolic bone disease, with an estimated 200
million people affected worldwide [1]. Aging is one of the
main risk factors for osteoporosis and osteopenia.
Clinicians believe that the decline in bone density and its
complications solely affect postmenopausal women, which
may create health disparities. However, osteoporosis and its
complications affect both genders but at different ages and
rates [2]. Osteoporosis is four times more common in women
than in men, but some evidence indicates that men tend to have
more osteoporosis-related complications [3, 4].
Peak Bone Mass and Maturation
To understand gender differences in osteoporosis, the physiol-
ogy of bone maturation and the skeletal growth must rst be
understood. Boys usually achieve similar or higher bone den-
sity but at a later age compared with girls, which was shown
in a Swiss study that assessed the bone mass in 207 healthy
girls and boys, aged 9 - 18 years [5]. They determined the bone
density and content using dual energy X-ray absorptiometry
(DXA) at three major sites: the lumbar spine, femoral neck and
mid-femoral shaft. Boys compared with girls showed a signi-
cant age-related delay in lumbar spine density irrespective of
puberty, but at the age of 18 years, both boys and girls reached
a similar bone density. Lumbar spine bone content and femoral
shaft bone density were signicantly higher at age 18 years in
boys, which was related to a reduction in bone mass growth
that was observed after the age of 15 years in girls. Femoral
neck bone density was not signicantly higher in boys at age
18 years compared with girls. Some weaknesses of this study
were that it was limited to the Caucasian population, the sam-
ple size was small and it was not controlled for other important
variables such as maternal vitamin D, which has been shown to
impact the peak bone maturation [6]. The observed difference
in bone mineral density (BMD) may be caused by an increase
in the bone size and this is also supported by similar volumet-
ric bone density observed between both genders [7, 8].
Information on the impact of activity and nutrition on the
skeletal maturation is limited. A study evaluated the impact of
diet and physical activity on bone density in the lumbar spine,
the entire femur and the distal third of the radius using a DXA
scan in a sample of 51 male and 75 female students, aged 19
- 25 years [9]. Bone density was higher in males at the three
measured sites compared to females, with males achieving
peak density later than females, especially in the lumbar spine.
This difference was not explained by varying nutrition or the
level of physical activity. However, physical activity and nutri-
tion play a role in osteoporosis prevention [10].
Males tend to have a higher lean mass percentage com-
pared with females, which was shown in a small study of a
group of 36 healthy males and females with a comparable
body size and a mean age of 18 years. Controlling for lean
mass, males had 8% higher bone density at the hip than fe-
males [11]. In a subset of males and females in the same study
who were matched for hip bone area, males still had greater
bone mineral density and content at the hip.
In summary, males tend to have higher bone density and
content and they achieve it at later age compared with females.
This difference is not explained by nutrition, level of physical
activity, body weight or lean mass, but it may be because of
the bone size.
Bone Loss
Gradual bone loss is common with aging and here we will
Manuscript accepted for publication March 01, 2017
Department of Internal Medicine, Taif University School of Medicine, Taif,
Saudi Arabia. Email: kalswat@hotmail.com
doi: https://doi.org/10.14740/jocmr2970w
Articles © The authors | Journal compilation © J Clin Med Res and Elmer Press Inc™ | www.jocmr.org
383
Alswat J Clin Med Res. 2017;9(5):382-387
evaluate the role of gender in the rate of annual loss, age of
onset, risk factors and the bone markers.
Women tend to have younger onset of bone loss compared
with men. A longitudinal study, which included 769 men and
women 60 years of age and older, evaluated the annual bone
loss using DXA scans at an interval of 2.5 years. The estimated
annual bone loss at the femoral neck was 0.82% per year for
men and 0.96% per year for women, which was statistically
signicant, but there was no signicant loss at the lumbar spine
in either group, likely because of coexistent osteoarthritis [12].
In the same study, the age range where the rapid decline oc-
curred was 74 - 79 years for men compared with 65 - 69 years
for women.
Women also tend to lose bone at a faster rate, which was
positively correlated with weight loss in both genders and
with smoking in men. The Framingham Osteoporosis Study
evaluated the BMD at the hip, lumbar spine and the radius in
800 elderly men and women with mean age of 74 years [13].
They showed that the average 4-year bone loss at all sites
was 0.2-3.6% for men compared with 3.4-4.8% for women.
This study also showed that weight loss for both genders was
signicantly associated with osteoporosis, while men who
smoked at baseline were more likely to lose BMD at the hip
than women.
Bone loss markers and periosteal apposition may explain
the difference that is seen in the amount of the bone loss be-
tween genders. A small study evaluated the bone turnover
markers in 28 healthy elderly men and women; there was no
gender difference in bone formation markers but men tended
to have higher parathyroid hormone and lower urinary N-telo-
peptide compared with women [14]. The ratio of the periosteal
to the endosteal bone is an important factor in bone strength.
Men, to a greater degree than women, lose more endosteal
bone but men gain more periosteal bone, which results in a net
loss of bone in men [15].
Estrogen deciency plays an important role in osteoporo-
sis development for both genders, and it is more pronounced
for women and at younger (menopausal) ages compared with
men [16, 17]. It is been estimated that approximately 20% of
the elderly men with osteoporosis have hypogonadism [18].
In summary, men and women tend to lose bone but wom-
en tend to lose bone at younger age and at a more rapid pace
than men and they also have higher bone resorption markers.
Smoking and weight loss are important modiable risk factors
that should be targeted when such patients are evaluated. The
periosteal gain in men ameliorates the endosteal bone loss and
results in more bone strength compared with women.
Prevalence of Osteopenia and Osteoporosis
The World Health Organization (WHO) established a classi-
cation for BMD (using DXA) in which the T-score of 2.5
SD or more below the young-adult mean BMD is dened as
osteoporosis [19]. The National Health and Nutrition Exami-
nation Survey (NHANES) that was performed from 1988 to
1994 evaluated hip bone density using a DXA scan for men
and women aged ≥ 50 years. The prevalence of hip osteope-
nia and osteoporosis was 18% and 2% for men compared with
56% and 16% for women, respectively [20].
The NHANES 2005 - 2008 study that evaluated the bone
density of the hip and lumbar spine showed that the preva-
lence of osteopenia and osteoporosis at either site was 38%
and 4% for men compared with 61% and 16% for women, re-
spectively [21]. Comparing data from both NHANES studies,
the prevalence of osteopenia and osteoporosis was doubled for
men while it was remained about the same for women. This is
likely because the screened population in both studies included
a much older male population. A recent study showed the com-
parable prevalence of osteoporosis for men aged 70 years or
older and women aged 65 years [22].
The age-specic increase in the prevalence of low bone
density according to the recent NHANES data showed a rapid
increase in the prevalence of osteopenia and osteoporosis in
both genders but at different ages and magnitudes [21]. In
women, the prevalence of osteopenia rapidly increased at age
of 60 years and that of osteoporosis rapidly increased (tripled)
at age of 70 years. In men, prevalence increased at the age of
80 years and the rate of osteoporosis doubled.
In summary, women aged 50 years or older have a four
times higher rate of osteoporosis and a two times higher rate of
osteopenia compared with men.
Screening Recommendations
Screening recommendations from health-related societies and
organizations vary and few have clear recommendations for
osteoporosis screening in men; most recommend screening for
any men aged 70 years and older (Table 1).
Despite these recommendations, few studies showed what
can be best described as disparities for males regarding the
osteoporosis screening. In a study that evaluated 8,262 patients
who were eligible for osteoporosis screening based on the age
criteria, only patients who had at least one health maintenance
examination since becoming eligible for screening based on
age were included, to ensure that the physician had the chance
to discuss preventive services [22]. They found that 60% of the
women and only 18.4% of the men had undergone DXA for
osteoporosis screening.
Another study evaluated the osteoporosis screening rate
for 310 male patients, aged 70 years or older, in a primary care
clinic setting [23]. Only 11% of the eligible men, based on age,
had undergone a DXA scan and the majority of the screened
men were 80 - 89 years of age, while none of the men aged >
90 years had undergone a DXA scan.
A retrospective study evaluated the rate of osteoporosis
screening for high-risk patients, including 95 men and 344
women aged 50 years and older who had a distal radial fracture
[24]. They found that 10% of the women and only 9% of the
men had undergone a DXA scan for osteoporosis.
Another study, which included patients aged 65 years or
older, evaluated the rate of osteoporosis screening with DXA
scan after a hip fracture diagnosis and showed that 12.1% of
women and only 5.4% of the men underwent a DXA scan [25].
A similar study evaluated the screening rate among 363 pa-
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Gender Disparities in Osteoporosis J Clin Med Res. 2017;9(5):382-387
tients aged 50 years and older who had history of atraumatic
hip fracture, and only 11% of men and 27% of women had
undergone a DXA scan within 5 years before the fracture [26].
It is still unclear why men tend to be offered less screening
than women. The older age of onset, the high amount of co-
morbidities that such patients may have, the physician’s and
patient’s lack of awareness and the insurance coverage in part
may explain this phenomenon [23].
In summary, clinicians need to improve osteoporosis
screening among eligible individuals, and in general, men tend
to be under-screened for osteoporosis compared with women.
Age may play a main role in such differences seen in osteopo-
rosis screening.
Screening Tools
Several technologies are currently available to assess bone
density, but few have been validated to predict the future risk
of fractures. The most widely available, well-validated tool
to screen for osteoporosis and predict the risk of future frac-
tures for both genders is the central DXA scan [27]. The cen-
tral DXA device measures the BMD at the hip, distal radius
and spine, while peripheral DXA measures BMD at the wrist,
heel or nger. Other than central DXA, other technologies like
pDXA and quantitative CT scan may be used to screen for os-
teoporosis, but they are limited to the age and the gender group
for which they were validated. In addition, these technologies
other than cDXA scan should not be used for treatment moni-
toring until more data are published.
The currently available screening tools have been validat-
ed to predict the risk of the future fracture for postmenopausal
women, while only the central DXA and the quantitative ultra-
sound have been validated for men (Table 2).
Although The Fracture Risk Assessment Tool (FRAX) is
widely used to predict the risk of future fractures, it has been
shown to underestimate the risk of fractures in men compared
with women [28, 29]. However, it is still useful and recom-
mended to be used for fracture risk predictions in men and
women [30].
In summary, central DXA scan still is the best modality
to diagnose osteoporosis and to predict the risk of the future
fractures for men and women. More studies are needed to as-
sess the validity of the other tools to be used routinely in eligi-
ble men who are at risk. The FRAX calculator can be used to
predict the fracture risk, but clinicians should be aware that it
underestimates the risk in men.
Fractures
Before the age of 50 years, men tend to have more fractures
than women, and these fractures mainly involve the limbs and
result from a higher frequency of trauma from sports activi-
ties [31]. In a study that evaluated the gender-specic fracture
site among 5 million adults aged 20 years and older, the most
common fracture was the carpal bone in men compared with
forearm fractures for women [31]. In the same study, the esti-
mated lifetime risk was 20.7% for men compared with 53.2%
for women.
Table 1. Summary of the Osteoporosis Screening Recommendations
Society/organization
Recommendations
Women Men
National Osteoporosis Foundation
International Society for Clinical Densitomety
Endocrine Society
All women > 65 years and postmenopausal
women with risk factors
All men > 70 years or men aged 50 - 69
years with risk factors
World Health Organization
American Association of Clinical Endocrinologist
United States Preventive Services Task Force
American Academy of Family Physicians
Women > 65 years old No recommendation
Canadian Osteoporosis Society Women > 65 years Men > 65 years
American College of Physician
UK National Osteoporosis Guideline Group
Assess the risk factors and consider DXA scan for those at risk for osteoporosis
Table 2. Fracture Risk Prediction Using Different Technologies in Men and Women
Technology Fractures risk prediction in men Fractures risk prediction in women
Quantitative ultrasound (QUS) Non-vertebral and hip fractures
only (men > 65 years old)
Hip, vertebral and global fractures (postmenopausal only)
Peripheral DXA (pDXA) Lack of evidence Vertebral and global fractures- weaker than QUS (postmenopausal only)
Quantitative computer
tomography (QCT)
Lack of evidence Vertebral fractures only-as good as central DXA (postmenopausal only)
Peripheral QCT (pQCT) Lack of evidence Hip fractures only (postmenopausal only)
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Alswat J Clin Med Res. 2017;9(5):382-387
For the vertebral fractures, the fracture incidence rapidly
rises for women at the age of 55 years compared with an age of
65 years for men. For the hip fractures, the fracture incidence
rapidly rises at the age of 65 years for women compared with
the age of 75 years for men [32].
The increased fractures that are observed in women may
be explained by their smaller bone size, early onset increased
bone resorption and fall risk. Larger bones in men are some-
what protective and increase the bone strength compared with
women [33]. The risk of falls increases as patients age, and by
the age of 85 years, it is estimated to reach to 138.5 for men
and 158.8 for women per 1,000 patients [34]. Higher androgen
levels are associated with a decreased risk of falls [35].
A DXA scan as a predictor for the non-vertebral and hip
fractures was evaluated in a population-based cohort study con-
ducted in 1990 - 1993, which enrolled 7,806 men and women
aged 55 years and older [36]. Men tended to have fractures at
non-vertebral sites with a higher bone density compared with
women, while BMD is comparable in both genders for hip
fractures. This can be explained by the degenerative changes
in men, which can falsely increase the BMD. We conclude that
a DXA scan alone may not be a sensitive enough tool to predict
non-vertebral fractures for men aged 50 years and older.
In summary, women tend to have fractures about 5 - 10
years earlier than men and have a higher lifetime risk of frac-
tures. The excess fractures observed in women may be ex-
plained by their smaller bone size and their increased risk of
falls. In addition, men usually have fractures at a higher bone
density and at non-vertebral sites.
Mortality After Fractures
Overall, men have a shorter life expectancy compared with
women [37]. Men also have a higher mortality rate after sus-
taining a hip fracture compared with women. The risk of mor-
tality after a hip fracture was assessed in a population-based
prospective study that included 1,338 women and 487 men
with hip fractures, aged 50 years and older, who were matched
with 11,086 and 8,141 controls, respectively [38]. In the rst
year and irrespective of age, men had a higher mortality rate
after hip fracture compared with women (31% and 17%, re-
spectively). Compared with the control and for patients aged <
75 years, the relative risk of mortality was 4.2 for men and 3.3
for women, and for those aged > 85 years, the relative risk of
mortality was 3.1 for men and 1.6 for women.
More recently, a nationwide Danish registry-based cohort
study that included > 41,000 patients with hip fracture from
1999 to 2002 with a follow-up period until 2005, was published
[39]. Men had fractures at an age that was 4 years younger than
of women, with a cumulative mortality at 1 year of 37.1% in
men and 26.4% in women compared with the general popula-
tion. Long-term survival, which was assessed after controlling
for age, medications, fracture site and comorbidities, showed
that men had a 70% higher risk of mortality compared with
women, which was statically signicant.
Infection is one possible explanation for the observed
mortality rate. One study evaluated the possible predisposing
factors for such excess mortality after hip fracture and con-
cluded that the preexisting comorbidity, type of fracture, type
of surgery and operative complications did not explain the ob-
served gender difference [40]. However, infection, especially
septicemia and pneumonia, may explain the higher risk of
mortality in men who have a greater magnitude of infection.
When they adjusted for the infection, the risk of mortality was
similar for both genders.
Both intravenous and oral bisphosphonate has been shown
to independently reduce the risk of mortality when instituted
after a patient’s sustained hip fracture and for frail older pa-
tients [41, 42]. Men tended to receive less bisphosphonate pre-
scriptions compared with women after hip fractures [25].
In summary, regardless of age or comorbidities, men have
a higher risk of mortality following hip fracture. Infection and
poor medical management may explain the higher rate of mor-
tality observed in men.
Medical Management
While all of the currently available agents for osteoporosis
management are approved for postmenopausal women, most
are validated for men with osteoporosis. For men with osteo-
porosis, the preferred bisphosphonate agents are alendronate,
zoledronic acid and risedronate [43-45].
Prevention and management of osteoporosis after frac-
tures is not optimal for both genders, but it is worse for men.
A study was performed that included 615 patients aged 55
years or older who are on prednisone (≥ 7.5 mg for at least 3
months), and osteoporosis prophylaxis management who were
evaluated between 2001 and 2005 [46]. In 2005, osteoporosis
prevention treatment in women improved signicantly while
that in men was unchanged compared with 2001. In 2005,
women received more osteoporosis prevention treatment (Ca,
vitamin D, and/or bisphosphonate) compared with men (72%
vs. 45%) and bisphosphonate was used in their treatment more
frequently than for men (61% vs. 39%).
The improvement of bisphosphonate use within 6 months
from the osteoporosis-related fractures was assessed in a ret-
rospective cohort study that included 1,171 men aged 65 years
and older between 1998 and 2001 [47]. There was an increase
in bisphosphonate use, but it did not reach statistical signi-
cance (13% in 1998 compared to 18% in 2001). Men were also
undertreated after distal radial fractures and the male gender is
an independent predictor for subsequent treatment failure after
the fracture [24].
Between 2000 and 2010, 417 patients with the discharg-
ing diagnosis of hip fracture were analyzed [25]. Men were
less likely to receive osteoporosis treatment (8%) compared
with women (23.3%). Another study evaluated the percent of
patients who received the appropriate medical treatment after
fragile hip fractures, 1 - 5 years after discharged. Only 9% of
men compared with 48% of women received the appropriate
medical treatment [26].
In summary, men were less likely to receive medical treat-
ment for osteoporosis prevention and treatment even when
they sustained fractures.
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Gender Disparities in Osteoporosis J Clin Med Res. 2017;9(5):382-387
Conclusion
Men have a higher BMD at the hip and a higher bone mineral
content at the lumbar spine. Women start losing bone at an ear-
lier age and at a faster rate than men. Women ≥ 50 years of age
have a four times higher rate of osteoporosis and a two times
higher rate of osteopenia, and they tend to have fractures 5 - 10
years earlier compared with men. Men usually have fractures
at a higher bone density, especially at the lumbar spine, and
they tend to have a higher mortality risk after the hip fracture.
Men are under-screened for osteoporosis and they are also un-
dertreated even when they have fractures.
Conicts of Interest
None.
Funding
None.
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