Best Practice & Research Clinical Rheumatology xxx (2017) 1e23

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Rheumatology
journal homepage: www.elsevierhealth.com/berh

Fragility Fractures & Their Impact on Older

People

nchez-Riera a, b, *, Nicholas Wilson b
Lídia Sa
a
University Hospital Bristol NHS Foundation Trust, Bristol, UK
b
Institute of Bone and Joint Research, The Kolling Institute, Sydney Medical School, St Leonards, NSW,
Australia

a b s t r a c t
Keywords:
Osteoporosis Osteoporotic fractures, in particular hip and vertebral, are a major
Fracture health burden worldwide. The majority of these fractures occur in
Elderly the elderly population, resulting in one of the most important
Burden causes of mortality and disability in older ages. Their cost for so-
Mortality cieties is enormous and is forecast to steadily increase over the
Costs
coming decades globally. Low bone mineral density (BMD) re-
Prevention
Fracture liaison services (FLS)
mains a key preventable risk factor for fractures. Screening and
treatment of individuals with high risk of fracture is cost-effective.
Predictive tools including clinical risk factors, minimisation of falls
risk and public authorities' support to create Fracture Liaison
Services are paramount strategies.
© 2017 Elsevier Ltd. All rights reserved.

Definition of osteoporosis and osteoporotic fractures

Osteoporosis is defined as a systemic skeletal disease characterised by a low bone mass and a
microarchitecture deterioration of bone tissue, with a subsequent increase in bone fragility and
susceptibility to fracture [1]. It behaves as a silent disease. A high percentage of affected people are
not aware that they have the condition. Consequently, osteoporosis burden is better assessed by
measuring the burden of its clinical outcome, i.e. osteoporotic fractures (also known as ‘fragility
fractures), which usually occur after a low-energy trauma, such as a casual fall ‘from standing height
or less’. The osteoporotic fractures with the highest health burden are hip and vertebral fractures,

* Corresponding author. Consultant Rheumatologist, University Hospital Bristol NHS Foundation Trust, Bristol Royal
Infirmary, Rheumatology Department, Upper Maudlin St, Bristol BS2 8HW, UK.

nchez-Riera).
E-mail addresses: [email protected], [email protected] (L. Sa

https://doi.org/10.1016/j.berh.2017.10.001
1521-6942/© 2017 Elsevier Ltd. All rights reserved.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001
2
nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa

which represent a major cause for social and economic costs in present societies. Almost three-
quarters of hip and spinal (vertebral) fractures occur among patients 65 years old or over [2].
There are other peripheral fractures considered to be related to osteoporosis, such as forearm,
proximal humerus, pelvis, rib, distal femur, proximal tibia and clavicle. Some authors have found that
other fracture sites, such as ankle, hand and foot, are associated with low bone mineral density
(BMD) and a subsequent increased risk of fracture [3e5], albeit their presence is not always a sign of
bone fragility and may reflect a certain mechanism of injury.
Interestingly, fractures occurring in sites other than hip and vertebrae (non-hip non-vertebral
fractures) constitute more than half of all fractures in elderly population. The health and economic
burden derived of such fractures has probably been underestimated in the past, in view of the recent
and growing evidence of their contribution in terms of morbidity and mortality [6e9].

Key Messages

Osteoporosis is a silent disease that affects bone mass and quality and increases risk of
fracture.

Hip and vertebral fractures are the fracture types with the highest health burden.

The majority of hip and vertebral fractures occur in populations from 65 years of age.

Non-hip non-vertebral fractures in the elderly are altogether the most common sites of
fracture in the elderly, and they have a significant contribution in the health burden derived
from fragility fractures.

Health consequences of osteoporotic fractures

The consequences of osteoporotic fractures for an individual range from chronic pain, loss of
mobility, and loss of independence to institutionalisation and death [10e12].
Hip is the location of fracture leading to the poorest health outcomes, in part because of the peak
incidence of such fractures occurring in populations that are 70e79 years old [10]; therefore, the
incidence and subsequent loss of health is considerably higher in developed countries [10]. At 1 year
after the hip fracture event, cumulative mortality reaches up to 37% in men and 25% in women, and it is
significantly higher than that in the general population [13,14]. This increase in mortality is particularly
higher in men [13]. About half of the patients lose their prior level of physical function, and many lose
their independence and require long-term care [15e17]. Only half of the survivors will walk again, and
often not at the same level as prior to the fracture [15e17]. A high percentage of affected individuals
report chronic pain after 1 year post-fracture [11].
Vertebral fractures cause pain and limitation of the spinal movement and can have considerable
adverse effect on the overall quality of life [18]. Both prevalent and incident fractures increase steadily
with age from 50 to 80 years [19,20]. One-fifth require hospitalisation, and some will require subse-
quent long-term care [21,22]. Pain and disability become worse with each new fracture, as does the risk
of mortality. Fractures occur more often in the thoracolumbar transition. Spinal mobility is impaired
even in the absence of significant pain. Despite only one-third of the vertebral fractures being
symptomatic [23], undiagnosed vertebral fractures are also associated with pain and disability [21,22].
Comorbidity is common, e.g. kyphosis, restrictive lung disease and spinal stenosis, in particular at
advanced ages, and contributes to the burden on quality of life and increased mortality [24]. In a large
prospective study in the United States of America (USA), women with one or more vertebral fractures
showed 23% greater age-adjusted mortality rate, and this rate doubled in women with 5 or more
vertebral fractures [24]. Similar results were drawn from a longitudinal study in Sweden, where 28% of
all deaths associated with vertebral fracture requiring hospital admission could be attributable to the
fracture itself [25].
Forearm fractures tend to occur in earlier ages than hip and vertebral locations with a peak inci-
dence in women between 40 and 65 years old. Around one-fifth of Colles' fractures (fractures of the
distal radius with dorsal radius displacement, with or without ulna fracture) in developed countries

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001

nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa 3

result in hospitalisation [26], which is often very prolonged in elderly patients [27]. Only 50% report a
good functional outcome at 6 months [28].
Premature death in the first year after a fracture, particularly at the hip site, is closely related to
the short-term outcomes of the fracture [29e31], including the risks associated with prolonged
hospitalisation and those related to the surgical repair or joint replacement that most individuals
require (except for vertebral fractures that more often do not require surgical intervention).
Nevertheless, excess risk for premature mortality after an osteoporotic fracture remains high for
many years. Recent population-based studies with long-term follow-up periods have estimated that
mortality rates remain significantly higher than in the general population for up to 5e15 years after
the fracture event, and this includes not only hip fractures, but also most of the other sites for
osteoporotic fractures (vertebral, pelvis, distal femur, proximal tibia, proximal humerus and multiple
ribs) [5,32]. For all ages, mortality following a fracture is higher in men than in women, particularly
within the first year after the fracture, albeit the difference between mortality rates in both sexes
tends to disappear over time [32].
Hip fractures and clinical vertebral fractures have been shown to be the first and second most
important sites for osteoporotic fractures-related deaths, respectively [5,30,33]. However, some au-
thors have observed that individuals suffering osteoporotic fracture in other sites have a higher risk of
long-term mortality compared to age- and gender-matched peers [5,32,34].
Recently, data from prospective population-based studies have helped to increase the awareness on
the importance of non-hip non-vertebral fractures in the overall burden of osteoporosis, particularly in
elderly population. Non-hip non-vertebral fractures represented three-quarters of all fractures iden-
tified in the nation-wide Canadian multicentre osteoporosis study (CaMos), which included 5526
community-dwelling women and 2163 men aged 50 years and over followed from 1995 to 2013. In
women, the impact of non-hip non-vertebral fractures on population levels of mortality was greater
than that of hip and vertebral fractures because of their higher absolute numbers [9]. Similarly, a
prospective population-based study conducted over an 18-year period in Australia, the Dubbo Oste-
oporosis Epidemiology Study (DOES), showed that non-hip non-vertebral fractures were responsible
for one-fourth of all fracture-related excess mortality for the first 5 years post fracture [5,6]. Mortality
was higher in individuals over 75 years old than in the 60e74 year group and in major osteoporotic
fractures (pelvis, distal femur, proximal tibia, three or more simultaneous ribs and proximal humerus).
Yet, half of that excess in mortality was attributable to the risk of subsequent fractures with high
burden such as hip fracture. The negative outcomes on pain, function, and quality of life have similarly
been highlighted both for major and minor (wrist, hand, ankle and foot) non-hip non-vertebral frac-
tures [8], supporting the notion that the population-wide morbidity associated with these fractures
may have been neglected for a long time.
Predictors of long-term mortality after a fragility fracture include age, quadriceps weakness, frac-
ture site (hip fracture being the site with the highest mortality burden), smoking, low BMD and
comorbidities [5,13,14,35e38].

Key messages

Consequences of osteoporotic fractures include chronic pain, loss of function, institutional-

isation and death.

Hip fractures are associated with high mortality within the first year after the fracture, and
mortality remains higher than in the general population for up to 10 years after the fracture
event.

Vertebral fractures are also associated with higher mortality rates and cause high disability
burden, even when they are asymptomatic.

Non-hip non-vertebral fractures constitute the most frequent type of fractures in the elderly.
Their contribution to population levels of morbidity and mortality has been for long
neglected.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001
4
nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa

Epidemiology of osteoporotic fractures: population trends

Osteoporosis has been estimated to affect 200 million women worldwide, approximately one-tenth of
women aged 60, one-fifth of women aged 70, two-fifths of women aged 80 and two-thirds of women aged
90 [39]. For a person over 50 years living in a developed country, the lifetime risk of sustaining any fracture
in their remaining years of life has been estimated to be approximately 50% for women and 20% for men,
and most of these will be related to osteoporosis [40,41]. Age and female gender are the first and second
most important risk factors, respectively. Almost three quarters of hip and spinal fractures occur among
patients 65 years old or over [2] and, approximately 70% and 58%, respectively, occur in women [12].
The global burden of diseases initiative estimated 9.0 million osteoporotic fractures in the world in
the year 2000, of which 1.6 million were at the hip (70% women), 1.7 million were at the forearm (80%
women) and 1.4 million were clinical vertebral fractures (58% women) [12]. Although hip fractures only
accounted for 18.2% of all fractures, they represented 40% of all the global health burden due to frac-
tures, reflecting the higher mortality and disability of hip fractures compared to other sites. The
greatest number of fractures was in Europe, followed by the Western Pacific region, Southeast Asia and
the Americas. Collectively, these regions accounted for the 97% of the overall number of fractures
worldwide, highlighting the influence of the aging populations on the incidence of osteoporotic
fractures, in particular on hip fracture rate, with a peak number between 75 and 79 years for both men
and women [12]. In Europe, osteoporotic fractures accounted for more health burden lost than
rheumatoid arthritis and all sites of cancer, with the exception of lung cancer [12].
In Western countries, some studies have shown a trend towards a decline in fracture rates in the
elderly. In Australia, there was a significant reduction in the overall fracture incidence rate in women
(4% per year) and men (6% per year) over a 12-year follow-up period from 1989 to 2000 [42]. In the
USA, a study with a stratified random sample of all community hospitals found that the overall
prevalence of osteoporotic hip fracture hospitalisations in the population over age 50 declined 29% in
women and 18% in men, although the proportion of all-cause hospitalisations decreased almost
exclusively in women [43]. In Denmark and Sweden, a recent publication also reported a decreasing
trend of age-standardised hip fracture rates in women from 1987 to 2010 [44]. Overall, age-specific
incidence rates of hip fracture steadily increased in Western populations from the second half of the
20th century until around 1980 and have subsequently reached a plateau or decreased, more pro-
nouncedly in women than in men. This has been shown in North America, Australasia and Europe. In
contrast, a limited number of studies in Asia and South America suggest that age-adjusted rates of hip
fracture are still increasing in these world regions, with the exception of Hong Kong and Taiwan, that
may be following the Western paradigm [45,46]. While forearm fractures seem to follow a similar
pattern to that observed in hip fractures, few studies have suggested that radiologically diagnosed
vertebral fractures and other non-hip non-vertebral major fractures, such as pelvic and rib fractures,
may be increasing in Western population, in particular among very old subjects [45].
Several factors have been argued to potentially contribute to the above-mentioned variations in age-
adjusted incidence rates of osteoporotic fractures, including risk factors affecting bone strength and
susceptibility to fractures in early life and those playing a particular important role relatively late in the
lifetime course [45]. Among them, the lifestyle changes in the second half of the century that led to a
change in the patterns of physical activity and vitamin D insufficiency, as well as the increased survival of
the frail elderly, might all have contributed to the increase in hip fracture rates observed up to the 1980s.
Explanations behind the subsequent plateau of age-adjusted fracture rates are somehow unknown. The
better nutrition, increase in obesity prevalence, and progressive decrease in smoking are among those
postulated as potential contributors. The higher rates of osteoporosis screening and anti-resorptive
prescription therapy seen in the last years, particularly in postmenopausal women, are likely to have
aided the decrease in hip fracture rates. Nonetheless, the plateau in age-adjusted incidence rates
appeared around the same time as the first bisphosphonates were commercialised, which anyway had
low levels of compliance among elderly population. Consequently, it is not so clear how the pharma-
cological treatment of osteoporosis has influenced the age-adjusted fracture rates at a population level.
Finally, the improved methods and accuracy of disease coding and the creation of central databases and
health registries are likely to have biased the uptrend increase in fracture rates. This, for example, could
partially explain the still increasing age-adjusted rates of radiologically diagnosed vertebral fractures.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001

nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa 5

Observing the global incidence, there is an expected increase in the total annual number of fractures
in the following years worldwide because of the changes in population demography. In the European
Union, this increment has been estimated to be 28% from 2010 to 2025 [47]. The number of hip
fractures worldwide increased by 25% in the 10 years from 1990 to 2000 [12], and its global frequency is
projected to increase by three-fold by 2050 compared to 1990 [48]. These figures reflect the predicted
inversion of the population pyramid in developing countries because of their higher birth rates, the
dramatic improvement of perinatal deaths and the general decreasing mortality, resulting in 70% of all
older people worldwide living in developing countries by 2025 [49]. This will result in an enormous
increase in the number of those at high risk for osteoporotic fractures in the world. Epidemiological
studies suggest that Asia will assume the greatest proportion of the global burden of osteoporosis
within a few decades. In fact, 26% of all hip fractures occurred in Asia in 1990, and this rate could
increase to 37% by the year 2025 and 45% by 2050 [48]. In Latin America, the prevalence of vertebral
fractures appears only slightly lower than that observed in the non-Hispanic White population in the
USA and similar to some countries in Europe, which reflects the increasing burden of osteoporosis in
this highly populated and growing world region [50].
The epidemiology of osteoporosis was recently gathered from 58 countries around the world from an
important systematic review on hip fracture incidence [51]. Prevalence of osteoporosis defined by
T-score of 2.5 or less using international reference standard (20e29 White females from NHANES III)
was around 3% and 10% in men and women of 50e59 years of age, respectively. This percentage
increased to 6% and 19%, respectively, in population aged 60e69, followed by 9% and 35%, respectively, in
those aged 70e79, and finally, 19% and 51%, respectively, in people aged 80 or over. The countries
included in this study accounted for around four-fifth of the world population aged 50 years or more.
Extrapolating the data to the world, the authors estimated that approximately 2.7 million hip fractures
occurred in 2010, of which approximately half were attributable to osteoporosis (264,000 for men and
1.10 million for women) and therefore were potentially preventable. The same core authors estimated
that using the fracture risk assessment tool (FRAX®), 158 million individuals aged 50 years or more
could be at high risk of osteoporotic fracture worldwide in 2010 and that number was meant to double
by 2040 [52].
As mentioned previously, age is the most important risk factor for fracture. It has been shown
that the risk of fracture increases with age at any given value of BMD and the fracture risk increases
dramatically from 50 to 80 years of age at the classical threshold of a T-score of 2.5 standard
deviation (SD) for osteoporosis definition [53]. This fact is explained not only by the physiological
deterioration of bone quality, but also by the influence of clinical risk factors, such as comorbidities
affecting bone health and falls risk. Moreover, longitudinal population-based studies have shown a
clear association with BMD loss and ageing in both genders in many different ethnicities and world
regions [54e58].
Gender is the second clinical risk factor that appears to be important in fracture risk: both osteo-
porosis and fractures are more common in women [12,51]. In 2000, of all the 9.0 million osteoporotic
fractures estimated worldwide, 61% occurred in women; the percentage was 70% for hip fractures, 80%
for forearm fractures and 58% for vertebral fractures [12]. Reasons behind the female/male ratio pre-
dominance are diverse [1]. Physiological: women reach lower levels of peak bone mass at young ages,
and higher bone loss rates as older adults than men because of estrogen deprivation after menopause
[59]. The lack of estrogens also involves a faster speed of deterioration of bone structure in females than
in males [60], therefore compromising bone strength [2]. Epidemiological; women have a higher life
expectancy in most of the world regions [3,61]. Females exhibit an increased risk of falling compared to
men [62e64] in age-standardised fall rates [63], and the role of falls is well proven as an independent
predictor of fracture risk [62,63].
The history of a previous fracture event is one of the other major risk factors for fractures. A meta-
analysis estimated that the risk of any osteoporotic fracture, including hip fracture, doubled in pop-
ulation 50 years and over when a previous fracture history was present [65]. Interestingly, the relative
risk (RR) for fracture decreased little when adjusted by BMD, indicating that the prior fracture was an
independent risk relating to factors additional to BMD. There was no significant difference in the RR
between men and women. One of the population-based studies included in the aforementioned meta-
analysis reported that 30% of women and 22% of men with a prior history of a fracture were

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001
6
nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa

Table 1
Ten-year probability of hip fracture averaged for age and gender and adjusted to the probabilities of Sweden (risk ratio of 10-year
hip fracture for Sweden ¼ 1.00).

Europe Non-Europe

Country Relative Probability Country Relative Probability

Norway 1.24 USA 0.78

Iceland 1.02 China (TW) 0.72
Denmark 0.85 Canada 0.65
Germany 0.72 Singapore 0.62
Switzerland 0.71 Kuwait 0.59
Finland 0.68 Australia 0.57
Greece 0.66 China (HK) 0.49
Netherlands 0.64 Japan 0.39
Hungary 0.63 Argentina 0.36
Italy 0.61 China 0.29
UK 0.60 Turkey 0.18
Portugal 0.57 Korea 0.18
France 0.41 Venezuela 0.17
Spain 0.39 Chile 0.08

Note that relative probabilities are expressed here without the 95% confidence intervals from the original source. TW: Taiwan;
HK: Hong Kong. Adapted from Kanis JA et al., 2002 [53].

experiencing a new fracture within the next 5 years [5]. A five-fold probability of new vertebral fracture
was observed during the first year after a vertebral fracture compared to people without vertebral
fractures [66]. Similarly, a prior wrist fracture was shown to increase the risk of a future wrist fracture
about three-fold and doubled the risk of any osteoporotic fracture [67].
Another important observation is that fracture incidence is country specific [68]. Variabillity among
countries can be as high as a 15-fold range in the 10-year probability of hip fracture [68] (Table 1). This
observation outlines the limited weight of the life expectancy and the BMD to explain the important
differences between countries, given the variations in life expectancy and BMD are much less than
variations in risk of hip fracture [68]. A clear example of this is the lower risk of fracture in Southern
countries in Western Europe than in Northern countries, despite BMD levels being higher in the latter
[68] (Table 1). A major longitudinal study showed that differences in fall incidence across countries
could play a major role in such geographical variation [63]. This probably reflects the role of other
underlying factors such as diet, comorbidities, sunlight exposure, physical activity, and other cultural
and environmental conditions.
Marked geographical variation is also observed in population levels of BMD [69]. Ethnicity back-
ground, anthropometric variables and nutritional habits may account for a significant part of the
observed worldwide differences, as shown in some studies where geographical differences in the BMD
were related to such factors [70].

Key messages

Despite recent declines in age-specific hip fracture incidence rates in Western countries,
absolute burden of hip and other fractures is increasing around the world because of the
ageing of the global population and the population pyramid inversion in developing
countries.

Age-specific fracture rates are still increasing in Asia and South America.

Asia will soon assume the highest burden of osteoporotic fractures in the world, with almost
half of all global fractures forecast for 2050. The population at high risk of fracture is meant to
double from 2010 to 2040.

Age, female gender and previous history of fracture are the strongest clinical risk factors.

Fracture risk is country specific, and prevention strategies should be tailored for each region's
needs and resources.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001

nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa 7

Economic cost of osteoporotic fractures

The economic burden of osteoporosis results both from acute outcomes, such as hospital admission
and surgery after an incident fracture, and long-term consequences related to chronic disability and
costs of pharmacological and non-pharmacological interventions. Simultaneously, the costs are clas-
sified as direct (e.g. treatment of incident fractures, pharmacological prevention, institutionalisation,
etc.), indirect, corresponding to the productivity losses of the sufferer and carers, and intangible,
referring to the pain and suffering and monetary value of quality-adjusted life years (QALYs) lost. The
term QALY refers to the number of years lived in ‘perfect health’. If an individual's health is below this
maximum, QALYs are accrued at a rate of less than 1 per year, while dead is associated with 0 QALYs.
QALYs are often combined with costs to assess overall cost-effectiveness and cost-utility of medical
interventions [71].
In a recent review elaborated in collaboration with the International Osteoporosis Foundation (IOF)
and the European Federation of Pharmaceutical Industry Associations, several aspects of the osteoporosis
epidemiology in Europe were thoroughly reviewed [47,72]. The cost of osteoporosis, including phar-
macological intervention in the European Union (EU) in 2010 was estimated at V37 billion. Costs of
treating incident fractures represented 66% of this cost, pharmacological prevention represented 5% and
long-term fracture care represented 29%. Excluding the cost of pharmacological prevention, hip fractures
represented 54% of the costs, ‘other fractures’ represented 39%, and vertebral and forearm fractures
represented 5% and 1%, respectively [47]. Costs derived from fragility fractures were estimated to be
superior to some disorders with high disabling potential such as strokes, Parkinson's and rheumatoid
arthritis [72].
Despite the individual cost of treating non-hip non-vertebral fractures being inferior to those
derived from hip and vertebral fractures, some studies have lately underlined their relevant contri-
bution to the overall costs derived from fragility fractures because of their higher incidence rates. In the
USA, an insurance claims-based retrospective study showed that non-hip non-vertebral fractures
accounted for two-thirds of the total fracture costs in people aged 50e64 years and just above one-
third in those aged 65 years or over [73].
Because of changes in population demography in Europe, there is an expected increase in the
number of people affected with osteoporosis (using the World Health Organisation (WHO) diagnostic
criteria) and in the annual number of fractures in the following years (estimated at 23% and 28%,
respectively, from 2010 to 2025). Therefore, the number of QALYs lost annually because of fractures has
been predicted to increase from 1.2 million in 2010 to 1.4 million in 2025, corresponding to an increase
of 20%. The total cost including values of QALYs lost (valued at 2  gross domestic product per capita) in
the EU would then increase from V98 billion in 2010 to V121 billion in 2025, corresponding to an
increase of 22% [47].
The increasing incidence of fragility fractures over time has been likewise predicted for North
America, Latin America, Australasia, Middle East-North Africa and Asia [48,74]. As mentioned before,
the role of the rapid changes in demographics in Latin America and Asia is shifting the global burden of
osteoporosis towards such regions. In China, the cost of hip fracture has been increasing at a rate of 6%
per year. In 2006, China spent around 1.5 billion USD treating hip fracture, and it has been estimated
that this will increase to 12.5 billion USD in 2020 and to more than 264.7 billion USD by 2050 [75].
To understand the magnitude of the problem in Western societies, it is helpful to compare with
other common diseases. In Sweden, for example, the annual cost resulting from most typical osteo-
porotic fractures (hip, vertebral and wrist) was estimated to be very close to that resulting from dia-
betes and to account for about 3% of the total health care cost [76]. The greatest annual costs resulted
from the acute care (58%) and community care (38%), with hip fractures being responsible of over
three- fourths (78%) of the total costs, followed by vertebral fractures (17%) and wrist fractures (5%).
The economic impact of osteoporosis compared with other common conditions was also reflected by
Swiss administrative data on women hospitalisation. For the year 2000, incidence of hospitalisation for
osteoporosis or its complications was double that of breast cancer, myocardial infarction or stroke;
three-times as high as that for chronic obstructive pulmonary disease; and six-times higher than that
for diabetes [77] (Fig. 1). The mean length of stay for osteoporosis was comparable to that of all the
other diseases included in the analysis, except stroke (twice as long) (Fig. 2).

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001
8
nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa

Key messages

The costs of osteoporotic fractures in the EU in 2010 were 37 billion euros.

Only 5% of the costs from osteoporotic fractures are attributable to pharmacological inter-
vention. The greatest annual costs result from the acute fracture treatment and community
care, with hip fractures being responsible for over three-fourths of the total costs.

The rates of hospital admission for women suffering osteoporotic fractures in Western
countries is higher than those due to cardiovascular events and breast cancer.

Costs are expected to dramatically increase in the next few decades worldwide. Increases will
be more dramatic in densely populated developing regions.

600
Incidence of HospitalisaƟons / 100,000

500

400
women

300

200

100

Fig. 1. Incidences of hospitalisation for osteoporosis and other frequent diseases in Swiss women in year 2000. Adapted from
Lippuner et al., 2005 [77].

35
Mean length of stay (days)

30
25
20
15
10
5
0

Fig. 2. Mean length of stay for osteoporosis and other frequent diseases in Swiss women in year 2000. Adapted from Lippuner et al.,
2005 [77].

Prevention strategies for osteoporotic fractures

Low bone mineral density as a preventable risk factor for fractures

For the last two decades, the operational definition of osteoporosis has been based on BMD values:
osteoporosis may be diagnosed in postmenopausal women and in men aged 50 years and older if the

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001

nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa 9

BMD measured by dual X-ray absorptiometry (DXA) at lumbar spine, total hip or femoral neck (in
certain circumstances, the 33% distal radius may be utilised) is 2.5 SD or less from the mean BMD
value in young females (T-score 2.5 or less) [1] (Fig. 3). The young reference values should be obtained
by population-based studies and T-scores should be calculated within the reference population as BMD
shows great geographical variation at population level. Osteoporosis is less common in premenopausal
women and younger men, and screening of secondary causes of osteoporosis needs to be thorough as
they account for a significant proportion of all the cases of osteoporosis in this subpopulation [78].
Diagnosis in younger individuals may be defined by the presence of a fragility fracture or a Z-score
(number of SD compared to the mean BMD of the age- and sex-matched peers) of  e2.0 SD in the
presence of risk factors for osteoporosis [79].
The above definitions for osteoporosis are pragmatic for diagnostic and therapeutic decisions.
However, based on such definitions, there is no burden associated with osteoporosis per se, and it
becomes difficult to have a real prevalence of the condition in a given population. Consequently, the
real burden of osteoporosis is assessed through the measurement of fracture risk. Despite its impor-
tance, BMD is not the only factor contributing to fracture susceptibility, which is better predicted when
other factors are taken into account. Therefore, life-time risks and 10-year probability of fractures are
more suitable for risk stratification. Both the WHO and the IOF have indeed recommended the 10-year
time frame to base public health analysis and intervention thresholds [80,81].
Despite all these considerations above, low BMD as a risk factor seems to remain as a key component
of prevention strategies of osteoporosis burden. Bone strength primarily reflects the integration of BMD
and bone quality, but the latter may be cumbersome to assess on individuals and more so at a popu-
lation level. In contrast, BMD is a well-defined predictor of fracture risk [82,83] and can be easily
measured using standard techniques that are objective, reproducible, non-invasive, fast and relatively
inexpensive. Moreover, BMD is potentially modifiable through a great variety of non-pharmacological
(calcium intake, sunlight exposure, physical activity, smoking cessation, etc.) and pharmacological
interventions. Therefore, it provides an excellent scenario for the management and follow-up of the
individuals at high risk of fracture. Central DXA (i.e. DXA measurements at the spine and hip) remains
the most broadly used and validated technique to measure BMD and is the recommended technique for
both clinical management and research purposes. Moreover, strong evidence supports the correlation
between the change in BMD and fracture risk reduction [84,85]. The risk of fracture due to reduced BMD
is gradual over a continuum, and in fact, most osteoporotic fractures occur in patients with osteopenia
(i.e. between 1 and 2.5 SD below the mean BMD of young population) [86]. Thus, the threshold to define
osteoporosis by DXA, somehow arbitrary, has low sensitivity for detecting individuals at high risk of

Fig. 3. Classification Criteria by the World Health Organisation (WHO) T-score represents the number of SD below the mean value of
bone mineral density of the young female reference, which follows a normal distribution. Z-scores are based in the same concept,
although the Gaussian curve is within a specific sex and age group. BMD: bone mineral density. Adapted from World Health
Organisation [1].

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001
10
nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa

fracture. Specificity is better because less frequently fractures occur in subjects with normal BMD (T-
score above 1.0). Interestingly, such threshold for diagnosis is not more arbitrary than the threshold
set for other important biological variables such as blood pressure for hypertension or BMI for obesity.
In fact, the predictive value of BMD for fractures is similar to the ability of hypertension and hyper-
cholesterolemia to predict stroke and myocardial infarction, respectively [82].
The gradient of risk (GR) for fractures due to low BMD has been defined as the RR for fracture for
each unit (either SD in T-score or absolute value of BMD measured in g/cm2) of BMD decrease. An
important meta-analysis on the relationship between BMD and fractures published in 1996 [82] found
that measurements at any site (hip, spine and wrist) predicted any osteoporotic fracture with a GR of
approximately 1.5 per SD decrease in BMD. Risk assessment was improved by site-specific mea-
surements, so to predict hip fractures and vertebral fractures, accuracy was better when measurement
was performed in the hip or in the lumbar spine, respectively (Table 2). The highest GR was found at
the hip to predict hip fracture, where the GR was 2.6. This means that a subject with a T-score of 3 SD
at the hip would have a 2.63 or about 17-fold higher risk than the same subject with a T-score of 0 SD.
Almost 10 years later, a new meta-analysis based on 12 population-based studies from Western
Europe, the USA, Canada, Japan and Australia found similar values [83]. Although fracture events
occurred more often in women, the GR per BMD unit measured at femoral neck was equivalent for
men and women, which means that the ‘excess’ of fracture risk due solely to BMD is comparable
between both sexes.

Osteoporotic fractures: underdiagnosed and undertreated: the gap between the evidence for cost-effective
treatment and the real world

We have explained how enormous the costs from fragility fractures are and the way the ageing of
the global population will affect the increasing economical toll on most societies worldwide.
Screening strategies followed by pharmacological interventions have shown to be cost-effective in
osteoporosis [87e90]. Several agents have been shown to increase BMD and reduce the risk of
vertebral fracture in randomised clinical trials. Some have also been shown to reduce the risk of non-
vertebral fractures and, in some cases, the risk of hip fracture (Table 3). Risk reductions of 30%e70%
have been demonstrated for vertebral fractures, around 15%e20% for non-vertebral fractures and up to
40% for hip fracture [91]. Mortality reduction attributable to anti-resorptive therapy has been esti-
mated to be approximately 11% globally in one meta-analysis including randomised controlled trial
data for four different agents (risedronate, zoledronic acid, strontium ranelate and denosumab) [92].
Recent reviews have demonstrated the cost-effectiveness of treating osteoporosis [72,93]. Branded
alendronate was shown to be cost-effective in nine countries of Western Europe in a longitudinal
fracture intervention trial [94], and complementary data indicate that the cost-effectiveness of such
intervention is probably maintained in both men and women over 50 years of age at high risk of
fracture in most Western countries [72]. Cost-effectiveness has been shown to improve with the
increasing number of risk factors [72].
The mechanism of action of osteoporosis treatments is diverse, but most of the agents produce their
effect through the inhibition of bone resorption, except recombinant parathyroid hormone (PTH) (1-34
PTH and 1-84 PTH). It is likely that the long-term anti-fracture efficacy of anti-osteoporosis medica-
tions is only partly dependent on the extent to which they increase or maintain BMD [95]. Never-
theless, serial BMD testing can detect non-responding individuals by finding loss of bone density,
suggesting the need for re-evaluation of diagnosis and treatment.

Table 2
Age-adjusted relative increase in risk of fracture (with 95% confidence interval) in women for every 1 SD decrease in bone
mineral density measured by Dual X-Ray Absorptiometry below the mean value for age.

Site of measurement All Fractures Forearm Fracture Hip Fracture Vertebral Fracture

Femoral Neck 1.6 (1.4e1.8) 1.4 (1.4e1.6) 2.6 (2.0e3.5) 1.8 (1.1e2.7)
Distal Radius 1.4 (1.3e1.6) 1.7 (1.4e2.0) 1.8 (1.4e2.2) 1.7 (1.4e2.1)
Lumbar Spine 1.5 (1.4e1.7) 1.5 (1.3e1.8) 1.6 (1.2e2.2) 2.3 (1.9e2.8)

Adapted from Marshall et al 1996 [82].

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001

nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa 11

Table 3
Anti-fracture efficacy of the most commonly used treatments for postmenopausal osteoporosis.

Effect on non-vertebral fracture risk Effect on vertebral fracture risk

Treatment Osteoporosis Established Osteoporosisa Osteoporosis Established Osteoporosisa

Alendronate þ þ NA þ (including hip)

Denosumab þ þb þ (including hip) þb
HRT þ þ þ þ (including hip)
Ibandronate NA þ NA þc
Raloxifene þ þ NA NA
Risendronate þ þ NA þ (including hip)
Strontium ranelate þ þ þ (including hipc) þ (including hipc)
Teriparatide and PTH NA þ NA þd
Zolendronic Acid þ þ NA þb

Fracture efficacy when given with calcium and vitamin D supplements. Results of randomised controlled trials. NA: no evidence
available; þ: effective drug.
a
women with a prior vertebral fracture.
b
mixed group of patients with or without prevalent vertebral fractures.
c
in subsets of patients only (post hoc analyses).
d
shown for teriparatide (1-34 PTH) only. Adapted from Kanis JA et al., 2013 [91].

Duration of treatment will first depend on individual medical reasons. In general, evidence of
fracture risk reduction has been shown up to 5 years for some of the antiresorptive drugs and up to 10
years for strontium ranelate. Moreover, the use of PTH analogues is only approved for a 24-month
period. Sequential treatment is advisable in patients exhibiting high risk of fracture despite long-
term antiresorptive therapy who may benefit from anabolic treatment, followed by resuming anti-
resorptive therapy upon the finalisation of PTH analogues [96,97]. Although optimised improvement of
BMD has been achieved on combination treatment (simultaneous administration of antiresorptive and
anabolic therapy) [98,99], the influence of such an approach on fracture risk and the cost-effectivity of
this type of intervention is not well established yet, and therefore not globally recommended in the
clinical practice.
In general, the safety profile of all major pharmacological interventions is quite favourable [91]. An
exception is the use of hormonal replacement therapy (HRT), which is not recommended as first line
for the treatment of osteoporosis anymore, given the increased risk in cardiovascular events and breast
cancer [91]. Most of guidelines only recommend HRT for climacteric symptoms and with a total
accumulative dose as small as possible. Another exception is the prolonged use of bisphosphonates
because of the occurrence of subtrochanteric femoral fractures, despite this being a rare secondary
effect [100]. Other treatments, such as calcitonin and vitamin D derivates (i.e. alfacalcidiol), have been
abandoned because of their low cost-effectivity and the presence of risks (e.g. cancer in long-term use
of calcitonin; hypercalcemia and nephrocalcinosis in alfacalcidiol) that possibly outweigh the potential
benefits. Recently, the European Medicines Agency put a black box warning for strontium ranelate in
patients with known cardiovascular disease.
It has been previously highlighted that the ability and utility of BMD to predict fractures is similar to
that of hypertension and hypercholesterolemia to predict stroke and myocardial infarction, respec-
tively [82]. The cost-effectiveness of therapeutical interventions for the three risk factors (hyperten-
sion, hypercholesterolemia and osteoporosis defined by BMD) has been shown for each of them at a
population level. Interestingly, the cost-effectiveness of osteoporosis treatment improves with
increasing age of the population, but this is not always the case for cholesterol lowering and antihy-
pertensive therapy [101].
These observations contrast enormously with the lack of osteoporosis screening and treatment
among people suffering fragility fractures [72]. Systematic reviews of international studies have shown
that most patients are not offered proper osteoporosis management after the acute care of a fragility
fracture. This includes a low rate of laboratory tests for secondary causes, such as vitamin D deficiency,
and BMD testing referrals (less than one-third of the patients), as well as a low rate of pharmacological
interventions in those with an osteoporosis diagnosis, with less than 20% of patients discharged on any
bone medication [102,103]. In contrast, more than 75% of elderly patients discharged after a myocardial

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001
12
nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa

infarction are prescribed beta-blockers as secondary prevention for ischaemic heart disease [104],
clearly showing the gap in disease awareness between osteoporosis and cardiovascular diseases. These
observations explain the important role of the emerging Fracture Liaison Services (FLS) in the secondary
prevention of osteoporotic fractures, which should become a key component of population health
prevention strategies for the elderly, similar to what is nowadays better established for classical car-
diovascular risk factors.
Despite some efforts towards the implementation of systematic screening of osteoporosis in
populations at high risk of fracture, there is still a generalised lack of awareness of the magnitude of
the problem both by professionals and the general population [105]. It has been estimated that
almost half of European men and women considered to be at high risk of major osteoporotic fracture
and above the treatment threshold are not receiving osteoporosis treatment. Furthermore, in Europe
and the USA, there was a general trend towards an increase in osteoporosis treatment uptake until
2006e2008, albeit followed by a plateau and subsequent decrease in many countries up to 2012. The
reasons behind this treatment gap are believed to be diverse, including non-adherence of clinicians
to treatment guidelines, poor patient adherence to treatments (possibly influenced by co-
medication, particularly in very elderly individuals with multiple co-morbidities, and treatments'
side effects), and the excessive fear of patients and clinicians to very rare treatment complications,
such as osteonecrosis of the jaw. Moreover, most treatments have an only moderate effect on fracture
risk, and even more a discrete effect on very high-risk patients, which does not re-inforce prescribing
habits [106].

Importance of risk stratification and value of predictive tools for the early detection of individuals at high risk
of fracture

At present, there is no universally accepted policy for population screening to identify individuals at
high risk of fracture. Instead, patients are identified opportunistically using a case finding strategy
when a previous fragility fracture or significant risk factors are present (Table 4). A general approach to
risk assessment is shown in Fig. 4, where subjects are screened for fracture probability according to
their clinical risk factors. When the probability of fracture is high, treatment is recommended inde-
pendently of the results of the BMD test. In contrast, BMD information becomes more relevant in cases
where fracture probability is intermediate and BMD will lead to the re-classification of the case as
having high or low risk of fracture. Finally, subjects falling into the low risk group probably need
neither screening with BMD testing nor pharmacological intervention.
To take therapeutical decisions, BMD should be measured using DXA at the spine and femur if
possible, as this is the most broadly validated method to measure BMD and its relationship with
fracture risk and treatment response has been widely established. Nonetheless, this basic decision-
making strategy is valid using other non-central DXA devices for BMD measurement, such as quan-
titative ultrasound (QUS), bone quantitative computerised tomography (QCT) in the spine and femur,
peripheral QCT (pQCT) or peripheral DXA (pDXA). Spinal trabecular BMD and total femur trabecular
BMD as measured by QCT have at least the same ability to predict vertebral fractures and hip fractures,
respectively, as the equivalent site-specific BMD measurements by central DXA in postmenopausal
women. Total femur trabecular BMD measured by QCT also predicts hip fractures in older men. Integral
and trabecular BMD of the proximal femur measured by QCT can be used to monitor age- and
treatment-related BMD changes. However, central DXA is preferred because of its lesser radiation
exposure. Validated heel QUS devices predict hip, vertebral and global fracture risk in postmenopausal
women and hip and all non-vertebral fractures in men over the age of 65 years. Measurement by
validated pDXA devices can be used to assess vertebral and global fragility fracture risk in post-
menopausal women; however, its vertebral fracture predictive ability is weaker than central DXA and
heel QUS. Both heel QUS and radius pDXA, in conjunction with clinical risk factors, can be used to
identify a population at very low fracture probability in which no further diagnostic evaluation may be
necessary, but they cannot be used to monitor the skeletal effects of treatments for osteoporosis [108].
Ultimately, assessment of fracture risk and the risk/benefit of intervention has to be individualised
in each case taking into account other factors, such as comorbidities, insurance coverage, accessibility
to pharmacological treatments and medication adherence.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001

nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa 13

Table 4
Ten-year probability (%) of a major osteoporotic fracture (clinical spine, hip, forearm and humerus fracture) according to bone
mineral density and the number of clinical risk factors for women aged 60 years in the UK.

Number of CRFs BMD T-Score at the Femoral Neck

1.0 0.0 1.0 2.0 3.0 4.0

0 4.1 4.6 5.5 7.7 12 23

1 6.0 (3.9e8.4) 6.8 (4.5e9.5) 8.0 (5.5e11) 11 (8.2e14) 18 (15e21) 32 (29e37)
2 8.6 (4.6e14) 9.8 (5.4e16) 12 (6.7e18) 16 (10e24) 25 (19e34) 44 (38e54)
3 12 (5.9e22) 14 (6.9e25) 16 (8.7e28) 23 (14e36) 35 (25e49) 58 (48e68)
4 17 (9.4e28) 19 (11e31) 22 (14e35) 31 (22e44) 46 (35e59) 71 (59e78)

The range is not a confidence interval; but, because the weight of different risk factors varies is a true range. BMD: bone mineral
density; CRF: clinical risk factor. Adapted from Kanis et al., 2009 [107].

Clinical Risk
Factors

Fracture
Probability

High Intermediate Low

Treatment BMD

Reassess
Probability

High Low

Treatment

Fig. 4. Fracture probability and decision-making. Applicability of screening tools and interventional thresholds based on multi-
factorial risk assessments such as FRAX® are variable depending on the geographical area. Reasons for this are multiple, such as the
availability of DXA machines, the cost and availability of the main pharmacological interventions, and the existence of cost-
effectiveness studies in the target population (keeping in mind that fracture risk is country-specific). Adapted from Kanis JA
et al., 2009 [82].

A systematic review published in 2013 found 48 fracture risk predicting tools, of which 20 had
been externally validated [109]. Of those, authors found that only six had been tested more than once
in a population-based setting with acceptable methodological quality as assessed with the Quality
Assessment Tool for Diagnostic Accuracy Studies checklist [110]: Osteoporosis Self-assessment Tool
(OST), Osteoporosis Risk Assessment Instrument, Garvan Fracture Risk Calculator (Garvan), Simple
Calculated Risk Estimation Score (SCORE), WHO FRAX®, and Qfracture. Probably, the most widely
used of such predictive tools is the FRAX®. The FRAX® model is a WHO initiative currently available
for different countries on-line (http://www.shef.ac.uk/FRAX), and it has been developed through the
analysis of 12 longitudinal population-based cohorts from North America, Europe, Asia and Australia
[83]. This index takes into consideration 12 risk factors apart from femoral neck BMD: age, sex,
weight, height, previous history of fracture, smoking habit, glucocorticoid therapy, rheumatoid
arthritis, secondary osteoporosis and alcohol intake (Table 5). It allows introduction of T-scores and
BMD values with different DXA manufacturers and for one manufacturer of bone QCT (with no need

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001
14
nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa

for conversion equations). The tool estimates the 10-year probability of hip and any osteoporotic
fracture at a country-specific level, even in the absence of BMD information. Interestingly, authors
from the above-mentioned review [109] found that simple tools such as OST and Garvan often
performed as well as the more complex ones such as FRAX® and SCORE. Furthermore, a previous
study with an international cohort of almost 20,000 postmenopausal women found that FRAX® and
Garvan tools were not superior in predicting fracture in the absence of BMD than a simple model
using only age at and history of prior fracture [112].

Prevention of falls and nutritional deficiencies

One of the limitations of FRAX tool is the non-inclusion of falls, which represent one of the major
risk factors for fractures in an elderly population [36,63,113]. Physical activity is a good predictor of
BMD [114e117] and fracture risk [36,118e120]; the latter explained by several potential different
mechanisms. On the one hand, exercise increases the quantity and quality of trabecular and cortical
bone, thereby increasing bone strength and resistance [121,122]. On the other hand, exercise also
improves muscle strength, balance and gait, important components of the risk of falling. In addition,
different measures of physical function (such as grip strength, balance and walking speed) have been
related to a reduced fall risk both in community-dwelling [36,118,123] and institutionalised individuals
[124]. Immobilisation constitutes an important cause of bone loss and should always be avoided when
possible (e.g. prolonged hospitalisations, elderly living in age care facilities, etc.). Risk factors for falls
(Table 6) should be identified and corrected or minimised if feasible (e.g. by prescribing walkers in
those with impaired gait, correcting visual loss, reducing medication that alters balance, etc.), together
with improvement of the home environment (shower chairs, handrails, removal of ground obstacles,
etc.). Albeit physical activity and participation in social activities could lead to an increased chance of
falling, evidence shows that elderly people with poor physical performance are more likely to suffer
injurious falls than those showing better physical parameters [36,118,123].
Adequate intake of calcium, vitamin D and proteins are required to achieve a good musculoskeletal
health during all human life. In older individuals, appropriate nutrition is important in minimising
the physiological bone loss that occurs with ageing and to maintain a good level of such nutrients to
avoid sarcopenia and osteoporosis. Vitamin D deficiency leads to secondary hyperparathyroidism and
has been found to be related to osteoporosis [125], hip fractures [126e128] and non-hip fractures
[129]. Osteomalacia changes, characterised by the accumulation of unmineralised matrix in the bone,

Table 5
Risk factors for fracture included in the FRAX® tool.

Different Risk Factors

Age
Sex
Low body mass
Previous fragility fracture, particularly of the hip, wrist and spine including morphometric vertebral fracture
Parental history of hip fracture
History of fragility fracture
Glucocorticoid treatment (5 mg oral prednisolone daily for 3 months or more)
Current smoking
Alcohol intake 3 or more units daily
Rheumatoid arthritis
Other secondary causes of osteoporosis
- Untreated hypergonadism in men and women, e.g. premature menopause, bilateral oophorectomy, anorexia nervosa,
chemotherapy for breast cancer, and hypopituitarism
- Inflammatory bowel disease, e.g. Crohn's disease and ulcerative colitis
- Prolonged immobility, e.g. spinal cord injury, Parkinson's disease, stroke, muscular dystrophy, and ankylosing spondylitis
- Organ transplantation
- Type I diabetes
- Thyroid disorders, e.g. untreated hyperthyroidism, over-treated hypothyroidism
- Chronic obstructive pulmonary disease

Adapted from Kanis et al., 2008 [111].

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001

nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa 15

Table 6
Common risk factors associated with falling.

Risk Factors Associated with Falls

Age
Cognitive Impairment
Heart disorders
History of falls
Impaired gait and balance
Impaired mobility and disability
Impaired vision
Medication
Neurological disorders
Neuromuscular or musculoskeletal disorders

Adapted from Kanis et al. [91].

can occur in the presence of persistent severe vitamin D deficiency and have been found in a sig-
nificant percentage of individuals sustaining a hip fracture [130,131]. The potential mechanisms
behind the role of vitamin D on fracture risk reduction are believed to be beyond its positive effect on
the bone mineralisation. Vitamin D has shown to influence muscle strength [132], with vitamin D
supplementation being shown to significantly reduce the risk of falling in many older individuals
[133,134]. However, the supplementation with vitamin D as part of the standard treatment for in-
dividuals at high risk of fracture is an ongoing debate. This is partly because of the heterogeneity of
the study populations and doses used in different randomised clinical trials. The latest Cochrane
updated review on the topic concluded that vitamin D alone, irrespective of the dose used, is unlikely
to prevent hip fractures or any new fractures in older people. However, there was high-quality evi-
dence that combined supplementation of calcium and vitamin D confers a small reduction in hip
fracture and any osteoporotic fracture, particularly in high-risk population (elderly residents in in-
stitutions) [134].
Calcium is the major component of the inorganic bone matrix. Achieving a good peak bone mass as
a young adult contributes to a lesser impact of the physiological ageing process of the bone. Therefore,
prevention starts as early as the childhood. Human requirements of calcium intake are higher in certain
life stages, such as childhood, teenage, menopause and pregnancy. Nevertheless, the impact of a high
calcium intake on the adult skeleton is believed to be of little relevance because of the tight regulation
of calcium homeostasis. Evidence has shown that an increased calcium intake in adults (irrespective of
being diet or supplements) leads to statistically significant increases in BMD that are, however, tran-
sient and presumably of very little clinical relevance [135]. Calcium supplements have been classically
among general recommendations in osteoporosis management for decades, but scientific evidence has
shown their minimal impact on BMD and fracture risk [136]. More recently, the observation that
calcium supplements could be related with a higher rate of cardiovascular events have raised concerns
about the risks and benefits of such intervention in osteoporotic patients [137], although this has not
been confirmed by posterior studies [134, 138]. Additionally, a meta-analysis has shown an increase in
renal stones and gastrointestinal symptoms with the use of calcium and vitamin D supplements but
not with vitamin D alone [134]. Overall, it seems plausible that combined calcium and vitamin D
supplements would still be of help in fracture reduction when there is a severe deficiency on calcium
intake or absorption to prevent PTH-driven bone resorption. In fact, the positive effects of calcium and
vitamin D on fracture risk in frail institutionalised individuals may largely be explained through the
prevention or correction of secondary hyperparathyroidism.
The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and
Musculoskeletal Diseases (ESCEO) recommends optimal dietary protein intake of 1.0e1.2 g/kg of
bodyweight per day, with at least 20e25 g of high-quality protein at each main meal, as well as an
adequate vitamin D intake of 800 IU/day to maintain serum 25-hydroxyvitamin D levels >50 nmol/L,
and calcium intake of 1000 mg/day; in addition, it recommends regular physical activity/exercise 3e5
times/week combined with protein intake in close proximity to exercise in postmenopausal women for
prevention of age-related deterioration of musculoskeletal health [139]. Dietary sources of calcium are

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001
16
nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa

the preferred option, and calcium supplementation should only be targeted to those who do not get
sufficient calcium from their diet and who are at high risk for osteoporosis or have already been
diagnosed. The IOF provides with a free-access calculator to estimate the personal requirements and
daily calcium intake on the basis of regular diet (http://www.iofbonehealth.org/calcium-calculator).

Secondary prevention: the key role of Fracture Liaison Services

The traditional osteoporosis screening in Western countries has classically been based on a case-
finding strategy where numerous resources have been utilised in primary prevention, often target-
ing populations with relative low absolute risk for fracture (mainly post-menopausal women younger
than 70 years with low number of risk factors). In these recent years, the attention has shifted towards
earlier identification and treatment for those individuals who have already suffered a fracture, thus
advocating for a secondary fracture prevention approach. The best model of secondary preventative
care following a fracture involves the use of an FLS. Although not evaluated in a randomised controlled
trial, where implemented, they have been shown to be a clinically and a highly cost-effective inter-
vention to prevent further fractures or re-fractures [140]. Furthermore, because of their success, many
countries now have FLS as part of their official government policies with regard to the standard care of
preventing further fractures [141e143]. The IOF launched the Capture the Fracture Campaign as part of
the 2012 World Osteoporosis Day report, aiming to support the global implementation of FLS [144].
This has since grown to include: a website, an educational portal, with resources supporting the
initiation and improvement of FLS, including national toolkits in country- and language-specific for-
mats; webinars, online seminars with global experts with established high-performing FLS knowledge
of guidelines and policy on secondary fracture prevention; and the Best Practice Framework (BPF),
which defines essential and aspirational elements of service delivery and states the 13 globally
endorsed standards of the BPF used to award ‘Capture the Fracture Best Practice Recognition’ in
celebration of successful FLS worldwide [145].
The proposed policy developed in 2009 by the Department of Health for England, and now used
by many other Western countries, involves assessing hip fractures using a complimentary Ortho-
geriatrics Services, leaving the FLS model to capture and care for the remaining 80% of individuals
suffering from fragility fracture of the wrist, humerus, spine, pelvis and other sites [141]. A FLS
serves to ensure that all individuals over the age of 50 who present to emergency care with a
fragility fracture undertake a fracture risk assessment and receive treatment following their rele-
vant guidelines for osteoporosis.
This is summarised using ‘The 5IQ’, which outlines the key objectives of an FLS: ‘Identify’, the
identification of individuals at the time of a new, low-trauma fracture who will benefit from inves-
tigation and possible intervention; ‘Investigate’, assessing fracture risk using DXA, falls risk and
causes of secondary osteoporosis; ‘Inform’, educating individuals about their falls and fracture risk
and the benefits and risks of treatment; ‘Intervene’, including pharmacological and non-
pharmacological options for maintaining a reduction in secondary fracture risk and falls; ‘Inte-
grate’, dissemination of patient-specific management plans with professionals involved in the pa-
tient's ongoing care plan, aiding in the long-term consistency of treatment among patients; and
‘Quality’, optimising the FLS through data collection, audits, continuing professional development,
peer review and benchmarking [146].
There is compelling evidence from around the world showing FLS to be beneficial with diverse
models of FLS achieving favourable results in various clinical outcome measures, such as re-fracture
rate, medication compliance and mortality. A Swedish study that evaluated a minimal resource FLS
over a 2-year period showed a 51% reduction in the risk of new fractures, indicating that minimal
resource FLS can improve secondary prevention of fractures [147]. In Australia, a Minimal Trauma
Fracture Liaison service implemented in a hospital environment reduced the risk of re-fracture by 80%
over a 4-year follow-up compared with a non-FLS cohort [148]. In Holland, a significantly lower risk of
a subsequent non-vertebral fracture (35%) and consequently lower mortality (33%) was observed 2
years after the introduction of a dedicated fracture nurse who offered fracture risk evaluation and
treatment [149]. Additionally, in Holland, FLS were associated with a higher adherence with an anti-
osteoporosis medication regimen [150].

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001

nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa 17

Among older people aged 75 years and older in the USA, the use of a primary care FLS nurse pro-
duced an increase in the recording of any fracture from 2.2% to 4.8%; (p < 0.001) and a fragility fracture
from 1.2% to 3.4%, and an increase in cases recorded and prescribed bone therapy from 39.5% to 70.5%
(p < 0.001) [151]. In Scotland, community-dwelling women aged >65 years who reported a history of
fracture after the age of 50 years were followed through a mailed questionnaire. The percentage of
patients receiving treatment for osteoporosis increased from 9.4% to 64% following a primary care-
based FLS comprising a nurse specialising in osteoporosis, working with primary care services [152].
In Italy, participants aged over 65 and undertaking a surgical repair of a proximal femoral fracture were
followed in a prospective observational study utilising a Fracture Prevention Service model, consisting
of a pre-intervention and post-intervention phase. Following the intervention, hip-fracture patients
were more likely to receive BMD testing (47.6% vs 14.5%, P < 0.0001), pharmacological therapy at
initiation (48.5% vs 17.2%, P < 0.0001) and at 1 year (44.1% vs. 14.0%, P < 0.0001), as well as fall and
fracture risk evaluation (52.5% vs 2.4%, P < 0.0001) [153].
The cost-effectiveness of FLS has been increasingly documented. In Scotland, an estimated 18
fractures, including 11 hip fractures, were prevented and £21,000 saved per 1000 patients when
comparing FLS to usual care [154]. A less intensive FLS from Canada, involving the education and
referral of patients for secondary prevention of osteoporotic fractures, improved QALYs by 4.3 years
and reduced overall costs, showing that a less intensive FLS could still be cost-effective. When BMD
testing was included in the model, this resulted in an even more cost-effective service [155]. In
Australia, an economic evaluation of the Minimal Trauma Fracture Liaison Service shown to reduce the
risk of re-fracture by 80% estimated an incremental cost-effectiveness ratio (ICER) versus standard care
of AUD $17,291 per QALY gained, which was well under the Australian acceptable standard of AUD
$50,000 per QALY gained [148]. Moreover, in Australia, and among non-hospitalised individuals
suffering from a fragility fracture, a FLS would improve QALYs by 0.054 and cost AUD $1716 per patient
over 5 years, equating to an overall ICER of AUD $31,749 [156]. Finally, an American model estimated
that an FLS would result in 37.43 more QALYs and save US $66,879 compared with normal post-fracture
care per every 10,000 patients [157].
Despite this evidence, it seems that the integration of FLS remains problematic [158]. The IOF's
recently released report, issued in conjunction with 2016 World Osteoporosis Day, identified secondary
prevention as one of the 10 key gaps of fragility fracture care and recommended FLS as a solution [141].
The IOF recently summarised reducing the incidence of secondary fractures throughout the world
through the implementation of FLS as ‘the single most important thing that can be done to directly
improve patient care, for women and men, and reduce spiralling fracture-related health care costs
worldwide’ [145].

Key messages

Screening and treatment of individuals at high risk of fracture is cost-effective.

The predictive value of BMD for fractures is not inferior to that of hypertension to predict
stroke or of hypercholesterolemia to predict myocardial infarction.

The majority of elderly patients admitted for an acute fracture are still discharged with no
bone treatment.

Measurement of BMD using DXA at the spine and hip remains as the method of choice to
evaluate fracture risk associated with low BMD and monitor treatment response.

The use of predictive tools that take into account clinical risk factors is essential to stratify
individuals in risk groups and decide on their management. The FRAX® tool is the most
broadly used and validated one and is country-specific.

The emerging FLS are a key component for secondary prevention of fractures and require
urgent support from health care administrations as they have proven to effectively reduce the
incidence and costs of fractures.

Capture the Fracture’ is an IOF-promoted campaign that offers free-access tools and re-
sources to help in the creation of an FLS.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001
18
nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa

Research Agenda

Cost-effectiveness studies in each region where FLS are implemented will be key to
encourage financial support from local authorities and public health institutions to make
these fracture prevention services more universally available.

Periodic updated epidemiological data are needed at regular intervals on a country-specific
(at least region-specific) basis to re-evaluate time trends in fracture rates, absolute number of
fractures and osteoporosis treatment uptake, so public health policies can be adjusted
accordingly.

Digital medical record systems and improvements in disease coding can facilitate a better
identification of those individuals at high risk of fracture, at least in Western countries.

New drugs with an improved fracture reduction rate and good tolerance are required,
particularly for high-risk patients. There are currently two new osteo-anabolic agents under
investigation (abaloparatide and romosozumab) with preliminary good results, but their cost-
effectivity in the population will have to be tested.

The current knowledge on the role of calcium-vitamin D supplements for fracture prevention
is largely based in sub-analysis of existing clinical trials with multiple cofounders. High-
quality data of large randomised clinical trials specifically designed to answer this ongoing
question will help in clarifying controversies.

Increasing the awareness of the magnitude of the problem among health professionals, in-
stitutions and general population is key in preventing the burden from osteoporotic fractures.
Information should be broadly available to general public, including general media and ed-
ucation across the life course, beginning at a young age to encourage good habits for bone
health.

Conflict of interest statement

No conflicts of interest to declare.

References

[1] World Health Organization (WHO). Assessment of fracture risk and its application to screening for postmenopausal
osteoporosis. World Health Organ Tech Rep Ser 1994;843:1e129.
[2] Melton 3rd LJ, Crowson CS, O'Fallon WM. Fracture incidence in Olmsted County, Minnesota: comparison of urban with
rural rates and changes in urban rates over time. Osteoporos Int 1999;9(1):29e37.
[3] Gehlbach S, Saag KG, Adachi JD, et al. Previous fractures at multiple sites increase the risk for subsequent fractures: the
Global Longitudinal Study of Osteoporosis in Women. J Bone Min Res 2012;27(3):645e53.
[4] Schuit SC, van der Klift M, Weel AE, et al. Fracture incidence and association with bone mineral density in elderly men
and women: the Rotterdam Study. Bone 2004;34(1):195e202.
[5] Bliuc D, Nguyen ND, Milch VE, et al. Mortality risk associated with low-trauma osteoporotic fracture and subsequent
fracture in men and women. JAMA 2009;301(5):513e21.
[6] Bliuc D, Nguyen TV, Eisman JA, Center JR. The impact of nonhip nonvertebral fractures in elderly women and men. J Clin
Endocrinol Metab 2014;99(2):415e23.
[7] Holloway KL, Henry MJ, Brennan-Olsen SL, et al. Non-hip and non-vertebral fractures: the neglected fracture sites.
Osteoporos Int 2016;27(3):905e13.
[8] Roux C, Wyman A, Hooven FH, et al. Burden of non-hip, non-vertebral fractures on quality of life in postmenopausal
women: the Global Longitudinal study of Osteoporosis in Women (GLOW). Osteoporos Int 2012;23(12):2863e71.
[9] Tran T, Bliuc D, van Geel T, et al. Population-wide impact of non-hip non-vertebral fractures on mortality. J Bone Min Res
2017;32(9):1802e10.
[10] Johnell O, Kanis JA. An estimate of the worldwide prevalence, mortality and disability associated with hip fracture.
Osteoporos Int 2004;15(11):897e902.
[11] Bertram M, Norman R, Kemp L, Vos T. Review of the long-term disability associated with hip fractures. Inj Prev 2011;
17(6):365e70.
[12] Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures.
Osteoporos Int 2006;17(12):1726e33.
[13] Kannegaard PN, van der Mark S, Eiken P, Abrahamsen B. Excess mortality in men compared with women following a hip
fracture. National analysis of comedications, comorbidity and survival. Age Ageing 2010;39(2):203e9.
[14] Kanis JA, Oden A, Johnell O, et al. The components of excess mortality after hip fracture. Bone 2003;32(5):468e73.
[15] Magaziner J, Simonsick EM, Kashner TM, et al. Predictors of functional recovery one year following hospital discharge for
hip fracture: a prospective study. J Gerontol 1990;45(3):M101e7.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001

nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa 19

[16] Melton 3rd LJ. Adverse outcomes of osteoporotic fractures in the general population. J Bone Min Res 2003;18(6):1139e41.
[17] Sernbo I, Johnell O. Consequences of a hip fracture: a prospective study over 1 year. Osteoporos Int 1993;3(3):148e53.
[18] Naves Diaz M, Diaz Lopez JB, Rodriguez Rebollar A, et al. Effect of vertebral fracture on health related quality of life in a
Spanish population older than 54 years. Med Clin Barc 2001;116(14):533e5.
[19] Jansson KA, Blomqvist P, Svedmark P, et al. Thoracolumbar vertebral fractures in Sweden: an analysis of 13,496 patients
admitted to hospital. Eur J Epidemiol 2010;25(6):431e7.
[20] O'Neill TW, Felsenberg D, Varlow J, et al. The prevalence of vertebral deformity in european men and women: the Eu-
ropean Vertebral Osteoporosis Study. J Bone Min Res 1996;11(7):1010e8.
[21] Ross PD. Clinical consequences of vertebral fractures. Am J Med 1997;103(2a):30Se42S. discussion S-3S.
[22] Silverman SL. The clinical consequences of vertebral compression fracture. Bone 1992;13(Suppl 2):S27e31.
[23] Cooper C, Atkinson EJ, O'Fallon WM, Melton 3rd LJ. Incidence of clinically diagnosed vertebral fractures: a population-
based study in Rochester, Minnesota, 1985-1989. J Bone Min Res 1992;7(2):221e7.
[24] Kado DM, Browner WS, Palermo L, et al. Vertebral fractures and mortality in older women: a prospective study. Study of
Osteoporotic Fractures Research Group. Arch Intern Med 1999;159(11):1215e20.
[25] Kanis JA, Oden A, Johnell O, et al. Excess mortality after hospitalisation for vertebral fracture. Osteoporos Int 2004;15(2):
108e12.
[26] O'Neill TW, Cooper C, Finn JD, et al. Incidence of distal forearm fracture in British men and women. Osteoporos Int 2001;
12(7):555e8.
[27] Lubbeke A, Stern R, Grab B, et al. Upper extremity fractures in the elderly: consequences on utilization of rehabilitation
care. Aging Clin Exp Res 2005;17(4):276e80.
[28] Kaukonen JP, Karaharju EO, Porras M, et al. Functional recovery after fractures of the distal forearm. Analysis of radio-
graphic and other factors affecting the outcome. Ann Chir Gynaecol 1988;77(1):27e31.
[29] Cooper C, Atkinson EJ, Jacobsen SJ, et al. Population-based study of survival after osteoporotic fractures. Am J Epidemiol
1993;137(9):1001e5.
[30] Ioannidis G, Papaioannou A, Hopman WM, et al. Relation between fractures and mortality: results from the Canadian
multicentre osteoporosis study. CMAJ 2009;181(5):265e71.
[31] Leibson CL, Tosteson AN, Gabriel SE, et al. Mortality, disability, and nursing home use for persons with and without hip
fracture: a population-based study. J Am Geriatr Soc 2002;50(10):1644e50.
[32] Melton 3rd LJ, Achenbach SJ, Atkinson EJ, et al. Long-term mortality following fractures at different skeletal sites: a
population-based cohort study. Osteoporos Int 2013;24(5):1689e96.
[33] Browner WS, Pressman AR, Nevitt MC, Cummings SR. Mortality following fractures in older women. The study of
osteoporotic fractures. Arch Intern Med 1996;156(14):1521e5.
[34] Morin S, Lix LM, Azimaee M, et al. Mortality rates after incident non-traumatic fractures in older men and women.
Osteoporos Int 2011;22(9):2439e48.
[35] Cawthon PM, Marshall LM, Michael Y, et al. Frailty in older men: prevalence, progression, and relationship with mortality.
J Am Geriatr Soc 2007;55(8):1216e23.
[36] Ensrud KE, Ewing SK, Taylor BC, et al. Frailty and risk of falls, fracture, and mortality in older women: the study of
osteoporotic fractures. J Gerontol A Biol Sci Med Sci 2007;62(7):744e51.
[37] Patel KV, Brennan KL, Brennan ML, et al. Association of a modified frailty index with mortality after femoral neck fracture
in patients aged 60 Years and older. Clin Orthop Relat Res 2014;472(3):1010e7.
[38] Tosteson AN, Gottlieb DJ, Radley DC, et al. Excess mortality following hip fracture: the role of underlying health status.
Osteoporos Int 2007;18(11):1463e72.
[39] Level WSGotAoOaPHC. Summary meeting report brussels. Belgium: World Health Organization University of Sheffield;
May 2004. p. 5e7. UK.
[40] Sanders KM, Nicholson GC, Ugoni AM, et al. Health burden of hip and other fractures in Australia beyond 2000. Pro-
jections based on the Geelong Osteoporosis Study. Med J Aust 1999;170(10):467e70.
[41] van Staa TP, Dennison EM, Leufkens HGM, Cooper C. Epidemiology of fractures in England and wales. Bone 2001;29(6):
517e22.
[42] Chang KP, Center JR, Nguyen TV, Eisman JA. Incidence of hip and other osteoporotic fractures in elderly men and women:
Dubbo Osteoporosis Epidemiology Study. J Bone Min Res 2004;19(4):532e6.
[43] Sehgal ASG, Mithal A, Mannalithara A, Triadafilopoulos G. A new frontier in the war on osteoporosis: US hospitalizations
for osteoporotic hip fractures have decreased only in women and not in men. Ann Rheum Dis 2009;68(Suppl3):145.
[44] Rosengren BE, Bjork J, Cooper C, Abrahamsen B. Recent hip fracture trends in Sweden and Denmark with age-period-
cohort effects. Osteoporos Int 2017;28(1):139e49.
[45] Cooper C, Cole ZA, Holroyd CR, et al. Secular trends in the incidence of hip and other osteoporotic fractures. Osteoporos
Int 2011;22(5):1277e88.
[46] Ballane G, Cauley JA, Luckey MM, Fuleihan Gel H. Secular trends in hip fractures worldwide: opposing trends East versus
West. J Bone Min Res 2014;29(8):1745e55.
[47] Hernlund E, Svedbom A, Ivergard M, Compston J, Cooper C, Stenmark J, et al. Osteoporosis in the european union:
medical management, epidemiology and economic burden. A report prepared in collaboration with the international
osteoporosis foundation (IOF) and the european federation of pharmaceutical Industry associations (EFPIA). Arch
Osteoporos 2013;8(1e2):136.
[48] Gullberg B, Johnell O, Kanis JA. World-wide projections for hip fracture. Osteoporos Int 1997;7(5):407e13.
[49] Health and Ageing: a discussion paper WHO Dept of Health Promotion. NCDPS, Population Reference Bureau: www.prb.
org.
[50] Clark P, Cons-Molina F, Deleze M, et al. The prevalence of radiographic vertebral fractures in Latin American countries:
the Latin American Vertebral Osteoporosis Study (LAVOS). Osteoporos Int 2009;20(2):275e82.
[51] Oden A, McCloskey EV, Johansson H, Kanis JA. Assessing the impact of osteoporosis on the burden of hip fractures. Calcif
Tissue Int 2013;92(1):42e9.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001
20
nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa

[52] Oden A, McCloskey EV, Kanis JA, et al. Burden of high fracture probability worldwide: secular increases 2010-2040.
Osteoporos Int 2015;26(9):2243e8.
[53] Kanis JA, Johnell O, Ode n A, et al. Ten year probabilities of osteoporotic fractures according to BMD and diagnostic
thresholds. Osteoporos Int 2001;12:989e95.
[54] Burger H, de Laet CE, van Daele PL, et al. Risk factors for increased bone loss in an elderly population: the Rotterdam
Study. Am J Epidemiol 1998;147(9):871e9.
[55] Jones G, Nguyen T, Sambrook P, et al. Progressive loss of bone in the femoral neck in elderly people: longitudinal findings
from the Dubbo osteoporosis epidemiology study. BMJ 1994;309(6956):691e5.
[56] Kaptoge S, Reid DM, Scheidt-Nave C, et al. Geographic and other determinants of BMD change in European men and
women at the hip and spine. a population-based study from the Network in Europe for Male Osteoporosis (NEMO). Bone
2007;40(3):662e73.
[57] Steiger P, Cummings SR, Black DM, et al. Age-related decrements in bone mineral density in women over 65. J Bone Min
Res 1992;7(6):625e32.
[58] Yoshimura N, Kinoshita H, Danjoh S, et al. Bone loss at the lumbar spine and the proximal femur in a rural Japanese
community, 1990-2000: the Miyama study. Osteoporos Int 2002;13(10):803e8.
[59] Berger C, Goltzman D, Langsetmo L, et al. Peak bone mass from longitudinal data: implications for the prevalence,
pathophysiology, and diagnosis of osteoporosis. J Bone Min Res 2010;25(9):1948e57.
[60] Zhang F, Tan LJ, Lei SF, Deng HW. The differences of femoral neck geometric parameters: effects of age, gender and race.
Osteoporos Int 2010;21(7):1205e14.
[61] Wang H, Dwyer-Lindgren L, Lofgren KT, et al. Age-specific and sex-specific mortality in 187 countries, 1970-2010: a
systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380(9859):2071e94.
[62] Kayan K, Johansson H, Oden A, et al. Can fall risk be incorporated into fracture risk assessment algorithms: a pilot study of
responsiveness to clodronate. Osteoporos Int 2009;20(12):2055e61.
[63] Roy DK, Pye SR, Lunt M, et al. Falls explain between-center differences in the incidence of limb fracture across Europe.
Bone 2002;31(6):712e7.
[64] Winner SJ, Morgan CA, Evans JG. Perimenopausal risk of falling and incidence of distal forearm fracture. BMJ 1989;
298(6686):1486e8.
[65] Kanis JA, Johnell O, De Laet C, et al. A meta-analysis of previous fracture and subsequent fracture risk. Bone 2004;35(2):
375e82.
[66] Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA 2001;285(3):
320e3.
[67] Barrett-Connor E, Sajjan SG, Siris ES, et al. Wrist fracture as a predictor of future fractures in younger versus older
postmenopausal women: results from the National Osteoporosis Risk Assessment (NORA). Osteoporos Int 2008;19(5):
607e13.
[68] Kanis JA, Johnell O, De Laet C, et al. International variations in hip fracture probabilities: implications for risk assessment.
J Bone Min Res 2002;17(7):1237e44.
[69] Sanchez-Riera L, Wilson N, Kamalaraj N, et al. Osteoporosis and fragility fractures. Best Pract Res Clin Rheumatol 2010;
24(6):793e810.
[70] Lunt M, Felsenberg D, Adams J, et al. Population-based geographic variations in DXA bone density in Europe: the EVOS
study. European vertebral osteoporosis. Osteoporos Int 1997;7(3):175e89.
[71] Hodgson TA, Meiners MR. Cost-of-illness methodology: a guide to current practices and procedures. Milbank Meml Fund
Q Health Soc 1982;60(3):429e62.
[72] Strom O, Borgstrom F, Kanis JA, et al. Osteoporosis: burden, health care provision and opportunities in the EU: a report
prepared in collaboration with the international osteoporosis foundation (IOF) and the european federation of phar-
maceutical Industry associations (EFPIA). Arch Osteoporos 2013;6(1e2):59e155.
[73] Shi N, Foley K, Lenhart G, Badamgarav E. Direct healthcare costs of hip, vertebral, and non-hip, non-vertebral fractures.
Bone 2009;45(6):1084e90.
[74] Cooper C, Campion G, Melton 3rd LJ. Hip fractures in the elderly: a world-wide projection. Osteoporos Int 1992;2(6):
285e9.
[75] China Health Promotion Foundation (2008). White Paper China 2008, Osteoporosis a summary statement of China.
[76] Borgstro€ m F, Sobocki P, Stro
€ m O, Jonsson B. The societal burden of osteoporosis in Sweden. Bone 2007;40:1602e9.
[77] Lippuner K, Golder M, Greiner R. Epidemiology and direct medical costs of osteoporotic fractures in men and women in
Switzerland. Osteoporos Int 2005;16(Suppl 2):S8e17.
[78] Khosla S, Lufkin EG, Hodgson SF, et al. Epidemiology and clinical features of osteoporosis in young individuals. Bone
1994;15(5):551e5.
[79] Watts NB, Leslie WD, Foldes AJ, et al. 2013 International Society for Clinical Densitometry Position Development Con-
ference: Task Force on Normative Databases. J Clin Densitom 2013;16(4):472e81.
[80] Genant HK, Cooper C, Poor G, et al. Interim report and recommendations of the World Health Organization Task-Force for
Osteoporosis. Osteoporos Int 1999;10(4):259e64.
[81] Kanis JA, Gluer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Sci-
entific Advisors, International Osteoporosis Foundation. Osteoporos Int 2000;11(3):192e202.
[82] Marshall D, Johnell O, H W. Meta-analysis of how well measures of bone mineral density predict occurrence of osteo-
porotic fractures. BMJ 1996;312:1254e9.
[83] Johnell O, Kanis JA, Oden A, et al. Predictive value of BMD for hip and other fractures. J Bone Min Res 2005;20(7):
1185e94.
[84] Hochberg MC, Greenspan S, Wasnich RD, et al. Changes in bone density and turnover explain the reductions in incidence
of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 2002;87(4):
1586e92
[85] Delmas PD, Li Z, Cooper C. Relationship between changes in bone mineral density and fracture risk reduction with
antiresorptive drugs: some issues with meta-analyses. J Bone Miner Res 2004;19(2):330e7.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001

nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa 21

[86] Siris ES, Chen YT, Abbott TA, et al. Bone mineral density thresholds for pharmacological intervention to prevent fractures.
Arch Intern Med 2004;164(10):1108e12.
[87] Hiligsmann M, Gathon HJ, Bruyere O, et al. Cost-effectiveness of osteoporosis screening followed by treatment: the
impact of medication adherence. Value Health 2010;13(4):394e401.
[88] Mobley LR, Hoerger TJ, Wittenborn JS, et al. Cost-effectiveness of osteoporosis screening and treatment with hormone
replacement therapy, raloxifene, or alendronate. Med Decis Mak Int J Soc Med Decis Mak 2006;26(2):194e206.
[89] Nayak S, Roberts MS, Greenspan SL. Cost-effectiveness of different screening strategies for osteoporosis in post-
menopausal women. Ann Intern Med 2011;155(11):751e61.
[90] Schousboe JT, Ensrud KE, Nyman JA, et al. Universal bone densitometry screening combined with alendronate therapy for
those diagnosed with osteoporosis is highly cost-effective for elderly women. J Am Geriatr Soc 2005;53(10):1697e704.
[91] Kanis JA, McCloskey EV, Johansson H, et al. European guidance for the diagnosis and management of osteoporosis in
postmenopausal women. Osteoporos Int 2013;24(1):23e57.
[92] Bolland MJ, Grey AB, Gamble GD, Reid IR. Effect of osteoporosis treatment on mortality: a meta-analysis. J Clin Endocrinol
Metab 2010;95(3):1174e81.
[93] Zethraeus N, Borgstrom F, Strom O, et al. Cost-effectiveness of the treatment and prevention of osteoporosisea review of
the literature and a reference model. Osteoporos Int 2007;18(1):9e23.
[94] Strom O, Borgstrom F, Sen SS, et al. Cost-effectiveness of alendronate in the treatment of postmenopausal women in 9
European countriesean economic evaluation based on the fracture intervention trial. Osteoporos Int 2007;18(8):
1047e61.
[95] Rabenda V, Bruyere O, Reginster JY. Relationship between bone mineral density changes and risk of fractures among
patients receiving calcium with or without vitamin D supplementation: a meta-regression. Osteoporos Int 2011;22(3):
893e901.
[96] Black DM, Bilezikian JP, Ensrud KE, et al. One year of alendronate after one year of parathyroid hormone (1-84) for
osteoporosis. N. Engl J Med 2005;353(6):555e65.
[97] Eastell R, Nickelsen T, Marin F, et al. Sequential treatment of severe postmenopausal osteoporosis after teriparatide: final
results of the randomized, controlled European Study of Forsteo (EUROFORS). J Bone Min Res 2009;24(4):726e36.
[98] Muschitz C, Kocijan R, Fahrleitner-Pammer A, et al. Antiresorptives overlapping ongoing teriparatide treatment result in
additional increases in bone mineral density. J Bone Min Res 2013;28(1):196e205.
[99] Leder BZ, Tsai JN, Uihlein AV, et al. Two years of Denosumab and teriparatide administration in postmenopausal women
with osteoporosis (The DATA Extension Study): a randomized controlled trial. J Clin Endocrinol Metab 2014;99(5):
1694e700.
[100] Rizzoli R, Akesson K, Bouxsein M, et al. Subtrochanteric fractures after long-term treatment with bisphosphonates: a
european society on clinical and economic aspects of osteoporosis and osteoarthritis, and international osteoporosis
foundation working group report. Osteoporos Int 2011;22(2):373e90.
[101] Zethraeus N, Strom O, Borgstrom F, et al. The cost-effectiveness of the treatment of high risk women with osteoporosis,
hypertension and hyperlipidaemia in Sweden. Osteoporos Int 2008;19(6):819e27.
[102] Giangregorio L, Papaioannou A, Cranney A, et al. Fragility fractures and the osteoporosis care gap: an international
phenomenon. Semin Arthritis Rheum 2006;35(5):293e305.
[103] Elliot-Gibson V, Bogoch ER, Jamal SA, Beaton DE. Practice patterns in the diagnosis and treatment of osteoporosis after a
fragility fracture: a systematic review. Osteoporos Int 2004;15(10):767e78.
[104] Austin PC, Tu JV, Ko DT, Alter DA. Factors associated with the use of evidence-based therapies after discharge among
elderly patients with myocardial infarction. Cmaj 2008;179(9):901e8.
[105] https://www.iofbonehealth.org/sites/default/files/PDFs/how_fragile_is_her_future.pdf.
[106] Kanis JA, Cooper C, Rizzoli R, et al. Identification and management of patients at increased risk of osteoporotic fracture:
outcomes of an ESCEO expert consensus meeting. Osteoporos Int 2017;28(7):2023e34.
[107] Kanis JA, Johansson H, Oden A, McCloskey EV. Assessment of fracture risk. Eur J Radiol 2009;71(3):392e7.
[108] https://www.iscd.org/official-positions/2015-iscd-official-positions-adult/.
[109] Rubin KH, Friis-Holmberg T, Hermann AP, et al. Risk assessment tools to identify women with increased risk of osteo-
porotic fracture: complexity or simplicity? A systematic review. J Bone Min Res 2013;28(8):1701e17.
[110] Hollingworth W, Medina LS, Lenkinski RE, et al. Interrater reliability in assessing quality of diagnostic accuracy studies
using the QUADAS tool. A preliminary assessment. Acad Radiol 2006;13(7):803e10.
[111] Kanis JA. Assessment of osteoporosis at the primary health care level, technical report. UK: World Health Organization
Collaborating Centre for Metabolic Bone Diseases, University of Sheffield; 2008.
[112] Sambrook PN, Flahive J, Hooven FH, et al. Predicting fractures in an international cohort using risk factor algorithms
without BMD. J Bone Min Res 2011;26(11):2770e7.
[113] Deprey SM. Descriptive analysis of fatal falls of older adults in a Midwestern county in the year 2005. 2001 J Geriatric
Phys Ther 2009;32(2):67e72.
[114] Bonaiuti D, Shea B, Iovine R, et al. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane
Database Syst Rev [Internet] 2002;(2). Available from: http://www.mrw.interscience.wiley.com/cochrane/clsysrev/
articles/CD000333/frame.html.
[115] Broussard DL, Magnus JH. Risk assessment and screening for low bone mineral density in a multi-ethnic population of
women and men: does one approach fit all? Osteoporos Int 2004;15(5):349e60.
[116] Devine A, Dhaliwal SS, Dick IM, et al. Physical activity and calcium consumption are important determinants of lower
limb bone mass in older women. J Bone Min Res 2004;19(10):1634e9.
[117] Morseth B, Emaus N, Wilsgaard T, et al. Leisure time physical activity in adulthood is positively associated with bone
mineral density 22 years later. The Tromso study. Eur J Epidemiol 2010;25(5):325e31.
[118] Cauley JA, Harrison SL, Cawthon PM, et al. Objective measures of physical activity, fractures and falls: the osteoporotic
fractures in men study. J Am Geriatr Soc 2013;61(7):1080e8.
[119] Cawthon PM, Blackwell TL, Marshall LM, et al. Physical performance and radiographic and clinical vertebral fractures in
older men. J Bone Min Res 2014;29(9):2101e8.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001
22
nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa

[120] Feskanich D, Flint AJ, Willett WC. Physical activity and inactivity and risk of hip fractures in men. Am J public health 2014;
104(4):e75e81.
[121] Cousins JM, Petit MA, Paudel ML, et al. Muscle power and physical activity are associated with bone strength in older
men: the osteoporotic fractures in men study. Bone 2010. In Press, Uncorrected Proof.
[122] Janz KF, Letuchy EM, Burns TL, et al. Objectively measured physical activity trajectories predict adolescent bone strength:
Iowa Bone Development Study. Br J sports Med 2014;48(13):1032e6.
[123] Nevitt MC, Cummings SR, Hudes ES. Risk factors for injurious falls: a prospective study. J Gerontol 1991;46(5):M164e70.
[124] Wilson N, Hilmer S, March L, et al. Physical functioning measures and risk of falling in older people living in residential
aged care facilities. Ther Adv Musculoskelet Dis 2011;3(1):9e15.
[125] Holick MF. Vitamin D deficiency. N. Engl J Med 2007;357(3):266e81.
[126] Bischoff-Ferrari HA, Can U, Staehelin HB, et al. Severe vitamin D deficiency in Swiss hip fracture patients. Bone 2008;
42(3):597e602.
[127] Cauley JA, Lui LY, Barnes D, et al. Successful skeletal aging: a marker of low fracture risk and longevity. The Study of
Osteoporotic Fractures (SOF). J Bone Min Res 2009;24(1):134e43.
[128] LeBoff MS, Kohlmeier L, Hurwitz S, et al. Occult vitamin D deficiency in postmenopausal US women with acute hip
fracture. JAMA 1999;281(16):1505e11.
[129] Nakamura K, Saito T, Oyama M, et al. Vitamin D sufficiency is associated with low incidence of limb and vertebral
fractures in community-dwelling elderly Japanese women: the Muramatsu Study. Osteoporos Int 2010;22(1):97e103.
[130] Harma M, Parviainen M, Koskinen T, et al. Bone density, histomorphometry and biochemistry in patients with fractures of
the hip or spine. Ann Clin Res 1987;19(6):378e82.
[131] Arnala I, Kyrola K, Kroger H, Alhava EM. Analysis of 245 consecutive hip fracture patients with special reference to bone
metabolism. Ann Chir Gynaecol 1997;86(4):343e7.
[132] Bischoff HA, Stahelin HB, Tyndall A, Theiler R. Relationship between muscle strength and vitamin D metabolites: are
there therapeutic possibilities in the elderly? Z fur Rheumatol 2000;59(Suppl. 1):39e41.
[133] Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin
D: a meta-analysis of randomised controlled trials. BMJ 2009;339, b3692.
[134] Avenell A, Mak JC, O'Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women
and older men. Cochrane Database Syst Rev 2014;4, Cd000227.
[135] Tai V, Leung W, Grey A, et al. Calcium intake and bone mineral density: systematic review and meta-analysis. BMJ 2015;
351, h4183.
[136] Shea B, Wells G, Cranney A, et al. Calcium supplementation on bone loss in postmenopausal women. Cochrane Database
Syst Rev 2004;1, Cd004526.
[137] Bolland MJ, Avenell A, Baron JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular
events: meta-analysis. BMJ 2010;341, c3691.
[138] Lewis JR, Radavelli-Bagatini S, Rejnmark L, Chen JS, Simpson JM, Lappe JM, et al. The effects of calcium supplementation
on verified coronary heart disease hospitalization and death in postmenopausal women: a collaborative meta-analysis of
randomized controlled trials. J Bone Min Res 2014;30(1):165e75.
[139] Rizzoli R, Stevenson JC, Bauer JM, et al. The role of dietary protein and vitamin D in maintaining musculoskeletal health in
postmenopausal women: a consensus statement from the European Society for Clinical and Economic Aspects of
Osteoporosis and Osteoarthritis (ESCEO). Maturitas 2014;79(1):122e32.
[140] Javaid MK, Kyer C, Mitchell PJ, et al. Effective secondary fracture prevention: implementation of a global benchmarking of
clinical quality using the IOF Capture the Fracture(R) Best Practice Framework tool. Osteoporos Int 2015;26(11):2573e8.
[141] Harvey N, McCloskey E. Gaps and solutions in bone health. A global Framework for improvement. Int Osteoporos Found
2016. https://www.iofbonehealth.org/thematic-report-2016.
[142] Mitchell PJ. Best practices in secondary fracture prevention: fracture liaison services. Curr Osteoporos Rep 2013;11(1):
52e60.
[143] Mitchell PJ. Fracture liaison services in the United Kingdom. Curr Osteoporos Rep 2013;11(4):377e84.
[144] Åkesson K, Mitchell PJ. Capture the fracture. A global campaign to break the fragility fracture cycle. Int Osteoporos Found
2012. https://www.iofbonehealth.org/capture-fracture.
[145] Akesson K, Marsh D, Mitchell PJ, et al. Capture the Fracture: a Best Practice Framework and global campaign to break the
fragility fracture cycle. Osteoporos Int 2013;24(8):2135e52.
[146] Gittoes N, McLellan A, Cooper A, et al. Effective secondary prevention of fragility fractures: clinical standards for fracture
liaison services. Natl Osteoporos Soc 2015. https://staging.nos.org.uk/media/1776/clinical-standards-report.pdf.
[147] Axelsson KF, Jacobsson R, Lund D, Lorentzon M. Effectiveness of a minimal resource fracture liaison service. Osteoporos
Int 2016;27(11):3165e75.
[148] Cooper MS, Palmer AJ, Seibel MJ. Cost-effectiveness of the Concord Minimal Trauma Fracture Liaison service, a pro-
spective, controlled fracture prevention study. Osteoporos Int 2012;23(1):97e107.
[149] Huntjens KM, van Geel TA, van den Bergh JP, et al. Fracture liaison service: impact on subsequent nonvertebral fracture
incidence and mortality. J Bone Jt Surg Am Volume 2014;96(4):e29.
[150] Eekman DA, van Helden SH, Huisman AM, et al. Optimizing fracture prevention: the fracture liaison service, an obser-
vational study. Osteoporos Int 2014;25(2):701e9.
[151] Chan T, de Lusignan S, Cooper A, Elliott M. Improving osteoporosis management in primary care: an audit of the impact of
a community based fracture liaison nurse. PloS one 2015;10(8), e0132146.
[152] Brankin E, Mitchell C, Munro R. Closing the osteoporosis management gap in primary care: a secondary prevention of
fracture programme. Curr Med Res Opin 2005;21(4):475e82.
[153] Ruggiero C, Zampi E, Rinonapoli G, et al. Fracture prevention service to bridge the osteoporosis care gap. Clin In-
terventions Aging 2015;10:1035e42.
[154] McLellan AR, Wolowacz SE, Zimovetz EA, et al. Fracture liaison services for the evaluation and management of patients
with osteoporotic fracture: a cost-effectiveness evaluation based on data collected over 8 years of service provision.
Osteoporos Int 2011;22(7):2083e98.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001

nchez-Riera, N. Wilson / Best Practice & Research Clinical Rheumatology xxx (2017) 1e23
L. Sa 23

[155] Yong JH, Masucci L, Hoch JS, et al. Cost-effectiveness of a fracture liaison serviceea real-world evaluation after 6 years of
service provision. Osteoporos Int 2016;27(1):231e40.
[156] Yates CJ, Chauchard MA, Liew D, et al. Bridging the osteoporosis treatment gap: performance and cost-effectiveness of a
fracture liaison service. J Clin Densitom 2015;18(2):150e6.
[157] Solomon DH, Patrick AR, Schousboe J, Losina E. The potential economic benefits of improved postfracture care: a cost-
effectiveness analysis of a fracture liaison service in the US health-care system. J Bone Min Res 2014;29(7):1667e74.
[158] Seibel MJ. No more excuses: fracture liaison services work and are cost-effective. Med J Aust 2011;195(10):566e7.

Please cite this article in press as: S
anchez-Riera L, Wilson N, Fragility Fractures & Their Impact on Older
People, Best Practice & Research Clinical Rheumatology (2017), https://doi.org/10.1016/j.berh.2017.10.001