Special Contribution

Yonago Acta medica 2012;55:21–28

Fragility Fracture Prevention: Review from a Japanese
Perspective
Hiroshi Hagino
Department of Fundamental Nursing, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan

Osteoporosis has been named “the silent disease” because there are no symptoms until
a fragility fracture occurs. With the rapid rise in the elderly population, the number ofpatients with osteoporosis and fragility fractures has increased in most developed countries. Fragility fractures increase societal burdens in terms of mortality and quality oflife, as well as economic costs. Fragility fractures of the hip have the most impact on theambulatory status of the elderly and its incidence is reported to be lower among Asians orAfricans than Caucasians. Increases in the age-specific and gender-specific incidence of
hip fracture with time have been reported in Asian countries, including Japan; however,studies in North America, Europe and Oceania have reported decreases in the incidence.
A new fragility fracture increases fracture risk, resulting in possible recurrence or othernew fractures. The most important strategy for preventing such fractures is a systematic
approach to educating and following patients in the immediate postoperative period after
the initial fragility fracture.
Key words: hip fracture; osteoporosis; secondary fracture prevention

Japan currently has the largest aged population,and it is expected to increase until 2050 while thetotal population decreases (Fig. 1). Even among thedeveloping countries, graying of the population will
become a serious concern in the future. With therapid increase in the elderly population, the numberof patients with osteoporosis and fragility fractures
has increased in most developed countries. Fragility fractures increase societal burdens with respect
to mortality, quality of life (QOL), and economic
costs. The combined annual cost of all osteoporotic
fractures has been estimated to be $20 billion in
the Uninted States and €30 billion in the European
Union (Cummings and Melton, 2002; Cooper et al.,2011). Fractures account for about 1–2% of the total
health care costs, of which inpatient care costs dom-

inate. Although fractures affect older people to alarger extent, indirect costs, such as the loss in productivity due to sick leave, also play an importantrole that has been estimated at approximately 10%of the total costs (Zethraeus et al., 2007). In Japan,
the annual cost for the treatment of hip fractures is
estimated to be approximately ¥130 billion, excluding the cost of patient care after discharge (Committee for Osteoporosis Treatment of The Japanese
Orthopaedic Association, 2004).
A new fragility fracture does not only reduce
daily activity but can also increase fracture risk,
resulting in possible recurrence or other new fractures: “fracture begets fracture.” However, it is reported that the vast majority of patients who experience a hip fracture do not receive anti-osteoporotic
therapy after the fracture (Cadarette et al., 2008;
Roerholt et al., 2009). In Japan, there is a paucity ofdata available on the proportion of patients with aAbbreviations: AFF, atypical femoral fractures; FLS,
Fracture Liaison Service; ONJ, osteonecrosis of the jaw;
POSHIP, Prevention of Second Hip Fracture study; QOL,
quality of life21

H. Hagino

new fragility fracture who are started on an intervention (Hagino et al., 2012). Novel strategies are
required to disseminate and implement best practices at the point of care to reduce the risk of recurrent fractures. In this review, the current status ofosteoporosis and fragility fractures and strategies toreduce their burden are discussed.
What are osteoporosis andfragility fractures?
Osteoporosis

Fig. 1. Population projections for Japan. The total population of Japan is projected to decrease until 2050 but a substantial increase in the proportion aged 85 years and over is
expected. (Data source: National Institute of Population andSocial Security Research; http://www.ipss.go.jp/syoushika/
tohkei/newest04/sh2401smm.html)

Osteoporosis has been named “the silent disease”
since there are no symptoms until a fracture occurs
after minimal trauma. Osteoporosis is a skeletal disorder characterized by compromised bone strength
predisposing a person to an increased risk of fracture. Bone strength primarily reflects a combinationof bone density and bone quality (NIH Consensus
Development Panel, 2001). A fragility fracture occurs when a failure-inducing force such as trauma
is applied to osteoporotic bone (NIH Consensus Development Panel, 2001). Bone density is expressed
as grams of mineral per area or volume, which ismeasured by bone densitometry. Bone quality refers to its architecture (macro and micro), turnover,damage accumulation (e.g., microfractures) andmineralization. Bone quality is thought to be thepart of bone strength that is not explained by bonedensity, which is estimated to be 30% of total bonestrength (NIH Consensus Development Panel, 2001).
In 2005, there were an estimated 13 million
patients with osteoporosis in Japan. This number
was calculated from the data on bone density inhealthy Japanese subjects and the diagnostic criteria
for primary osteoporosis.
Fragility fractures
Fragility fractures are thought to be osteoporosisrelated geriatric fractures, as opposed to traumatic
fractures. However, there is no conclusive definition
for fragility fracture. Based on the recent papers,
fragility fractures are those due to mild injuries,
such as a fall from standing height, and not occurring as a result of significant trauma, such as a motor vehicle collision (ASBMR Task Force on Osteoporotic Fracture Secondary Prevention, in press).
Incidence of fragility fractures

Fig. 2. Age-specific and gender-specific incidences of hip fractures in Japan. The age-specific and gender-specific incidenceof hip fractures increases exponentially with age after 70 years
in both men and women. Adapted from: Hagino et al., 2009a;
Orimo et al., 2009; Arakaki et al., 2011.

Among the Japanese population, the age-specificand gender-specific incidence of hip fractures increased exponentially after 70 years of age (Fig. 2)
22

Fragility fracture prevention(Hagino et al., 2009a; Orimo et al., 2009; Arakaki
et al., 2011). Based on the incidence in Tottori Prefecture, Japan, the annual number of patients withnew hip fractures is estimated to be approximately
190,000 in 2012 and 320,000 in 2040 (Fig. 3).
There have been many epidemiologicalsurveys of hip fractures worldwide. One of theconclusions derived from these studies is that theincidence of hip fractures is lower among Asian or
African populations than Caucasian populations.
Table 1 compares the incidence of hip fractures
among different populations based on studies fromJapan , China (Yan et al., 1999), Korea (Lim etal., 2008), Turkey (Tuzun et al., 2011), Argentina(Morosano et al., 2005), Finland (Lönnroos et al.,2006) and Norway (Bjørgul and Reikerås, 2007).
Incidences for both genders in Asian populations,
including Japanese, are substantially lower thanthose in Caucasian populations living in Northern
Europe or South America. Since Asians are known
to have similar or lower bone mass than Caucasians,
differences in bone mass do not explain the differences in the incidence of hip fractures. Elucidating
the causes for ethnic differences in the incidence of
hip fractures may suggest preventive measures that
could protect against fragility fractures. Therefore,
several approaches have been tried to explain why
hip fracture incidence is lower in Asian populations.
One hypothesis is the different risk of falls between
Asians and Caucasians (Aoyagi et al., 1998), presumably based on differences in lifestyles. It wasreported that aspects of the Japanese lifestyle, such

Fig. 3. Expected number of patients with hip fractures inJapan. Approximately 190,000 hip fractures are expected tooccur in 2012, and the estimate increases up to more than
300,000 for 2040 based on the incidence in Tottori Prefecture, Japan. (Data source: National Institute of Populationand Social Security Research; http://www.ipss.go.jp/syoushika/tohkei/newest04/sh2401smm.html)

as drinking Japanese tea and the use of a futon,
are effective for preventing fractures (Suzuki et al.,
1997; Hagino et al., 2004). However, there havebeen no conclusive explanations for the differences
observed.
Recent data from Asia, including Japan,
showed an increase in the age-specific and genderspecific incidence of hip fractures over time (Hagino
et al., 2009a; Arakaki et al., 2011; Xia et al., 2011).
In Japan, a steady increase has been observedfor 20 years in Tottori (Hagino et al., 2009a) andOkinawa (Arakaki et al., 2011) Prefectures (Fig. 4).
In Beijing, China, the incidence of hip fracturesrose very rapidly from 2002 to 2006, about 10%
per year (Xia et al., 2011). It is
speculated that the increased risk
Table 1. Comparison of the incidence of hip fractures among difof hip fracture is due to the changes
ferent populations
in lifestyle with urbanization. On
Geographic area
Survey year
Men
Women
the other hand, studies in North
2004–2006
94.9
326.6
Japan
Tottori Prefecture
America, Europe and Oceania haveJapan
Okinawa Prefecture
2004
89.8
329.0
generally reported increases in hip
Japan
Nationwide
2007
94.2
324.5
fracture incidence through the secChina
Shenyang
1994
72.2
65.2
Korea
Nationwide
2001–2004
164.5
290.4
ond half of the 20th century, but
Turkey12 regions
2009
89.8
432.3
those continuing to follow trends
Argentina
Rosario
2001–2002
116.7
479.4
over the last 2 decades have foundFinlandCentral Finland
2002–2003
195.6
399.6
NorwaySoutheastern Norway 1998–2003
264.4
615.5
that rates have stabilized with ageData are incidences (per 100,000 person-years) adjusted to the population adjusted decreases being observed
structure for all of Japan in 2010 (≥ 35 years).
in certain centers (Cooper et al.,23

H. Hagino2011). However, no conclusive cause has been
elucidated for why the incidence in North
America, Europe and Oceania are decreasing
and why those in Asia are increasing.
In contrast to the incidence of the limb
fractures, epidemiological surveys found ahigher incidence of incident vertebral fractures
evaluated morphometrically among the Japanese (Fujiwara et al., 2003) than in European
counterparts (Van der Klift et al., 2002; European Prospective Osteoporosis Study Group,2002). The prevalence of vertebral fractures isalso higher among the Japanese population thanthe Caucasian population in the United States(Ross et al., 1995). It is suspected that smallbone size or lifestyle differences, including low
calcium intake, are responsible for this difference; however, there are no studies to explain
this difference.

Fig. 4. Recent changes in the incidence of hip fractures in Japan.
The number of patients with hip fractures calculated from previous surveys from Tottori (Hagino et al., 2009a), Niigata (Morita
et al., 2002) and Okinawa (Arakaki et al., 2011) Prefectures andthroughout the country (Orimo et al., 2009) are shown. Data areadjusted to the population structure (2010 Japan).

ter the first hip fracture and then plateau (Yamanashi
et al., 2005; Hagino et al., 2012). A recent nationwide study in Denmark involving a large number of
hip fracture patients demonstrated that the risk of asecond hip fracture was 12-fold higher at 1 monthand more than doubled at 1 year (Ryg et al., 2009).
These findings indicate that the period immediately
following the first fracture is a window of opportunity for implementing a fracture prevention strategy.

Risk of a second fracture
Investigators from Rochester, Minnesota describedthe epidemiology of hip fractures in their locality
during the period between 1965 and 1974. They
found that 68% of women and 59% of men had
experienced at least 1 other fracture prior to breaking their hip (Gallagher et al., 1980), suggesting that
almost one-half of today’s hip fracture patients havesuffered prior fractures (ASBMR Task Force on Osteoporotic Fracture Secondary Prevention, in press).
Very little data is available on the risk of sustaining asecond hip fracture after an initial hip fracture in the
Asian population, although there is a large differencein the incidence of fragility fractures between Asians
and Caucasians. Recently we performed a registrybased study consisting of 2,328 patients with first hip
fracture treated in 25 hospitals in Japan (Preventionof Second Hip Fracture study; POSHIP) (Hagino etal., 2012). The 1-year incidence rate as determined in
the POSHIP study was 3.40% and rate ratio of a second hip fracture compared to the general populationin Japan was as high as 4.0.
The likelihood of sustaining a second hip fracture tended to rise during the first 6 or 8 months af-

Burden of fragility fractures
Changes in ambulatory ability
Hip fracture is the fragility facture with the highest impact on the ambulatory status of the elderly.
A fixed-point observation project involving coreorthopedic hospitals throughout Japan examineda larger number of variables including the 1-year
prognosis (Sakamoto et al., 2006). In this study,
a total of 10,992 hip fractures were enrolled from1999 to 2001 and a 24.1% decrease in the numberof patients who were independently ambulatory wasobserved at 1 year after fracture. In a recent large
prospective study, changes in ambulatory ability after hip fracture were evaluated (Fukui et al., 2012).
24

Fragility fracture prevention

were significantly lower than pre-fracture scores.
At 1 year after fracture, EQ5D values were not significantly different from pre-fracture values for thevertebral and wrist fracture groups; however, theyremained significantly lower for the hip fracturegroup. Another recent study demonstrated that men
and women with hip and clinical vertebral fractures
and women with rib fractures had adverse changes
in their QOL but forearm and pelvic fractures did
not appear to substantially influence QOL scores(Papaioannou et al., 2009).

In this cohort, patients who sustained hip fracturessuffered obvious deterioration in ambulatory ability
and the number of ambulatory subjects in the community setting was nearly halved 6 months after
surgery, whereas that of patients who cannot walk
unaided was almost doubled. In a retrospective 10year observational study, the proportion of patients
who were able to walk outdoors alone, with or without an assistive device, was 68% before a hip fracture and 56% at 1 year afterwards, and remained
stable for 10 years (Tsuboi et al., 2007).
Mortality

Prevention of fragility fractures

In a prospective study in Japan, the 1-year mortality rate for the entire hip fracture patient population
was 10.1% (Sakamoto et al., 2006). In a retrospective study, the survival rate decreases rapidly for 2
years after fracture before stabilizing (Tsuboi et al.,2007). However, the survival rate was still well below that of the general population for up to 10 years
and the increased mortality risk was approximately
double that of the general population.
A comparative study of hip fractures with a
median follow-up duration of 276 days after surgery demonstrated that the survival rate was 89.5%
in Japan and 77.2% in the United States (Kondo etal., 2010). Japanese patients had a significantly longer length of hospital stay after surgery but higher
survival rates than American patients, and longer
length of hospital stay after surgery was associatedwith a lower risk of mortality after discharge after
adjusting for patient characteristics and country.

Who are the targets?
It is well established that a history of a prior fracture at any site is an important risk factor for future fractures (Klotzbuecher et al., 2000). Patientswith a history of a prior fracture, therefore, should
receive further evaluation and treatment for osteoporosis to prevent subsequent fractures. However,
it is reported that the vast majority of patients who
experience a hip fracture as well as other fragility
fractures do not receive anti-osteoporotic therapy
after fracture (Cadarette et al., 2008; Roerholt et al.,2009). Among patients who begin anti-resorptive
osteoporosis treatment after fracture, adherence totreatment decreases over time and remains suboptimal (Roerholt et al., 2009; Rabenda et al., 2008). It
was recently reported that the situation has not improved; in 2007 to 2008, fewer than 20% of untreated individuals with a low-trauma fracture received
intervention despite increased attention to gaps inpost-fracture osteoporosis management in the last
10 years (Leslie et al., 2012). The POSHIP study
found a high risk of a second hip fracture during the
1-year period after the initial fracture; however, anti-osteoporosis pharmacotherapy was given in only
18.7% and 53.3% received no treatment (Hagino etal., 2012). Thus, inadequate treatment after the first
hip fracture is now evident as well as other fragility
fractures.

Quality of life
In a prospective observational study, health-related
QOL was evaluated by Euroqol (EQ5D) in elderly
women following incident hip, vertebral and wrist
fractures (Hagino et al., 2009b). The reduction in
EQ5D values was greatest in the hip fracture groupduring the observational period. EQ5D values at
6 months after fracture in the wrist fracture group
showed recovery; however, at 6 months the hip andvertebral fracture groups had EQ5D scores that25

H. Hagino

history. If necessary, the nurse informs the patientof the risk for osteoporosis, and then provides a letter to give to the primary physician. Such systematic
approaches have been started globally in campaigns
such as “Capture the Fracture” (International Osteoporosis Foundation).

Fracture liaison service
A systematic approach is important for educating
and following patients in the immediate postoperative period after a hip fracture as well as for otherfragility fractures in order to provide adequate intervention for patients at high risk for subsequent fracture (Gardner et al., 2005; Rozental et al., 2008). In
the United Kingdom, Canada and the United States,
a consensus on systematic and multidisciplinary approaches to secondary fragility fracture prevention,
called the Fracture Liaison Service (FLS), has beendeveloped over the last decade (Mitchell, 2011).
The FLS is operated by mainly nurse specialists
supported by a lead clinician in osteoporosis. They
identify patients with new fragility fractures whoare either admitted to the orthopedic inpatient wardor managed as outpatients through the fracture clinic and then arrange for appropriate patients to attend
the FLS clinic where bone density is measured.
After bone mass measurement, the nurse specialist
assesses future fracture risk by taking the patient’s

Anti-osteoporosis drugs
The recent development of anti-osteoporosis drugs,
especially anti-resorptive agents, has revolutionized
the field of fracture prevention. It is now known thatoral bisphosphonate treatment for 3 years (Osaki etal., 2012) or an annual infusion of zoledronic acidfor 1.9 years (Black et al., 2007) after a hip fracture
is associated with a reduction in the rate of newclinical fractures including hip fracture, as well as
an improvement in survival (Lyles et al., 2007).
Since bisphosphonates can reduce the incidenceof fragility fractures, including hip fractures, inpatients with osteoporosis, they have become firstline drugs for the treatment of osteoporosis. Thoughbisphosphonates have a relatively good safety record and are well tolerated by most patients, serious
adverse events have been associated with their use.
Over the past few years, there has been growing
concern about the potential relationship between
long-term use of bisphosphonates and osteonecrosis of the jaw (ONJ) and atypical femoral fractures(AFF) (Fig. 5). Regarding AFF, recent nationwide
population-based analyses were reassuring for patients receiving bisphosphonates (Schilcher et al.,2011). Recently, a survey of AFF was conducted inJapan (Hagino, 2011). The 3,116 hospitals surveyedreported 398 cases of AFF, of which 29.9% wereassociated with previous bisphosphonate therapy.
Although there seems to be a higher prevalence of
current bisphosphonate use among patients with
AFF or ONJ, the absolute risk of these complications is very small and the beneficial effects ofbisphosphonates far outweigh these risks.
In addition to anti-resorptive agents, an anabolic agent, teriparatide, is available and widelyused globally. Many clinical trials have found that
teriparatide can reduce the incidence of new fractures (Neer et al., 2001). Recently, weekly teripa-

Fig. 5. Case of an atypical femoral fracture. An 81-year-old
women suffered a right femoral shaft fracture upon fallingon the road. She has been on alendronate for 6 years. Complete fractures extend through both cortices and a medial
spike of the right femur was observed on a radiograph (leftpanel). An increase in the cortical thickness of the diaphysisof the lateral cortex of the left femur is noted (right panel;arrow).

26

Fragility fracture prevention

ratide became available in Japan for the treatmentof osteoporosis. Teriparatide has a potential for
desired effects in secondary fracture prevention(Nakamura et al., 2012).

9 Cummings SR, Melton LJ. Epidemiology and outcomesof osteoporotic fractures. Lancet 2002;359:1761–1767.
10 European Prospective Osteoporosis Study (EPOS) Group,
The. Incidence of vertebral fracture in europe: resultsfrom the European Prospective Osteoporosis Study(EPOS). J Bone Miner Res 2002;17:716–724.
11 Fujiwara S, Kasagi F, Masunari N, Naito K, Suzuki G,
Fukunaga M. Fracture prediction from bone mineraldensity in Japanese men and women. J Bone Miner Res
2003;18:1547–1553.
12 Fukui N, Watanabe Y, Nakano T, Sawaguchi T,
Matsushita T. Predictors for ambulatory ability and thechange in ADL after hip fracture in patients with different levels of mobility before injury: a 1-year prospective
cohort study. J Orthop Trauma 2012;26:163–171.
13 Gallagher JC, Melton LJ, Riggs BL, Bergstrath E. Epidemiology of fractures of the proximal femur in Rochester,
Minnesota. Clin Orthop Relat Res 1980;(150):163–171.
14 Gardner MJ, Brophy RH, Demetrakopoulos D, Koob J,
Hong R, Rana A, et al. Interventions to improve osteoporosis treatment following hip fracture. A prospective,
randomized trial. J Bone Joint Surg Am 2005;87:3–7.
15 Hagino H. [Result of a survey of atypical femoral fractures]. Nippon Seikei Geka Gakkai Zasshi 2011;85:879–
884 (in Japanese).
16 Hagino H, Fujiwara S, Nakashima E, Nanjo Y, Teshima
R. Case-control study of risk factors for fractures of the
distal radius and proximal humerus among the Japanese
population. Osteoporos Int 2004;15:226–230.
17 Hagino H, Furukawa K, Fujiwara S, Okano T, Katagiri
H, Yamamoto K, et al. Recent trends in the incidence andlifetime risk of hip fracture in Tottori, Japan. Osteoporos
Int 2009a;20:543−548.
18 Hagino H, Nakamura T, Fujiwara S, Oeki M, Okano T,
Teshima R. Sequential change in quality of life for patients with incident clinical fractures: a prospective study.
Osteoporos Int 2009b;20:695–702.
19 Hagino H, Sawaguchi T, Endo N, Ito Y, Nakano T,
Watanabe Y. The risk of a second hip fracture in patients
after their first hip fracture. Calcif Tissue Int 2012;90:14–21.
20 Klotzbuecher CM, Ross PD, Landsman PB, Abbott
TA 3rd, Berger M. Patients with prior fractures havean increased risk of future fractures: a summary of theliterature and statistical synthesis. J Bone Miner Res
2000;15:721–739.
21 Kondo A, Zierler BK, Isokawa Y, Hagino H, Ito Y,
Richerson M. Comparison of lengths of hospital stay after surgery and mortality in elderly hip fracture patients
between Japan and the United States - the relationshipbetween the lengths of hospital stay after surgery andmortality. Disabil Rehabil 2010;32:826–835.
22 Leslie WD, Giangregorio LM, Yogendran M, Azimaee M,
Morin S, Metge C, et al. A population-based analysis of
the post-fracture care gap 1996–2008: the situation is not
improving. Osteoporos Int 2012;23:1623–1629.
23 Lim S, Koo BK, Lee EJ, Park JH, Kim MH, Shin KH,
et al. Incidence of hip fractures in Korea. J Bone Miner
Metab 2008;26:400–405.

Conclusion: A rapid increase in the number ofpatients with fragility fractures is projected in many
Asian counties, including Japan. The most important strategy for preventing such fractures is a multidisciplinary approach for educating and following
patients in the immediate postoperative period after
the initial fragility fracture.
Acknowledgments: The author would like to express sincere appreciation to Dr. Masato Shimizu and Dr. Masako
Hayashibara for providing images of an atypical femoral
fracture.
This study was partially supported by a grant-in-aid
from the Ministry of Health, Labour and Welfare of Japan(H23-Choujyu Ippan-002).

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Corresponding author: Hiroshi Hagino, MD

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