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C H A P T E R

27Geographic Variability in Hip and Vertebral

FracturesGhada Ballane1, Jane A. Cauley2, Asma Arabi1, Ghada El-Hajj Fuleihan1

1Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, Division of Endocrinology and Metabolism, American University of Beirut Medical Center, Beirut, Lebanon,

2Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA, USA

INTRODUCTION

Osteoporosis, usually a disease of old age, is an ancient disease documented to date back to the Bronze age [1]. The demographic explosion, with increased life expec-tancy, global urbanization, and the obesity epidemic, are major contributors to the exponential rise in the inci-dence of chronic noncommunicable diseases (NCDs) and their staggering health toll. The World Health Orga-nization identified NCDs as the cause for two-thirds of all deaths worldwide [2]. Osteoporosis is no exception to this rising tide, with vertebral and hip fractures being the hallmark of this costly disease. About 30% to 50% of patients who sustain a hip fracture lose functional independence, and 10% fracture the contralateral hip. Survival rates posthip and vertebral fractures are also reported to be substantially decreased, by 10% to 20% in western countries, and possibly more in developing countries [3–6].

Although hip fractures only represent 20% of all osteoporotic fractures, they are nevertheless the most serious consequence of osteoporosis and the most reli-ably identified, because they present to medical atten-tion and require hospitalization in most regions of the world. Wide geographic differences in age-standard-ized hip fracture rates worldwide have been reported, varying by at least 10-fold, with higher estimates in many publications [7–15]. Some of the variability in these reports is explained, in part, by differences in the time frame during which fractures were captured for each specific country, the representativeness of the pop-ulation of interest, racial groups and regions included (urban vs. rural), accuracy of the capture of fractures,

steoporosis. http://dx.doi.org/10.1016/B978-0-12-415853-5.00027-3 62

and differences in reference population used for stan-dardization. Notwithstanding all of the above, the high-est fracture rates are consistently reported in northern European countries and North America, and the lowest rates in some, but not all, countries in South America and Asia.

Conversely, while vertebral fractures are the most common, accounting for over 50% of all osteoporotic fractures, they are the least well characterized in terms of rates. Unlike hip fractures, the identification and documentation of vertebral fractures is often poor making accurate characterization of their epidemiol-ogy more difficult. Two-thirds of vertebral fractures are silent, only 10% are hospitalized, and the rate estimates vary widely depending on whether mor-phometric fractures (i.e., those identified by X-ray regardless of the presence of symptoms) and/or clini-cal fractures (those which come to clinical attention because of symptoms) are reported [16]. Studies that have evaluated the prevalence of morphometric frac-tures using the same definitions and methodology, have noted much less variation in vertebral fractures rates between regions of the world, as compared to hip fractures [17–21].

While the majority of hip fractures have traditionally occurred in northern Europe, the US, and Oceania, the demographic and lifestyle changes occurring world-wide are rapidly modifying this landscape. Cooper et al. estimated that the number of hip fractures will increase from 1.66 million in 1990 to 6.26 million in 2050, assum-ing that age-specific hip fracture rates are stable [17]. However, the same author has reported secular trends in hip fracture rates, in opposite directions, depending

Copyright © 2013 Elsevier Inc. All rights reserved.3

27. GEOGRAPHIC VARIABILITY IN H624

on the region of interest in the world [12,18]. Some esti-mates suggest that while hip fracture rates in developed countries of the world are stabilizing or declining, they continue to rise in the most populous part of the world, namely Asia [18]. In 2010, Asia represented 60% of the world population and will still represent 59% in 2050 and thus account for over half of the total projected number of hip fractures worldwide [19]. The aging population worldwide is affecting fracture incidence in developing, much more than developed countries, yet these are the regions of the world with the least avail-able information on fracture rates. Indeed, two of the most populous countries in the world, namely India and Indonesia, have no reliable data on hip fracture rates.

Accurate information on fracture rates is critical for the assessment of the contribution of osteoporosis to the healthcare burden and the appropriate allocation of healthcare resources, be it at the country, regional, or global level. Furthermore, reliable country-specific hip fracture rates are essential for the development of country-specific FRAX calculators (see also Chapter 68). FRAX is an online, easily accessible tool that allows the calculation of a 10-year hip fracture probability or major osteoporotic fracture probability (hip, spine, forearm, humerus), taking into account an individual’s risk factor profile, with or without bone mineral density (BMD). Utilizing country-specific rates of fractures and of mortality, FRAX is used in many countries including the US, Canada, and the UK to target pharmacologic therapy to high-risk patients. As of September 2012, there were 51 FRAX models in 47 countries across the world [20]: eight countries in Asia, including China (with separate models for China and Hong Kong), Indonesia, Japan, Philippines, South Korea, Singapore (with Chinese, Malay and Indian models), Sri Lanka, and Taiwan; 25 countries in Europe including Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Lithuania, Malta, Netherlands, Norway, Poland, Portugal, Roma-nia, Russia, Slovakia, Spain, Sweden, Switzerland, Turkey and the UK; five countries in the Middle East and Africa, including India, Jordan, Palestine, Leba-non, Tunisia; two countries in north America including Canada and the US (with Caucasian, Hispanic, Black, and Asian models); five Latin American countries, including Argentina, Chile, Columbia, Ecuador, and Mexico; and two countries in Oceania including Aus-tralia and New Zealand (FRAX calculator accessed online http://www.shef.ac.uk/FRAX/; accessed 6 March 2013).

In this chapter we aim to define crude and age-standardized hip fractures rates in countries across the world, examine secular trends in such fractures, overview the epidemiology of vertebral fractures, and

V. EPIDEMIOLOGY O

IP AND VERTEBRAL FRACTURES

discuss factors that may contribute to the observed vari-ability in fracture rates across the world.

HIP FRACTURES

Incidence of Hip Fractures by Region

Evidence for substantial variability in the incidence of hip fractures worldwide is supported by numerous country-specific and regional studies. Incidence has been reported as highest in the northern part of the globe (Scandinavia and North America), and lowest in Asia and southern Europe, Latin America, and Africa [7,8,21]. Within the same continent and region, rates also vary markedly: a study of national register sources in Europe covering the period between 1979 and 1987 [22], showed an 11-fold variation range in the age- standardized hip fracture incidence rates within the same continent, with a north to south gradient. The highest rates were reported in northern Europe with the excep-tion of Finland, which was found to have rates simi-lar to those reported in countries from central Europe. Similarly, more moderate rates were observed in central Europe with the exception of Poland, which had fracture rates similar to those reported in southern Europe. The Mediterranean Osteoporosis Study (MEDOS) [9], also reported varying incidence rates from 12 Mediterranean countries in 1988 whereby age-standardized incidence of hip fractures varied more than four-fold among men and 11-fold among women, with the highest rates observed in Seville, Crete, and Rome approaching those of north-ern Europe, and the lowest rates were observed in Tur-key. A review of geographic trends in the incidence of hip fractures [11] involving 46 publications until 2009 spanning 33 countries and using rates standardized to the 2005 United Nations estimates of the world popu-lation, again showed that the highest rates occurred in Scandinavian countries and the lowest rates in Africa, Latin America, and Asia. However, the following excep-tions were noted. In Austria, rates were more similar to those found in Scandinavia than in its neighboring coun-tries. Unusually high rates of hip fractures, comparable to Scandinavian rates, were also seen in Shiraz, Iran, and Oman, rates that were much higher than those in the neighboring countries of Saudi Arabia and Kuwait. In southeast Asia, Taiwan also had rates close to those observed in North America. In Latin America, Argentina had rates similar to those in Ontario, Canada, and cen-tral Europe, but much higher than those from Mexico and Brazil. However, methodological issues may have played a role in some of these findings. Around 40 publi-cations selected for this review reported regional, rather than national data, and half of them did not rely on the International Classification of Diseases (ICD) coding

F OSTEOPOROSIS

http://www.shef.ac.uk/FRAX/

HiP FRAC

V. EPIDEMIOLOGY O

system to define hip fracture, both of which factors can influence estimates of fracture rates.

The most recent and extensive review [14] was pub-lished in 2012, based on an update of a systematic search conducted by the FRAX International Task Force 2010 [13] for the Official International Osteoporosis Foundation (IOF) and International Society for Clini-cal Densitometry (ISCD) Positions on FRAX [23], with one additional year added up to November 2011. In this review, hip fracture incidence was age-standardized to the 2010 United Nations world population for 63 countries. The review revealed some unexpected major changes in the landscape of the world’s hip fractures: in Europe, Austria again showed rates in the same range as Scandinavian countries, but Turkey, Iran, Oman, Tai-wan, and Argentina, countries previously reported to have low rates of fractures, now had rates in the high-est fracture group, close to those of Germany and the UK and above those of North America and other coun-tries in Central and South America. This review used the most recent and best-quality data available for each country and national as compared to regional data in 37 out of 63 countries, and when only regional data were available, the average for all the regions studied was calculated. These findings raise questions about the accuracy of previous epidemiologic data and about how much of these changes in country-specific fracture rates are related to database selection, the availability of higher-quality epidemiologic studies in many of the developing countries, the impact of aging populations worldwide on age-standardized rate calculations, or a combination of all of the above. In addition to these methodological issues, it is also likely that we are witnessing a true makeover of the world map of hip fractures.

For the purpose of this chapter, we conducted a new independent systematic search of the literature, from 1966 to early 2012, to clarify the epidemiology of the major osteoporotic fractures, namely hip and vertebral fractures, worldwide.

Data Selection

A MEDLINE OVID search covering the period between 1 January 1966 and 29 February 2012 was con-ducted. Search was limited to English language and to human adults aged 19 and above. Two Boolean models were created: the first model consisted of the following concepts and their related MESHS* terms: hip fracture, incidence, and country X with each concept searched singly, then merged through the AND term; the second model also consisted of three concepts: osteoporotic fracture, incidence, and country X and the same search strategy was applied. The first model retrieved 3734 publications and the second model 2826 publications.

TuREs 625

F OSTEOPOROSIS

All articles were scanned by title to select relevant titles; duplicate titles for the two models were then removed, thus resulting in a total of 645 articles. The abstracts for these were reviewed, leading to 202 publications of interest covering relevant information for 54 countries. These were all retrieved and underwent full review and quality rating by one of the authors (GEHF). The quality of each study was graded according to criteria originally developed by our group for the FRAX International Task Force Statement [13], and detailed as follows:

• Good:ifatleastfourofthefollowingcriteriaweremet: • prospective study, • study population representative of the entire

population, • study duration more than 1 year, • adequate definition of fracture or ICD codes used, • ethnicities defined when applicable.• Poor:ifatleastfourofthefollowingcriteriaweremet: • retrospective study, • study duration of 1 year or less, • not population based, • inadequate definition of fracture, • only abstract available, • no definition of ethnicities provided.• Fair:sourcesthatdidnotmeetthecriteriaforeither

good or poor (i.e., met some but not all criteria).

Additional selection criteria included provision of age and sex-specific crude rates by 5- or 10-year age groups starting at age 50 years and above with a few exceptions (see footnote to Table 27.1). A total of 56 original publi-cations were ultimately selected for the final analysis: for each country the most recent study with good level of evidence was chosen. For countries without good evidence data, the most recent study with fair evidence was chosen as the next best alternative. India [24], Saudi Arabia [25] and Colombia [23] only had poor-to-fair studies and were included. Some countries have more than one regional study, but no national data; in such cases the average of the studies was used to calculate crude and age-standardized incidence rates.

For some countries (Canada, France, Hong Kong, Singapore, Sweden, and Switzerland) clarifications or additional data were obtained from the author of the original publication through personal communications, and these investigators are acknowledged herein.

Crude Hip Fracture Incidence Rates

Current, reliable, and accurate crude incidence rates for hip fractures are essential for multiple reasons. They provide critical information to public health and other national authorities regarding disease burden, be it medical, social, or financial; they are instrumental for the development of country-specific FRAX calculators,

HIP AND VERTEBRAL FRACTURES
27. GEOGRAPHIC VARIABILITY IN 626
a tool that is a major advance in the formulation of ratio-nal public health policies and management of the indi-vidual osteoporotic patient. Crude incidence rates are also helpful to guide countries without FRAX models for the selection of the best surrogate country FRAX model. Although 47 countries to date have already developed, and some have even updated, a FRAX calculator, the majority still lack adequate resources to collect the high-quality national fracture data needed to create a country-specific FRAX calculator. For these countries, a surrogate FRAX model can be constructed using the FRAX model from another country, which has similar crude incidence rates of hip fractures that is then adjusted with country-specific life expectancy data. Thus, age and sex-specific crude rates are of primary importance.

Tables 27.1A–F provide a summary of age-, gender-, and country-specific crude incidence rates for hip frac-tures, by continent (1A Asia, 1B Oceania, 1C Middle East and Africa, 1D Europe, 1E North America, 1F Latin America), and includes information on the relevant study period and the quality of data. For studies/coun-tries providing age- and gender-specific rates by 5-year age group increments, and to avoid very lengthy sum-mary tables, the rates for the 70–74 and 75–79-year age ranges are reported. These age groups were selected as the most enriched and thus representative, of the popu-lation at risk for hip fractures. For studies/countries pro-viding rates in 10-year age group, the ranges of 60–69 and 70–79 years were considered the most representa-tive. Invariably, and as expected, crude rates increase with increasing age in both genders, with the exception of China [26,27] where rates in women are slightly lower in the 75–79 age group compared to the 70–74 age group (133/100,000/year vs. 155/100,000/year, respectively). For South Africa [24], where the only data available are very old, dating back to 1968, rates appear lower for men in the 75–79 age-group as compared to the younger group; however, rates are already too low to be reliably compared and interpreted. Rates are also consistently lower in men than in women with few exceptions: for China [26,27], rates in both genders are close and even tended to be higher in men for the age group 75–79 years (151/100,000/year and 133/100,000/year in men and women, respectively); in Morocco [29], rates are 132/100,000 and 85/100,000 in men and women, respec-tively, in the 70–74 age group; in Croatia [30] and Finland [31,32], rates in men and women were very close in the 70–74 age group for Croatia and the 60–69 age group for Finland. No data on the incidence in men is available in Slovenia [33].

Comparison of rates within the same continent show that, in Asia, the highest age-specific rates for both gen-ders aged 70–74 and 75–79 are in Taiwan [34,35], fol-lowed by Singapore [23] and Hong Kong [36], and are lowest in mainland China [26,27]. In Oceania, studies

V. EPIDEMIOLOGY

reporting incidence rates in the 1990s in southeastern Australia [37] and national data from New Zealand [38,39] show similar hip fracture rates for the same age group; however, the more recent data we used in our analysis [40,41] for these two regions is not reported for the same age groups. For the Middle East and Africa, comparison becomes more difficult because few coun-tries reported their data for the same age groups. How-ever, Iran [42] shows very high rates in both genders for the 70–74 and 75–79 age groups, and other countries with relatively high rates include Oman [43] and Israel [44] with the lowest apparent rates in Morocco and South Africa [28]. In Europe, Scandinavian countries (Denmark [45], Norway [46], and Sweden [47,48]) report the high-est rates along with Belgium [49] in both genders for the age groups 70–74 and 75–79, while Spain [9,50] and Poland [51] report the lowest rates. In North America, rates for non-Hispanic whites in the US [52] are slightly higher, but close to, those of Canada [53] for the same age groups. It is important to note, however, that Canada reports one rate that includes all ethnic groups, but in a regional study from Manitoba, Leslie et al. reported a two-fold higher rate in Canadian First Nations [54]. In Latin America, direct comparisons between countries are not possible because different age groups are reported, but Argentina and Colombia seem to have the highest age-specific rates while Ecuador reports the lowest rates.

When comparing rates between continents, it is evi-dent that the highest age-specific crude incidence rates for the 70–74 and 75–79 age groups are reported in northern Europe although some Asian countries such as Taiwan [34,35], Hong Kong [36,55], and Singapore (Chionh, personal communication), report rates in the same range as many countries in central Europe such as Austria [56,57], Germany [58], and Switzerland [59,60]. Age-specific rates in northern America [52,53] and New Zealand [41] are also similar to those of central Europe. Rates in the Middle East and Africa are very variable, but it is worth mentioning that rates reported from Iran [42] are in the range of the Scandinavian countries for the 70–74 and 75–79 age groups. Although age-specific crude rates are difficult to compare between countries and continents especially when different studies provide different age ranges, they are truly reflective of the bur-den of hip fractures in a specific population. However, in order to compare incidence rates systematically across populations with differing demographics and longevity, age-standardized rates are preferred.

Age-Standardized Hip Fracture Incidence Rates

Age-standardized rates for men, women, and for both genders combined were calculated using crude incidence rates as available for all age groups above 50 years, in the original publications, standardized to

OF OSTEOPOROSIS

HiP FRACTuREs 627

TABLE 27.1A Crude Rates of Hip Fractures by Gender and by Age-Group for Asia

Country Reference Study yearsLevel of evidence

Rates for men/100,000/year

Rates for women/100,000/year

Age range 70–74 years

China* Xu 1996 [26] 1990–1992 G 125 155

Schwartz 1999 [27] 1990–1992 G

Hong Kong* Tsang 2009 [55] 2000–2004 G 201 362

Lau 2001 [36] 1997 G

Japan* Hagino 1999 [108] 1986–1994 G 119 277

Hagino 2009 [109] 2006 G

Singapore Chionh, personal communication

2007–2009 G 228 432

Taiwan* Chie 2004 [35] 1996–2000 G 287 546

Huang 2000 [34] 1996 G

Thailand Lau 2001 [36] 1997 F 144 361

Aged range 75–79 years

China* Xu 1996 [26] 1990–1992 G 151 133

Schwartz 1999 [27] 1990–1992 G

Hong Kong* Tsang 2009 [55] 2000–2004 G 427 825

Lau 2001 [36] 1997 G

Japan* Hagino 1999 [108] 1986–1994 G 257.3 549.9

Hagino 2009 [109] 2006 G

Singapore* Chionh, personal communication

2007–2009 G 478.1 896.2

Taiwan* Chie 2004 [35]

Huang 2000 [34]

1996–2000

1996

G

G

514.05 984.05

Thailand Lau 2001 [36] 1997 F 227 657


Korea* Lim 2008 [110]

Yoon 2011 [111]

2004

2005–2008∝G

G

124 130


Korea* Lim 2008 [110]

Yoon 2011 [111]

2004

2005–2008∝G

G

272.5 455


Malaysia Lau 2001 [36] 1997 F 96.5 230

Age range 75+ years

Malaysia Lau 2001 [36] 1997 F 320 644


India Dhanwal 2011 [24] 2009 P/F 95 162.5

Age range 75+ years

India Dhanwal 2011 [24] 2009 P/F 289.5 374.5

V. EPIDEMIOLOGY OF OSTEOPOROSIS

27. GEOGRAPHIC VARIABILITY IN HIP AND VERTEBRAL FRACTURES628

TABLE 27.1B Crude Rates of Hip Fractures by Gender and by Age-Group for Oceania





Australia Brennan 2011 [40] 2006–2007 G 30 50


Australia Brennan 2011 [40] 2006–2007 G 260 300


New Zealand Brown 2011 [41] 2003–2005 G 155 278


New Zealand Brown 2011 [41] 2003–2005 G 357 654

TABLE 27.1C Crude Rates of Hip Fractures by Gender and by Age-Group for Middle East and Africa





Iran Soveid M 2005 [42] 2000–2003 F/G 402.5 932

Lebanon∝ Sibai AM 2011 [10] 2006–2009 G 107 269

South Africa Solomon 1968 [28] 1957–1963 F 2 4


Iran Soveid M 2005 [42] 2000–2003 F/G 928 1208

Lebanon∝ Sibai AM 2011 [10] 2006–2009 G 260 498

South Africa Solomon 1968 [28] 1957–1963 F 0 7


Israelλ Levine 1970 [44] 1957–1966 F/G 166 372

Morocco El Maghraoui A 2005 [29] 2002 F 132 85

Age range 75+ years

Israelλ Levine 1970 [44] 1957–1966 F/G 572 813

Morocco El Maghraoui A 2005 [29] 2002 F 157 215


Kuwaitφ Memon 1998 [76] 1992–1995 F 96 124


Kuwaitφ Memon 1998 [76] 1992–1995 F 348.5 457.5


Oman Shukla 2008 [43] 2002–2007 F 170 310

Saudi Arabia Al Nuaim 1995 [25] 1990–1991 P/F 36 79

Age range 70+ years

Oman Shukla 2008 [43] 2002–2007 F 720 730

Saudi Arabia Al Nuaim 1995 [25] 1990–1991 P/F 251 394


HiP FRACTuREs 629

TABLE 27.1D Crude Rates of Hip Fractures by Gender and by Age-Group for Europe





Austria* Koeck CM 2001 [56] 1995 GG

236 436.5

Dimai HP 2011∋ [57] 1989–2008 G

Belgiumμ Reginster JY 2001 [49] 1993 G 310 1050

Denmarkϒ Abrahamsen B 2010 [45] 1997–2006 G 375 725

France Couris CM 2011 [112] 2004 G 145 277

Germanyϒ Icks et al. 2008 [58] 1995–2004 G 201 374

Greece Elffors et al. 1994 [9] 1988–1989 F 160 360

Hungary Pentek et al. 2008 [96] 1999–2003 G 212 351

Ireland Dodds MK 2009 [113] 2002–2004 G 180 379

Netherlands Lalmohamed A 2012 [114] 2004–2005 G 169 286

Norway Emaus et al. 2011 [46] 1994–2008 F/G 357 607

Poland Czerwinsky et al. 2009 [51] 2005 F 125 168

Portugal De Pina MF 2008 [115] 2000–2002 G 131.5 316

Spain* Elffors et al. 1994 [9] 1988–1989 F 80.5 165.5

Hernandez et al. 2006∋ [50] 1988–2002 F

Sweden* Kanis et al. 2000 [47] 1991 F 265 493

Bergstrom et al. 2009 [48] 2001–2005 F/G

Switzerland* Lippuner et al. 2009 [59] 2000 G 202.5 373.5

Lippuner et al. 2011∋ [60] 2000–2007 G

Turkey Tuzun 2012 [116] 2009 F 137 257


Austria* Koeck CM 2001 [56] 1995 G 389 784

Dimai HP 2011∋ [57] 1989–2008 G

Belgiumμ Reginster JY 2001 [49] 1993 G 310 1100

Denmarkϒ Abrahamsen and Vestergaard 2010 [45]

1997–2006 G 700 1385

France Couris CM 2011 [112] 2004 G 302 621

Germanyϒ Icks et al. 2008 [58] 1995–2004 G 340 721

Greece Elffors et al. 1994 [9] 1988–1989 F 300 670

Hungary Pentek et al. 2008 [96] 1999–2003 G 487 695

Ireland Dodds MK 2009 [113] 2002–2004 G 319.5 771

Netherlands Lalmohamed A 2012 [114] 2004–2005 G 323 536

Norway Emaus et al. 2011 [46] 1994–2008 F/G 594 1218

Poland Czerwinsky et al. 2009 [51] 2005 F 199 320

Portugal De Pina MF 2008 [115] 2000–2002 G 269 649

Spain* Elffors et al. 1994 [9] 1988–1989 F 272 436

Hernandez et al. 2006∋ [50] 1988–2002 F

(Continued)






Sweden* Kanis et al. 2000 [47] 1991 F 559 1075.5

Bergstrom et al. 2009 [48] 2001–2005 F/G

Switzerland* Lippuner et al. 2009 [59] 2000 G 410 787.5

Lippuner et al. 2011∋ [60] 2000–2007 G

Turkey Tuzun S 2012 [116] 2009 F 190.5 722


Croatiaϕ Matkovic V 1979 [30] 1968–1973 F/G 153 150

Age range 75+ years

Croatiaϕ Matkovic V 1979 [30] 1968–1973 F/G 207 343


Finland* Luthje et al. 1993 [31] 1988 G 127 112.5

Lonnroos et al. 2006 [32] 2002–2003 F


Finland* Luthje et al. 1993 [31]

Lonnroos et al. 2006 [32]

1988

2002–2003

G

F

446 639


Slovenia Dzajkovska et al. 2007 [33] 2003 F NA 308

UK∋ Wu TY 2010 [117] 1998–2009 G 112 204


Slovenia Dzajkovska et al. 2007 [33] 2003 F NA 900

UK∋ Wu 2010 [117] 1998–2009 G 431 884


Italyϒ Piscitelli 2010 [118] 2000–2005 G 150.5 323

Age range 75+ years

Italyϒ Piscitelli 2010 [118] 2000–2005 G 849 1812.5

TABLE 27.1D Crude Rates of Hip Fractures by Gender and by Age-Group for Europe—Cont’d

TABLE 27.1E Crude Rates of Hip Fractures by Gender and by Age-Group for North America





Canada Leslie et al. 2011 [53] 2005 G 179 302

USAα Ettinger B 2010 [52] 2006 G 210 394


Canada Leslie et al. 2011 [53] 2005 G 337 639

USAα Ettinger et al. 2010 [52] 2006 G 402 793

the 2010 United Nations World Population estimates [61] (Tables 27.2A–F). Countries were then ordered from the highest to the lowest age-adjusted hip fracture rates for men, women and both genders combined, and

categorized into three risk groups by tertiles of the age-standardized distributions: high (>144/100,000 in men, >320/100,000 in women, >237/100,000 in both gen-ders), medium (between 97/100,000 and 144/100,000


1

HiP FRACTuREs 63

TABLE 27.1F Crude Rates of Hip Fractures by Gender and by Age-Group for Latin America





Colombia Jaller, unpublished 2004–2006 P/F 107 218

Venezuela Riera-Espinoza 2008 [119] 2005–2006 F 62.5 159


Colombia Jaller, unpublished 2004–2006 P/F 276 349

Venezuela Riera-Espinoza 2008 [119] 2005–2006 F 129 326


Argentina∝ Wittich 2010 [69] 2001–2002 G 89 176.5

Ecuador Orces 2009 [120] 2005 G 17.5 29


Argentina∝ Wittich 2010 [69] 2001–2002 G 343 554

Ecuador Orces 2009 [120] 2005 G 50.5 84.3


Brazil∝ Komatsu 2004 [121] 1994–1995 F/G 44 124

Age range 70+ years

Brazil∝ Komatsu 2004 [121] 1994–1995 F/G 356 952

NA data not available.* For countries with more than one regional study, average of age-specific crude rates for all studies were calculated.ϒ Average of age-specific rates for first and last years calculated.∝ Average of age-specific rates for all study years calculated.φ Age-specific rates for Kuwaitis and non-Kuwaitis (63% of total population) given in original paper; only reported in table are age-specific rates for Kuwaitis.λ Average of age-specific rates for Jewish from Asia and Africa, Jewish from Europe and America and Jewish from Israel calculated.ϕ Average of age-specific rates for 2 districts (Podravina and Istra) calculated; data published before independence in 1991.μ Study period is 1984–1996 but rates given in original paper are those of 1993.α Data on non-Hispanic whites.∋ Age-specific rates for the last year of the study.Note: the study by Piscitelli et al. [24] in Italy provided age groups of 45–64, 65–74, and above 75 years, but it was included because it was the only nationwide studywith good level of evidence; the study by Abrahamsen et al. [25] in Denmark provided age groups starting at the age of 60 and was included because it was the most recent study with good level of evidence. The study included from the United Kingdom (UK) [26] included age groups starting at 55 was also the most recent nationwide representative with good level of evidence. For Saudi Arabia [27] and Oman [32], rates were given starting at the age of 40 and by 10-year age groups but age-standardization was done starting at the age of 50 years. Two good level studies from New Zealand were included with rates provided by 5-year age groupstarting at 65 years. References available in the author’s libraries and studies published after February 2012 were also included in this review.

V. EPIDEMIOLOGY

in men, between 242/100,000 and 320/100,000 in women, between 177/100,000 and 237/100,000 in both genders), and low (<97/100,000 in men, <242/100,000 in women, <177/100,000 in both genders). The risk groups were color-coded for illustrative purposes (Fig. 27.1). To enable a more encompassing overview, the age-standardized hip fracture rates are also repre-sented in a map (Fig 27.2) with the same risk categories and color codes for both genders combined, as previ-ously described [14].

Age-standardized rates in women were approxi-mately twice as high as in men, a trend that was consis-tent across 46 countries from six continents. As shown in Figure 27.3, the correlation between the fracture rates in women and men was highly significant (R = 0.45, y = 0.42x + 20.63, R2 = 0.803).

OF OSTEOPOROSIS

If the very old data from South Africa are excluded,there is a 14-fold variation in age- and sex-adjustedincidence rates worldwide, a 13-fold range in men and 14.7-fold range in women.

For both genders and as previously reported, Scandi-navian countries still lead the high-risk category [11,14].However, countries previously thought to belong to amoderate- to low-risk category have rates in men thatare now in the same range as Scandinavian countrieswith Iran ranking second and Oman third after Den-mark, having rates that are higher than in Finland andSweden. Rates in Hungary are also higher than thoseof Sweden. Taiwan and Kuwait have rates slightlylower but in the same range as countries in CentralEurope and higher than the US. In the moderate-riskcategory for men, some southeastern Asian countries


TABLE 27.2A Age-standardized Hip Fracture Rates in Asia

Country Source Year Quality CatchmentRates for men/100,000/year


Rates for both genders/100,000/year

China* Xu et al. 1996 [26] 1990–1992 G R 74 76 75

Schwartz et al. 1999 [27] 1990–1992 G R

Hong Kong* Tsang et al. 2009 [55] 2000–2004 G N 146 324.5 239.5

Lau et al. 2001 [36] 1997 G N

India Dhanwal et al. 2011 [24] 2009 P/F R 118 181 151

Japan* Hagino et al. 1999∋[108] 1986–1994 G R 91 245 172

Hagino et al. 2009 [109] 2006 G R

Malaysia Lau et al. 2001 [36] 1997 F N 70 158 116.5

Singapore* Chionh, personal communication

2007–2009 G N 144 320 236.5

Koh et al. 2001∋[75] 1985–1998 G N

Korea* Lim et al. 2008 [110] 2004 G N 139 234 189

Yoon et al. 2011 [111] 2005–2008γ G N

Taiwan* Chie et al. 2004 [35]Huang et al. 2000 [34]

1996–20001996

GG

NR

180.5 365 277.5

Thailand Lau et al. 2001 [36] 1997 F N 90 203 150

TABLE 27.2B Age-standardized Hip Fracture Rates in Oceania




Australia Brennan et al. 2011 [40]

2006–2007 G R 65.5 77.5 72

New Zealand Brown et al. 2011 [41]

2003–2005 G N 139 285 216

TABLE 27.2C Age-standardized Hip Fracture Rates in Middle East and Africa




Iran Soveid et al. 2005 [42] 2000–2003 F/G R 268 402 338.5

Israelλ Levine et al. 1970 [44] 1957–1966 F/G R 130 245 190.5

Kuwaitφ Memon et al. 1998 [76] 1992–1995 F N 173.5 236 206

Lebanon∝ Sibai et al. 2011 [10] 2006–2009 G N 105 242 177

Morocco El Maghraoui et al. 2005 [25]

2002 F R 48 63.5 56

Oman Shukla et al. 2008 [43] 2002–2007 F R 237 312 276

Saudi Arabia Al Nuaim et al. 1995 [25] 1990–1991 P/F R 76 135 107

South Africa Solomon et al. 1968 [28] 1957–1963 F R 5 5 5


HiP FRACTuREs 633

TABLE 27.2E Age-standardized Hip Fracture Rates in North America




USAα Ettinger et al. 2010 [52]

2006 G N 152 334 248

Canada Leslie et al. 2011 [53] 2005 G N 130.5 285.5 212

TABLE 27.2D Age-standardized Hip Fracture Rates in Europe




Austria* Koeck et al. 2001 [56] 1995 G N 181 374 282.5

Dimai et al. 2011∋ [57] 1989–2008 G N

Belgiumμ Reginster et al. 2001 [49] 1993 G N 236 570 411

Croatiaϕ Matkovic et al. 1979 [30] 1968–1973 F/G R 90 106 98

Denmarkϒ Abrahamsen and Vestergaard 2010 [45]

1997–2006 G N 421 938 703

Finland* Luthje et al. 1993 [31] 1988 G N 212 372 296

Lonnroos et al. 2006 [32] 2002–2003 F R

France Couris et al. 2011 [112] 2004 G N 124 287.5 210

Germanyϒ Icks et al. 2008 [58] 1995–2004 G N 153 318 239

Greece Elffors et al. 1994 [9] 1988–1989 F R 142 306 228

Hungary Pentek et al. 2008 [96] 1999–2003 G N 204 364 288

Ireland Dodds et al. 2009 [113] 2002–2004 G N 123 320.5 227

Italyϒ Piscitelli et al. [118] 2000–2005 G N 138 329 237

Netherlands Lalmohamed et al. 2012 [114]

2004–2005 G N 118 243 183

Norway Emaus et al. 2011 [46] 1994–2008 F/G R 260 558 417

Poland Czerwinsky et al. 2009 [51]

2005 F N 88 144 117

Portugal De Pina et al. 2008 [115] 2000–2002 G N 97 266 186

Slovenia Dzajkovska et al. 2007 [33]

2003 F N NA 308 NA

Spain* Elffors et al. 1994 [9] 1988–1989 F R 86 214 153

Sosa et al. 1993 [122] 1990 F R

Hernandez et al. 2006∋ [50]

1988–2002 F R

Sweden* Kanis et al. 2000 [47] 1991 F R 192 389 295

Bergstrom et al. 2009 [48] 2001–2005∝ F/G R

Switzerland* Lippuner et al. 2009 [59] 2000 G N 168.5 373 276

Lippuner et al. 2011∋ [60] 2000–2007 G N

Turkey Tuzun et al. 2012 [116] 2009 F R 110 354 238

UK∋ Wu et al. 2010 [117] 1998–2009 G N 97 292 199



TABLE 27.2F Age-standardized Hip Fracture Rates in Latin America




Argentina∝ Wittich et al. 2010 [69] 2001–2002 G R 77 151 116

Brazil∝ Komatsu et al. 2004 [121] 1994–1995 F/G R 114 301 212

Colombia Jaller et al. unpublished

2004–2006 P/F R 78 138 109

Ecuador Orces et al. 2009 [120] 2005 G N 32 65 49.5

Venezuela Riera-Espinoza et al. 2008 [119]

2005–2006 F R 44.5 148.5 99

NA data not available.* For countries with more than one regional study, average of age-standardized rates for all studies were calculated.ϒ Average of age-standardized rates for first and last year calculated.∝ Average of age-standardized rates for all study years calculated.φ Age-specific rates for Kuwaitis and non-Kuwaitis (63% of total population) given in original paper; only reported in table are age-standardized rates for Kuwaitis.λ Average of age-standardized rates for Jewish from Asia and Africa, Jewish from Europe and America and Jewish from Israel calculated.ϕ Average of age-standardized rates for 2 districts (Podravina and Istra) calculated; data published before independence in 1991.μ Study period is 1984–1996 but rates given for 1993 in original paper.α Data on non-Hispanic whites.∋ Age-standardized rates calculated based on rates for the last year of the study.
Rates for European ethnic group (most widely represented in New Zealand).
V. EPIDEMIOLOGY O

(Singapore and Korea) and southern European coun-tries (Greece and Italy) had rates that were unexpectedly similar or slightly higher than Canada and France. In contrast, men in some Asian countries (Japan, Thailand, China, Malaysia, and Saudi Arabia), southern European (Portugal and Spain), Latin American (Colombia, Argentina, Venezuela, and Ecuador), and African coun-tries (Morocco and South Africa) belonged to the low-risk category.

In women, Iran had rates higher than Sweden and Finland. Taiwan and Turkey had rates in the same range as countries in central Europe and slightly higher than the US. In contrast to men, women from Oman had rates in the moderate-risk category, but still higher than the UK, France, and Canada; Kuwait was in the low-risk category. Comparable to men, women in Hong Kong, Singapore, Italy, and Greece were in the lower portion of the high-risk category and upper end of moderate-risk category, with rates in the same range as central European coun-tries and slightly higher than rates in France and Canada. In addition, one Latin American country (Brazil) had rates higher than France and Canada. Turkey also showed unusually high rates in women ranking in the high-risk category. Again, other Asian, southern European, Latin American, and African countries belonged to the low-risk category. Only Poland from central Europe unexpectedly ranked in the low-risk category.

Comparison with age- and sex-adjusted rates and risk stratification provided by Kanis et al. in his review [14], points to an overall similar picture with the high-est rates observed in northern European countries, Iran showing again rates in the same range, and the lowest rates reported in most countries of southeast Asia, the

F OSTEOPOROSIS

Middle East, Africa, and Latin America. In concordance with our findings, countries from regions previously iden-tified as low risk unexpectedly showed rates in the same range as central European countries, and higher than those of Canada. These include Oman, Taiwan, Singapore, Hong Kong, Greece, Italy, and Turkey. However, some sig-nificant discrepancies in fracture rates and risk categories for certain countries stand out. The fracture rates in the US fall in the high-risk category in our study, which assessed fracture rates in only white people from the US, but the US was characterized as a moderate-risk country in the Kanis study [14], which included fracture rates in African-Americans, Hispanics, and Asians as well as white peo-ple. Fracture risk categorization also differed for Japan, Malaysia, Australia, Finland, Ireland, Poland, Brazil, and Argentina. These differences all resulted from the choice of different studies, with different reported crude frac-ture rates, which were then used to calculate age-adjusted fracture incidence. In his review, Kanis used unpublished data obtained by personal communication for a number of countries whereas we relied on the best-quality data pub-lished. This included countries such as Japan (information only available in Japanese) [62], Malaysia (Chionh, per-sonal communication), Australia [40], Finland [31,32], and Ireland to name a few. Although most of the personally communicated data was rated as good level of evidence in that review, it remains unpublished and thus cannot be independently examined or rated. In addition, the person-ally communicated data provided more recent informa-tion for some countries (Belgium, Finland, Ireland, Italy, Morocco, Russia), and constitutes the only information available for many others (Czech, Jordan, Indonesia, Lithuania, Philippines, Romania, Slovakia, Tunisia).

HiP FRACTuREs 635


FIGURE 27.1 Age-standardized rates for hip fracture in men (A), women (B), and both genders (C).



FIGURE 27.1 Cont’d

FIGURE 27.2 Map of the world representing age-standardized rates in both genders by tertiles. Green represents countries with rates in the lowest tertile (<177/100,000), orange for countries with rates in the middle tertile (177/100,000 to 237/100,000), and red for countries in the high-est tertile (>237/100,000).

HiP FRACTuREs 637

Women (rate/100,000)

0 200 400 600 800 1000

Men

(rate/100,000)

0

100

200

300

400

500

FIGURE 27.3 Regression line for hip fracture incidence rates, men versus women in 46 countries in five continents. The countries represented are color coded and include: Asia in yellow (China, Hong Kong, India, Iran, Israel, Japan, Korea, Kuwait, Lebanon, Malaysia, Oman, Saudi Arabia, Singapore, Taiwan, Thailand, and Turkey), Europe in green (Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, and the UK), North America in blue (Canada and US), South America in dark blue (Argentina, Brazil, Colombia, Ecuador, and Venezuela), Oceania in orange (Australia and New Zealand), and Africa in brown (South Africa and Morocco).

These differences between our two studies highlight the inherent uncertainly in the estimates of country-specific fracture rates in much of the world where data have been collected from a limited portion of the popula-tion or from a single small region, perhaps from an older time period, and often using less than ideally rigorous epidemiologic methodology (see discussion below). For this reason, the estimates of fracture rates for many coun-tries can be expected to change and become more accu-rate as better studies become available. However, even with improved methodology, the geological distribution of fractures is not likely to remain static because secular trends in fracture rates, which differ in different countries and regions, will also change the world’s fracture map.

Secular Trends in Hip Fracture Rates

The total number of hip fractures is rising worldwide. While it was estimated at 1.3 million in the year 1990 [5], it rose to 1.6 million in the year 2000, representing approximately a 25% increase. This is, in part, explained by aging of the world population, with a doubling of the number of individuals above age 50 years between 1950 and 1990, and a 1.5-fold increase between 1990 and 2010 [61]; an explosion that is more pronounced in developing countries. Based on these demographic changes, Cooper et al. estimated that half of hip fractures in women above age 65 years would be expected to occur in Asia by 2050

V. EPIDEMIOLOGY

and only 13% in Europe [17]. Similarly, Gullberg et al., in 1997 [63] expected the number of hip fractures to increase most markedly in Asia, Africa, and Latin America (around 500% from 1990 to 2050).

In addition to changes in fracture prevalence due to aging populations, there is good evidence that age-specific incidence rates of hip fracture are also changing around the world. A temporal trend for sex- and age-adjusted hip fracture rates was first noted in a study by Melton in 1987 [64] spanning the period between 1928 and 1980 in which he noted that while fracture rates rose steeply in the US and Europe in the first half of the 1900s, the incidence rates in Rochester, Minnesota, where follow-up was the longest, began to plateau from 1950 onwards. A review on worldwide secular trends in the incidence of osteoporotic fractures [12] showed that, overall, age-specific hip fractures increased steeply in the first half of the century until the 1980s in northern America and Europe with a similar trend in Oceania; since that time they have plateaued or started to decrease. The limited data from Asia reveals the reverse pattern with the most striking increases still expected to occur in this continent in the coming 25 to 50 years.

Limitations of Hip Fracture Incidence Studies

Among all osteoporotic fractures, the estimate of hip fracture incidence is the most reliable because hip

OF OSTEOPOROSIS


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fractures in most countries, but certainly not all [65], lead to hospitalization. Nevertheless, numerous sources of errors may still affect the accuracy of hip fracture inci-dence rates and these include the following.

Quality of StudiesObviously, not all countries have good-quality data,

which leads to inaccuracies when comparing incidence rates between countries with differing levels of evi-dence. In our review, we tried to select the best evidence level data available for each country: 26 out of 47 (55.3%) countries had a good level of evidence data and six had fair- to good-evidence data. Fair-level data were selected for 12 countries because no superior quality data were available. Only three countries had poor (India) or poor-to-fair data (Saudi Arabia, Colombia) as the only data available.

Case Identification and AscertainmentOver- and undercounting of hip fractures when con-

ducting a register-based study or using hospital dis-charge data can influence the accuracy of hip fracture incidence rates, especially when retrospective data col-lection is undertaken. Adequate definition of fracture (i.e., review of the radiology report and use of ICD codes) was among the criteria used in our rating of stud-ies, reflecting a higher-quality evidence and minimiz-ing the risk of misclassification. In contrast, use of ICD codes does not define the level of trauma, and thus it is also important to exclude pathologic and high trauma fractures: for example, in Iran, the study conducted by Soveid et al. [42] used ICD codes and excluded patho-logical and high trauma fractures and reported rates up to two-fold lower than rates reported by Valizadeh et al. [66] who did not use ICD codes and included high trauma fractures.

Regional versus Nationwide Representative DataMany countries, including some of the most developed

(Finland, Norway, Sweden) lack published nationwide data. This is an important source of error because, within the same country, incidence rates have been shown to vary two- to four-fold by latitude, socioeconomic, and educational status [40,67,68] with higher incidence observed in the most socially deprived. In addition, frac-ture rates have been consistently reported to be higher in urban as compared to rural areas. In Argentina hip fracture rates are lower in the northern as compared to the central region of the country, but Wittich et al. [69] also demonstrated a higher incidence in the city of San Miguel de Tucuman than in the rural province. In Sweden [70], all types of fragility fractures were more common in urban (Malmö) than in rural (Sjöbo) areas with an odds ratio of 1.75 for urban dwellers 40 years of age and older. This difference was attributed to differences


F OSTEOPOROSIS

in bone mass, physical activity, and a higher likelihood of falls in the urban population. Similarly in Switzerland, in a study conducted in Geneva, composed of both urban and rural populations, the age-adjusted incidence of hip fractures was 40% higher in urban compared with rural areas over a 5-year period. Interestingly, this differ-ence was not related to the higher proportion of elderly people living in institutional settings in urban districts. A study by Jacobsen [71] in the US identified a north–south gradient of risk with a cluster of high incidence in the southeastern area. These studies along with oth-ers, mainly from Norway [72–74] and Croatia [30], high-light regional differences within the same country in the incidence of hip fractures and the importance of nation-wide representative data when comparing rates between countries.

In addition to regional differences, ethnic differ-ences also confer significant variability in hip fracture incidence within the same country (see also Chap-ter 27). Data on hip fracture incidence in each ethnic group can be used to derive rate ratios for different ethnicities allowing ethnic-specific risk stratification. This was done for the US [23] and Singapore [75], but is still not well characterized in other countries such as New Zealand where hip fracture rates in Europeans are approximately 30% higher than for Mãori, Pacific, and Asian people [41]; in Kuwait, where non-Kuwaitis represent 63% of the total population, the rates are five times higher in Kuwaiti men [76]; and in Israel, Jewish women of European and American descent had 1.5 higher fracture rates than those from Asian and African origin [44].

Study Duration and the RECENCY of the DataStudies extending beyond 1 year confer more con-

sistency in the data. Thirty-three out of the 56 studies (59%) selected for our analysis extended beyond 1 year. Because of secular changes in hip fracture rates, con-sideration of when the data are accessed is important. For example, the only data from South Africa is over 40 years old.

VERTEBRAL FRACTURES

Vertebral fractures are the most common osteoporotic fractures worldwide occurring in 30% to 50% of people over the age of 50 years [77]; however, many factors limit the availability of reliable information on their epidemi-ology. The majority are silent, less than 10% require hos-pitalization, they are often missed and underreported in medical records, and rate estimates vary due to meth-odological differences in definition and classification [78–80]. Prevalence studies have generally relied on X-rays to identify morphometric vertebral fractures, but

VERTEbRAL F

the methodology used has varied widely from a subjec-tive interpretation by an expert observer to sophisticated morphometric measurements which have defined frac-tures variously as percent reductions in vertebral height relative to a normative population database; relative to other vertebrae in the same individual; or by compar-ing anterior, posterior, and mid-vertebral heights of a single vertebral body. Even when similar methodology is employed, the percent reduction in height used to define a fracture may vary. Clinical vertebral fractures are those that come to clinical attention because of pain, but even here, other causes of back pain may have led to the identification of an asymptomatic (nonclinical) ver-tebral fracture [52] or other causes of fractures, such as high-energy trauma or malignancy, may not have been excluded if ICD codes were not used.

Studies that have evaluated the prevalence of mor-phometric fractures using the same definitions and methodology have noted much less variation in vertebral fractures among regions of the world, compared to hip fracture rates [17–21]. Prevalence rates varied between 19% and 24% in elderly women from the Middle East, Europe, and North America [23,81]. A 25% prevalence of morphometric vertebral fractures was also reported in postmenopausal women from three countries in Asia, namely Hong Kong, Beijing, and Taiwan [82]. Simi-larly, in the Latin America Vertebral Osteoporosis Study (LAVOS), the prevalence of morphometric fractures, was also almost identical to rates reported in other areas of the world [83].

Reports on the incidence of vertebral fractures are scarce [47,81]. From observational studies using the same methodology for identifying and reporting clinical verte-bral fractures, Bow et al. reported that vertebral fracture incidence rates were similar or up to two-fold higher in Asians (Hong Kong Chinese and Japanese) compared to Swedish Caucasians [81], a finding that differs signifi-cantly from the rank order of hip fracture rates In the fol-lowing section, we will exclusively address studies that investigated the incidence of clinical vertebral fractures documented by ICD codes.

Vertebral Fracture Incidence

The majority of data on vertebral fractures stem from studies conducted in Europe and North America [33,37,47,59,81,84–96]. Ten published studies use ICD codes for vertebral fracture definition, and of those, half report incidence of both hospitalized and outpa-tient clinical vertebral fractures [33,59,87,88,91] and half report only report incidence of hospitalized vertebral fractures [85,86,89,95,96]. An additional five studies are prospective and report both the baseline prevalence and the longitudinally measured incidence of mor-phometric fractures, with the exception of one study

V. EPIDEMIOLOGY O

RACTuREs 639

from Hong Kong, which was only an incidence study [81,84,90,92,94].

Among the five incidence studies using ICD codes and reporting data on both ambulatory and hospitalized vertebral fractures, the oldest European study from the UK [87] spans 10 years in the 1990s and covers 6% of the population over age 20 years. The overall incidence rate was reported as 45/100,000 person-years (32/100,000 in men and 56/100,000 in women), rates that are five- to 20-fold lower than those reported in Slovenia and Swit-zerland [33,59]. These may be related, at least in part, to the fact that the UK study reported incidence in patients aged 20 years and older, markedly decreasing the over-all incidence whereas the studies from Slovenia and Switzerland included only postmenopausal women or subjects above age 50 years, populations expected to be at higher risk for osteoporotic fractures. In addition, these latter two studies used a fracture definition that favored osteoporotic fractures. Two additional studies report-ing incidence of both outpatient and hospitalized verte-bral fractures using ICD codes are from North America. The study from Canada was conducted between 1981 and 1984 and reported rates in all adults in Manitoba of 64/100,000/year, close to the rate reported in UK [88]; the US study by Melton et al. [91] in Olmsted county reported rates in patients aged 35 years and above using ICD-9 codes confirmed by a radiologist’s report of compression or collapse of thoracic and lumbar vertebra. The over-all incidence rate was 439/100,000/year (316/100,000/year in men and 521/100,000/year in women). Of note, these data were re-examined by Ettinger et al. [52], who concluded that the incidence rates reported are probably significantly inflated by the inclusion of prevalent mor-phometric fractures which were brought to clinical atten-tion by spine X-rays performed for other indications.

In summary, there are few studies reporting incidence rates of combined ambulatory and hospitalized vertebral fractures using ICD codes. The results of these studies are very heterogeneous and do not allow reliable conclu-sions regarding geographic variability in the incidence of osteoporotic vertebral fractures.

Five other studies reported the incidence of hospital-ized vertebral fractures exclusively. The largest among them, conducted in Europe in the 1990s, included eight countries, used the same ICD-9 code, evaluated subjects above age 50 years, and age-standardized rates to the 1990 Swedish population [95]. A north–south gradient with a three- to four-fold variability was evident, with highest rates observed in Scandinavia for both genders, and the lowest in cental and southern Europe, with the exception of Slovakia where rates in men were com-parable to those observed in Scandinavian countries. Another large study reporting incidence of hospitalized vertebral fractures examined rates in white people as compared to black people aged 65 years and above in the

F OSTEOPOROSIS

27. GEOGRAPHIC VARIABILITY IN HI640

US for the years 1986 to 1989 [89]. It showed overall rates in white men and women that were approximately four-fold higher than in black people; and similarly, three- to five-fold higher age-specific rates for whites of both gen-ders across all age groups.

It should be kept in mind, however, that only about 10% of vertebral fractures result in hospitalization and the rates of hospitalization for these fractures could differ across countries and/or populations. For these reasons, it is highly likely that the incidence of vertebral fractures is underestimated in all of these studies. Despite the dif-ficulty in comparing across studies, one can conclude from the few studies reporting incidence of hospitalized vertebral fracture, that there is less geographic variabil-ity as compared to hip fractures.

Possible Factors Contributing to International Variability in Fracture Rates

The 14-fold range in the variation of hip fracture incidence across the world raises important questions about the etiology of hip fracture. The reasons for this variability are unknown, but it is highly likely that genetic, environmental, and lifestyle factors all play a role. Twin and family studies have shown that 50% to 80% of the variance in BMD is genetically determined and BMD is the single best predictor of fracture after age [97]. Osteoporotic fractures have also been shown to be heritable, independent of BMD [98]. A genome-wide association analysis of almost 83,000 individu-als identified 56 BMD loci and 14 loci associated with fracture risk [99]. Thus, a large part of the international variability on fracture rates may reflect differential genetic susceptibility.

Given the importance of BMD as a major predictor of fracture in both men and women geographic variability in BMD, due to genetic and/or environmental factors, could contribute to geographic differences in fractures. We have compared standardized areal BMD measures in several populations of older men [100] and women [101]. Lumbar spine, total hip, and femoral neck BMD were compared in US white people, US Asians, US Hispanics, US black people, Afro-Caribbean people from Tobago, Hong Kong Chinese, and Koreans. We showed that hip BMD in Afro-Caribbean men was 8% to 10% higher than US black people, despite the fact that both populations are of African origin. The lower BMD among US black people may have reflected their greater European admix-ture, but the more rural lifestyle in Tobago may also have contributed. Within the Asian groups, BMD was much lower in the Koreans compared to the Hong Kong Chinese. The Korean men experienced relative nutri-tional defects during the Korean War (1950–1953) when these men were in their childhood and adolescence and might have led to lower peak skeletal mass.

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V. EPIDEMIOLOGY OF

P AND VERTEBRAL FRACTURES

Areal BMD is a two-dimensional measure and does ot account for differences in bone size and geometry, hich may also contribute to international variability

n hip fractures. For example, Asians have shorter hip xis length and smaller neck shift angle [102], and bet-er bone structural parameters (greater cortical thickness nd trabecular volumetric BMD) [103].

Body mass index (BMI) is a major determinant of MD and higher BMI has been linked to a lower risk f hip fracture. Thus, variability in BMI and the preva-

ence of obesity may also contribute to the variability in ip fractures worldwide. For example, the mean body eight varied from a low of 61.8 kg in the South Korean en to 87.1 kg in US black men and accounting for dif-

erences in body weight attenuated the differences in MD although they remained significant [100].

Other lifestyle factors vary across the world. Differ-nces in physical activity and diet could contribute to he variability in hip fracture. In our previous study, orean men had the lowest dietary calcium (323 mg/ay) compared to about 600 mg/day in the Hong Kong hinese and US Asians [100]. Differences in physical ctivity could underlie the differences in hip fracture ates in urban versus rural settings. For example, Xia t al. hypothesized that the rapid increasing rates of hip racture in Beijing could reflect increased urbanization

hich is characterized by increased reliance on cars nd buses instead of walking or cycling [18]. In addi-ion, other changes in urban environments such as the ncrease in hard surfaces upon which to fall, sitting in hairs rather than on the floor, and substituting western tyle for traditional squat toilets could also play a role. t is possible that these environmental factors related to rbanization may help to explain the large differences in ip fracture rates in genetically similar and geographi-ally close populations such as the Han Chinese living in eijing or Taiwan.

There are also geographic differences in hormonal fac-ors known to influence bone homeostasis. The preva-ence of vitamin D deficiency varies across the world. For xample, the prevalence of insufficiency (defined as <75 mol/L) was about 50% in Thailand and Malaysia, 70%

n the US, and 90% in Japan and South Korea [104]. This idespread epidemic of vitamin D deficiency raises the ossibility that hip fracture rates could be lowered with imple relatively inexpensive vitamin D supplementa-ion. We have shown substantial geographical variation n the levels of sex steroid precursors and metabolites nd sex hormone binding globulin (SHBG) [105]. For xample, Asian men in Hong Kong and Japan, but not n the US, had levels of total testosterone approximately 0% higher than in other groups. Even greater variation as present in levels of estradiol, SHBG, and dihydrotes-

osterone. Group differences in BMI did not explain ost geographical differences in these concentrations. In

OSTEOPOROSIS

G
ACkNOwLEd
addition, BMI-independent racial differences were pres-ent; black men had higher levels of estrogens (estradiol, estrone), and Asian men had lower levels of glucuroni-dated androgen metabolites. Factors that contribute to these global variations in sex steroid hormones could include differences in physical activity, diet, exposure to chemicals, and smoking. The prevalence of reproductive disorders could vary and contribute as well. In addition, differences in genetics of sex steroid metabolism might be reflected in differences in circulating levels. Nevertheless, this geographic variability in sex steroid hormones, major etiologic factors for osteoporotic fractures, could also con-tribute to the international variability in fractures.

Most fractures occur because of a fall and the inci-dence of falling and differential risk factors for falling might also contribute. In Europe, fall rates varied in men and women from a low of 5/100 person-years in Rotterdam, Netherlands (both sexes combined) to more than 20/100 person-years in Oslo, Norway [106].

Comorbidity has a major influence on osteoporotic frac-tures. Individuals with greater comorbidity have a higher risk of fractures. For example, diabetes is a major risk factor for fractures including hip fracture and the preva-lence of diabetes varies dramatically across the world. For example, the prevalence of diabetes was about 35% in New Guinea and about 10% in China and India [107].

The difference between the magnitude of international variability in hip and vertebral fractures is striking but, as yet, unexplained. It is likely, however, that the etiology of hip fractures is more complex and the large variability in hip fractures worldwide reflects a multitude of factors including genetic, lifestyle, medical, and environmental. International comparisons of these factors could make major contributions to our understanding of the etiology of all osteoporotic fractures, and provide new avenues for prevention. Future studies will need to standardize data collection materials and methods to facilitate these international comparisons.

CONCLUSION

Osteoporosis is a very old disease, dating to antiq-uity, with increasingly staggering social and economic costs in our modern age. The rapidly changing world demographics, increased life expectancy, and global urbanization are major contributors to the exponen-tial rise in the incidence of hip fractures, particularly in developing countries in the Middle East and Asia. There are substantial geographic and ethnic variations in fracture risk, a difference that is most striking for hip fractures for which 10- to 14-fold differences in age-standardized rates have been reported across the world while vertebral fractures vary by two- to four-fold or less. While some of these differences may be the result

V. EPIDEMIOLOGY O

EMENTs 641

of limitations in data collection within individual stud-ies, it is very likely that biologic and lifestyle etiologies are also involved. In addition, intriguing secular trends have been noted across regions, with a general trend for a plateau or decline in fracture rates in western coun-tries, and a continued rise in eastern parts of the world. Understanding the etiology of these geographic differ-ences in fractures will further our understanding of the pathophysiology of fractures and lead to new therapeu-tic interventions. Accurate characterization of the inci-dence of fractures and their epidemiology is of direct relevance and is specific to each nation/ethnic group, and individuals within a nation. Such information is key to the formulation of national public health policies, the allocation of healthcare resources, the development of country-specific fracture risk calculators, and the assess-ment of an individual’s fracture risk to implement suit-able therapies.

ACKNOWLEDGEMENTS

Special thanks to Ms Aida Farha, Medical Information Specialist, Saab Medical Library, American University of Beirut, for her advice and assistance in designing comprehensive and complex searches of the various medical literature resources, and provision of select articles.

The authors also thank Mr Samir Hannoun for his help with the maps and figures and Mr Ali Hammoudi for his assistance in manu-script preparation.

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[4] Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 1999;353(9156):878–82.

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chapter 27 – geographic variability in hip and vertebral ...conversely, while vertebral fractures...

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