Geographic variability in the incidence of hip and vertebral fractures






Introduction


Osteoporosis, a disease of old age, is documented to date back to the Bronze age . The demographic explosion, increased life expectancy, global urbanization, and the obesity epidemic are major contributors to the exponential rise in the incidence of chronic noncommunicable diseases (NCDs) and their staggering health burden toll. The World Health Organization identified NCDs as the cause of 71% of the world’s deaths in 2016 . Osteoporosis is no exception to this rising tide, vertebral and hip fractures being the hallmark of this costly disease. Thirty to fifty percent of patients who sustain a hip fracture lose functional dependence, and ten percent fracture the contralateral hip. Previously, survival rates posthip and vertebral fractures were reported to be substantially decreased, by 10%–20% in western countries, and possibly more in developing countries . Recent studies still report an increase by two to eight fold in mortality during the first few months postfracture . A 2019 systematic review on mortality rates 1 year posthip fracture shows a variability between continents ranging from 2.4% to 34.8% .


Although hip fractures only represent 20% of all osteoporotic fractures, they are nevertheless the most serious and costly consequence of osteoporosis and the most reliably identified, because they present to medical attention and require hospitalization, in most regions of the world. Several publications have reported wide geographic differences in age-standardized hip fracture rates worldwide, varying by at least 10-fold . The wide range reported is in part explained by the time frame during which fractures were captured for each specific country, representativeness of population of interest, racial groups and regions captured (urban vs rural), accuracy to identify such fractures, and differences in the reference population used for standardization. Notwithstanding all of the above, the highest rates are still reported in Northern European countries, while the lowest rates are from South Africa and countries from South America.


Conversely, while vertebral fractures are the commonest, accounting for over 50% of all osteoporotic fractures, they are the least well characterized in terms of rates. Unlike hip fractures, the identification of such fractures is not readily available, making accurate characterization of their epidemiology more challenging. Two-third of such fractures are silent, only 10% are hospitalized, and the rates may vary widely depending on whether morphometric and/or clinical fractures were reported . Studies that have evaluated the prevalence of morphometric fractures using the same method have noted much less relative variation in fractures rates between regions of the world, as compared to hip fractures. Prevalence rates varied between 19% and 24% in elderly women from the Middle East, Europe, and North America . Some of the highest rates are from North America and surprisingly Asia . Similar prevalence of morphometric vertebral fractures, of 25%, was also reported in postmenopausal women from three countries in Asia, namely, Hong Kong, Beijing, and Taiwan . Conversely, the mean prevalence of morphometric fractures across countries in the Latin America Vertebral Osteoporosis Study [LAVOS was lower at 15%. Reports on the incidence of vertebral fractures are scarce . Bow et al. reported that vertebral fracture incidence rates were similar or up to twofold higher in Asians (Hong Kong Chinese and Japanese) compared to Swedish Caucasians .


While ageing societies, urbanization, and obesity may in part explain the highest rates of hip fracture previously registered in Northern Europe, America, and Oceania, the demographic and lifestyle changes occurring worldwide 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, assuming that age-specific hip fracture rates are stable . However, these authors also reported secular trends in hip fracture rates, and in opposite directions, depending on the region of interest in the world . Indeed, estimates suggest that while hip fracture rates in western regions are stabilizing or are on the decline, they continue to rise in the most populous part of the world, namely, Asia . In 2019 Asia represented 61% of the world population and will still represent 59% in 2050 and thus would account for over half of the total projected number of hip fractures worldwide . The demographic explosion is affecting developing much more than developed countries, regions of the world with the least available, and reliable information on fracture rates worldwide. Indeed, two of the most populous countries in the world, namely, India and Indonesia, have no reliable data on hip fracture rates.


An accurate assessment of fracture rates is critical for the assessment of the contribution of osteoporosis to the health care burden, and the appropriate allocation of health care 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 fracture risk assessment tool (FRAX) calculator which serves as a major advancement for the development of a clinical care pathways, guidelines, and public health policies. Accurate crude country-specific fracture rates are helpful to guide countries without FRAX models in their selection of the best surrogate country (country with the closest crude incidence rates of hip fractures and closest life expectancy) with a FRAX model, as recommended by the International Osteoporosis Foundation (IOF)-International Society for Clinical Densitometry (ISCD) Position Statement . For these the use of a surrogate model will help in the estimation of the 10-year major osteoporotic and hip fracture risk. FRAX allows the calculation of a 10-year hip fracture probability or major osteoporotic fracture probability (hip, spine, forearm, and humerus), taking into account an individual risk factor profile or country-specific longevity and fracture incidence rates. As of Jan 2020, there are 65 country-specific FRAX worldwide and 2 specify ethnic-specific calculators; Singapore (with 3) and United States (US with 4) posted on line : 10 countries in Asia; 35 countries in Europe; 9 countries in the Middle East and Africa; 2 in North America; 7 in Latin America; and 2 countries in Oceania (FRAX calculator accessed on-line February 06, 2020; www.shef.ac.uk/FRAX/ ).


In this chapter, we review key points captured in the previous chapter version in the Background section and aim to provide updated crude and age-standardized hip fracture rates in countries across the world. We also examine secular trends in such fractures, overview the epidemiology of vertebral fractures, and explore possible factors accounting for variability in such fractures across the world.



Background on hip fracture incidence


Evidence for substantial variability in the incidence of hip fractures worldwide is supported by numerous country-specific and regional studies. Incidence is highest in the Northern part of the globe (Scandinavia), and lowest in countries from Asia, and some from Southern Europe, Latin America, and South Africa . Within the same region, rates also vary markedly. A study of national register sources in Europe, covering the period between 1979 and 1987, showed an 11-fold variation 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 exception of Finland, which was found to have rates similar to those reported in countries from central Europe. Similarly, slightly lower rates were observed in central Europe with the exception of Poland, a country with rates similar to those reported in southern Europe. Such North to South trend is not as consistent in this update as will be discussed later. The Mediterranean Osteoporosis Study (MEDOS) reported incidence rates from 12 Mediterranean regions in 1988 . The differences in age-standardized incidence of hip fractures varied more than 4-fold among men and 11-fold among women, with the highest rates observed in Seville, Crete, and Rome approaching those of Northern Europe and the lowest rates in Turkey. A review on geographic trends in the incidence of hip fractures involving 46 publications until 2009, that spanned 33 countries and used rates standardized to the 2005 United Nations estimates of the world population, again showed that the highest rates occurred in Scandinavian countries and the lowest rates in Africa, Latin America, and Asia . However, the following exceptions were noted: in Austria, rates were more similar to those found in Scandinavian than in its neighboring countries.


An extensive review , published in 2012, was based on an update of a systematic search conducted by the FRAX International Task Force 2010 for the Official IOF and ISCD Positions on FRAX and simply added one additional year up until November 2011. It derived age-standardized rates to the 2010 United Nations world population for 63 countries and revealed some unexpected major changes in the landscape for the world map for hip fractures. In Europe, Austria again showed rates in the same range as Scandinavian countries; Turkey had rates close to those in Germany and United Kingdom (UK) and well above those of North America, while Finland, France, Canada, and New Zealand ranged in the lower end of the rates reported for Europe, and close to those reported for several countries in Asia and Latin America. Conversely, age-standardized rates in countries from North America were in the moderate-risk category, and well below those calculated for many South East Asian and Southern European countries. While previously reported to have some of the lowest rates of hip fractures, South East Asia, except for China and Philippines, had rates in the moderate-risk category, while Taiwan fell in the high-risk category. In the Middle-East, Iran and Oman fell in the high-risk category, close to Scandinavian countries, and Lebanon, previously placed at the lower end of risk for hip fractures, was assessed to fall in the moderate-risk category, with rates comparable to the US when combining both genders. In Latin America, Argentina stood out among neighboring countries with rates similar to countries in Central Europe. The above review used the best quality data available for each country and national as compared to regional data in 37 out of 63 countries. When only regional data was available, the average for all the regions was calculated. These findings raise the question about the accuracy of previous epidemiologic data based on which regions and countries were risk-stratified for hip fracture, and whether one is witnessing a true makeover of the world map for the epidemiology of hip fractures, or whether the changes noted above reflect the influence of database selection, the more readily available superior quality of epidemiologic studies in many of the developing countries, the impact of an ageing population worldwide as the target population to which standardization of rates are calculated, or a combination of all of the above.



Methodology



Search and data selection


The original Medline OVID search used in the fourth chapter edition covered the period between January 1, 1966 to February 29, 2012. In this update the same search strategy was implemented regarding hip fractures for the period spanning January 1, 2012 to November 30, 2018 for hip fractures. 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 MeSH 1


1 MeSH is used by the indexers at National Library Medicine to describe the content of an article. These MeSH terms are also organized in a hierarchy or tree structure, and this would allow users to explode a MeSH to ensure that narrower MeSH terms are also included in the search results.

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: vertebral fracture, incidence, and country X and the same search strategy was applied. All articles were scanned by title to select relevant titles, common titles for the 2 models were then removed, thus resulting in a total of 645 articles for the previous search and 99 articles in the updated search. The abstracts for these were reviewed, leading to a total of 241 publications of interest covering relevant information for 50 countries. Articles from the updated search were all retrieved and underwent full review and quality rating by one of the authors (GEHF). For vertebral fractures, we kept articles retrieved from the original search strategy (detailed earlier) and included updates using data captured in a recent review our group performed , coupled with a PubMed search current until December 2019.


For hip fractures, selection criteria included the provision of age and sex-specific crude rates that are necessary to calculate age-standardized rates for each gender and country. The age groups of were provided in all publications starting at age 50 and above with the following exceptions: the study by Piscitelli et al. in Italy provided age groups of 45–64, 65–74, and above 75; studies from France , Denmark , Sweden , Caribbean , Ecuador , Saudi Arabia , Spain , and South Africa provided age groups starting at the age of 60 and were included because they were recent studies with good level of evidence. One study from the UK included age groups starting at 55 but was nationwide representative with good level of evidence. For Oman , 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. In this update, we selected studies conducted after year 2000 for the final detailed analysis outlined in tables and figures. This new selection criterion was chosen in an attempt to avoid the confounding effect of secular trends on the currently reported and age-standardized hip fracture rates. Exceptionally, the national large good-quality study from Iceland is included although spanning the years 1989–2008 because the author reported the average for all years. For each country the most recent studies with good evidence level were chosen. For countries without good evidence data the most recent study with fair evidence was chosen as the next best alternative. For Armenia, clarifications and additional data were obtained from the author of the original publication through personal communications. A total of 69 original publications (of which 37 from the updated search) were ultimately selected to be highlighted in the tables and figures on hip fracture incidence.


For studies providing the age-specific rates in a figure format , we used “Plotdigitizer,” a computer software to extract numerical data from plots, to obtain accurate rates ( plotdigitizer.sourceforge.net/ ).



Quality rating


The quality assessment implemented to rate the studies retrieved was that which was originally developed by our group for the FRAX International Task Force Statement and detailed as follows:




  • Good: If at least four of the following criteria were met:




    • prospective study



    • study population representative of the entire population



    • study duration more than 1 year



    • adequate definition of fracture or International Classification of Diseases (ICD) codes used



    • ethnicities defined when applicable




  • Poor: If at least four of the following criteria were met:




    • retrospective study



    • study duration of 1 year or less



    • nonpopulation based



    • inadequate definition of fracture



    • only abstract available



    • no definition of ethnicities provided




  • Fair: Sources that did not meet the criteria for either good or poor (i.e., met some but not all criteria).


    Studies with good level of evidence and those with fair level of evidence, spanning more than 1 year, are detailed in tables and figures. Studies with fair level of evidence with spanning just 1 year are only detailed in tables.




Calculation of age-standardized rates


Age-standardized rates for men, women, and for both genders combined were calculated using the 2010 United Nations World Population estimates , because most studies were conducted before 2012. For countries with more than one study, the average of age-standardized rates for good-quality studies was calculated. In the absence of a good-quality study the average of fair quality studies was calculated. Some studies spanning many years provided the age-specific rates for each year; in this case, we averaged the crude hip fracture rate across the years for each age group, and then we calculated average age-standardized rates.



Crude hip fracture incidence rates


Table 20.1 provides a summary of age and gender specific crude incidence rates for hip fractures, by continent [(A) Asia, (B) Oceania, (C) Middle East and Africa, (D) Europe, (E) North America, (F) Latin America] and by country. It captures information on the relevant study period and quality of data. For studies/countries providing age and gender specific rates by 5-year age group increments and to avoid excessively lengthy summary tables, only the rates for the 70–74 and 75–79 years age ranges are reported. These specific age groups are selected as the most enriched and thus representative of the population at risk for hip fractures. Similarly, for studies/countries providing rates in 10-year age group, the ranges of 60–69 and 70–79 are considered the most relevant. Invariably, and as expected, crude rates increase with increasing age in both genders ( Table 20.1 ). In general, rates are 1.5–2 fold lower in men than in women, for most age groups, with few exceptions and select age groups, including indigenous Australia, Kuwait, Spain, and Finland. Comparison of rates within the same continent, and exclusively focusing on good-quality studies, show that in Asia the highest age-specific rates for both genders in patients aged 70–74 and 75–79 are in Taiwan , followed by Singapore and Hong Kong . Korea and Japan are comparable for age groups 60–69 years and 70–79 years. In Oceania, previous studies reporting incidence rates in the 1990s in South Eastern Australia and national data from New Zealand showed similar hip fracture rates for the same age groups. However, the more recent data from the same regions do not report rates for the same age groups to allow similar comparisons. Surprisingly, a study in Western Australia , spanning 10 years, reports age-specific rates in nonindigenous residents closer to those in New Zealand; while, rates in indigenous residents are closer to those of Northern Europe ( Table 20.1B ). The authors underscored several risk factors in indigenous populations such as vitamin D insufficiency, diabetes, smoking, excessive alcohol consumption, physical inactivity, as well as their belonging to underserved areas that could potentially account for the higher rates . For the Middle-East and Africa, comparison becomes even more challenging, because fewer countries report data for comparable age groups. However, some studies reported unexpectedly high rates like Saudi Arabia and Oman . While an older study conducted in Shiraz, Iran (2000–03) shows very high rates in both genders for the 70–74 and 75–79 age groups, a more recent study in the same region shows rates more than 50 times lower . Indeed, the previously reported rates were 403/100,000 in men and 932/100,000 in women versus 11/100,000 for men and 15/100,000 for women in the more recent study for the 70–74 age group. This raises concerns about the methodology used in these studies.



Table 20.1

Crude yearly incidence rates of hip fractures by continent, country, gender, and age group in order.
















































































































































































































(A) Asia
Country Reference Study years Level of evidence Rates for men/100,000 Rates for women/100,000
70–74
China a Wang et al. 2010 F 88 174
Fa-ming Tian et al. 2015 F
Hong Kong Tsang et al. d 2000–04 G 212 364
Japan Hagino et al. b 2004–06 G 124 254
Singapore Chionh 2007–09 G 228 432
Taiwan Chen et al. d 2004–11 G 320 480
Thailand Wongtriratanachai et al. 2006 F 165 389
75–79
China a Wang et al. 2010 F 167 322
Fa-ming Tian et al. 2015 F
Hong Kong Tsang et al. d 2000–04 G 450 831
Japan Hagino et al. b 2004–06 G 271 621
Singapore Chionh 2007–09 G 478 896
Taiwan Chen et al. d 2004–11 G 550 950
Thailand Wongtriratanachai et al. 2006 F 223 793
60–69
Korea a Lim et al. 2004 G
Yoon et al. b 2005–08 G 92 106
Park et al. b 2001, 2011 G
Ha et al. d 2008–12 G
Japan Orimo et al. b 2002, 2007, 2012 G 50 86
70–79
Korea a Lim et al. 2004 G
Yoon et al. b 2005–08 G
Park et al. b 2001, 2011 G 252 401
Ha et al. d 2008–12 G
Japan Orimo et al. b 2002, 2007, 2012 G 175 391
65–74
India Dhanwal et al. 2009 P/F 95 163
75+
India Dhanwal et al. 2009 P/F 290 375





















































































(B) Oceania
60–69
Australia Brennan et al. 2006–07 G 30 50
Australia, Western Wong et al. d 1999–2009 G
Indigenous 247 237
Nonindigenous 47 66
70–79
Australia Brennan et al. 2006–07 G 260 300
Australia, Western Wong et al. d 1999–09 G
Indigenous 811 588
Nonindigenous 166 337
70–74
New Zealand Brown et al. f / d 2003–05 G 155 278
75–79
New Zealand Brown et al. f / d 2003–05 G 357 654



































































































































































(C) Middle-East and Africa
70–74
Iran a Soveid et al. d 2000–03 F 207 474
Maharlouei et al. 2011–12 F
Lebanon a Sibai et al. b 2006–09 G
Saad et al. b 2006–17 G 88 212
South Africa Paruk et al. 2010–11 G 50 57
Saudi Arabia Sadat-Ali et al. 2013 F 491 574
75–79
Iran a Soveid et al. d 2000–03 F 470 618
Maharlouei et al. 2011–12 F
Lebanon a Sibai et al. b 2006–09 G
Saad et al. b 2006–17 G 195 426
South Africa Paruk et al. 2010–11 G 171 110
Saudi Arabia Sadat-Ali et al. 2013 F 628 862
70–74
Morocco a El Maghraoui et al. 2002 F 144 141
El Maghraoui A et al. d 2006–09 F
75+
Morocco a El Maghraoui et al. 2002 F 254 295
El Maghraoui et al. d 2006–09 F
60–69
Kuwait Azizieh b 2009–12 G 90 136
70–79
Kuwait Azizieh b 2009–12 G 380 316
60–69
Oman Shukla et al. b 2002–07 F 170 310
70+
Oman Shukla et al. b 2002–07 F 720 730

































































































































































































































































































































































































































































































































































(D) Europe
70–74
Austria Dimai et al. b 2000–08 G 280 469
Armenia Lesnyak et al. c 2011–13 G 190 210
Czech Stepan et al. 2008–09 G 260 383
Denmark Abrahamsen et al. b 2000–06 G 350 684
France Couris et al. 2004 G 145 277
Germany Icks et al. b 2000–04 G 205 369
Hungary Pentek et al. d 1999–2003 G 212 351
Iceland Siggeirsdottir et al. d 1989–2008 G 239 453
Ireland a Dodds et al. d 2002–04 G 171 365
Karayiannis et al. b 2001, 2011 G
Italy Piscitelli et al. 2008 G 167 371
Lithuania Tamulaitiene et al. 2010 F 230 261
The Netherlands a Lalmohamed et al. 2004–05 G 138 240
Klop et al. d 2002–11 G
Norway a Emaus et al. d 1994–2008 G 360 600
1999–2003
Søgaard et al. c 2004–08 2009–13 G
Poland Czerwinski et al. 2005 F 125 168
Portugal De Pina et al. d 2000–02 G 132 316
Romania Grigorie et al. 2010 F 219 283
Russia Lesnyak et al. 2008–09 G 251 273
Spain Azagra et al. b 2000–10 G 262 124
Sweden Bergstrom et al. 2001–05 F/G 269 590
Switzerland a Lippuner et al. 2000 G 216 403
Lippuner et al. b 2000–07 G
Turkey Tuzun et al. 2009 F 137 257
United Kingdom van der Velde R.Y. et al. b / g 2000–12 G 94 207
75–79
Austria Dimai et al. b 2000–08 G 514 964
Armenia Lesnyak et al. c 2011–13 G 258 386
Czech Stepan et al. 2008–09 G 507 876
Denmark Abrahamsen et al. b 2000–06 G 673 1317
France Couris et al. 2004 G 302 621
Germany Icks et al. b 2000–04 G 376 797
2008–09
Hungary Pentek et al. d 1999–2003 G 487 695
Iceland Siggeirsdottir et al. d 1989–2008 G 395 892
Ireland a Dodds et al. d 2002–04 G 382 812
Karayiannis et al. b 2001, 2011 G
Italy Piscitelli et al. 2008 G 351 774
Lithuania Tamulaitiene et al. 2010 F 330 484
The Netherlands a Lalmohamed et al. 2004–05 G 254 446
Klop et al. d 2002–11 G
Norway a Emaus et al. d 1994–2008 G 657 1199
Søgaard et al. c 1999–2003
2004–08 2009–13 G
Poland Czerwinski et al. 2005 F 199 320
Portugal De Pina et al. d 2000–02 G 269 649
Romania Grigorie et al. 2010 F 311 490
Russia Lesnyak et al. 2008–09 G 278 487
Spain Azagra et al. b 2000–10 G 259 611
Sweden Bergstrom et al. 2001–05 F/G 657 1061
Switzerland a Lippuner et al. 2000 G 434 835
Lippuner et al. b 2000–07 G
Turkey Tuzun et al. 2009 F 191 722
United Kingdom van der Velde et al. b / g 2000–12 G 197 439
60–69
Estonia Jürisson et al. b 2005–12 G 173 107
Finland Lonnroos et al. 2002–03 F 125 70
Greece Lyritis et al. b 2002, 2007 F 88 165
Spain Sosa et al. d 2007–11 G 55 77
70–79
Estonia Jürisson et al. 2005–12 G 319 368
Finland Lonnroos et al. 2002–03 F 479 523
Greece Lyritis et al. b 2002, 2007 F 294 639
Spain Sosa et al. d 2007–11 G 161 348
65–74
Slovenia Dzajkovska et al. 2003 F NA 308
United Kingdom Wu et al. b 2000–09 G 102 209
Finland Korhonen et al. b 2000, 2005, 2010 G 225 250
75–84
Slovenia Dzajkovska et al. 2003 F NA 900
United Kingdom Wu et al. b 2000–09 G 399 907
France Briot et al. b 2002–13 G 362 792
Finland Korhonen et al. b 2000, 2005, 2010 G 725 1136
65–74
Italy Piscitelli et al. b 2000–05 G 149 322
75+
Italy Piscitelli et al. b 2000–05 G 848 1835
65–79
Sweden Nilson et al. b 2000–09 G 346 714
80+
Sweden Nilson et al. b 2000–09 G 2106 3514

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Oct 27, 2020 | Posted by in ENDOCRINOLOGY | Comments Off on Geographic variability in the incidence of hip and vertebral fractures
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