Fragility Fractures in the Developing World

“A global call to action to improve the care of people with fragility fractures” was recently made by the Fragility Fracture Network, with co-sponsors and endorsers [1]. It urges cooperative action, to address the “enormous increase in fragility fracture incidence …imposing a massive burden on patients, their families, health systems and societies globally.” The intent is to move the world’s policymakers to recognize and address the burden of fragility fractures (FFxs), especially in poorer countries. The purpose of this review is to emphasize the special challenges that FFxs pose for countries with more limited resources and to consider some possible solutions.

Fragility Fractures

The World Health Organization defined fragility fracture as “a fracture caused by injury that would be insufficient to fracture a normal bone...the result of reduced compressive and/or torsional strength of bone.” Clinically, a fragility fracture may be defined as a fracture “...that occurs as a result of a minimal trauma, such as a fall from a standing height or less, or no identifiable trauma” [2].

Fractures, especially low-energy fractures, are relatively common among the elderly [3]. Their overall frequency increases with age, especially in women after menopause. The high incidence of fractures among elders was recognized long ago, but under-appreciated because short life expectancies resulted in fewer older individuals and thus fewer fractures. Increases in the number of elderlies are causing a worldwide increase in the number of their fractures. The vast majority of these injuries result from low-energy forces and are associated with reduced bone strength, as well as greater risk of falling, due to impaired mobility and frailty [4, 5]. An estimated nine million FFxs occurred worldwide in 2000 [6]. After age 50, approximately a third of women will sustain an FFx, while the figure for men is about 20%.

Women sustain the majority of hip fractures, but the 30% occurring in men carry higher mortality and morbidity [7]. The costs of caring for FFxs are immense. For EU countries, they totaled $37,000,000,000 in 2010. The US cost in 2015 was $20,000,000,000 [8•].

Frequency Increasing

Estimates for the number of hip fractures worldwide generally show significant increases. In 1990, there were 1.3 million, and in 2010, 2.7 million. The projected incidence for 2050 is 4.5 million, but it could range from 7 to 21 million cases per year [6]. Similar increases can be expected for all FFx. Since recovery from these injuries is often incomplete, there is an expanding population of disabled individuals. For hip fractures alone, the number living with disability (prevalence) is expected to exceed 21 million in the next 40 years.

Anatomic Sites

FFxs most commonly affect the proximal femur (hip), vertebral body (spine), or distal forearm. In Johnell’s review, 18% involved the proximal femur, 19% the distal forearm, 16% the spine, 8% the humerus, and 40% were at other sites [9]. Hip fractures receive the bulk of attention, because their impact and burden are the most significant, with increased mortality as well as morbidity. Their costly treatment often involves hospitalization and surgery, when these resources are available [10].

Geographic Variation

There is significant geographic and ethnic variation of FFx incidence, ranging from less than 100/100,000 to over 500/100,000 per year, corrected for age [11••, 12]. Rates are increasing in Asia and Latin America. More developed countries have higher hip fracture incidence, raising the possibility that lifestyle differences might play a role. The reasons for variation in FFx incidence are not known but both genetic and environmental factors are likely to be involved [13,14,15].

Risk Factors

In addition to age and female sex, a most clinically compelling risk factor for a FFx is the history of a previous such injury, particularly involving hip, wrist, or spine. This risk is highest during the first several months, more than doubling the probability of another fracture [16, 17].

Epidemiology studies continue to inform us about factors associated with FFx risk and potential measures for prevention and treatment [18]. Table 1 lists a number of recognized risk factors for FFxs. With regard to developing countries, it is important to recognize lifestyle issues, like tobacco and alcohol consumption, as well as physical activity and nutritional factors (vitamin D and calcium deficiency, obesity, excessively low weight, etc.) [19,20,21,22].

Table 1 Risk factors for fragility fractures
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Recently, HIV with and without anti-retroviral medication has been associated with reduced bone density and FFxs [23,24,25,26].

Relationship of Fragility Fractures to Osteoporosis [27]

Bone fragility is of course an essential feature of FFxs. Bone strength is largely dependent upon its mineral content. Bones grow in strength and mineral density during adolescence and early adulthood [28]. This is stimulated by weight-bearing activity and requires adequate calcium, vitamin D, and protein. By age 40, bone mineral density gradually declines, accelerating in women at menopause. Bone strength decreases along with mineral content, although it depends upon anatomic factors as well. Individuals who fail to acquire sufficient strength during their early years are likely to have earlier and more profound bone fragility, with increased risk of FFxs. Other factors are also important, so that reduced bone mineral density, below the threshold set to define osteoporosis (≤ 2.5 standard deviations below a healthy young adult), does not predict 100% likelihood of a FFx. Furthermore, many individuals with lesser degrees of low bone mineral density do sustain FFxs. In fact, these individuals, with T scores in the range from − 1.0 to − 2.5, defined as the bounds for osteopenia, are the majority of patients with FFxs.

Since bone density alone does not determine FFx risk, other factors must also be considered [29••]. There is a clear trend away from relying only on BMD for FFX risk assessment. Several assessment tools have been developed to include other risks [30]. The FRAX algorithm is prominent among these, though it does not include all important risks, particularly those related to falling. Adapting FRAX to a new population group requires accurate and voluminous epidemiologic data. Because FRAX can be used with or without bone mineral density measurements, it has been adopted by a number of less developed countries [31,32,33,34]. Oden et al. used country-specific FRAX data to estimate the number of individuals at high risk of FFx [35]. They determined that this population was 158 million globally in 2010 and predicted it would double by 2040. Fifty-five percent of these patients live in Asia.

Impact and Burden

The impact of FFxs is manyfold. They cause disability, pain, and loss of participation in society.

Substantial burden falls on family and friends. Care for FFxs strains the capacity and finances of healthcare systems and social services [36•]. Total costs include acute treatment, rehabilitation, ongoing support for those whose disabilities necessitate assistance, and reduced productivity by patient and caregivers. Where facilities are available, hip fracture patients may become institutionalized [37]. Williamson et al. recently reviewed costs and their drivers for patients with fragility hip fractures. Their pooled studies included over 670,000 patients, from 27 different countries (none from Africa, since no data were available). This study reported the cost of index hospitalization, as well as the total health and social costs for the first 12 months. The pooled estimate for the former was $10,075, and the total was $43,669 per patient. Prior co-morbidity and the development of complications were the two most significant drivers of higher costs [38].

The costs of caring for FFxs are challenging for the wealthiest of nations and hard to imagine for the majority of economies, which have far fewer resources to devote to the foreseeable needs of the looming FFx epidemic [39].

Disability-adjusted life years (DALYs) provide a quantitative measure of morbidity and mortality. Johnell and Kanis report a burden estimated at 5,800,000 DALYs, 0.8% of the global burden due to noncommunicable diseases [9]. Eighteen percent of their total fractures involved the hip, which accounted for 40% of the DALYs. However, 60% of the overall burden was due to other than hip fractures.

Papadimitriou’s recent study robustly assessed the burden of hip fractures with a pooled analysis of prospective cohorts and real-life follow-up data [40••]. During 13 years, 3.5% of almost 224,000 men and women sustained hip fractures, with 5.3% mortality and 5964 DALYs, 70% of which were attributed to disability and the rest to premature death. The 27/1000 individual DALY rate was similar to those found in the same pool for breast or pancreatic cancer.

The International Osteoporosis Foundation’s Regional Surveys, from 2010 to 2013, obtained data from selected countries worldwide. In the Asia-Pacific region, population percentage over 50 ranged from 10 to 45%, reported annual hip fracture rates ranged from 90 to 400 per 100,000, and several countries reported surgical treatment for hip fractures of 50% or less [41,42,43,44].

The Institute for Health Metrics and Evaluation (IHME) has developed a truly remarkable approach to studying the global burden of disease (GBD) and presenting data about the relative significance of death and disability of each health problem [45]. Hoy et al. point out that these studies have progressively improved, but in the case of musculoskeletal conditions, the impact of disability probably remains under-appreciated especially for LMICs [46, 47••]. Musculoskeletal conditions contribute much more to the global burden through the disability they cause than from premature mortality. Over 20% of the world’s disability burden, measured as years lived with disability (YLD), is due to musculoskeletal conditions. Failure to consider properly the musculoskeletal disability burden may result in misappropriation of resources (scarce enough already in LMICs). Presently, a disproportionately low level of resources is devoted to prevention, treatment, and research of MSK conditions, including FFxs. More high-quality local data, with improved aggregation, may provide a stronger stimulus for prevention and treatment of the expanding problem of FFxs.

The GBD, for all its many strengths, does not specifically identify FFxs, nor proximal femur (hip) fractures or others by anatomic location. To date, the IHME’s GBD presents osteoporosis as a risk factor, not as a diagnosis per se. GBD 2016, as presented online by the IHME, indicates that the proportion of the World’s disease burden in DALYs due to falls with a low BMD 1.49%, with a 19.5% risk factor attribution. It is hard to know how valid an indicator this is for the worldwide contribution of FFxs [46, 47••, 48, 49••].

The World Health Organization played a significant role in early studies of osteoporosis and FFxs. However, in 1998, the World Health Assembly urged a more comprehensive approach to noncommunicable diseases (NCDs), focusing on the four major ones—cardiovascular, chronic respiratory disease, cancer, and diabetes—with their greater contribution to mortality rates compared to disability [50]. Subsequently, osteoporosis and FFxs have received scant mention among the “other NCDs” in current WHO documents, regarding NCDs, aging, universal health care, and other international public health issues [51, 52]. Disability, often severe and long-lasting, contributes more than early death to the burden of FFxs. Measured in DALYs, the most significant contributors to disease burden of those 60 years and older are cardiovascular diseases (30%), cancer (15%), chronic respiratory diseases (10%), musculoskeletal diseases (8%), and neurological and mental disorders (7%) [53]. It is understandable why fragility fractures (2016 estimate of approximately 1.5%) have been assigned a lower priority.

Developing World

There is no universally accepted definition for “the developing world.” This term is commonly applied to those countries classified by the World Bank as either low (N = 31) or middle (N = 109) income, based on the gross national income per capita [54, 55]. For the 2018 fiscal year, the defining levels are based on the 2016 GNI figures for annual per capita income. Those at $1005 or less were defined as low income. Those from $1006 to $3995 were defined as lower-middle-, those from $3996 to $12,235 as upper-middle-, and those equal to or greater than $12,236 as high-income economies. The majority of the world’s population lives in countries classified as either low- or middle-income countries (LMICs). Low levels on the Human Development Index and limited industrialization are associated features of LMICs.

Table 2 presents 2017 population data for the world and the four World Bank economic groups, with their predicted population in 2050. The proportion of people aged 65 and over and those 80 and over are included, to represent elderly and extreme elderly populations. Table 3 lists the World Bank geographic regions, with percentage population in the LMIC range. These two tables demonstrate predicted growth and aging of the regional populations, of which Asia and sub-Saharan Africa are most notable. Elderly and extreme elderly populations are those with the highest rates of FFxs. While these age groups are still relatively less numerous in many LMICs, significant increases, along with an epidemic of FFxs, are foreseen in the next few decades.

Table 2 Population data for World Bank Economic Groups, actual 2017, and projected 2050, with percentages for age groups ≥ 65 and ≥ 80
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Table 3 Populations (2017) in World Bank geographic regions, LMICs, and age > 65
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The UN has a separate category for the world’s poorest and weakest countries—the so-called least developed countries (LDCs) [56]. There are currently 47 such countries, 33 from Africa, 13 from Asia-Pacific, and 1 from Latin America. The LDCs include 31 of the 34 low-income countries and 15 of the 47 lower-middle-income countries. Their total population is over 880 million (approximately 12% of the world’s), but generates less than 2% of the world’s gross domestic product. The LDCs share a number of significant socioeconomic weaknesses.

By any measure, the human and institutional capacities of LMICs are limited. Their overall incomes are low and distributed unequally. Political instability, fragile governance, and various conflicts are common. Education levels are low. Their environmental conditions are poor (sanitation, indoor and outdoor air quality, water quality). Their primarily agrarian economies are typified by low productivity and limited investment. Seeking work, many citizens of LMICs are moving from rural to urban areas, with steadily growing slums. LMICs’ primary external source of income is a small, non-diverse number of agricultural and extractive exports, vulnerable to international market variation. Manufacturing, if present, is very limited and primarily labor-intensive. Their economies are seriously constrained, with chronic deficits, debts, and dependence on external support. Those LMICs not included among the LDCs have similar features, although less concentrated and in different proportions. Table 4 lists major characteristics of developing economies.

Table 4 Major characteristics of developing economies
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While the economic status of countries is defined by average income levels, it is important to remember that the distribution of income, and other resources, is far from uniform. Low- and middle-income countries vary greatly from one to another, just as they do internally. Pockets of relative wealth, and of significant poverty, are the norm. The overriding reality is that each of the countries in this group lacks the resources necessary for addressing various needs which might reasonably be regarded as essential. These needs, and efforts to meet them, are comprehensively set forth by the United Nations Sustainable Development Goals (SDGs), “a universal call to action to end poverty, protect the planet, and ensure that all people enjoy peace and prosperity” [57]. There is a strong association between low income, low socioeconomic status, low education, and noncommunicable diseases [58•]. The SDG program recognizes the need for concurrently addressing all 17 goals.

Efforts to meet the interconnected SDGs began in January 2016, with a target date of 2030. Progress is being monitored through use of 230 specific, measurable indicators. The world’s health needs are addressed by the third SDG, “Good Health and Wellbeing.” This seeks to ensure healthy lives and promote well-being for all at all ages. Its overriding thrust is to “Achieve universal health coverage, including financial risk protection, access to quality essential healthcare services and access to safe, effective, quality and affordable essential medicines and vaccines for all.” Health-related indicators and progress toward meeting them are being collected and presented by the IHME [59]. Their most recent report, using data from the 2016 Global Burden of Disease study showed “many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off” [60]. This report holds out hope that the ambitious targets can be met, but clearly demonstrates the gaps between present status and attainment of the health-related SDG.

Healthcare Resources in Developing Countries

Access to healthcare resources is significantly limited in developing countries. This is true on both the supply side (available healthcare services) and the demand side (people in need of healthcare) [61•, 62•, 63•].

Striking disparities exist in healthcare funding and necessary resources for healthcare generally and surgical care in particular. Worldwide, in 2015, the percentage of GDP devoted to health expenditures was 9.9%. In the low-income (LI) population, it was 6%, in the lower-middle (L-M) 4%, and in the upper-middle (U-M) 5.7%, vs. 12.4% in the high-income group. Using purchasing power parity–adjusted US dollars per capita per year, the LI group was $98, L-M $259, U-M $904, and high income (HI) $5280 [64]. Available human resources are similarly limited in poorer countries. The numbers of physicians per 1000 people are 0.3 in LI, 0.7 in L-M, and 1.9 in U-M countries, vs. 3.0 in the HI group. The numbers of surgical specialists (surgeons, anesthesiologists, and obstetricians) per 100,000 population are 1.6 in LI countries, 10.1 in L-M, 40 in U-M vs. 67 in HI countries [64].

The entire health systems of LMICs are deficient. Mills has reviewed and listed various deficiencies and provided suggestions for funding options and incentives for improvement [65].

Limited Access to Surgical Treatment

Recently, surgical treatment has been recognized as an essential, yet deficient, part of healthcare for all countries [66, 67]. Almost one third of conditions which contribute to the global burden of disease can only be addressed through surgical treatment. However, it is estimated that more than 5 billion of the world’s 7.4 billion population lack access to safe, effective surgical care. Furthermore, in LI and L-M countries, nine of ten people are unable to obtain basic surgical care [68]. While prodigious efforts are underway to rectify these shortcomings by the energetic Global Surgery movement, including WHO, World Bank, and UN, it is clear that in many parts of the developing world, the necessary resources for operative care of FFxs are simply missing [62•, 69, 70]. This is true for all types of surgery, including for fractures and other essential musculoskeletal conditions [71•, 72••]. Essentially every element of the complex set of required resources required for safe effective surgery is missing, in short supply, or available only at costs which are impoverishing for those in need. A good picture of the impact of these limited resources is that they include essentially every element of what DeVries and Rosenberg call the global surgical ecosystem [73]—from surgeons and anesthesiologists to medications, X-rays, electricity, water, sanitation, hygiene, sterile supplies, and workable systems to procure, deploy, deliver, and dispose, not to mention information management and financing [71, 74, 75]. Hospital accreditation is in its infancy in LMICs [76]. The Global Surgery target for musculoskeletal care is to provide surgical treatment for open fractures, thus decreasing the mortality and morbidity associated with non-operative care for these injuries. Complex open or radiologically guided minimally invasive internal fixation procedures are beyond the horizon of current goals for LMICs. In fact, surgical care for FFxs presently plays a minor role in the developing world. (For example, in many of the poorest countries, few patients with hip fractures receive any operative care [41,42,43,44]. Many are never seen by accredited healthcare providers in clinics or hospitals. The injured, or their families, may choose not to seek care for various reasons [61•, 77•, 78]. Sometimes, they choose traditional healers or bone setters [79,80,81,82]. Subsequently, some whose care has been initiated by traditional providers change to “western medicine” through national, non-governmental, or other private institutions. Their delayed presentations are often associated with poor results.

Possibilities for Improving Care of Fragility Fractures in Developing World

Optimal Treatment for Fragility Fractures in the Developed World

A number of advances in the treatment of FFxs have improved outcomes in well-resourced settings. Regrettably, most of these are difficult if not impossible to implement in the developing world, but we should consider them as now-established standards for optimal care of an aged population with multiple co-morbidities, reduced physical function, mechanically fragile bone, and a limited lifespan. It is clear that every effort must be made to minimize complications related to either medical or surgical issues, since these increase morbidity, mortality, and costs [83]. A robust multidisciplinary quality assurance program is an essential component of the overall care bundle [84]. Others are as follows:

  • A co-management team combining geriatric medicine and surgeons with interest and expertise in the care of patients with FFx. Anesthesia staffing and care must be optimal as well [85].

  • A fracture-liaison service to plan and execute osteoporosis treatment and follow-up to reduce the risk of secondary fractures [86, 87].

  • Organized clinical pathways for expeditious, well-planned care [88, 89].

  • Appropriate implants and surgical techniques, including intra-operative imaging, are key, including options for augmenting fixation and using special implants and techniques, including prostheses, when more standard treatments are unlikely to succeed [90,91,92,93].

  • Comprehensive rehabilitation, both in-patient and community-based [94, 95].

  • Ongoing research to assess and address needed improvements going forward [96].

However, it is noteworthy that these measures have not been successfully adopted throughout the developed world [97••]. For the few fortunate LMIC citizens who can gain access to developed world care in their own countries, through their own resources, through travel elsewhere, or through proximity to better-prepared institutions, adequate care may be possible. However, the vast majority of their countrymen will need to await substantially more progress toward the goals of universal healthcare.

Prevention of Fragility Fractures

Various strategies are being developed to identify individuals with an increased risk of FFxs and to provide cost-effective treatments. Primary preventive measures seek to identify individuals at higher, but reducible, risks and provide timely prevention. On a patient by patient basis, this might be considered as a component of primary medical care [50]. However, the costs would probably exceed benefits if this approach were applied on a population basis in the developing world. Secondary prevention, vs. additional FFxs, has an obvious role, since an individual who has sustained one FFx does have substantial risk of subsequent occurrences [16]. The so-called primordial prevention (prevention of risk factors themselves) might reasonably be considered to reduce FFx risks through population-based public health measures. The normal life course of bone development and aging leads to a peak in bone mass in early adulthood, with a subsequent gradual decline, which accelerates in women during menopause. Measures to promote bone formation during early life, such as nutritional support (adequate calcium, vitamin D, and protein) as well as encouragement of physical activity, and avoidance of tobacco use, alcohol consumption, obesity, and sedentary lifestyle, help promote maximal peak bone mass [98]. If this becomes high enough, bone mineral density may never decline into the range of high FFx risk. Nutritional and lifestyle factors may also help reduce the risk of FFxs throughout life [99]. Other factors, such as medications or diseases that cause secondary osteoporosis, are also associated with potentially preventable FFx risk. Fortunately, many of these risk factors are being included in WHO efforts toward controlling noncommunicable diseases and promoting healthy aging [51, 52]. Osteoporosis screening and management guidelines are best tailored according to the needs and resources of individual counties. While a few countries have succeeded in generating valuable epidemiological data on osteoporotic fractures, to validate risk calculation tools and formulate treatment guidelines, most have not yet done so [33].

Morales-Torres offers several recommendations to control osteoporosis and thus the frequency of FFxs in developing countries: (1) campaigns to increase awareness of individuals at risk and relevant healthcare professionals, (2) healthy lifestyle strategies, (3) evidence-based medical guidelines, (4) emphasis on prevention of falls, quality fracture care, and effective rehabilitation, (5) collection and monitoring of economic data, and (6) the use of country-specific FFx databases [34]. Ultimately, the leaders of each LMIC will need to determine appropriate priorities for their country, based on their own evidence as well as worldwide experience. The major challenge will probably always involve financing the priority-driven needs.