Epidemiological Comparison of Osteoporotic Hip Fractures in Spain and China: A Multicenter Study

Objective Compare the epidemiological differences of hip fracture patients in Spain and China. Materials and Method This was a retrospective study. The study population came from patients with hip fractures who underwent surgery between January 1, 2017 and December 30, 2017 at the University Hospital Virgen Macarena (UHVM) in Seville, Spain and Xi’an Daxing Hospital (XDH) in Shaanxi Province, China. Through medical history review and telephone follow-up, the differences of demographic and anthropometric characteristics, lifestyle, personal medical history, variables related to injury, anesthesia, and surgery, length of stay in hospital, days of bed rest, and mortality of patients in the two hospitals were compared. Results A total of 757 patients were enrolled, of which 426 were from UHVM and 331 were from XDH. The average age was 81.4±9.26 years and 76.0±8.08 years, respectively; the male and female distribution was 25.1% and 74.9% vs. 32.0% and 68.0%. The average BMI of Spanish patients was higher than that of Chinese patients. The proportion of drinking and smoking among Spanish patients was signicantly higher than that of Chinese patients (p = 0.000, p = 0.000, respectively). The proportion of patients with ≥ 3 comorbidities in Spain was higher than that in China (p = 0.002). The surgery delay time of Spanish patients was signicantly longer than that of Chinese patients (p = 0.000). Spanish patients had a shorter hospital stay, but a longer time in bed. During the one-year follow-up, there were 81 deaths in Spain and 43 deaths in China (p = 0.026). Conclusiones There are large epidemiological differences between hip fracture patients in Seville, Spain and Xi'an, China in terms of demographics, lifestyle, comorbidities, surgical methods, and mortality.

Introduction the average heights of Spanish men and women were higher than that of Chinese patients (1.70 ± 0.08 m vs. 1.68 ± 0.05m and 1,59 ± 0.07m vs. 1.58 ± 0.05m), p = 0.008 and p = 0.006 respectively. For the comparison of Body Mass Index (BMI), the average BMI of Spanish and Chinese patients were 26.1 ± 4.3 and 22.6 ± 2.0, p = 0.000. Regarding the type of BMI, more than half (60.0%) of Spanish patients were overweight and obese, while Chinese patients with normal weight accounted for 87.9%, p = 0.000. The demographic and anthropometric characteristics are shown in Table 1. Note: * p < 0.05; ** p < 0.01; *** p < 0.001.

Lifestyle and activity levels before fracture
In general, alcohol consumption in Spanish patients was signi cantly higher than in Chinese patients, with non-drinkers only 22.8% in Spain and 66.0% in China, p = 0.000. From a gender perspective, Spanish women consume signi cantly more alcohol than Chinese women, but there was no signi cant difference between men in the two countries, p = 0.000 and p = 0.295, respectively. The number of smokers in the Spanish patients was signi cantly higher than that of the Chinese patients, p = 0.000. From a gender perspective, the proportion of Chinese women smokers was signi cantly lower than that of Spanish women, and the difference was statistically signi cant, p = 0.000. But there was no difference between male smokers in the two countries, p = 0.276. The lifestyle of Spanish patients and Chinese patients are shown in Table 2.  45.6%), the differences were statistically signi cant, p = 0.031, p = 0.010, p = 0.000, p = 0.000, p = 0.000, p = 0.002, p = 0.015, p = 0.018 and p = 0.014, respectively. However, the incidence of anemia in Chinese patients was higher than that of Spanish patients (70.1% vs. 42.3%), p = 0.000. There were no signi cant differences between the patients of two countries in lung, cerebrovascular, gastrointestinal, liver and rheumatoid arthritis disease. Through the previous comparison, we found that the proportion of Spanish patients with multiple pathologies, with more or equal to three, was signi cantly higher than that of China (69.3% vs. 58.6%), p = 0.002. The summary of the comparison of personal medical history between Spain and China is detailed in Table 3.   Asians. Another reason may be that the birth and development of Chinese patients in this age group was in a period of war and poverty, resulting in their height and weight lower than Spanish patients. On the other hand, regarding overweight and obesity rates, Spanish patients are signi cantly higher than Chinese patients, especially women. According to reports, as the living conditions of Chinese people continue to improve, the proportion of overweight and obese hip fracture patients in China will gradually increase in the coming decades [17]. A meta-analysis found that there is a correlation between BMI and bone mass, that is, the higher the BMI, the better the bone density, which is considered to be a protective factor for osteoporotic hip fractures, and put forward the viewpoint of increasing the BMI of the elderly to reduce the incidence of hip fractures [18]. However, from the study we conducted, the percentage of overweight and obese patients with hip fractures in Spain is close to 60%, which is signi cantly higher than the percentage in the normal population [19]. Perhaps this is because obese patients do not have much exibility, are more likely to fall, and the excessive weight at the time of injury exerts more force, which offsets the better bone density [20,21]. In addition, it is well known that obesity is also a risk factor for many diseases, such as cardiovascular and cerebrovascular diseases, diabetes, and arthritis [22]. Moreover, the BMI level is negatively correlated with the postoperative rehabilitation effect of hip fractures, that is, the higher the BMI, the worse the postoperative functional rehabilitation [23]. For these reasons, we suggest that maintaining a normal BMI is the healthiest option, rather than increasing BMI to reduce the incidence of hip fractures.
Many studies have shown that alcohol affects bone metabolism, not only inhibits bone synthesis, but also increases bone resorption through direct and indirect pathways, leading to osteopenia and osteoporosis, thereby increasing the risk of fractures [24,25]. In our comparative study, we found that the proportion of Spanish women drinking is signi cantly higher than that of Chinese women. According to a survey conducted by the Spanish National Statistics O ce, only 11.5% of men and 29.2% of women have never drunk alcohol [26]. These data are similar to our research. And the proportion of habitual drinking continues to increase, especially among Spanish women [26]. As we all know, China is a country with massive alcohol intake. However, because of the culture and different occupations they hold, the number of Chinese women who drink is very small, especially among those born before 1980. To be sure, as social patterns and activities change in this country, this proportion of Chinese women who drink will gradually increase [27]. Indeed, the diversi cation of the culture and the diverse occupations to which women are joining will make a greater number of them consume alcohol in a greater proportion in the coming year[28]. As for smoking, low bone density is one of its negative impacts. And smoking is associated with increased fracture risk in men and women and delayed fracture healing [29]. Research by Dimitris showed that compared with never-smokers, ex-smokers or active smokers have an increased risk of hip fractures, but the longer they quit smoking, the lower the risk of fractures. Our research shows that the proportion of smokers among Spanish patients is signi cantly higher than that of Chinese patients, which is mainly due to the difference in tobacco consumption among women in these two countries. Like drinking, with the openness of perceptions and the diversi cation of occupations, the proportion of Chinese women who smoke is also slowly rising, especially in cities [30]. Therefore, the higher consumption of tobacco and alcohol by Spanish women may be one of the reasons why they account for a higher proportion of hip fractures than Chinese women.
Hip fracture patients over 65 years of age often have multiple personal medical histories. The internal homeostasis of the patient is altered by the hip fracture, which causes a continuous deterioration of his general condition. It is noteworthy to note that 75% of patients do not die due to the pathology of the hip fracture itself, but rather as a consequence of a comorbidity prior to the injury [31]. Yoon et al. have shown that dementia and DM have a signi cant effect on postoperative functional outcomes [32]. Anemia will increase hospital complications as well as hospitalization costs [33]. A meta-analysis shows that malignant tumors, lung disease, DM, and cardiovascular disease signi cantly increase the risk of death after hip fracture surgery [34]. Studies have shown that personal history of fracture is one of the major risk factors for hip fractures [35]. A survey of hip fractures carried out in 45 Spanish hospitals showed that 36.5% of patients have personal history of fracture, with 10.2% of them having personal history of hip fracture [36]. This result is similar to the result of the Spanish sample in our study. In addition, some studies have shown that having more than 3 common comorbidities are risk factors that lead to the death of patients in one year [37]. In this study, we have found that the proportion of patients with 3 or more types of comorbidities is signi cantly higher in Spain than in China. This especially happens in relation to visual problems, DM, HT, cardiovascular diseases, personal history of fracture, osteoporosis, etc., which may be one of the reasons why the mortality rate of Spanish patients is higher, comparatively with Chinese. In summary, the comorbidities of elderly patients with hip fractures are not only related to the increased risk of osteoporosis and falls, but also to the increased risk of postoperative hip fracture death. Therefore, active prevention and treatment of elderly comorbidities can reduce the incidence and mortality of hip fractures.
Falls are the main cause of hip fractures, which have important psychological consequences in patients, such as the fear of them, from that moment on, and the loss of self-con dence. These reasons can affect self-restricted activity, reduced physical function, and social interactions, which normally place great pressure on the family. Among the most common causes of falls, the highest incidence is when walking. After that, when getting up or sitting down, and falling in the bathroom. Prevention measures, therefore, should include: exercise, particularly balance, strength, and gait training; take vitamin D supplements with or without calcium; take medications, especially psychoactive ones; modifying the home environment, such as improving lighting or installing handrails in bathrooms; and attend to postural hypotension, vision, foot and shoe problems. Acting according to these aspects causes an effective reduction in falls, both in private homes and in nursing homes [38]. In addition, we also found an interesting phenomenon: although the pre-fracture activity of Spanish patients is worse than that of Chinese patients (50.4% in Spain have no activity or little activity, and 40.3% in China), but more Spanish patients fell during the day and outside. We think this is because Spain has better public auxiliary transportation facilities, which makes it more convenient for elderly people with mobility impairments. The main method of treatment for elderly hip fracture patients is surgery, which can signi cantly reduce the mortality rate and achieve the bene ts of treatment. In our study, there are signi cant differences in the choice of surgical methods for patients between the two countries. In femoral neck fractures, although most patients in both countries have received more prosthetic treatment, 12 cases of fractures in China have received osteosynthesis, while only 5 cases in Spain. The main reason is that these Chinese patients are relatively younger, and osteosynthesis with femoral head preservation is the preferred treatment [39]. However, for intertrochanteric fractures, all Spanish patients received osteosynthesis, while 31 Chinese patients received prostheses. Studies have shown that the use of prosthesis for the treatment of unstable intertrochanteric fractures is signi cantly better than internal xation in terms of walking time, postoperative complications, Harris hip score and mortality [40]. Among Chinese patients with intertrochanteric fractures, 31 patients who received prostheses had a one-year mortality rate of 12.9%, while the remaining 116 patients who received osteosynthesis had a mortality rate of 22.4%. This indicates that the prosthesis is a good therapeutic alternative for unstable intertrochanteric fractures. Therefore, Spanish orthopedic surgeons should also consider the choice of prosthesis for intertrochanteric fractures.
We also found that Spanish patients had longer surgery delays than Chinese patients. This is because there are many patients in Spain waiting for surgery on weekends, while 14.8% of Chinese patients have surgery on weekends. The main reason for this difference is the healthcare system and the medical environment. In fact, in Spain, except for emergencies, they only perform operations on working days, while in China, they are also undergoing intensive operations on Saturdays.
In the medical environment, Chinese patients and their families are more rude to medical staff and even more aggressive, so they require doctors to sacri ce their time to perform operations as soon as possible [41]. A number of studies have shown that surgical delay is an independent risk factor for postoperative death in patients with hip fractures, and early surgery can reduce perioperative complications and mortality [42,43]. Some scholars also believe that optimizing diagnosis and treatment channels can reduce the waiting time before surgery and improve the prognosis of patients [44]. This may also be a reason for the higher mortality rate among Spanish patients.
In terms of anesthesia, XDH in China prefers general anesthesia, while UHVM in Spain most commonly uses regional anesthesia. This difference only appeared in the two hospitals evaluated, and it does not represent the two countries. In fact, according to our review of Chinese literature [45], many Chinese hospitals use more regional anesthesia than general anesthesia. However, more research evidence shows that different anesthesia methods will not affect the complications and mortality of patients with hip fractures [46]. In the comparison of ASA classi cation, the high-risk ratio of Spanish patients is signi cantly higher than that of Chinese patients, indicating that the overall condition of Spanish patients is worse. The Wang's study shows that the high risk of ASA is an independent risk factor for death from hip fracture within one year [47]. This may be one of the reasons why the mortality rate of Spanish patients is higher than that of Chinese patients. In our study, there are more Chinese elderly people suffering from anemia, and the preoperative hemoglobin is signi cantly lower than that of the Spanish. Studies have shown that the higher the BMI, the lower the possibility of anemia [33], which may be the reason why the elderly in China are more likely to suffer from anemia. Therefore, more Chinese patients have to receive blood transfusions.
Compared with other closed fractures, patients with hip fractures have longer hospital stays because of more comorbidities, longer surgical delays, and other postoperative complications [48]. In this study, the average hospital stay of Chinese patients is longer than that of Spanish patients. The main reason is that many Chinese patients do not have clinics or hospitals near their homes, making it di cult to change dressings and remove sutures from wounds after surgery. However, a longer hospital stay may be bene cial to the patient. A national cohort study in Sweden showed that a hospital stay of less than 10 days, each day less spent in hospital, had an 8% increase in the probability of death within 30 postoperative day. Conversely, when the hospital stay was more than 11 days, the decrease in the hospital stay of one day was not associated with an increased risk of death after discharge [49]. Similarly, a South Korean study found that elderly patients with hip fractures who were hospitalized for less than 10 days had a higher mortality rate within one year after discharge [50]. Reducing the length of hospital stay means shortening the time for patients to receive nursing care in the hospital after the operation, as well as shortening the time for comprehensive assessment of the medical condition during this period. However, this comprehensive geriatric assessment has the advantage of being able to reduce the risk of complications after hip fracture, as well as death after discharge [49,51]. Therefore, it is recommended that the discharge time for patients with hip fracture be done once the wound sutures have been removed. We consider it important for two reasons: rst, that patients and their families can learn more necessary knowledge of nursing, as well as rehabilitation; The second reason is that after removing the sutures, patients no longer have to worry about the wound and can perform rehabilitation exercises more assured and bolder.
In fact, the length of time in bed is closely related to the patient's prognosis. The incidence of pressure ulcers, pulmonary infections, venous thrombosis, muscle atrophy, and cardiovascular complications increases with time spent in bed [52]. In this study, the average number of days of bed rest for Chinese patients was signi cantly lower than that of Spanish patients, and the bed rest time of prosthesis treatment was signi cantly shorter than that of osteosynthesis treatment. In this study, the average number of days of bed rest for Chinese patients was signi cantly lower than that of Spanish patients, and the bed rest time for prosthetic treatment was signi cantly shorter than that for osteosynthesis treatment.
Because Chinese patients are relatively young, have better abilities before injury, and have received more rehabilitation exercises and nursing knowledge guidance during their hospitalization, there are even 31 patients with femoral intertrochanteric fractures who have received prosthetic treatment. These favorable reasons enable them to return to underground activities faster after the operation.
Regarding hospitalization costs, Spanish patients are signi cantly higher than Chinese patients. However, due to differences in price levels and purchasing power, we must compare them in another way. We believe that in this case, the average wage is a good method. For example, the average annual income of residents of Seville in 2019 was 16,271 euros [53], while in Xi'an it was 58,080 RMB, approximately 7,260 euros [54]. In other words, the hospitalization costs for hip fractures in the two countries are relatively similar, about 10 months' salary. Finally, we must point out that as the elderly population increases, prevention has become the best strategy to reduce the cost of hip fractures, thereby reducing the high costs borne by the health system and families.
Hip fracture is called the last fracture in life due to the high mortality and disability rate. The one-year mortality rate after a hip fracture is 15-40%, which is 3 to 4 times higher than the general population [55,56]. In this study we have seen one-year mortality rates of 19.01% in Spain and 12.99% in China. A recent meta-analysis carried out in China showed that the one- year mortality rate was 13.96% [14]. In Spain, a study using national data showed that the annual mortality rate for men and women under 80 years of age is 22%; that of women over this age was 25.2%, while that of men was 30.1% [57]. Based on these data, we can conclude that the one-year mortality rate of hip fracture patients in China is lower than that of Spain. However, in terms of postoperative functional recovery, the results of both countries are satisfactory, and the excellent and good rate of Harris score has reached a high level.
This is the rst study to compare the epidemiology and mortality of hip fractures in Spain and China. This study has the following advantages. First, the two selected hospitals, UHVM in Seville and XDH in Xi'an, are large-scale comprehensive tertiary hospitals and are typical representatives of hospitals in the two countries. Secondly, the sample size is large, with a total of 757 patients included. In addition, the study includes a wide range of variables, such as pre-injury status, lifestyle and comorbidities, and the content of the comparison is very detailed. However, some limitations have affected the research: First, each hospital has its own culture and environment, and the data may not be representative of other hospitals in the two countries, such as anesthesia methods. Another important limitation of this study is related to the follow-up method. Especially for Chinese patients, because the electronic medical record systems between hospitals are not connected to the Internet, we cannot obtain information about patients going to other hospitals after they are discharged.
Therefore, for some of the Chinese patients, their death information was obtained by calling their family members, which may lead to the loss of some important information related to the death. In addition, the risk factors that affect the death of patients are an important research topic, but they were not carried out in this study.

Conclusion
In summary, our research shows that there are large epidemiological differences between hip fracture patients in Seville, Spain and Xi'an, China. Among them, differences in gender, age, injury location, comorbidities, etc. cannot be changed by admonishing patients or choosing treatment methods. However, we can narrow the difference by advising patients to maintain a normal BMI, develop a good lifestyle, and choosing appropriate surgical methods to provide patients with a better foundation for rehabilitation and reduce mortality. Authors' contributions: Shuai-Shuai Gao and Wen-Tting Zhang conceived, designed and wrote the article; Yan-Jun Wang, Yong-Feng Yao, Ya-Hui Zhang and Aurelio Borrás Verdera conducted data collection and analysis. Luis C Capitan-Morales revised and corrected the article. All authors reviewed the nal manuscript. All authors agree to be accountable for all aspects of the work.