To the best of our knowledge, this is the first population study to use competing risk analysis to explore mortality and readmission due to medical complications as well as reoperation due to surgical complications after hip fracture among nonagenarians based on data from a nationwide database. A number of meta-analyses have revealed that age is an important risk factor for death in elderly adults after hip fracture [4, 6, 7]. In this study, we investigated the outcomes of 11,184 nonagenarians after hip fracture surgery in Taiwan. We found that the mortality rates were 5.5% at 1 month, 13.8% at 3 months, 20.3% at 6 months, 29.5% at 1 year, 45.0% at 2 years, 78.1% at 5 years, and 95.9% at 10 years after surgery. Previous studies reported that the 1-, 3-, 6-months, and 1-year mortality rates ranged from 5.9 to 26.4%, 15 to 36%, 24.7 to 42%, and 24 to 51%, respectively [9–26]. The short-term mortality rates in Taiwan were lower than those in New Zealand, Spain, Scotland, Netherlands, Canada, and the United States; but higher than those in Japan and Korea [9–26]. Previous studies reported that the short-term mortality rates among nonagenarians varied from region to region [9–26]. Japan, Korea, and Taiwan seem to have lower short-term mortality rates after hip fracture among nonagenarians than those of Western countries. However, the sample sizes in the previous studies were relatively small (from 32 to 919 nonagenarians) compared to that in our study [9–26]. Differences in findings among the studies from different countries might be due to differences in selection criteria, distributions of gender-stratified nonagenarians in the populations, distributions of smoking status, physical activity, bone mineral density, nutrition, hip strength, and comorbidities, in addition to sample sizes.
In a review on hip fracture-related mortality among elderly adults from 1996 to 1998, Haleem et al. found that the rates of mortality ranged from 11 to 23% at 6 months and from 22 to 29% at 1 year [3]. In a meta-analysis of mortality after hip fracture in patients of advanced age, Abrahamsen et al. found that the crude mortality rates ranged from 3.3 to 17.2% at 1 month, 6.4 to 20.4% at 3 months, 7.1 to 23% at 6 months, and 5.9 to 59% at 1 year [4]. They also found that excess mortality was highest in the first 6 months and that it decreased after 1 year, but remained high throughout the next several years. Several studies have shown that hip fractures affected short-term but not long-term mortality among elderly adults [1, 8, 12, 13, 24, 41]. However, others have shown that there is a gradual increase in mortality for up to 5 years after fracture [1, 41–46]. The 1-, 2-, 5-years, and 10-years mortality rates were 29.5, 45.0, 78.1, and 95.9% in this study. We found that the first-year mortality of nonagenarians after hip fracture was similar to that of elderly adults [1–8]. However, after the first year, the mortality rates increased more rapidly among nonagenarians after hip fracture than those among other elderly age groups in other studies [15, 26]. Nonagenarians, due to their advanced age, naturally have a very high mortality rate, irrespective of any past history of hip fracture. Whether excess mortality caused by hip fracture among nonagenarians increases persistently for several years after hip fracture remains unclear. We believe that hip fracture and aging both continue to have effects on mortality 1 year after fracture among nonagenarians.
The results of our multivariate survival analysis showed that age, male gender, and higher CCI were significant predictors of mortality after hip fracture in nonagenarians. In a meta-analysis, Hu et al. reported that the yearly HR for age was 1.05 among elderly adults after hip fracture [7]. In our study, the estimated yearly HR for age was 1.015 (95% CI: 1.012–1.020). The age effect on mortality in nonagenarians was not as high as in elderly adults. Several previous studies also did not find that age was a risk factor for mortality among nonagenarians [12, 17]. One possible reason for the discrepancy is that our patient population (>90 years) was more homogeneous than the populations included in other population-based studies (>65 years) on predictors of mortality after fracture.
We found that men were at 31% greater risk for mortality than women (HR, 1.31, 95% CI: 1.26–1.37). Many meta-analyses have found that elderly men are at higher risk for mortality than elderly women after hip fracture [4, 6, 7]. Hu et al. estimated that men had a 70% greater risk of overall death than females (HR 1.70; 95% CI: 1.51–1.04) [7]. Although several studies have reported that male nonagenarians have higher mortality rates than their female counterparts [16, 17, 22, 26], other studies have shown that male gender is not a significant predictor of mortality among nonagenarians [12, 20, 25]. In our study, the HR of male gender in nonagenarians was not as high as that of other age subgroups of elderly adults. Males had more comorbidities, specifically chronic obstructive pulmonary disease, than females in our study. The higher prevalence of multiple comorbidities in males may explain the higher risk. However, in a number of population-based studies, men had higher mortality rates and died earlier than women; therefore, nonagenarians represent a more homogeneous population in which more healthy males survived compared with the younger elderly adults. This explains, at least in part, why the effect of male gender in nonagenarians was not as high as that in the younger elderly subgroups, and may further suggest why some studies did not find that male gender was a predictor of mortality after hip fracture among nonagenarians. The small sample sizes and shorter follow-up durations might also have contributed to some of the differences in the previous studies.
We found that trochanteric fracture was associated with a 14% greater likelihood of death than cervical fracture (HR, 1.14: 95% CI: 1.06–1.23). Previous studies on elderly adults after hip fracture have also reported that trochanteric fracture is associated with higher risk for mortality than cervical fracture [2, 47–52]. However, the association between fracture type and mortality in nonagenarians is not consistent among studies [11, 12, 14, 17, 20, 22, 23, 25]. Most studies on hip fracture in nonagenarians have reported that mortality rates are similar between trochanteric fracture and cervical fracture [11, 12, 17, 20, 23, 25]. Only Ishida et al. and Kang et al. demonstrated that trochanteric fracture was associated with a higher risk for mortality than cervical fracture among nonagenarians [14, 22]. In this study, patients with trochanteric fracture were older and nonagenarians had more comorbidities than those reported in studies on younger elderly adults. Gender and age may have a mixed effect on risk of trochanteric fracture.
We found no significant difference between internal fixation and arthroplasty in mortality among nonagenarians, a finding consistent with that reported by Takamine et al. and Tay et al. [20, 25]. However, Ishida et al. demonstrated that hemiarthroplasty was a significant risk factor for mortality among 74 nonagenarians [14]. In our study, most (82.8%) patients with cervical fracture received hemiarthroplasty and most (96.1%) with trochanteric fracture received internal fixation. Natural causes of death among nonagenarians and unbalanced mixed subject-variable distributions between types of operations and fractures all contributed to the reasons for the non-significant differences between internal fixation and arthroplasty for mortality.
In this study, higher CCI was associated with higher risk of mortality among nonagenarians. Several studies have explored the relationship between comorbidities and mortality after hip fracture among nonagenarians and many of the results varied from study to study [15, 16, 19, 20, 26]. Two studies found that a larger number of comorbidities increased mortality [16, 19] and three studies reported no association between comorbidities and mortality after hip fracture among nonagenarians [15, 20, 26]. Many previous studies have explored whether American Society of Anesthesiologist (ASA) score is predictive of mortality after hip fracture among nonagenarians, but the results were not conclusive [12, 14–18, 22, 23, 25]. Some studies found that a higher ASA score was associated with mortality [12, 14, 16, 18]. However, other studies did not find that ASA score was associated with mortality after hip fracture among nonagenarians [15, 17, 22, 23, 25]. Aging, higher CCI and higher ASA scores are all associated with a larger number of and more severe comorbidities. Differences in competing risk of death, confounding variables, such as age, CCI, ASA score, and sample size, may interact with one another within studies resulting in different conclusions among studies about the effects of comorbidities. However, there is still no agreement among researchers as to how comorbidities should be measured and how the measurement should be evaluated statistically.
Postoperative readmission and reoperation rates increase the use of healthcare resources and are often indicative of healthcare quality for hip fractures. Major medical complications result in readmission, whereas major surgical complications result in reoperation. Several studies on outcomes after surgery for hip fracture in patients ≥ 65 years revealed that the readmission rate within 3 months varied from 10 to 20%, the 1-year reoperation rate varied from 7 to 13% and the 2-years reoperation rate varied from 15 to 28% [27–32, 34, 35]. To the best of our knowledge, only two studies have reported on the readmission and reoperation rates after hip fracture among nonagenarians [11, 15]. Those studies found that the 2-years complication rates were as high as 30–50% [11, 15]. Osteoporotic hip fracture, aging, and comorbidities all contributed to excess mortality. If subjects died, these subjects could not have any complications after their death. Readmission or reoperation rate cannot be estimated without considering competing death, which may cause overestimation of the risk, especially for nonagenarians. Using traditional Kaplan-Meier method, the cumulative medical complication and reoperation rates would be overestimated. Kaplan-Meier estimates are biased because the death rate is large and will increase with the follow-up time. Therefore, to obtain a more valid estimate of the risk for medical or surgical complication, we applied a competing risk analysis to estimate the cumulative incidence of the readmission and reoperation [36, 37]. We found that the 1-, 2-, and 5-years cumulative incidence rates of the first reoperation were 7.3, 9.2, and 11.6% for the nonagenarians, respectively. Moreover, the 1- and 3-months cumulative incidence rates of the first medical readmission were 18.9 and 24.1%, respectively, for the nonagenarians in Taiwan. Because competing death was not considered, previous studies had higher long-term reoperation rates than those of the current study [36, 37]. Our finding implies that nonagenarians appeared to have a higher all-cause hazard ratio for death, had lower risks for various surgical complications when we considered the competing death in our analysis. Therefore, nonagenarians had a slightly lower reoperation rate than those in the previous studies. However, even under this circumstance, male nonagenarians still had slightly higher short-term readmission rates of medical complications. The competing risk of death had less effect on the 3-months readmission rates than on the long-term reoperation rates. Nonagenarians did not die quickly due to aging during the 3-months follow-up after hip fracture. Therefore, nonagenarians in our study had similar short-term readmission rates after hip fracture as nonagenarians in the previous studies.
In this study, predictors of mortality included older age, male gender, trochanteric fracture, and higher CCI score. However, trochanteric fracture correlated with a low risk for reoperation (Table 3). After controlling for age, gender, operation type, and comorbidities, we found that patients with trochanteric fracture were at 14% greater risk for death than those with cervical fracture (HR = 1.14, 95% CI: 1.06–1.23) but that their risk of reoperation was 28% lower than patients with cervical fracture (HR = 0.72; 95% CI: 0.59–0.89). This finding implies that nonagenarians with trochanteric fracture appeared to have a higher all-cause hazard for death but lower risks of reoperation than those with cervical fracture. When the follow-up time was short, the cumulative mortality rate was still low; many subjects with trochanteric fracture still had a higher hazard ratio for 90-days readmission (sub-HR = 1.08) than those with cervical fracture. As described in the previous study [39], during the first 3-months follow-up, the short-term death rate was small, subjects with trochanteric fracture had larger readmission hazard rate (sub-HR = 1.08) than subjects with cervical fracture. In contrast, after 6-months follow-up, there were fewer subjects with trochanteric fracture during follow-up but they were healthier and therefore exposed to less risk for long-term surgical complications. Thus, subjects with trochanteric fracture had a smaller risk (sub-HR = 0.72) for surgical reoperation than those with cervical fracture. When a population had much higher mortality rate than complication rate during the early phase of follow-up, using high cost but more benefit treatments to reduce the long-term surgical complication would be limited. When the competing hazards of a risk factor on mortality and complication are different, it raises the difficulty of conducting analysis and interpretation. A cost-effective analysis from a competing risk viewpoint may be quite different from that without considering the competing death. In practice, competing risk analysis is a useful tool to address the actual risk and to provide a more realistic result to make a decision.
The competing death phenomenon not only affected the effect of fracture type, but also slightly affected other factors, such as age, gender, and operation type, during long-term follow-up after surgery in our study. Moreover, the competing death phenomenon may have no effect on short-term follow-up after surgery. As older age, male gender, trochanteric fracture, and higher CCI were significant risk factors for mortality, age, male gender, and higher CCI also had higher risks for medical readmission within the 3-months follow-up period after surgery (Table 3).
Most readmissions occur within 3 months [30, 35]. Some studies also found that readmissions or reoperations were associated with higher mortality within 1 year [27, 28, 31, 32, 34, 35]. We found that 984 (36.5%) of 2,694 nonagenarians died within 3 months after the first medical complications and that 859 (33.7%) of 1,296 nonagenarians died within 1 year after the first reoperation. Jennings and de Boer found that 12 (37.5%) of 32 nonagenarians who had surgical complications died within 6 months, and 17 (38.6%) of 44 who had medical complications died within 6 months [11]. Our analysis of nonagenarians revealed similar findings to those of previous studies on elderly adults after hip fractures [11, 28, 31–34]. Prevention of hip fracture among nonagenarians is likely the best way to reduce the high risk effect of aging on mortality, readmission, and reoperation after surgery.
The overall 3-months, 1- and 5-years mortality rates among nonagenarians in Taiwan were around 14, 30 and 78%, respectively. The 1- and 5-years reoperation rates were around 7 and 12%, respectively. The 30- and 90-days medical complication rates were around 19 and 24%, respectively. Once nonagenarians had the first readmission, 36.5% died within 3 months after medical complications. Once nonagenarians had the first reoperation, 33.7% died within 1 year after reoperation (data not shown in the tables). The impact of medical complications on mortality among the nonagenarians was extraordinarily high. Therefore, postoperative care to prevent medical complications should be the most effective strategy to reduce the mortality rates among nonagenarians with hip fracture. However, prevention of hip fracture in this patient population is the best way to reduce mortality, readmission and reoperation after surgery.
Limitations
All of the patients in this study were nonagenarians who underwent surgical treatment for hip fracture; however, there was great variation in follow-up period among the patients (2–11 years). The NHRI database differs from the hip fracture registry database in that the former does not record all clinical information [2, 53]. Therefore, some unknown clinical confounding factors might have existed or changed during the follow-up period. In addition, we did not adjusted for many of the risk variables, such as general condition prior to surgery, smoking and alcohol behavior, BMI, bone mineral density, comorbidities, and quality of life. Agreement about how comorbidities should be evaluated and how the measures of comorbidities should be placed into a statistical model is still absent. Aging, higher ASA cores, delayed surgery, and higher CCI are associated with one another. For example, a poor ASA score is caused by a large number of comorbidities, which implies that more time is needed to stabilize the medical comorbidities, and further suggests a long waiting time for surgery, as well as poor outcomes after surgery. We used the CCI to represent the combined severity of multiple comorbidities, which has been shown to be a key consideration in hip fracture [54, 55]. In addition, we used ICD9-CM codes to define the medical complications and reasons for reoperation, which might have lacked the precision needed for a precise evaluation of the estimated readmission and reoperation rates. Finally, the readmission rates and reoperation rates might also vary depending on the definitions used. Therefore, caution should be taken in extrapolating our results.
