Incidence and risk factors of medical complications and direct medical costs after osteoporotic fracture among patients in China

Osteoporosis is the most common systemic and metabolic skeletal disease, characterized by low bone mass, deterioration of bone tissue, disruption of bone architecture, compromised bone strength, and increased risk of fracture [1]. Osteoporotic fragility fractures, predominantly vertebral, hip, proximal humeral, and distal forearm fractures, are clinical consequences of osteoporosis [1]. Approximately 40–50% of females and 13–22% of males sustained at least one osteoporotic fracture over the course of their entire life [2]. The number of patients with any osteoporotic fracture in China in 2010 was 2.33 million, a number that is projected to increase to 5.99 million by 2050 [3].

Previous studies have indicated that osteoporotic fractures are significantly associated with a higher risk of subsequent fracture and excess mortality [4, 5]. The accumulative incidence of subsequent fracture within 5 years after an initial osteoporotic fracture was 24% in females and 20% in males, whereas the 5-year accumulative all-cause mortality rate was 24% in females and 27% in males, respectively [4]. Furthermore, fragility fractures could also significantly lower patients’ health-related quality of life, and this loss was sustained for at least 18 months for hip and vertebral fractures [5].

In addition, the economic strain on patients and the healthcare system resulting from osteoporotic fractures are heavy. The relevant annual treatment costs of osteoporotic fracture were calculated at $9.45 billion, and it will increase to roughly $25.43 billion by 2050 in China [3]. One study conducted in western China indicated that the average direct medical cost for osteoporotic fracture patients was approximately RMB 17007 ($2699) per year per patient; the economic burden attributed to hip fracture was highest, followed by vertebral fracture [6].

Previous studies showed that osteoporotic fractures are consistently followed by a large number of medical complications, such as cardiac diseases, venous thromboembolism, pneumonia, urinary tract complications, gastrointestinal tract bleeding, and fluid/electrolyte abnormalities [7‐10]. Published studies have shown that general complications following any osteoporotic fracture were markedly associated with a loss of function and can notably affect functional outcomes, resulting in poor prognosis and treatment satisfaction [11, 12]. Fracture patients with complications after a primary fracture always had higher mortality than those without complications. For instance, Roche et al. [13] demonstrated that the mortality at 30 days among hip fracture patients with postoperative heart failure or chest infection was 16.1-fold and 8.5-fold, respectively, compared with those without postoperative heart failure or chest infection. Panagiota et al. [14] pointed out that complications can dramatically extend patients’ length of stay and increase the economic burden related to fracture accordingly.

There has been research assessing the incidence of complications after an osteoporotic fracture [8, 10, 15‐17]. However, these studies, especially those in Chinese patients, either considered only complications resulting from fracture surgeries and not those related to conventional treatments or were based on small sample sizes that impacted the generalizability of their results [15‐17]. Moreover, no studies thus far have quantified the influence of medical complications on their economic burden in mainland China. Hence, this retrospective database cohort study focused on a broader set of complications and evaluated the associated economic burden in China. The osteoporotic fractures in this study included hip and vertebral fractures because they are the two most serious and commonly occurring osteoporotic fractures [5, 6].

This study aimed to (1) investigate the incidence of medical complications following an osteoporotic fracture and identify its risk factors and (2) estimate and quantify the related direct medical costs of osteoporotic fracture patients.

To our knowledge, our study is the first retrospective database cohort study to use a large sample to analyze medical complications not necessarily directly related to a surgery and the first to identify risk factors and quantify direct medical costs following osteoporotic fracture in China. Among published studies, the categories of medical complications vary significantly because the definitions differ [10, 20]. To better evaluate the presence and types of medical complications after osteoporotic fracture and to gain a comprehensive result, we defined medical complications by summarizing published literature [13, 19‐23], including four prospective studies [13, 19, 21, 22], one meta-analysis study [20], and one monograph [23].

After reviewing the existing literature, we found that a large majority of published research focused on the incidence of complications within a relatively short term after a fracture [9, 26, 27]. Especially, many studies on Chinese patients were restricted to complications within the perioperative period [17, 28‐30]. Hence, given the current lack of data on the long-term complications rate after osteoporotic fracture, our study analyzed the incidence of medical complications within 1 year, which provided a broader picture for the prognoses of osteoporotic fracture patients over a longer period.

A difficulty in evaluating the risk of complications following a fracture using a claims database was to confirm whether a complication was related to osteoporotic fracture. We overcame this by analyzing medical complications within 12 months before and after an osteoporotic fracture and assessed the elevated risk by comparing the incidences between the two periods. This comparative method allowed us to use the prefracture period of a patient as a control for the postfracture period, thus accounting for any confounding factors that did not change within each patient. As far as we know, our study is the first to apply this comparison method. We also conducted a sensitivity analysis using a 4-month period instead of a 12-month period to ensure that the elevated complication risks were not mainly due to aging within 12 months. The sensitivity analysis showed similar trends (data not shown).

Our study showed that the most common medical complications within 12 months after fracture among osteoporotic hip or vertebral fracture patients were stroke, constipation, pneumonia, urinary tract infection, arrhythmia, angina, and electrolyte imbalance (Figs. 2 and 3). Lawrence et al. [11] reported that the most common inpatient complications were cardiac and pulmonary complications (8 and 4% of patients, respectively) among hip patients aged ≥ 60 years. Another study based on the clinical records of discharged hip fracture patients aged 70–94 years in China [15] suggested that the most common postoperative complications in 167 elderly patients with hip fracture were cardiac events (n = 37), DVT (n = 35), delirium (n = 25), pneumonia (n = 7), and stroke (n = 5). Yet another study reported that complications also correlate with the type and severity of patients’ comorbidities [14]. Compared with these studies, we had a longer follow-up period, which may show a higher rate for some complications due to the development of comorbidities.

A retrospective cross-sectional study by Sever et al. [25] indicated that the most common postoperative complications in patients with osteoporotic vertebral fracture were urinary tract infection (15.1%) and pressure ulcer (12.2%), and the incidence of pneumonia was only 4.4%. Another observational comparative study suggested that in-hospital complications following an osteoporotic vertebral compression fracture, including urinary tract infection (5%), pressure ulcer (3.75%), pneumonia (3.75%), and constipation (1.25%), were common in patients receiving conservative treatment, whereas no complications occurred in patients treated with vertebroplasty [26]. In addition to prefracture comorbidities and study duration, the differences in treatment selection and disease management also may result in the differences between our results and those in the published literature.

Previous literature suggests that DVT and pulmonary embolism are two of the most common and serious complications following fracture surgery, as well as the primary causes of death [15]. In our series, 7.3% of hip fracture patients experienced DVT, similar to the results of a prospective study by Soon et al. [10] that reported an 8.6% incidence of DVT following hip fracture surgery. The 12-month accumulative incidence of pulmonary embolism in our study was 0.8%. A consecutive annual cohort study of 664 patients by Hansson et al. [12] reported a 1 and 2% incidence of DVT and pulmonary embolism within 1 year after hip fracture, respectively. Our study showed that the accumulative incidence of DVT and pulmonary embolism among vertebral fracture patients was 0.9 and 0.2%, respectively. The lower incidence of DVT and pulmonary embolism among vertebral fracture patients has been demonstrated in previous studies [9, 25].

We identified age and diagnosis of hypertension, chronic heart disease, cerebrovascular disease, hemiplegia, or Parkinson’s disease at baseline as independent risk factors that predict complications after osteoporotic fracture. These results are supported by previous research [27‐30]. Some previous studies suggested that diabetes contributed to the development of complications following hip fracture [28, 31], but it was not significant in our study. Moreover, our study showed that retired patients were at higher risk of complications, which can be interpreted as retired patients always being older. Furthermore, we also found that patients with higher baseline direct medical costs were more likely to develop complications after fracture. Currently, evidence of risk factors for complications in vertebral fracture is rare.

Finally, we assessed the accumulative direct medical costs of patients within 12 and 24 months after osteoporotic fracture. Total all-cause direct medical costs within 12 and 24 months were $3913 ± $4812 and $5665 ± $6818, respectively. A prospective observational data collection study published in 2014 suggested that the average direct medical care costs in western China were approximately RMB 17007 ($2699) per year per patient, which is lower than that in our study [6]. Our research showed that direct medical costs, especially osteoporosis related, within the first 12 months accounted for a vast majority. Subgroup analysis indicated that direct medical costs for patients with complications were significantly higher than those for patients without complications (all p < 0.001), which can be explained by the fact that complications can dramatically increase patients’ mean length of hospital stay [14].

Although the current study was carefully designed, the results must be interpreted within the context of the following limitations. First, we divided patients into subgroups depending on the presence or absence of complications and did not consider the severity of any complications, which may lead to bias in the results. Previous researchers differentiated complications using the Clavien-Dindo classification and found that most complications in geriatric hip fracture patients were grade II [21]. Second, we only identified the risk factors and evaluated the direct medical costs associated with any complication. Further studies are needed if burden and risk factor results related to a specific complication are desired. Third, the variables of height, weight, and smoking and drinking status, which may be related to the incidence of complications, cannot be identified in the UEBMI database. Studies have demonstrated that body mass index is associated with cardiac events and non-cardiac medical complications after hip fracture [30, 32]. Fourth, this study only included patients with continuous enrollment during 24 months after the index date and excluded those without continuous enrollment. Exact dates and reasons for insurance discontinuation, whether due to death, relocation, insurance cancelation, or any other reasons, were not available in the UEBMI database. By only including the insurance maintainers within 24 months post fracture, there may be underestimation in the incidence of medical complications and direct medical costs among patients with osteoporotic fractures.

This study was based on the UEBMI claims data in Tianjin, one of the four municipal cities and a typical tier-2 city of China. As the database mainly includes urban population, the generalizability of our findings to other, especially rural, areas of China may be limited. Among the research findings, direct medical costs may vary across developed and less-developed regions in China, but our findings on direct medical costs can reflect the economic burden of Chinese urban patients with osteoporotic fractures to some degree. For complication incidences, the variation across regions is considered to be relatively small, and therefore, the finding that incidence of medical complication increased after an osteoporotic fracture should be generalizable to other areas of China. Without national-level long-term data available in China, the findings of the present study could be considered as an important reference for the disease management among Chinese osteoporotic fracture patients.

The incidences of a number of medical complications increased significantly among patients after osteoporotic fracture. Common medical complications following osteoporotic fracture include constipation, stroke, pneumonia, urinary tract infection, arrhythmia, angina, and electrolyte imbalance. Medical complications following osteoporotic fracture were associated with increased direct medical costs. Advanced age, male sex, retirement status, baseline comorbidities, and baseline direct medical costs were associated with the occurrence of medical complications following osteoporotic fracture. Effective clinical strategies should be used to prevent osteoporotic fractures and their complications, especially for those at high risk of complications.