The vertebral fracture group had increased mortality across all age- and sex-based subgroups. The adjusted HR was highest in vertebral fracture patients aged less than 60 years and decreased as age at the time of vertebral fracture increased. Mortalities caused by neoplasms, neurologic diseases, circulatory diseases, respiratory diseases, digestive diseases, diseases in musculoskeletal system and connective tissue, and trauma were higher in the vertebral fracture group than in the control group, with diseases in musculoskeletal system and connective tissue having the highest OR, followed by digestive disease, respiratory disease, and trauma.
The higher overall HR for death in patients with vertebral fracture in all the age- and sex-based subgroups was in line with the results of previous studies.[7,9,12,18–20] In a study based on the US Medicare system data, the adjusted HR was 2.17 (95% CI = 2.11–2.24) for men and 1.72 (95% CI = 1.69–1.75) for women aged more than 65 years with vertebral compression fractures. Additionally, women aged more than 65 years with one or more vertebral fractures had a 1.23-fold greater age-adjusted mortality rate (95% CI, 1.10–1.37) using the Study of Osteoporotic Fractures in the United States. A 5-year prospective cohort study in the semi-urban city of Dubbo, Australia showed that men and women aged more than 60 years with low-trauma osteoporotic vertebral fractures showed age-standardized mortality ratios of 2.22 (95% CI = 1.91–2.52) and 1.66 (95% CI = 1.51–1.80), respectively. The age-adjusted relative risk of dying following a clinical fracture was 2.15 (95% CI = 1.36–3.42) in women aged 55 to 81 years with osteoporotic fracture using the data from the Fracture Intervention Trial in the United States. The overall standardized mortality ratio (SMR) of spinal fractures at 1 year post-fracture was 7.76 (95% CI = 7.63–7.89) in men and 4.70 (95% CI = 4.63–4.76) in women in South Korea. In another Korean study, the SMR was highest during the first 3 months and gradually declined to 2.53 in men and 1.86 in women at 2 years. Even though these studies and ours have consistently shown that the mortality increased in patients with vertebral fractures, the HR varied among the studies. The differences in the HRs could have resulted from differences in ethnicities, treatment modalities, patient care systems, and study designs.
The adjusted HR for mortality was relatively high in vertebral fracture patients with young age at the time of vertebral fracture and relatively low in those with old age at the time of vertebral fracture, even though the risk of mortality increased in all the age groups. The adjusted HRs (95% CI) were 1.50 (1.26–1.78), 1.34 (1.21–1.47), and 1.18 (1.13–1.23) in patients less than 60 years old, 60 to 69 years old, and more than or equal to 70 years old, respectively, in our study. Although most studies of mortality in vertebral fracture patients focused on osteoporotic vertebral fractures and were performed only in elderly populations, we included patients of all ages, starting in infancy; therefore, we are unable to directly compare our results to those of others. However, the phenomenon that the HR decreases as the patient's age at the time of diagnosis of vertebral fracture increases was observed in previous studies. Lau et al found that the HR for death following vertebral fracture decreased with advancing age: the HR adjusted for comorbidity was 2.99 among subjects 65 to 69 years, 2.62 among those 70 to 74 years, 2.17 among those 75 to 79 years, 1.84 among those 80 to 84 years, and 1.45 in those more than or equal to 85 years, after a maximum follow-up duration of 7.5 years. Kim et al showed that the 1-year SMRs were 8.34 (95% CI = 7.80–8.92) and 8.79 (95% CI = 8.04–9.69) in men and women aged 50 to 59 years, respectively, and it gradually decreased to 1.56 (95% CI = 1.45–1.68) and 1.09 (95% CI = 1.04–1.14) in men and women aged 90 to 100 years, respectively. This phenomenon could be attributed to the death rates themselves increasing in both the control and vertebral fracture groups as individual's age, which dilutes the impact of vertebral fracture on the mortality rate of older patients.
When we compared similar age groups, the absolute values of the adjusted HRs were similar to or lower than those previously reported. The overall odds of mortality in American patients more than or equal to 65 years old with vertebral compression fractures were 2.71:1; they were highest in the 65 to 69-year group and lowest in the more than 85-year group. Among 131 Japanese vertebral compression fracture patients more than or equal to 60 years or older, those with vertebral fractures (regardless of the number of fractures) showed a significant HR of 1.72, which increased with older age at the time of fracture; the number of vertebral fractures was also associated with the risk of mortality. The differences could have resulted from the differences in the patient care system, ethnicities, and treatment modalities. Our result would be helpful in providing insight into improving patient care for vertebral fracture patients in South Korea by comparing the differences between South Korea and countries of previous studies.
The causes of death with increased OR in vertebral fracture patients included diseases in musculoskeletal system and connective tissue (the highest), digestive diseases, respiratory diseases, and trauma, as well as neoplasms, neurologic diseases, circulatory diseases, and respiratory diseases. Our detailed analysis showed that disorders of bone density and structure, diseases of the liver, chronic lower respiratory diseases along with influenza and pneumonia, and toxic effects of substances chiefly nonmedical as to source were the most common causes among diseases in musculoskeletal system and connective tissue, digestive diseases, respiratory diseases, and trauma, respectively. Equipped with this knowledge, caregivers will be able to decrease the mortality of vertebral fracture patients in South Korea by providing more focused care and/or paying more attention to these diseases.
Our study had some limitations, as follows: (i) we were unable to identify the extent of vertebral fractures, even though mortality rates are reportedly determined by the number and severity of such fractures;[11,18] (ii) we included only diagnosed, symptomatic vertebral fractures, and clinically unapparent, asymptomatic vertebral fractures, especially vertebral compression fractures, might have been underestimated; (iii) we did not include a comparison of treatment options that might have affected the mortality rates of our study subjects;[10,15,21] (iv) we did not make a comparison between short-term and long-term survival; (v) we did not have information on the cause of vertebral fracture; and (vi) some confounding factors that may have affected mortality, including smoking, alcohol consumption, or obesity, were not adjusted for.[10–12] Due to these limitations, we were not able to define whether the vertebral fracture was causally related to the subsequent death or simply a reflection of underlying health issues that led to the fracture or were present at the time of fracture. Further research including information on factors present at the time of the fracture would be helpful in disentangling this cause and effect relationship.
Despite these limitations, our data are robust since we used a representative, large-scale sample from a cohort database consisting of 1 million subjects with an average 60-month follow-up period (maximum 12-year follow-up period), which is comparable to follow-up in previous studies (Lau: average 31.0 months, maximum 7.5 years; Kado: mean 8.3 years; Center: maximum 5 years; Cauley: average 3.8 years; Kim: maximum 1 year; Lee: maximum 2 years).[7,9,12,18–20] Furthermore, our approach minimized the risk of recall bias or missing information, as the dataset was based on claims to the HIRA. We chose matched controls adjusted for the potential confounding factors of age, sex, income, and region of residence. Our comorbidity data were consistent with those of previous epidemiologic studies in the Korean population, which was further evidence of our study's reliability.[22,23] Thus, our analysis is representative and reliable, and will foster future research on the factors contributing to the mortality of vertebral fracture patients.
In summary, our study demonstrated that the mortality increases in Korean patients with vertebral fractures, regardless of age or sex. Common causes of death in vertebral fracture patients included diseases in musculoskeletal system and connective tissue diseases, digestive diseases, respiratory diseases, trauma, neoplasms, neurologic diseases, circulatory diseases, and respiratory diseases, with the highest OR observed for diseases in musculoskeletal system and connective tissue.
The National Research Foundation of Korea (NRF-2015-R1D1A1A01060860) grant funds were received in support of this work.
No relevant financial activities outside the submitted work.
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Spine. 2020;45(5):E280-E287. © 2020 Lippincott Williams & Wilkins