Mortality in older adults following a fragility fracture: real-world retrospective matched-cohort study in Ontario

The link between osteoporosis-related fragility fractures and mortality has been established by studies conducted across the globe over the last 3 decades, especially for hip fractures [1‐10]. These studies show that in different countries with different types of healthcare systems, a fragility fracture was associated with a greater risk of mortality within the first year following the fracture and remained increased for several years after. Similar results have been reported in Canada [4, 7‐10], whereby a fragility fracture occurring at any osteoporotic site increased mortality risk by 1.4–1.5-fold in adults aged 50 years and older [4]. When examining specific fragility fracture sites, a 2–4-fold mortality risk increase was observed after hip, vertebral or humerus (in men) fractures in Canadians aged 50 and older [4, 7, 8], while several other fracture sites were found to be associated with a 1.4–2-fold mortality risk increase (rib, humerus, forearm, or pelvic fracture in women; wrist fracture in men) [4, 8].

In spite of this mortality burden, a large gap currently exists for the primary prevention of fracture, and studies show that an estimated 80–90% of adults do not receive appropriate osteoporosis management even in the secondary prevention setting [11‐13]. In contrast, approximately 90% of patients with cardiovascular disease are provided appropriate secondary preventive care [14]. System-level and country-level healthcare initiatives have been implemented worldwide to focus on addressing the secondary fracture prevention gap [15, 16], with several reports showing these initiatives being effective in not only reducing subsequent fragility fracture rates but also associated mortality [17‐20]. Considering these data and the current fracture prevention gap, it is important to further improve knowledge of mortality associated with fragility fractures among medical or non-medical professionals involved in osteoporosis care [11‐13, 21‐23].

Studies examining post-fracture mortality after non-hip fractures over the past decade have typically focused on younger patient populations (aged ≥ 50 years), while studies examining mortality risk in adults aged > 65 have focused primarily on hip fractures [4, 7‐10]. As such, there is a gap in understanding the mortality risks post fracture occurring at any or non-hip osteoporotic sites in adults aged > 65. Within this group, due to age-related fracture risk increase, more serious recommendations currently exist for fracture risk assessment or pharmacological intervention for osteoporosis [24, 25], and therefore the closing of the fracture prevention gap is that much more important.

The primary objective of this study was to utilize health services data from the publicly funded healthcare system in Canada to assess mortality post-fracture in a large, real-world cohort of adults aged > 65 years who experienced an index fragility fracture of any osteoporotic and non-hip site between 2011 and 2015, in comparison to matched non-fracture controls. Secondarily, surgeries and complications, which partly relate to mortality, were analyzed for all fragility fracture sites examined in this study.

This study of adults aged > 65 confirms that a fragility fracture of any site is associated with increased mortality risk [4]. Survival declined over 1–6 years post-fracture with the steepest reduction occurring within the first year, when the crude relative risk was 2.47- and 3.22-fold higher in matched fractured vs non-fractured women and men, respectively. Absolute mortality risk within 1-year post-fracture was 12.5% in women with fractures and 19.5% in men with fractures, with a large absolute risk difference when compared to matched non-fracture controls of 7.4% (95% CI 7.1–7.7%) in women and 13.5% (95% CI 12.9–14.0%) in men.

To add context to the 1-year absolute mortality risk of 14.4% post-index fracture at any site observed in our fracture cohort of women and men (50% aged ≥81), a 1-year absolute mortality risk of 9.7% was observed post-index acute myocardial infarction in Canadians admitted to a hospital between 2006 and 2010 (22% aged 65–74, 35% aged ≥75) [28]. When considering stroke-related mortality, an absolute mortality risk of 19.3% was reported at discharge in Canadians hospitalised due to ischemic stroke between 2003 and 2004 (aged ≥70, 55% aged > 80) [29]. Furthermore, an absolute mortality risk of 14.9% was observed within 30 days in-hospital in Canadians admitted to hospital with any stroke in 2012 (25% aged 70–79, 38% aged ≥80) [30]. Considering that significant reductions in mortality risks associated with cardiovascular events have been reported over the past few decades [30‐32], this data demonstrating a clear association between fragility fracture and mortality risk further highlights the need for effective measures to improve osteoporosis management and prevention of fragility fractures in older adults [11‐13, 17‐19, 21‐23].

Only one study published over the last decade examined mortality post-fragility fracture at any osteoporotic site in Canadians [4, 7‐10]. This study of the prospective CaMos cohort (N = 7689; 72% women) which was younger (mean age 66 and IQR 59–73 years) than our cohort observed age-adjusted hazard ratios (95% CI) of 1.43 (1.24–1.64) and 1.42 (1.12–1.79) in fractured women and men, respectively [4]. The higher relative mortality risk increase post-fracture observed in our cohort compared to the CaMos cohort was likely partly driven by the higher number of hip fractures in our older cohort, since hip fracture numbers increase in older individuals. The mortality rate observed in our cohort was approximately 2-fold higher in hip fracture compared to non-hip fracture cases in both women and men over the three years post-fracture. However, non-hip fractures also contributed to increased mortality rate observed for all fractures combined, considering the 1.4–1.9- and 1.7–2.4-times greater mortality rate observed, respectively, in women and men with non-hip fracture vs no fracture. Data on non-hip fracture mortality rates in similar cohorts is lacking; however, the 1-year hip fracture mortality rate of 21.5% in women and 32.3% in men observed in our cohort was relatively similar to a 2013 Canadian cohort study of adults aged ≥ 65 which observed a 1-year hip fracture mortality rate of 22% in women and 33% in men [9]. Although not as common as hip fracture, femur, multisite, pelvis and vertebral fractures were also associated with relatively high 1-year mortality rate in this cohort compared to other fracture sites. Prior studies conducted in similar cohorts have also reported significantly increased mortality after pelvis and vertebral fractures [4, 7, 8].

The relative difference in mortality rate between fracture and non-fracture cases was observed to decline with increasing age in both women and men, although it remained approximately 2-3x higher even in women and men aged 86+ years. This age-related trend was also observed in prior research and has been attributed to younger adults having much lower absolute mortality rates and as such the excess mortality discrepancy between the younger and older groups may reflect the life expectancy gap in the general population [33]. Alternatively, younger individuals who experience fragility fracture at younger age may have a poorer health status for their age, compared to older individuals with fragility fractures [33]. The latter explanation calls for urgency to prevent fragility fractures in younger populations, however, further research is needed to help elucidate this age discrepancy.

Gender trends in our study showed that, although men made up about one-quarter of index fracture cases, they contributed to about one-third of deaths. Although the mortality rate was also higher in men vs women in the non-fracture cohort, this gender difference was slightly larger in the fracture cohort for all fractures combined, hip fractures or non-hip fractures. Compared to women, Canadian men were also previously observed to have significantly higher mortality risk after hip [8, 9], vertebral [4, 7, 8], and humerus fractures [4, 8]. Interestingly, the range in absolute mortality rate based on age was found to be wider in women with approximately 6–7-fold difference between the oldest and youngest age groups compared to men with approximately 4–5-fold difference. Perhaps younger men with fragility fracture may be more vulnerable than older men when compared to women of their respective age groups, or alternatively older women approach closer to older men in terms of their vulnerability. Although we observed a higher relative risk difference in mortality rate between women and men of younger age groups compared to older age groups, this observation was not unique to the fracture cohort. Further, research examining mortality rate post-facture and interactions between sex and age is needed to help confirm and elucidate these observations.

Strengths of this study include having examined large fracture and non-fracture cohorts closely matched on age, sex, geography and comorbidities. A hard match method was used due to the limited number of covariates that were deemed important from a clinical point of view, and 88% of the full unmatched cohort was closely matched with the non-fracture cohort on these covariates. The matched fracture cohort was also similar to the full unmatched fracture cohort, supporting the generalizability of the findings of the matched analysis. Real-world data was captured through all fracture care-related public healthcare services from a province contributing to over one-third of fractures nationally [34]. Estimates of mortality risks in Canadian adults were reported as up to date, with previous studies relying on 1986–2013 data [4, 7‐10]. Finally, Canadians aged > 65 were examined, who based on age alone are recommended for fracture risk assessments due to their age-related fracture risk [24], but have not been the focus of prior non-hip fracture mortality studies [4, 7‐10].

Limitations of this study include the potential for residual confounding which always exists in any observational study, even after yielding a good match in our study based on a number of clinically relevant potential confounders. Another limitation stems from estimating crude mortality risks without adjusting for potential confounders that could not be used during matching, such as a number of and/or time to second fracture, which was previously found to be associated with increased mortality risk [6]. By excluding patients from the fracture cohort who had another fracture 5 years prior to their index event, but not beyond those 5 years, the fracture cohort was potentially biased towards an older population; this resulted in a mean age roughly 5 years higher than expected for adults aged > 65 [35]. By excluding patients from the non-fracture cohort who experienced a fracture 5 years prior to their index date, but not beyond those 5 years, the non-fracture cohort might have included a small proportion of fractured patients. There may be an underestimation of the number of fractures in this cohort, particularly non-hip, considering that only the ‘Most Responsible Diagnosis (ie, if no definite diagnosis was made, the main symptom, abnormal finding, or problem was selected)’ [26] and ‘Pre-Admit Comorbidity’ were used to identify index fractures. Vertebral fractures were likely underestimated considering that two-thirds are typically silent and that ‘Most Responsible Diagnosis’ was used to identify index fractures [36, 37]. Vertebral fractures could also be more thoroughly identified using the Wright et al. [27] algorithm which takes into account imaging codes in addition to fracture diagnosis codes. As in prior healthcare database research, the determination of fragility fracture was based on the exclusion of high-trauma ICD codes and not independent adjudication [9], which may have under/overestimated the number of fragility fractures in this cohort. Cause of death was unavailable and represents an opportunity for further research. Finally, while these results may be generalizable to populations similar to that of Ontario, there may be less generalizability to specific race and ethnic groups [27].

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In this large, real-world cohort of Canadian adults aged > 65 years, a fragility fracture at any site was associated with reduced survival up to 6 years post-fracture, with the greatest reduction occurring within the first year, when mortality risk more than doubled. Within the first year, deaths were observed in 1 in 8 women and 1 in 5 men following any fracture, in 1 in 11 women and 1 in 7 men following a non-hip fracture, and in 1 in 5 women and 1 in 3 men following a hip fracture.