Health-related quality of life of patients with a recent fracture attending a fracture liaison service: a 3-year follow-up study

The increasing prevalence of osteoporosis is associated with increased risk of a bone fracture [1]. A Dutch study based on claims data from all Dutch healthcare insurers reported an annual average of 114,116 patients with a fracture was identified between 2009 and 2011, of which 32% were attributed to osteoporosis [2]. Patients with a recent fracture after the age of 50 years have an increased risk of subsequent fractures. This risk, which is referred to as imminent subsequent fracture risk [3], is highest immediately after the initial fracture and then declines. In addition, the majority of deaths following fractures occur within the first year; thereafter, the excess mortality gradually declines [4]. From the perspective of caregivers, morbidity and mortality following a fracture are important clinical considerations, along with substantial loss of patients’ quality of life.

To improve secondary fracture prevention, Fracture Liaison Services (FLSs) are advocated as the most appropriate and effective approach to identify, investigate, and treat patients at risk of new fractures. The first FLS was introduced in 1999 by McLellan and colleagues in the UK [5]; since then, awareness of initiating FLSs worldwide has increased through the Capture the Fracture (CTF) campaign in 2012 by the International Osteoporosis Foundation (IOF) [6] and by other professional organizations [7, 8]. Until May 2021, 644 FLSs (registered in CTF) have been implemented in 48 countries; nearly half of these are in Europe.

To capture the full burden of fractures for a society, it is essential to assess their impact on health. Insight into the loss of healthy life years can facilitate rational decision-making when allocating resources across fracture types or diseases [9]. Health state utility value (HSUV) measures are a specified type of health-related quality of life (HRQoL) instruments that reveal the society’s preference or value for specific health states. HSUV is an essential component in economic evaluations, used to establish whether the cost of a new intervention can be justified in terms of expected health benefits [10]; it can help decision-makers in prioritizing health interventions.

In fracture research, a large number of studies were conducted to investigate HSUV in patients not attending an FLS. For example, the large ICUROS study [9] reported that fractures resulted in substantial HRQoL loss directly after fracture, and the HRQoL improved after 4 months but did not return to pre-fracture levels. In 2014, a meta-analysis identified 62 studies that reported HSUVs after hip, vertebral, or distal forearm fracture [13]; the study populations were heterogeneous (e.g., pre-fracture, post-hip/vertebral/wrist fracture), and most studies had a small sample size and were limited by short follow-up periods, indicating that fracture events were associated with decrements in HSUVs which differed between fracture types.

Very few studies were conducted to investigate HRQoL in patients with fractures attending an FLS [14, 15], especially the course of HSUV in the long term. Therefore, the main objective of this study was to investigate the course of HSUV in patients with a recent fracture presenting at an FLS in the Netherlands, as measured by two generic preference-based instruments: the EuroQol (EQ-5D-5L) and the Short Form Health Survey (SF-36), over a 3-year follow-up. In addition, considering previous studies [9, 11, 16, 17] indicated that demographics and fracture-related characteristics such as age, previous fracture, hospitalization, and treatment initiation were significantly associated with patients’ HSUV, our secondary objective was to identify factors associated with HSUV in patients at the FLS.

This study, to our knowledge, is the first longitudinal study using prospective data over 3 years, with the objective of estimating the HRQoL of patients following visits to a FLS because of a recent fracture. With regard to EQ-5D HSUV, no significant change was captured over 3 years, although a small but statistically significant improvement was observed at 6 and 12 months in comparison with baseline HSUV. This short-term improvement is more likely due to natural healing of the fracture rather than the effect of attending an FLS or having a fracture risk evaluation at the FLS. When patients were stratified by baseline fracture (femoral/vertebral/multiple fractures vs. other fractures), our results remained (i.e., there was no significant overall change). We did not find any previous study investigating the long-term HRQoL of patients attending a FLS. In contrast, two studies [14, 15] compared the HSUV of patients with a recent fracture before and after the introduction of a FLS; no significant difference between two groups was identified at the 6 or 12 months follow-up.

The primary potential reason for a non-significant change in HSUV over 3 years is that the patients included in our study attended the FLS 3–4 months after their index fracture; thus, their HRQoL might have already improved through natural fracture recovery and/or through treatment in the emergency department before attending the FLS, resulting in non-striking change after attending FLS. This was also found in the ICUROS studies [9, 11, 12]: although substantial loss of HRQoL was captured in the short term after fracture, patients’ HRQoL was largely improved at 4 months. Except for ICUROS studies, the improvement was also identified in patients who did not attend a FLS in recent studies [14, 15], which can also be attributable to natural healing (recovery) of the fracture. The second potential reason for lack of significant change may be selection bias; it is likely that patients with more severe fractures, older patients, or patients who were hospitalized did not attend the FLS. Furthermore, approximately half of FLS attenders did not consent to participate in this study. In this study, the average baseline HSUV was 0.81, which is a bit lower but still comparable to the HSUV of community-dwelling Dutch residents aged 65 years and older as reported by Mangen et al. [23]. Therefore, our study included relatively healthy patients, which may have resulted in a relatively good HRQOL after the index fracture, without a significant change over time.

Additionally, the greater increase in QOL in patients with a shorter time period (< 107 days) between index fracture and FLS visit may be attributed to the earlier stage of the fracture healing process, and by the timely treatment from FLS clinic compared to patients with a longer time period to FLS visit.

Of note, although patients’ baseline HRQoL was measured 3–4 months after their index fracture, patients with femoral, vertebral, or multiple fractures still had a lower HSUV in comparison with patients with other fractures. Also, significant improvement in HRQoL takes a longer time to capture (baseline HSUV as the reference) as reported in our study. Fisher et al. [24] assessed the timeline of functional recovery after hip fracture in seniors (aged 65 years and older) and reported that objective functional recovery (lower extremity function) was largely complete in the first 6 months, whereas subjective recovery (HRQoL) improved up to 9 months after hip fracture. In addition, we also identified that the number of baseline fractures impacted patients’ HRQoL. Patients with multiple fractures had a significantly lower HSUV in comparison with patients with only one index fracture such as clavicle/scapula, radius/ulna, hand/foot, rib/sternum fracture. This finding is supported by a previous study showing that patients with multiple clinical fractures would experience an additive effect, resulting in disability similar to a single hip or vertebral fracture [25] which is in line with our finding that the absolute average HSUV (over 3 years) difference between femoral, vertebral, and multiple fractures was not significant.

Suffering a subsequent fracture was associated with a decrease in HSUV; this finding is supported by several previous studies [26‐28] reporting that subsequent fractures have a significantly negative impact on the QoL, greater loss of function, and increased mortality. However, whether the effect of FLS is larger immediately after subsequent fracture, and whether the cost-effectiveness of FLS is somewhat better, it remains unknown based on our data and recently published studies. Furthermore, to accurately estimate the effect of FLS on QoL is even difficult given QoL is determined by multiple factors such as lifestyle, aging, and comorbidities; however, it would be interesting for future studies. Also, the presence of a moderate or severe prevalent VF was associated with a lower HSUV, which is in line with recent findings of Shah et al. [29]. Besides, patients who previously received treatment with AOM reported lower utility in comparison with their counterparts. The lower HSUV might be explained by two aspects: first, since the indication for treatment (according to the Dutch guideline) is osteoporosis and/or a moderate or severe VF, patients’ awareness of having osteoporosis and/or VFs and increased future fracture risk might result in over cautiousness and limiting daily activities; second, the potential side effects of oral AOM including bone, joint, or muscle pain, as well as nausea, difficulty swallowing, and heartburn might affect patients’ HRQoL, and the rare side effects such as osteonecrosis of the jaw and atypical femoral fracture actually scare many patients away from taking AOM, with the result that suboptimal persistence and adherence lead to an increased rate of fracture and to worse HRQoL [30]. Moreover, patients’ HSUVs following a fracture are clearly negatively associated with high BMI since excessive body fat produces inflammatory cytokines which may stimulate bone resorption and reduce bone strength [31]. Several recent studies reported that both low and high BMI are risk factors for fragility fracture. The study of Yan et al. [32] investigated the relationships of BMI with HRQoL in adults 65 years and older and revealed that compared with normal-weight people, both underweight and obese older adults reported impaired QoL, particularly worse physical functioning and physical well-being. Furthermore, some previous studies identified that gender [13, 16] and previous fracture [9] are important factors; these were not captured by EQ-5D in our study.

In a sensitivity analysis using another HRQoL measure, namely the SF-6D, comparable results were identified and our main message remained, though there were small differences. For example, the mean SF-6D HSUV was generally lower than the EQ-5D HSUV, and only SF-6D indicated that the course of HSUV for patients with hand/foot fracture was significant. Besides, when the median time to subsequent fracture (364 days) was applied to compare the HSUVs patients without subsequent fracture to those with a subsequent fracture, a higher median EQ-5D HSUV was captured in period 2 for both groups, however, which was only observed for patients without subsequent fracture by SF-6D HSUV. These discrepancies between the two instruments might result from differences in the content of the descriptive systems and in the variation of scoring algorithms [33]; a further head-to-head comparison will be conducted to explore the equivalency of EQ-5D-5L and SF-6D cross-sectionally, including scoring distribution, domain content, and longitudinal validity.

This study has some limitations. First, relatively healthy patients were included in this study (selection bias), so the generalizability of the findings of this study to patients with a fracture could therefore be questionable. Second, our patients attended the FLS approximately 3–4 months after their index fracture; we therefore lacked HRQoL data immediately after fracture, which might limit our capturing an overall significant change of HRQoL in the first several weeks of recovery from a fracture. Finally, 18 patients scored an item of EQ-5D twice; we calculated their two utility scores and used the average value for further analyses, which might affect the results.

In patients at the FLS, subsequent fracture, previous treatment with AOM, a prevalent VF (grade 2 or 3), use of a walking aid, previous falls, and higher BMI were negatively associated with EQ-5D HSUV. The change in HSUV over the total course of 3 years was not statistically significant, although significant improvements were observed at 6- and 12-month time points compared to baseline. There was no significant difference in the course of HSUV between the pre-defined ten fracture categories. A significant increase in HSUV was only captured for patients had shorter time period (< 107 days) between FLS visit and their index fracture. Suffering a subsequent fracture was associated with significant QoL loss.