This study showed a 1.5-fold increased hip fracture risk in patients who had undergone a KA. The risk of hip fracture was greatest in young patients (18–70 years). With increasing age, we found a rapid decrease in strength of association, which was no longer elevated in patients aged 81 years and above. The association tended to be greater during the first few years after surgery, but it did not reach statistical significance. Recent use of pain relievers or glucocorticoids did not alter the overall risk of hip fracture.
This is the second study that has evaluated risk of hip fracture in patients with a history of KA and is in line with the first study, which showed a 58% increased risk of hip fracture in British patients within the first year after their KA [23
]. Studies that investigated the association between OA (the main indication for KA) and risk of hip fracture have yielded conflicting findings. Some authors suggested a decreased fracture rate among patients with OA [5
], possibly due to higher BMD levels [8
]. Although data are controversial, patients with OA may have increased osteoblastic activity at the OA site, resulting into higher BMD levels and therefore lower fracture rates [5
]. On the other hand, others reported an increased hip fracture risk, which is in line with our study results. Bergink et al. [24
] found an increased risk of both vertebral (2.0-fold) and nonvertebral (1.5-fold) fractures in patients with knee OA. Similarly, Arden et al. [9
] demonstrated that patients with knee pain or a clinician diagnosis of knee OA have an increased risk of hip and nonvertebral fractures. This is probably explained by an increased severity of falls since they could not detect an increased number of falls. It should be noted, however, that data collection on falls is often incomplete. This could explain the results of a different study that found an increased occurrence of falls among patients with lower limb OA [25
]. Furthermore, looking at differences in fracture types, Arden et al. [9
] and Vestergaard et al. [6
] found a substantially higher increase in risk of hip fracture compared to other fractures (such as distal forearm fractures). This may suggest an important role for the nature of falls in patients with knee OA, as explained by Arden et al. A US case–control study has shown that hip fractures tend to result from falling sideways or straight down (low walking speed), whereas forearm fractures may be more likely to be the result of falling backward [26
]. However, Bergink et al. [24
] could not demonstrate a difference between hip and wrist fractures. Overall, our findings support the studies that found an increased hip fracture risk, indicating that the increased number and severity of falls may attenuate any potentially beneficial effects of higher BMD levels on fracture risk in these patients.
Given this proposed mechanism, we would have expected hip fracture rates to decrease after the KA procedure as the surgery relieves pain and partially restores the biomechanical properties of the knee. However, evidence regarding this hypothesis is conflicting. One study reported fewer falls within 1 year after the KA [27
], while a recent Danish study could not detect any decreases in hip fracture rates during that period [6
]. In line with the Danish study and the British study mentioned earlier [23
], we found no obvious decrease in hip fracture risk shortly after the surgery. A possible explanation for our findings is that patients become rapidly more active after their KA, due to effective knee pain relief [28
]. An overestimation of their physical stability may therefore increase the risk of falls. This could also explain our observed effect modification by age: the youngest patients were at highest hip fracture risk. Compared with elderly patients, these patients may be more likely to increase their physical activity quickly after surgery. In addition, residual knee pain and stiffness in the first months after surgery may be present in some KA patients and could further explain our observed increased hip fracture risk.
Strengths of our study include its population-based setting and that it had a reasonable sample size and longitudinal data collection [10
]. Linkage with the Dutch National Hospitalization Registry assured routinely collected KA surgeries and hip fractures. Limitations include the lack of data on physical activity, which could be an alternative explanation for our observed association between KA and hip fracture. Physical activity is significantly increased in KA patients within 9 months postoperatively [28
], while a rapid increase could potentially initiate falls. In addition, we did not have data on body mass index (BMI), which could have underestimated our observed association between KA and hip fracture. An increased BMI is a well-known risk factor for knee OA [29
], while it is inversely associated with risk of hip fracture [30
]. Nevertheless, our findings are similar to the BMI adjusted results from the General Practice Research Database (GPRD) study [23
]. Similar to the British study [23
], we could not differentiate between the sides of KA or the sides of hip fracture. This information could be helpful in understanding the mechanism of the observed increased risk of hip fracture following KA. Local bone loss may be induced on the side of the replaced knee, possibly resulting in an increased fracture risk of the hip on the same side [31
]. The only feasible way to investigate this is to link a dedicated joint registry to a hospital/general practitioner database, which has been planned for the UK National Joint Registry and the GPRD. Furthermore, we did not have data on BMD or falling, which could have been useful for the assessment of causality and the underlying mechanism. In addition, OA could only be identified in hospitalized patients. Frail, unexposed subject bias may have occurred if KA patients had lower mortality rates compared to subjects who had not undergone KA (due to clinical assessment of operative risk) [32
]. This was probably not the case: Within our control subjects (those without a hip fracture), proportions of cardiovascular hospitalizations were not lower in KA patients (6.7%) compared to patients without a history of KA (4.9%). Unfortunately, we did not have data on other fracture types (such as distal forearm fractures). As our data source only keeps track of hospitalizations, fractures other than those of the hip would suffer from underrecording. Although OA diagnosis and KA surgery have not been validated in this data source, we expect high completeness for KA registration. Our hospitalization source was primarily designed to keep track of economic parameters (e.g., health-care cost). Given the high cost of KA surgery, we would expect adequate recording of this procedure.
In conclusion, we showed that KA was associated with a 54% increased risk of hip fracture, which was not influenced by recent use of pain relievers or corticosteroids. The increase in risk was highest among younger patients (<71 years), which may reflect a rapid increase in physical activity immediately after surgery. Risk assessment of hip fracture could therefore be considered in patients who are about to undergo a KA. It is worthwhile to evaluate its health economic impact.