Mortality Rates After Metal-on-Metal Hip Resurfacing
Mortality Rates After Metal-on-Metal Hip Resurfacing
We found a survival advantage for patients undergoing metal-on-metal hip resurfacing compared with both cemented and uncemented total hip replacement. This advantage persisted after removing potential case mix issues and after accounting for confounding by indication using propensity score matching methods. Owing to the observational nature of the study, there remains the potential for residual confounders—such as health and lifestyle effects—that could attenuate the observed association.
An additional way of measuring the impact of treatment is the number needed to treat. This is the number of patients who would need to be treated with hip resurfacing rather than total hip replacement in order to prevent one adverse event (death at 10 years after surgery). The number of patients needed to treat with metal-on-metal hip resurfacing compared with cemented total hip replacement to prevent one excess death at 10 years was 34. The equivalent number for metal-on-metal hip resurfacing compared with uncemented total hip replacement was 55. The number of patients needed to treat with metal-on-metal hip resurfacing compared with cemented total hip replacement to prevent one excess death at 10 years was 34. The equivalent number for metal-on-metal hip resurfacing compared with uncemented total hip replacement was 55. Over 71,000 primary hip arthroplasties took place in the UK in 2011-12, of which only 2% were resurfacing procedures; a marked decrease from 10% of 59,000 in 2006. Our findings suggest that this reduction could lead to an increase in future mortality, and encourage continued prospective investigation of the relative merits of metal-on-metal hip resurfacing. Any survival advantage in the long term needs to be carefully balanced against the potential for harm. Metal-on-metal hip resurfacing has been reportedly associated with local soft tissue reaction, femoral neck fracture, elevated systemic ion levels, and early failure in women who need small hip components.
A similar survival advantage for men who underwent Birmingham hip resurfacing was described in 2012 using data from the UK National Joint Registry. Mortality hazards were 1.64 (95% confidence interval 1.33 to 2.02) times higher for cemented total hip replacement (number needed to treat of one in 23), and 1.47 (1.19 to 1.82) times higher for uncemented total hip replacement compared with this brand of metal-on-metal hip resurfacing. These findings were not only limited to men but also excluded other types of metal-on-metal hip resurfacing, together constituting about 40% of all resurfacings in 2005-10. Although the study applied flexible parametric modelling (Royston-Parmer) to adjust for confounding factors, this methodology was criticised for not dealing with potential confounding by indication (preselection bias) as well as for relying on American Society of Anesthesiologists (ASA) grading as an accurate predictor of future mortality risk. Patients who went on to have a revision procedure were also excluded, potentially distorting the true long term mortality after the first procedure. Investigation of cancer after metal-on-metal hip resurfacing, using data from the National Joint Registry, also found that patients who underwent resurfacing procedures had a lower risk of death than patients receiving other bearing surfaces.
We used the hospital episode statistics database, which provided a large, nationally representative dataset of all elective NHS admissions for primary total hip replacement and metal-on-metal hip resurfacing across England. The data are linked to national mortality records, ensuring accurate determination of the primary outcome measure. To overcome the effect of confounding by indication, we used propensity score matching on known measurable confounders, including age, sex, the Charlson comorbidity index, socioeconomic status, surgical volume, and time of the operation. Our study results apply to the matched population, which was a sample of younger and relatively healthy patients undergoing total hip replacement. We excluded patients who were older and who had complex total hip replacements after matching. To minimise bias due to confounding by indication, propensity score matching therefore runs the risk of limiting the generalisability of the findings to younger and healthier patients. This potential weakness reduced the mean age from 71.2 to 59.4 years in patients undergoing cemented total hip replacement, and from 65.2 to 57.7 years in patients undergoing uncemented total hip replacement, after matching ( Table 1 and Table 2 ). Although data from patients at extremes of age and associated comorbidities were excluded by the matching process, about 50% of patients undergoing a cemented total hip replacement and 40% undergoing an uncemented total hip replacement remained over 60 years of age. In addition, we failed to find a significant interaction between mortality and age alone.
It was difficult to assess generalisability. Metal-on-metal hip resurfacing was developed for young and active patients who were likely to have several hip replacement procedures of increasing complexity during their lifetimes. Guidance from the National Institute for Health and Care Excellence stated that metal-on-metal hip resurfacing "is recommended as an option for people with advanced hip disease who would otherwise receive a conventional primary total hip replacement (THR) and are likely to live longer than the device is likely to last." The inclusion of a higher proportion of younger patients in both total hip replacement groups arguably allows a clinically relevant comparison of their outcomes against similar patients undergoing metal-on-metal hip resurfacing.
The potential for residual confounding—despite propensity score matching—remains for two main reasons. The scope of known, measured confounders is limited; for example, age is not a reliable indicator of a patient's level of activity and Charlson comorbidity index does not fully assess risk factors predictive of future disease. In addition, there is a potential confounding effect of surgeon experience beyond the measurable "hospital trust surgical volume," whereby specialist hip surgeons performing high volume surgery are more likely to perform metal-on-metal hip resurfacing. Secondly, there are likely to be important unknown confounders that are not patient specific. These confounders could include inequalities in healthcare provision such that metal-on-metal hip resurfacings are more likely to be performed in specialist surgical centres. For these reasons, an important strength of the study is the Rosenbaum bounds sensitivity analyses, allowing us to estimate the likelihood that an unknown or immeasurable confounder could explain the observed differences in long term mortality. A γ value of 1.7 when comparing metal-on-metal hip resurfacing with total hip replacement suggests that it is unlikely that unaccounted confounding remains. Although we cannot fully exclude confounding by indication, our analyses suggest that such confounding would have to be due to an unmeasured confounder with a very large effect size or a cumulative effect of several unmeasured confounders relating to health and lifestyle. Regarding the comparison between metal-on-metal hip resurfacing and uncemented total hip replacement, an unmeasured confounder would need an effect size as small as 1.4 to attenuate the observed association with mortality and so bias our results.
In addition to equalising potential follow-up time in the operative groups, adjustment for time of operation allowed us to control for changing trends in mortality over time and trends in the usage of the different types of operation. The use of a multilevel model enabled us to further account for unexplained variation and clustering across hospital trust sites. A limitation is that routine hospital admissions data are collected for administrative rather than research purposes, and concerns have been raised over the completeness and accuracy of such data. Lastly, hospital episode statistics data underestimates the total number of procedures performed by excluding a minority of privately funded operations, but this is unlikely to bias the observed results.
It is currently unclear why there is a survival advantage after metal-on-metal hip resurfacing compared with after total hip replacement. Potential contributing factors could be broadly grouped into patient selection (discussed above), perioperative care of patients, operative techniques, and bearing surfaces.
Metal-on-metal hip resurfacing constituted a minority (<7%) of primary hip arthroplasty, and the most commonly used brand was the Birmingham hip resurfacing component (>60% in 2012). Compared with the more widespread use of total hip replacement, this difference could represent a discriminatory concentration of specialist skills in a small number of regional centres that could translate into a higher or more consistent standard of care. Early revision rates of metal-on-metal hip resurfacing could also affect long term survival by increasing the frequency of patient-hospital encounters. This trend is likely to continue after regulatory advice that patients with metal-on-metal bearings need annual monitoring for ion levels and local tissue reaction.
Metal-on-metal hip resurfacing only requires preparation of the head of the femur. But in total hip replacement, the femoral canal is mechanically reamed, rasped, cleaned and, if cemented, pressurised during polymethylmethacrylate (PMMA) cement insertion. These steps are associated with bone cement implantation syndrome, which is loosely characterised by hypoxia, hypotension, increased pulmonary vascular resistance, and cardiac dysrhythmias. The proposed pathophysiology of bone cement implantation syndrome includes polymethylmethacrylate toxicity, release of bone marrow emboli, and vasoactive inflammatory mediators. Embolic release could have more of an effect than polymethylmethacrylate toxicity, which alone cannot explain the survival advantage of metal-on-metal hip resurfacing over uncemented total hip replacement. Transoesophageal echocardiography has detected emboli throughout the preparation of the femoral canal, not just during cement pressurisation. Bone cement implantation syndrome might offer one explanation for the increase in relative risk of death from cardiopulmonary causes after cemented and uncemented total hip replacement versus metal-on-metal hip resurfacing. However, currently there is only limited evidence that metal-on-metal hip resurfacing releases fewer emboli than total hip replacement. Furthermore, no correlation has been shown between the extent of emboli and clinical sequelae—perhaps partly because bone cement implantation syndrome is a poorly defined disorder that is rarely fatal and thus risks under reporting.
The observed survival advantage after metal-on-metal hip resurfacing seems at odds with accumulating descriptions of local and systemic effects of metal wear debris. Metal bearings are more resistant to mechanical wear than polyethylene bearings, but overall they release a greater number of smaller wear particles that can drive chronic inflammation and "pseudotumour" formation. Systemically, high levels of cobalt and chromium ions have been found after metal-on-metal hip resurfacing. They continue throughout the life of the prosthesis, penetrate solid organs, and are further elevated in patients with loosening implants. Although both ions are known to be genotoxic, so far epidemiological studies have failed to show an increase in cancer related mortality after hip arthroplasty. Smith and colleagues recently observed lower rates of cancer in patients over a seven year period after metal-on-metal hip resurfacing than in the general population, but failed to account for confounding by indication. We observed an increased risk in cancer related deaths after cemented and uncemented total hip replacement compared with metal-on-metal hip resurfacing. It is still possible that metal-on-metal hip resurfacing will result in an increased mortality beyond the 10 year period of our study. Long latency periods are associated with occupational exposure to other metal ions—for example, nickel—and the reported increase in the incidence of melanoma and prostatic cancer in one meta-analysis only became apparent beyond 10 years after hip arthroplasty.
In our study, patients undergoing metal-on-metal hip resurfacing had a long term survival advantage compared with those undergoing cemented and uncemented total hip replacement. These findings were robust to adjustment for known and measured confounders. The observed survival advantage requires confirmation in randomised controlled trials or external cohorts with more detailed data on potential confounders, and should be balanced against known complications for an informed decision on surgical management of patients with symptomatic hip osteoarthritis.
Discussion
We found a survival advantage for patients undergoing metal-on-metal hip resurfacing compared with both cemented and uncemented total hip replacement. This advantage persisted after removing potential case mix issues and after accounting for confounding by indication using propensity score matching methods. Owing to the observational nature of the study, there remains the potential for residual confounders—such as health and lifestyle effects—that could attenuate the observed association.
Meaning of the Study's Findings
An additional way of measuring the impact of treatment is the number needed to treat. This is the number of patients who would need to be treated with hip resurfacing rather than total hip replacement in order to prevent one adverse event (death at 10 years after surgery). The number of patients needed to treat with metal-on-metal hip resurfacing compared with cemented total hip replacement to prevent one excess death at 10 years was 34. The equivalent number for metal-on-metal hip resurfacing compared with uncemented total hip replacement was 55. The number of patients needed to treat with metal-on-metal hip resurfacing compared with cemented total hip replacement to prevent one excess death at 10 years was 34. The equivalent number for metal-on-metal hip resurfacing compared with uncemented total hip replacement was 55. Over 71,000 primary hip arthroplasties took place in the UK in 2011-12, of which only 2% were resurfacing procedures; a marked decrease from 10% of 59,000 in 2006. Our findings suggest that this reduction could lead to an increase in future mortality, and encourage continued prospective investigation of the relative merits of metal-on-metal hip resurfacing. Any survival advantage in the long term needs to be carefully balanced against the potential for harm. Metal-on-metal hip resurfacing has been reportedly associated with local soft tissue reaction, femoral neck fracture, elevated systemic ion levels, and early failure in women who need small hip components.
Strengths and Weaknesses in Relation to Other Studies
A similar survival advantage for men who underwent Birmingham hip resurfacing was described in 2012 using data from the UK National Joint Registry. Mortality hazards were 1.64 (95% confidence interval 1.33 to 2.02) times higher for cemented total hip replacement (number needed to treat of one in 23), and 1.47 (1.19 to 1.82) times higher for uncemented total hip replacement compared with this brand of metal-on-metal hip resurfacing. These findings were not only limited to men but also excluded other types of metal-on-metal hip resurfacing, together constituting about 40% of all resurfacings in 2005-10. Although the study applied flexible parametric modelling (Royston-Parmer) to adjust for confounding factors, this methodology was criticised for not dealing with potential confounding by indication (preselection bias) as well as for relying on American Society of Anesthesiologists (ASA) grading as an accurate predictor of future mortality risk. Patients who went on to have a revision procedure were also excluded, potentially distorting the true long term mortality after the first procedure. Investigation of cancer after metal-on-metal hip resurfacing, using data from the National Joint Registry, also found that patients who underwent resurfacing procedures had a lower risk of death than patients receiving other bearing surfaces.
We used the hospital episode statistics database, which provided a large, nationally representative dataset of all elective NHS admissions for primary total hip replacement and metal-on-metal hip resurfacing across England. The data are linked to national mortality records, ensuring accurate determination of the primary outcome measure. To overcome the effect of confounding by indication, we used propensity score matching on known measurable confounders, including age, sex, the Charlson comorbidity index, socioeconomic status, surgical volume, and time of the operation. Our study results apply to the matched population, which was a sample of younger and relatively healthy patients undergoing total hip replacement. We excluded patients who were older and who had complex total hip replacements after matching. To minimise bias due to confounding by indication, propensity score matching therefore runs the risk of limiting the generalisability of the findings to younger and healthier patients. This potential weakness reduced the mean age from 71.2 to 59.4 years in patients undergoing cemented total hip replacement, and from 65.2 to 57.7 years in patients undergoing uncemented total hip replacement, after matching ( Table 1 and Table 2 ). Although data from patients at extremes of age and associated comorbidities were excluded by the matching process, about 50% of patients undergoing a cemented total hip replacement and 40% undergoing an uncemented total hip replacement remained over 60 years of age. In addition, we failed to find a significant interaction between mortality and age alone.
It was difficult to assess generalisability. Metal-on-metal hip resurfacing was developed for young and active patients who were likely to have several hip replacement procedures of increasing complexity during their lifetimes. Guidance from the National Institute for Health and Care Excellence stated that metal-on-metal hip resurfacing "is recommended as an option for people with advanced hip disease who would otherwise receive a conventional primary total hip replacement (THR) and are likely to live longer than the device is likely to last." The inclusion of a higher proportion of younger patients in both total hip replacement groups arguably allows a clinically relevant comparison of their outcomes against similar patients undergoing metal-on-metal hip resurfacing.
The potential for residual confounding—despite propensity score matching—remains for two main reasons. The scope of known, measured confounders is limited; for example, age is not a reliable indicator of a patient's level of activity and Charlson comorbidity index does not fully assess risk factors predictive of future disease. In addition, there is a potential confounding effect of surgeon experience beyond the measurable "hospital trust surgical volume," whereby specialist hip surgeons performing high volume surgery are more likely to perform metal-on-metal hip resurfacing. Secondly, there are likely to be important unknown confounders that are not patient specific. These confounders could include inequalities in healthcare provision such that metal-on-metal hip resurfacings are more likely to be performed in specialist surgical centres. For these reasons, an important strength of the study is the Rosenbaum bounds sensitivity analyses, allowing us to estimate the likelihood that an unknown or immeasurable confounder could explain the observed differences in long term mortality. A γ value of 1.7 when comparing metal-on-metal hip resurfacing with total hip replacement suggests that it is unlikely that unaccounted confounding remains. Although we cannot fully exclude confounding by indication, our analyses suggest that such confounding would have to be due to an unmeasured confounder with a very large effect size or a cumulative effect of several unmeasured confounders relating to health and lifestyle. Regarding the comparison between metal-on-metal hip resurfacing and uncemented total hip replacement, an unmeasured confounder would need an effect size as small as 1.4 to attenuate the observed association with mortality and so bias our results.
In addition to equalising potential follow-up time in the operative groups, adjustment for time of operation allowed us to control for changing trends in mortality over time and trends in the usage of the different types of operation. The use of a multilevel model enabled us to further account for unexplained variation and clustering across hospital trust sites. A limitation is that routine hospital admissions data are collected for administrative rather than research purposes, and concerns have been raised over the completeness and accuracy of such data. Lastly, hospital episode statistics data underestimates the total number of procedures performed by excluding a minority of privately funded operations, but this is unlikely to bias the observed results.
Unanswered Questions and Future Research
It is currently unclear why there is a survival advantage after metal-on-metal hip resurfacing compared with after total hip replacement. Potential contributing factors could be broadly grouped into patient selection (discussed above), perioperative care of patients, operative techniques, and bearing surfaces.
Metal-on-metal hip resurfacing constituted a minority (<7%) of primary hip arthroplasty, and the most commonly used brand was the Birmingham hip resurfacing component (>60% in 2012). Compared with the more widespread use of total hip replacement, this difference could represent a discriminatory concentration of specialist skills in a small number of regional centres that could translate into a higher or more consistent standard of care. Early revision rates of metal-on-metal hip resurfacing could also affect long term survival by increasing the frequency of patient-hospital encounters. This trend is likely to continue after regulatory advice that patients with metal-on-metal bearings need annual monitoring for ion levels and local tissue reaction.
Metal-on-metal hip resurfacing only requires preparation of the head of the femur. But in total hip replacement, the femoral canal is mechanically reamed, rasped, cleaned and, if cemented, pressurised during polymethylmethacrylate (PMMA) cement insertion. These steps are associated with bone cement implantation syndrome, which is loosely characterised by hypoxia, hypotension, increased pulmonary vascular resistance, and cardiac dysrhythmias. The proposed pathophysiology of bone cement implantation syndrome includes polymethylmethacrylate toxicity, release of bone marrow emboli, and vasoactive inflammatory mediators. Embolic release could have more of an effect than polymethylmethacrylate toxicity, which alone cannot explain the survival advantage of metal-on-metal hip resurfacing over uncemented total hip replacement. Transoesophageal echocardiography has detected emboli throughout the preparation of the femoral canal, not just during cement pressurisation. Bone cement implantation syndrome might offer one explanation for the increase in relative risk of death from cardiopulmonary causes after cemented and uncemented total hip replacement versus metal-on-metal hip resurfacing. However, currently there is only limited evidence that metal-on-metal hip resurfacing releases fewer emboli than total hip replacement. Furthermore, no correlation has been shown between the extent of emboli and clinical sequelae—perhaps partly because bone cement implantation syndrome is a poorly defined disorder that is rarely fatal and thus risks under reporting.
The observed survival advantage after metal-on-metal hip resurfacing seems at odds with accumulating descriptions of local and systemic effects of metal wear debris. Metal bearings are more resistant to mechanical wear than polyethylene bearings, but overall they release a greater number of smaller wear particles that can drive chronic inflammation and "pseudotumour" formation. Systemically, high levels of cobalt and chromium ions have been found after metal-on-metal hip resurfacing. They continue throughout the life of the prosthesis, penetrate solid organs, and are further elevated in patients with loosening implants. Although both ions are known to be genotoxic, so far epidemiological studies have failed to show an increase in cancer related mortality after hip arthroplasty. Smith and colleagues recently observed lower rates of cancer in patients over a seven year period after metal-on-metal hip resurfacing than in the general population, but failed to account for confounding by indication. We observed an increased risk in cancer related deaths after cemented and uncemented total hip replacement compared with metal-on-metal hip resurfacing. It is still possible that metal-on-metal hip resurfacing will result in an increased mortality beyond the 10 year period of our study. Long latency periods are associated with occupational exposure to other metal ions—for example, nickel—and the reported increase in the incidence of melanoma and prostatic cancer in one meta-analysis only became apparent beyond 10 years after hip arthroplasty.
Conclusion
In our study, patients undergoing metal-on-metal hip resurfacing had a long term survival advantage compared with those undergoing cemented and uncemented total hip replacement. These findings were robust to adjustment for known and measured confounders. The observed survival advantage requires confirmation in randomised controlled trials or external cohorts with more detailed data on potential confounders, and should be balanced against known complications for an informed decision on surgical management of patients with symptomatic hip osteoarthritis.
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