Copyright © 2009 by The Journal of Bone and Joint Surgery, Inc.

Commentary & Perspective

Commentary & Perspective on
"Cost-Effectiveness of Antibiotic-Impregnated Bone Cement Used in Primary Total Hip Arthroplasty"
by Justin S. Cummins, MD, MS, et al.

Commentary & Perspective by
Kevin J. Bozic, MD, MBA*,
University of California San Francisco Medical Center, San Francisco, California

Posted March 2009

The article, "Cost-Effectiveness of Antibiotic-Impregnated Bone Cement Used in Primary Total Hip Arthroplasty," by Cummins et al., addresses an important and controversial topic in orthopaedics. Clinicians and health policy-makers in the United States and other countries have long debated the appropriate indications for use of antibiotic-impregnated bone cement in total joint arthroplasty. Although the use of antibiotic-impregnated bone cement for single-stage or two-stage revision total joint arthroplasty for the treatment of periprosthetic joint infection is widely accepted and supported by a substantial body of evidence1,2, the routine use of antibiotic-impregnated bone cement in primary total joint arthroplasty continues to be a hotly-debated topic among experts in the fields of orthopaedic surgery, infectious diseases, and health policy. Proponents of the routine use of antibiotic-impregnated bone cement in total joint arthroplasty point to evidence from Scandinavian registry studies3,4, which demonstrated lower rates of revision due to infection or aseptic loosening after total joint arthroplasty when antibiotic-impregnated bone cement rather than standard bone cement had been used. Opponents cite the potential risks of the development of antibiotic-resistant microorganisms, the detrimental effects on the mechanical properties of the cement, and the higher costs associated with routine use of antibiotic-impregnated bone cement in primary total joint arthroplasty. The United States Food and Drug Administration has approved the use of antibiotic-impregnated bone cement for use only in the management of a suspected or confirmed periprosthetic infection.

In the study by Cummins et al., the authors used Markov decision-analysis modeling techniques to evaluate the clinical effectiveness and cost-effectiveness of antibiotic-impregnated bone cement for routine use in primary total hip arthroplasty. Some would argue that, in light of the registry3,4 reports of lower rates of revision due to either infection or aseptic loosening in association with the use of antibiotic-impregnated bone cement as well as no apparent indication of an increase in the number of antibiotic-resistant microorganisms, it is difficult to argue against the widespread use of antibiotic-impregnated bone cement for primary total joint arthroplasty. However, when considering the adoption of a technology or intervention that represents a departure from standard clinical practice, it is important for clinicians and policy-makers to consider these benefits in light of any potential clinical risks (e.g., the possible development of antibiotic-resistant microorganisms and potential detrimental effects on the mechanical properties of bone cement) and economic costs associated with its use. Decision-analysis techniques are particularly valuable in situations in which the evaluation of competing treatment strategies requires the simultaneous consideration of differential risks, benefits, and costs, especially when substantial uncertainty exists or when the timing of subsequent events are important. Furthermore, cost-effectiveness analyses are becoming increasingly pertinent in an era of limited health-care resources and expanding health-care needs. Therefore, decision-analysis models offer an appropriate tool to assess the risks, costs, and benefits of routine use of antibiotic-impregnated bone cement for primary total hip arthroplasty.

When interpreting the results of a cost-effectiveness analysis, it is important to consider the results of the sensitivity analyses rather than just the point estimate of the incremental cost-effectiveness of the intervention from the base-case analysis. Because the results of any cost-effectiveness analysis are highly dependent on the input assumptions, including costs, effectiveness, and clinical outcome probabilities, these inputs are often associated with a high degree of uncertainty. Therefore, the cost-effectiveness of any intervention or technology should not be considered in isolation, but rather in the context of the range of input assumptions used in the model. Furthermore, although interventions that are associated with an incremental cost-effectiveness ratio of <$50,000 per quality-adjusted life year (QALY) gained are often regarded as "cost-effective" by researchers and health policy-makers, this threshold is somewhat arbitrary and may not be relevant in modern day policy-making, particularly in the United States, where cost-effectiveness analyses have not been explicitly considered in policy-making. Instead, clinicians and policy-makers should consider the threshold costs, effectiveness, and clinical probabilities that make a particular intervention or technology more or less cost-effective in comparison with the gold-standard treatment.

In this study, the authors' findings suggest that although routine use of antibiotic-impregnated bone cement in primary total hip arthroplasty could lead to a reduction in the number of total hip arthroplasty failures in the United States, particularly in younger patients, the cost-effectiveness of this strategy from a societal perspective is questionable. This is because cemented fixation of total hip prostheses is rarely performed in the United States in patients who are younger than seventy years (due to the high rates of success and extremely low revision rates that are associated with cementless fixation in younger patients5 and because patients who are seventy years of age or older are less likely to benefit from the potential reduction in total hip revision rates associated with the use of antibiotic-impregnated bone cement). However, it should be noted that when the investigators considered all revisions (rather than only revisions due to infection) as the primary outcome measure, the cost-effectiveness of antibiotic-impregnated bone cement was evident over a much broader range of parameter estimates. Therefore, it is possible that antibiotic-impregnated bone cement may play an important role in reducing total hip arthroplasty failures, and this outcome may become more apparent as more information is gathered regarding the effect of antibiotic-impregnated bone cement on failure due to aseptic loosening after total hip arthroplasty.

Recent evidence from large administrative databases suggests that periprosthetic infection remains one of the most common reasons for revision total joint arthroplasty in the United States6. This may be due to the fact that, while incremental changes in implant designs have primarily been aimed at reducing failure rates associated with the consequences of bearing surface wear and implant loosening, there is no evidence that the prevalence of periprosthetic infection has decreased appreciably over the past several decades. Therefore, prophylactic strategies to minimize periprosthetic infection, including the use of antibiotic-impregnated bone cement, may become increasingly important in reducing total joint arthroplasty failures in the years to come. Furthermore, given that acrylic bone cements are used much more commonly in primary total knee arthroplasty than in primary total hip arthroplasty in the United States, future studies assessing the clinical effectiveness and cost-effectiveness of the routine use of antibiotic-impregnated bone cements in primary total knee arthroplasty may be warranted.

In summary, this well-designed study by Cummins et al. provides a useful framework for clinicians and policy-makers to consider the role of antibiotic-impregnated bone cement in primary total hip arthroplasty in the United States. Their finding that the routine use of antibiotic-impregnated bone cement in primary total hip arthroplasty could lead to a reduction in total hip arthroplasty revision rates and a decrease in lifetime costs (depending on patient age at the time of primary total hip arthroplasty, presumed reductions in failure rates associated with infection as well as aseptic loosening, and the cost of the antibiotic-impregnated bone cement) suggests that further investigation into the clinical and policy ramifications is warranted. Future efforts should be aimed at elucidating the mechanism by which the use of antibiotic-impregnated bone cement reduces the rate of revision due to aseptic loosening after total joint arthroplasty in the United States population; in addition, strategies should be formulated to make the widespread distribution and use of antibiotic-impregnated bone cement more economically feasible.

*In support of his research for or preparation of this work, the author received, in any one year, outside funding or grants in excess of $10,000 from the Orthopaedic Research and Education Foundation (OREF). The author or a member of his or her immediate family received, in any one year, payments or other benefits in excess of $10,000 or a commitment or agreement to provide such benefits from a commercial entity (United HealthCare and Blue Cross Blue Shield Association).

References

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2. Hanssen AD, Rand JA, Osmon DR. Treatment of the infected total knee arthroplasty with insertion of another prosthesis. The effect of antibiotic-impregnated bone cement. Clin Orthop Relat Res. 1994;309:44-55.
3. Engesaeter LB, Lie SA, Espehaug B, Furnes O, Vollset SE, Havelin LI. Antibiotic prophylaxis in total hip arthroplasty: effects of antibiotic prophylaxis systemically and in bone cement on the revision rate of 22,170 primary hip replacements followed 0-14 years in the Norwegian Arthroplasty Register. Acta Orthop Scand. 2003;74:644-51.
4. Malchau H, Herberts P, Ahnfelt L. Prognosis of total hip replacement in Sweden. Follow-up of 92,675 operations performed 1978-1990. Acta Orthop Scand. 1993;64:497-506.
5. Mäkelä KT, Eskelinen A, Pulkkinen P, Paavolainen P, Remes V. Total hip arthroplasty for primary osteoarthritis in patients fifty-five years of age or older. An analysis of the Finnish arthroplasty registry. J Bone Joint Surg Am. 2008;90:2160-70.
6. Bozic KJ, Kurtz SM, Lau E, Ong K, Vail TP, Berry DJ. The epidemiology of revision total hip arthroplasty in the United States. J Bone Joint Surg Am. 2009;91:128-33.