- Email: [email protected]
Anterior Cruciate Ligament Graft Fixation—A Myth Busted?
Level V Evidence
Anterior Cruciate Ligament Graft Fixation—A Myth Busted? Teppo L. N. Järvinen, M.D., Ph.D., Ghassan B. Alami, M.D., F.R.C.S.C., and Jón Karlsson, M.D., Ph.D.
Abstract: Anterior cruciate ligament graft fixation has become one of the most investigated topics in the sports traumatology literature. With over 400 publications within the past decade, a plausible explanation for the popularity of the topic would be that anterior cruciate ligament graft fixation represents an obvious clinical problem. Yet this does not seem to be the case. We set out to analyze the veracity of the notion that the fixation site is the weak link in a reconstructed knee in the early postoperative period. A mere temporal association is found between the first clinical reports on increased anterior tibial translation relative to the femur with soft-tissue grafts and the first pullout studies reporting lower ultimate failure loads with such grafts. This association was sufficient to convince the orthopaedic community at large that actual causality exists between soft-tissue graft fixation failure and increased knee laxity during healing. Thus the concept of “graft slippage” was born. Even with the imminent risk of being misconstrued as contentious, we submit that the entire concept of graft slippage is a myth, founded on poor scientific practice and affected by commercial bias. As a way forward, clinically important phenomena should be demonstrated through experiments with clear and sound clinical endpoints. As for preclinical studies, although they are indisputably helpful in the elaboration of such phenomena, serious hazards lie in declaring them a sufficient scientific basis for new research or, worse, for clinical standards of care. More importantly, no matter how sophisticated or fascinating their methodology, preclinical studies do not relieve us from the necessity and duty of proving our theories, whenever possible, with randomized controlled trials.
U
sing the search terms “ACL fixation” and “ACL graft fixation,” the Medline literature search results in nearly 600 studies during the last 26 years (1983 to January 2010), of which over 400 have been
From the Department of Surgery and Institute of Medical Technology, University of Tampere (T.L.N.J.), Tampere, Finland; Department of Surgery, Central Hospital of Central Finland (T.L.N.J.), Jyväskylä, Finland; Department of Orthopaedics, University of British Columbia (T.L.N.J., G.B.A.), Vancouver, British Columbia, Canada; and Department of Orthopaedics & Rehabilitation, Sahlgrenska Hospital (J.K.), Gothenburg, Sweden. Supported by competitive research funding from the Pirkanmaa Hospital District and by the Sigrid Juselius Foundation. Received September 13, 2009; accepted November 30, 2009. Address correspondence and reprint requests to Teppo L. N. Järvinen, M.D., Ph.D., Department of Surgery, University of Tampere, 33014 University of Tampere, Tampere, Finland. E-mail: [email protected] © 2010 by the Arthroscopy Association of North America 0749-8063/10/2605-9537$36.00/0 doi:10.1016/j.arthro.2009.11.023
published within the past decade. As such, anterior cruciate ligament (ACL) graft fixation is among the most investigated topics in recent sports medicine literature. The further backwards you are able to look, the further forward you are able to see. Winston Churchill
HOW DID ACL GRAFT FIXATION RESEARCH BEGIN? A plausible explanation for what initiated research on ACL graft fixation research would be that it represented an obvious clinical problem. However, this is not exactly the case. In reviewing the literature on the topic, a classic 1987 study by Kurosaka et al.1 can be identified as the first of the biomechanical studies on ACL graft fixation. They compared pullout strengths of bone–patellar tendon– bone (BPTB) grafts fixed
Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 26, No 5 (May), 2010: pp 681-684
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with a staple, sutures tied over buttons, or a titanium screw specifically designed for the interference fixation of the BPTB graft. On the basis of their experiments, they concluded that the fixation site is the weakest link of the reconstructed knee, a statement that has probably had the single most striking influence on the field in terms of generating further research. For example, the total number of studies reporting biomechanical testing of ACL graft fixations is now more than 200, and the original study by Kurosaka et al. has been cited in well over 300 articles. However, interest in ACL fixation was naturally not generated by just a single study, and at least 2 other landmark studies can be identified. Three years before the study by Kurosaka et al.,1 Noyes et al.2 began to set the stage with their biomechanical comparison of the strengths of various graft materials about the knee. They not only showed that the structural properties of BPTB graft per se were superior to soft-tissue grafts (fascia lata, single hamstring tendon, or multiple hamstring tendons) but also provided an estimation of the ACL in vivo loading during “normal activity.” In their experiments the mean strength of 5 young cadaveric ACLs tested in uniaxial tension was 1,730 N. By coupling this force value with a biological hypothesis that in nature, there existed a built-in safety margin of a 4-to-1 or 5-to-1 ratio of ultimate strength to in vivo force, the authors estimated that the loads developed on the ACL during normal activity were, on average, 445 N. They did not, however, characterize what normal activity actually represented, nor did they provide evidence of how their estimate was validated. Despite these 2 landmark studies, it still took another 5 years for ACL fixation research to explode. In the early 1990s the free-tendon soft-tissue grafts were making a strong emergence as an alternative for the BPTB graft. As with any new concept in medicine, the introduction of the use of free-tendon soft-tissue graft was associated with various problems, 1 of the most striking of which was the increase in postoperative anteroposterior knee laxity during healing. In 1993 Rodeo et al.3 published their classic canine study in which it was shown that at the 2-, 4-, and 8-week time periods, tendon grafts inserted into a proximal tibia failed by pullout of the tendon from the bone tunnel. These in vivo findings, coupled with the work of Kurosaka et al.,1 appeared to provide sufficient “proof” that the fixation site indeed was the weak link of the reconstructed knee in the early postoperative period. The mere temporal association between the first reports on increased knee laxity with the use of soft-tissue grafts and the previously noted experimental findings—particularly when
further “corroborated” by the first pullout studies reporting considerably lower ultimate failure load on soft-tissue fixations versus BPTB fixations1,4,5—were sufficient to convince the orthopaedic community at large that actual causality existed between soft-tissue graft fixation (slippage) and increased anterior translation of the tibia relative to the femur during healing. The concept of “graft slippage” has since been used as the rationale for virtually all recent ACL fixation studies. We measure things because we CAN. Accordingly, it is crucial to fully understand the context of one’s measurements. Anonymous
Even with the imminent risk of being misconstrued as contentious or using hindsight, one needs to critically evaluate the main conclusions, and particularly the interpretations, that have been made of the findings, of the landmark ACL studies of Noyes et al.2 and Kurosaka et al.1 To start with, we have a few remarks on the biomechanical study by Noyes et al., particularly on the validity of their estimate of 445 N for the in vivo loading of the ACL. By setting a single force value for ACL in vivo loading, the authors coupled the inherent human desire to set an exact threshold (single value) with the longstanding affinity of the orthopaedic research community for biomechanical testing. We believe that the extent to which this value (445 N) was approved by the field exemplifies how much such thresholds are desired and valued. However, an attempt to reduce such a complex issue as ACL in vivo loading to a single value unfortunately fails under scientific scrutiny. Even if a 1-to-4 or 1-to-5 safety margin indeed did exist for various properties of the human body, it is highly unlikely that the strength derived from such a simple testing configuration as ultimate uniaxial tensile testing would represent an appropriate property on which to base one’s calculations for the obviously complex and multidirectional in vivo loading of the ACL during locomotion. After all, Noyes et al. did point out in their article that the ACL has a complex fiber geometry in which different fiber lengths allow ligament function in different segments or portions of knee motion. Regarding the experiments of Rodeo et al.3 and their relevance to ACL reconstruction in humans, their most apparent limitation relates to the fact that in transplanting the long digital extensor tendon of a canine into a drill hole made in the proximal tibial metaphysis, the authors used a non–intra-articular experimental model of tendon-to-bone healing. More
ACL GRAFT FIXATION than 15 years after the publication of this classic study, we can now argue, based on strong experimental data from intra-articular models of soft-tissue ACL reconstruction,2,6-8 that the intra-articular portion of the replacement graft (rather than the graft–to– bone tunnel interface) is the weakest link of the ACL reconstruction even as early as 3 weeks,6 but at least at 6 to 9 weeks,7,8 postoperatively. Accordingly, if the fixation of the free-tendon soft-tissue graft indeed represented the weakest link of the ACL reconstruction during the immediate postoperative period, it seems that given the necrosis and remodeling of the graft, the structural integrity of the graft, rather than strength of fixation, becomes the rate-limiting factor in the allowance of more strenuous knee loading early in the rehabilitation. Naturally, the ultimate proof for the veracity of any concept in medicine has to be drawn from clinical studies. Thus the next plausible question is whether there are any data to either corroborate or refute the clinical relevance of the concept of “slippage of the ACL graft fixation.” To begin with, one needs to assess the validity of the proposals on the causality between the increased postoperative knee laxity and “graft slippage/fixation failure” of the free-tendon soft-tissue ACL reconstructions or, for that matter, bone-to-bone slippage in BPTB grafts. There is good clinical evidence showing that the bone blocks of the BPTB grafts do not migrate or at least migrate only marginally postoperatively.9 Despite the fact that the first randomized controlled trials between soft-tissue (single- or double-strand semitendinosus or gracilis tendon) and BPTB grafts showed increased anteroposterior knee laxity with the former graft type at 2-year follow up,10-12 the great majority of the more recent data with quadrupled hamstring grafts show that there is no evidence of increased laxity with these softtissue grafts.13-20 In fact, both soft tissue–reconstructed and BPTB-reconstructed knees display some increase in anteroposterior laxity over the early postoperative period, but the phenomenon is quite identical between the two. Most persuasively, the recent head-to-head comparisons of different soft-tissue fixation implants with vastly distinct biomechanical properties provide comparable clinical results at 2-year follow up.21,22 In the end, despite the enormous number of ACL reconstructions performed each year by surgeons with very different operative skills and experience, there are (to our knowledge) only 2 case reports of early, complete ACL fixation failures in the medical literature23,24 (in both studies the replacement graft was a BPTB, not a soft-tissue graft). For compar-
683
ison, an abundance of case reports of failed meniscal repairs have been published during the past 10 years. WHAT CAN BE LEARNED FROM ALL THIS? Some detrimental trends that are common in the current medical literature seem to have found their way into the area of ACL graft fixation. (1) Regarding publication bias, the concern about potential commercial bias has been raised recently in the field of arthroscopy and sports traumatology.25 In fact, similarly to recent reports on antidepressants,26,27 reports of a favorable outcome with a commercial product tested in a given study are in gross excess compared with negative findings among the studies published on ACL graft fixation. Not surprisingly, it turns out that a clear commercial agenda underlies a majority of published studies regarding ACL graft fixation. (2) Regarding methodologic deficiencies and selective use of references, there is no excuse for poor scientific practice, whether it be in the form of methodologic compromises or neglect of the “unpleasant” truth. Still, both of these approaches are very common in the field of ACL graft fixation. For example, the use of porcine bones is still the prevailing practice in ACL graft fixation studies despite the indisputable evidence against their suitability for that purpose.28 Arguments that this is “the common practice in the field” or that “cadaveric specimens are expensive and difficult to obtain” and the use of references to articles with flawed conclusions29 are equally condemnable attempts at justifying poor scientific practice. Why do we have no trouble reprimanding our children when they justify their bad deeds with the similar deeds of their peers while we fail to uphold such a level of morality in our own work? In conclusion, despite the massive commercially supported research interest in ACL soft-tissue graft fixation, virtually no evidence exists in support of our excessive concern over the failure of graft fixation implants. The subject of ACL graft fixation is actually an important example of the hierarchy of evidence of which we should be very wary when planning new studies in sports traumatology. Clinically important phenomena should be demonstrated through experiments with clear and sound clinical endpoints. As for preclinical studies, although they are indisputably helpful in the elaboration of such phenomena, serious hazards lie in declaring them a sufficient scientific basis for new research or, worse, for clinical standards of care. More importantly, no matter how sophisti-
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cated or fascinating their methodology, preclinical studies do not—whether we like it or not—relieve us from the necessity and duty of performing unbiased prospective, randomized controlled trials. REFERENCES 1. Kurosaka M, Yoshiya S, Andrish JT. A biomechanical comparison of different surgical techniques of graft fixation in anterior cruciate ligament reconstruction. Am J Sports Med 1987;15:225-229. 2. Noyes FR, Butler DL, Grood ES, Zernicke RF, Hefzy MS. Biomechanical analysis of human ligament grafts used in knee-ligament repairs and reconstructions. J Bone Joint Surg Am 1984;66:344-352. 3. Rodeo SA, Arnoczky SP, Torzilli PA, Hidaka C, Warren RF. Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog. J Bone Joint Surg Am 1993;75:17951803. 4. Robertson DB, Daniel DM, Biden E. Soft tissue fixation to bone. Am J Sports Med 1986;14:398-403. 5. Steiner ME, Hecker AT, Brown CH Jr, Hayes WC. Anterior cruciate ligament graft fixation. Comparison of hamstring and patellar tendon grafts. Am J Sports Med 1994;22:240-246, discussion 246-247. 6. Grana WA, Egle DM, Mahnken R, Goodhart CW. An analysis of autograft fixation after anterior cruciate ligament reconstruction in a rabbit model. Am J Sports Med 1994;22:344-351. 7. Weiler A, Hoffmann RF, Bail HJ, Rehm O, Sudkamp NP. Tendon healing in a bone tunnel. Part II: Histologic analysis after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep. Arthroscopy 2002;18:124-135. 8. Weiler A, Peine R, Pashmineh-Azar A, Abel C, Sudkamp NP, Hoffmann RF. Tendon healing in a bone tunnel. Part I: Biomechanical results after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep. Arthroscopy 2002;18:113-123. 9. Friden T, Ryd L, Lindstrand A. Laxity and graft fixation after reconstruction of the anterior cruciate ligament. A roentgen stereophotogrammetric analysis of 11 patients. Acta Orthop Scand 1992;63:80-84. 10. Anderson AF, Snyder RB, Lipscomb AB Jr. Anterior cruciate ligament reconstruction. A prospective randomized study of three surgical methods. Am J Sports Med 2001;29:272-279. 11. Beynnon BD, Johnson RJ, Fleming BC, et al. Anterior cruciate ligament replacement: Comparison of bone-patellar tendonbone grafts with two-strand hamstring grafts. A prospective, randomized study. J Bone Joint Surg Am 2002;84:1503-1513. 12. O’Neill DB. Arthroscopically assisted reconstruction of the anterior cruciate ligament. A prospective randomized analysis of three techniques. J Bone Joint Surg Am 1996;78:803-813. 13. Aglietti P, Giron F, Buzzi R, Biddau F, Sasso F. Anterior cruciate ligament reconstruction: Bone-patellar tendon-bone compared with double semitendinosus and gracilis tendon grafts. A prospective, randomized clinical trial. J Bone Joint Surg Am 2004;86:2143-2155. 14. Beard DJ, Anderson JL, Davies S, Price AJ, Dodd CA. Hamstrings vs. patella tendon for anterior cruciate ligament reconstruction: A randomised controlled trial. Knee 2001;8:45-50.
15. Ejerhed L, Kartus J, Sernert N, Kohler K, Karlsson J. Patellar tendon or semitendinosus tendon autografts for anterior cruciate ligament reconstruction? A prospective randomized study with a two-year follow-up. Am J Sports Med 2003;31:19-25. 16. Eriksson K, Anderberg P, Hamberg P, et al. A comparison of quadruple semitendinosus and patellar tendon grafts in reconstruction of the anterior cruciate ligament. J Bone Joint Surg Br 2001;83:348-354. 17. Jansson KA, Linko E, Sandelin J, Harilainen A. A prospective randomized study of patellar versus hamstring tendon autografts for anterior cruciate ligament reconstruction. Am J Sports Med 2003;31:12-18. 18. Laxdal G, Kartus J, Hansson L, Heidvall M, Ejerhed L, Karlsson J. A prospective randomized comparison of bone-patellar tendon-bone and hamstring grafts for anterior cruciate ligament reconstruction. Arthroscopy 2005;21:34-42. 19. Samuelsson K, Andersson D, Karlsson J. Treatment of anterior cruciate ligament injuries with special reference to graft type and surgical technique: an assessment of randomized controlled trials. Arthroscopy 2009;25:1139-1174. 20. Shaieb MD, Kan DM, Chang SK, Marumoto JM, Richardson AB. A prospective randomized comparison of patellar tendon versus semitendinosus and gracilis tendon autografts for anterior cruciate ligament reconstruction. Am J Sports Med 2002; 30:214-220. 21. Harilainen A, Sandelin J. A prospective comparison of 3 hamstring ACL fixation devices—Rigidfix, BioScrew, and Intrafix—Randomized into 4 groups with 2 years of follow-up. Am J Sports Med 2009;37:699-706. 22. Harilainen A, Sandelin J, Jansson KA. Cross-pin femoral fixation versus metal interference screw fixation in anterior cruciate ligament reconstruction with hamstring tendons: Results of a controlled prospective randomized study with 2-year follow-up. Arthroscopy 2005;21:25-33. 23. Cooper DE, Wilson TW. Clinical failure of tibial interference screw fixation after anterior cruciate ligament reconstruction. A report of two cases. Am J Sports Med 1996;24:693-697. 24. Doerr AL Jr, Cohn BT, Ruoff MJ, McInerney VK. A complication of interference screw fixation in anterior cruciate ligament reconstruction. Orthop Rev 1990;19:997-1000. 25. Lubowitz JH, Appleby D, Centeno JM, Woolf SK, Reid JB III. The relationship between the outcome of studies of autologous chondrocyte implantation and the presence of commercial funding. Am J Sports Med 2007;35:1809-1816 (published erratum appears in Am J Sports Med 2008;36:193). 26. Moreno SG, Sutton AJ, Turner EH, et al. Novel methods to deal with publication biases: Secondary analysis of antidepressant trials in the FDA trial registry database and related journal publications. BMJ 2009;339:b2981. 27. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008;358:252-260. 28. Nurmi JT, Sievanen H, Kannus P, Jarvinen M, Jarvinen TL. Porcine tibia is a poor substitute for human cadaver tibia for evaluating interference screw fixation. Am J Sports Med 2004; 32:765-771. 29. Nurmi JT, Jarvinen TL, Kannus P, Sievanen H, Toukosalo J, Jarvinen M. Compaction versus extraction drilling for fixation of the hamstring tendon graft in anterior cruciate ligament reconstruction. Am J Sports Med 2002;30:167-173.
Anterior Cruciate Ligament Graft Fixation—A Myth Busted? Teppo L. N. Järvinen, M.D., Ph.D., Ghassan B. Alami, M.D., F.R.C.S.C., and Jón Karlsson, M.D., Ph.D.
Abstract: Anterior cruciate ligament graft fixation has become one of the most investigated topics in the sports traumatology literature. With over 400 publications within the past decade, a plausible explanation for the popularity of the topic would be that anterior cruciate ligament graft fixation represents an obvious clinical problem. Yet this does not seem to be the case. We set out to analyze the veracity of the notion that the fixation site is the weak link in a reconstructed knee in the early postoperative period. A mere temporal association is found between the first clinical reports on increased anterior tibial translation relative to the femur with soft-tissue grafts and the first pullout studies reporting lower ultimate failure loads with such grafts. This association was sufficient to convince the orthopaedic community at large that actual causality exists between soft-tissue graft fixation failure and increased knee laxity during healing. Thus the concept of “graft slippage” was born. Even with the imminent risk of being misconstrued as contentious, we submit that the entire concept of graft slippage is a myth, founded on poor scientific practice and affected by commercial bias. As a way forward, clinically important phenomena should be demonstrated through experiments with clear and sound clinical endpoints. As for preclinical studies, although they are indisputably helpful in the elaboration of such phenomena, serious hazards lie in declaring them a sufficient scientific basis for new research or, worse, for clinical standards of care. More importantly, no matter how sophisticated or fascinating their methodology, preclinical studies do not relieve us from the necessity and duty of proving our theories, whenever possible, with randomized controlled trials.
U
sing the search terms “ACL fixation” and “ACL graft fixation,” the Medline literature search results in nearly 600 studies during the last 26 years (1983 to January 2010), of which over 400 have been
From the Department of Surgery and Institute of Medical Technology, University of Tampere (T.L.N.J.), Tampere, Finland; Department of Surgery, Central Hospital of Central Finland (T.L.N.J.), Jyväskylä, Finland; Department of Orthopaedics, University of British Columbia (T.L.N.J., G.B.A.), Vancouver, British Columbia, Canada; and Department of Orthopaedics & Rehabilitation, Sahlgrenska Hospital (J.K.), Gothenburg, Sweden. Supported by competitive research funding from the Pirkanmaa Hospital District and by the Sigrid Juselius Foundation. Received September 13, 2009; accepted November 30, 2009. Address correspondence and reprint requests to Teppo L. N. Järvinen, M.D., Ph.D., Department of Surgery, University of Tampere, 33014 University of Tampere, Tampere, Finland. E-mail: [email protected] © 2010 by the Arthroscopy Association of North America 0749-8063/10/2605-9537$36.00/0 doi:10.1016/j.arthro.2009.11.023
published within the past decade. As such, anterior cruciate ligament (ACL) graft fixation is among the most investigated topics in recent sports medicine literature. The further backwards you are able to look, the further forward you are able to see. Winston Churchill
HOW DID ACL GRAFT FIXATION RESEARCH BEGIN? A plausible explanation for what initiated research on ACL graft fixation research would be that it represented an obvious clinical problem. However, this is not exactly the case. In reviewing the literature on the topic, a classic 1987 study by Kurosaka et al.1 can be identified as the first of the biomechanical studies on ACL graft fixation. They compared pullout strengths of bone–patellar tendon– bone (BPTB) grafts fixed
Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 26, No 5 (May), 2010: pp 681-684
681
682
T. L. N. JA¨RVINEN ET AL.
with a staple, sutures tied over buttons, or a titanium screw specifically designed for the interference fixation of the BPTB graft. On the basis of their experiments, they concluded that the fixation site is the weakest link of the reconstructed knee, a statement that has probably had the single most striking influence on the field in terms of generating further research. For example, the total number of studies reporting biomechanical testing of ACL graft fixations is now more than 200, and the original study by Kurosaka et al. has been cited in well over 300 articles. However, interest in ACL fixation was naturally not generated by just a single study, and at least 2 other landmark studies can be identified. Three years before the study by Kurosaka et al.,1 Noyes et al.2 began to set the stage with their biomechanical comparison of the strengths of various graft materials about the knee. They not only showed that the structural properties of BPTB graft per se were superior to soft-tissue grafts (fascia lata, single hamstring tendon, or multiple hamstring tendons) but also provided an estimation of the ACL in vivo loading during “normal activity.” In their experiments the mean strength of 5 young cadaveric ACLs tested in uniaxial tension was 1,730 N. By coupling this force value with a biological hypothesis that in nature, there existed a built-in safety margin of a 4-to-1 or 5-to-1 ratio of ultimate strength to in vivo force, the authors estimated that the loads developed on the ACL during normal activity were, on average, 445 N. They did not, however, characterize what normal activity actually represented, nor did they provide evidence of how their estimate was validated. Despite these 2 landmark studies, it still took another 5 years for ACL fixation research to explode. In the early 1990s the free-tendon soft-tissue grafts were making a strong emergence as an alternative for the BPTB graft. As with any new concept in medicine, the introduction of the use of free-tendon soft-tissue graft was associated with various problems, 1 of the most striking of which was the increase in postoperative anteroposterior knee laxity during healing. In 1993 Rodeo et al.3 published their classic canine study in which it was shown that at the 2-, 4-, and 8-week time periods, tendon grafts inserted into a proximal tibia failed by pullout of the tendon from the bone tunnel. These in vivo findings, coupled with the work of Kurosaka et al.,1 appeared to provide sufficient “proof” that the fixation site indeed was the weak link of the reconstructed knee in the early postoperative period. The mere temporal association between the first reports on increased knee laxity with the use of soft-tissue grafts and the previously noted experimental findings—particularly when
further “corroborated” by the first pullout studies reporting considerably lower ultimate failure load on soft-tissue fixations versus BPTB fixations1,4,5—were sufficient to convince the orthopaedic community at large that actual causality existed between soft-tissue graft fixation (slippage) and increased anterior translation of the tibia relative to the femur during healing. The concept of “graft slippage” has since been used as the rationale for virtually all recent ACL fixation studies. We measure things because we CAN. Accordingly, it is crucial to fully understand the context of one’s measurements. Anonymous
Even with the imminent risk of being misconstrued as contentious or using hindsight, one needs to critically evaluate the main conclusions, and particularly the interpretations, that have been made of the findings, of the landmark ACL studies of Noyes et al.2 and Kurosaka et al.1 To start with, we have a few remarks on the biomechanical study by Noyes et al., particularly on the validity of their estimate of 445 N for the in vivo loading of the ACL. By setting a single force value for ACL in vivo loading, the authors coupled the inherent human desire to set an exact threshold (single value) with the longstanding affinity of the orthopaedic research community for biomechanical testing. We believe that the extent to which this value (445 N) was approved by the field exemplifies how much such thresholds are desired and valued. However, an attempt to reduce such a complex issue as ACL in vivo loading to a single value unfortunately fails under scientific scrutiny. Even if a 1-to-4 or 1-to-5 safety margin indeed did exist for various properties of the human body, it is highly unlikely that the strength derived from such a simple testing configuration as ultimate uniaxial tensile testing would represent an appropriate property on which to base one’s calculations for the obviously complex and multidirectional in vivo loading of the ACL during locomotion. After all, Noyes et al. did point out in their article that the ACL has a complex fiber geometry in which different fiber lengths allow ligament function in different segments or portions of knee motion. Regarding the experiments of Rodeo et al.3 and their relevance to ACL reconstruction in humans, their most apparent limitation relates to the fact that in transplanting the long digital extensor tendon of a canine into a drill hole made in the proximal tibial metaphysis, the authors used a non–intra-articular experimental model of tendon-to-bone healing. More
ACL GRAFT FIXATION than 15 years after the publication of this classic study, we can now argue, based on strong experimental data from intra-articular models of soft-tissue ACL reconstruction,2,6-8 that the intra-articular portion of the replacement graft (rather than the graft–to– bone tunnel interface) is the weakest link of the ACL reconstruction even as early as 3 weeks,6 but at least at 6 to 9 weeks,7,8 postoperatively. Accordingly, if the fixation of the free-tendon soft-tissue graft indeed represented the weakest link of the ACL reconstruction during the immediate postoperative period, it seems that given the necrosis and remodeling of the graft, the structural integrity of the graft, rather than strength of fixation, becomes the rate-limiting factor in the allowance of more strenuous knee loading early in the rehabilitation. Naturally, the ultimate proof for the veracity of any concept in medicine has to be drawn from clinical studies. Thus the next plausible question is whether there are any data to either corroborate or refute the clinical relevance of the concept of “slippage of the ACL graft fixation.” To begin with, one needs to assess the validity of the proposals on the causality between the increased postoperative knee laxity and “graft slippage/fixation failure” of the free-tendon soft-tissue ACL reconstructions or, for that matter, bone-to-bone slippage in BPTB grafts. There is good clinical evidence showing that the bone blocks of the BPTB grafts do not migrate or at least migrate only marginally postoperatively.9 Despite the fact that the first randomized controlled trials between soft-tissue (single- or double-strand semitendinosus or gracilis tendon) and BPTB grafts showed increased anteroposterior knee laxity with the former graft type at 2-year follow up,10-12 the great majority of the more recent data with quadrupled hamstring grafts show that there is no evidence of increased laxity with these softtissue grafts.13-20 In fact, both soft tissue–reconstructed and BPTB-reconstructed knees display some increase in anteroposterior laxity over the early postoperative period, but the phenomenon is quite identical between the two. Most persuasively, the recent head-to-head comparisons of different soft-tissue fixation implants with vastly distinct biomechanical properties provide comparable clinical results at 2-year follow up.21,22 In the end, despite the enormous number of ACL reconstructions performed each year by surgeons with very different operative skills and experience, there are (to our knowledge) only 2 case reports of early, complete ACL fixation failures in the medical literature23,24 (in both studies the replacement graft was a BPTB, not a soft-tissue graft). For compar-
683
ison, an abundance of case reports of failed meniscal repairs have been published during the past 10 years. WHAT CAN BE LEARNED FROM ALL THIS? Some detrimental trends that are common in the current medical literature seem to have found their way into the area of ACL graft fixation. (1) Regarding publication bias, the concern about potential commercial bias has been raised recently in the field of arthroscopy and sports traumatology.25 In fact, similarly to recent reports on antidepressants,26,27 reports of a favorable outcome with a commercial product tested in a given study are in gross excess compared with negative findings among the studies published on ACL graft fixation. Not surprisingly, it turns out that a clear commercial agenda underlies a majority of published studies regarding ACL graft fixation. (2) Regarding methodologic deficiencies and selective use of references, there is no excuse for poor scientific practice, whether it be in the form of methodologic compromises or neglect of the “unpleasant” truth. Still, both of these approaches are very common in the field of ACL graft fixation. For example, the use of porcine bones is still the prevailing practice in ACL graft fixation studies despite the indisputable evidence against their suitability for that purpose.28 Arguments that this is “the common practice in the field” or that “cadaveric specimens are expensive and difficult to obtain” and the use of references to articles with flawed conclusions29 are equally condemnable attempts at justifying poor scientific practice. Why do we have no trouble reprimanding our children when they justify their bad deeds with the similar deeds of their peers while we fail to uphold such a level of morality in our own work? In conclusion, despite the massive commercially supported research interest in ACL soft-tissue graft fixation, virtually no evidence exists in support of our excessive concern over the failure of graft fixation implants. The subject of ACL graft fixation is actually an important example of the hierarchy of evidence of which we should be very wary when planning new studies in sports traumatology. Clinically important phenomena should be demonstrated through experiments with clear and sound clinical endpoints. As for preclinical studies, although they are indisputably helpful in the elaboration of such phenomena, serious hazards lie in declaring them a sufficient scientific basis for new research or, worse, for clinical standards of care. More importantly, no matter how sophisti-
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cated or fascinating their methodology, preclinical studies do not—whether we like it or not—relieve us from the necessity and duty of performing unbiased prospective, randomized controlled trials. REFERENCES 1. Kurosaka M, Yoshiya S, Andrish JT. A biomechanical comparison of different surgical techniques of graft fixation in anterior cruciate ligament reconstruction. Am J Sports Med 1987;15:225-229. 2. Noyes FR, Butler DL, Grood ES, Zernicke RF, Hefzy MS. Biomechanical analysis of human ligament grafts used in knee-ligament repairs and reconstructions. J Bone Joint Surg Am 1984;66:344-352. 3. Rodeo SA, Arnoczky SP, Torzilli PA, Hidaka C, Warren RF. Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog. J Bone Joint Surg Am 1993;75:17951803. 4. Robertson DB, Daniel DM, Biden E. Soft tissue fixation to bone. Am J Sports Med 1986;14:398-403. 5. Steiner ME, Hecker AT, Brown CH Jr, Hayes WC. Anterior cruciate ligament graft fixation. Comparison of hamstring and patellar tendon grafts. Am J Sports Med 1994;22:240-246, discussion 246-247. 6. Grana WA, Egle DM, Mahnken R, Goodhart CW. An analysis of autograft fixation after anterior cruciate ligament reconstruction in a rabbit model. Am J Sports Med 1994;22:344-351. 7. Weiler A, Hoffmann RF, Bail HJ, Rehm O, Sudkamp NP. Tendon healing in a bone tunnel. Part II: Histologic analysis after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep. Arthroscopy 2002;18:124-135. 8. Weiler A, Peine R, Pashmineh-Azar A, Abel C, Sudkamp NP, Hoffmann RF. Tendon healing in a bone tunnel. Part I: Biomechanical results after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep. Arthroscopy 2002;18:113-123. 9. Friden T, Ryd L, Lindstrand A. Laxity and graft fixation after reconstruction of the anterior cruciate ligament. A roentgen stereophotogrammetric analysis of 11 patients. Acta Orthop Scand 1992;63:80-84. 10. Anderson AF, Snyder RB, Lipscomb AB Jr. Anterior cruciate ligament reconstruction. A prospective randomized study of three surgical methods. Am J Sports Med 2001;29:272-279. 11. Beynnon BD, Johnson RJ, Fleming BC, et al. Anterior cruciate ligament replacement: Comparison of bone-patellar tendonbone grafts with two-strand hamstring grafts. A prospective, randomized study. J Bone Joint Surg Am 2002;84:1503-1513. 12. O’Neill DB. Arthroscopically assisted reconstruction of the anterior cruciate ligament. A prospective randomized analysis of three techniques. J Bone Joint Surg Am 1996;78:803-813. 13. Aglietti P, Giron F, Buzzi R, Biddau F, Sasso F. Anterior cruciate ligament reconstruction: Bone-patellar tendon-bone compared with double semitendinosus and gracilis tendon grafts. A prospective, randomized clinical trial. J Bone Joint Surg Am 2004;86:2143-2155. 14. Beard DJ, Anderson JL, Davies S, Price AJ, Dodd CA. Hamstrings vs. patella tendon for anterior cruciate ligament reconstruction: A randomised controlled trial. Knee 2001;8:45-50.
15. Ejerhed L, Kartus J, Sernert N, Kohler K, Karlsson J. Patellar tendon or semitendinosus tendon autografts for anterior cruciate ligament reconstruction? A prospective randomized study with a two-year follow-up. Am J Sports Med 2003;31:19-25. 16. Eriksson K, Anderberg P, Hamberg P, et al. A comparison of quadruple semitendinosus and patellar tendon grafts in reconstruction of the anterior cruciate ligament. J Bone Joint Surg Br 2001;83:348-354. 17. Jansson KA, Linko E, Sandelin J, Harilainen A. A prospective randomized study of patellar versus hamstring tendon autografts for anterior cruciate ligament reconstruction. Am J Sports Med 2003;31:12-18. 18. Laxdal G, Kartus J, Hansson L, Heidvall M, Ejerhed L, Karlsson J. A prospective randomized comparison of bone-patellar tendon-bone and hamstring grafts for anterior cruciate ligament reconstruction. Arthroscopy 2005;21:34-42. 19. Samuelsson K, Andersson D, Karlsson J. Treatment of anterior cruciate ligament injuries with special reference to graft type and surgical technique: an assessment of randomized controlled trials. Arthroscopy 2009;25:1139-1174. 20. Shaieb MD, Kan DM, Chang SK, Marumoto JM, Richardson AB. A prospective randomized comparison of patellar tendon versus semitendinosus and gracilis tendon autografts for anterior cruciate ligament reconstruction. Am J Sports Med 2002; 30:214-220. 21. Harilainen A, Sandelin J. A prospective comparison of 3 hamstring ACL fixation devices—Rigidfix, BioScrew, and Intrafix—Randomized into 4 groups with 2 years of follow-up. Am J Sports Med 2009;37:699-706. 22. Harilainen A, Sandelin J, Jansson KA. Cross-pin femoral fixation versus metal interference screw fixation in anterior cruciate ligament reconstruction with hamstring tendons: Results of a controlled prospective randomized study with 2-year follow-up. Arthroscopy 2005;21:25-33. 23. Cooper DE, Wilson TW. Clinical failure of tibial interference screw fixation after anterior cruciate ligament reconstruction. A report of two cases. Am J Sports Med 1996;24:693-697. 24. Doerr AL Jr, Cohn BT, Ruoff MJ, McInerney VK. A complication of interference screw fixation in anterior cruciate ligament reconstruction. Orthop Rev 1990;19:997-1000. 25. Lubowitz JH, Appleby D, Centeno JM, Woolf SK, Reid JB III. The relationship between the outcome of studies of autologous chondrocyte implantation and the presence of commercial funding. Am J Sports Med 2007;35:1809-1816 (published erratum appears in Am J Sports Med 2008;36:193). 26. Moreno SG, Sutton AJ, Turner EH, et al. Novel methods to deal with publication biases: Secondary analysis of antidepressant trials in the FDA trial registry database and related journal publications. BMJ 2009;339:b2981. 27. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008;358:252-260. 28. Nurmi JT, Sievanen H, Kannus P, Jarvinen M, Jarvinen TL. Porcine tibia is a poor substitute for human cadaver tibia for evaluating interference screw fixation. Am J Sports Med 2004; 32:765-771. 29. Nurmi JT, Jarvinen TL, Kannus P, Sievanen H, Toukosalo J, Jarvinen M. Compaction versus extraction drilling for fixation of the hamstring tendon graft in anterior cruciate ligament reconstruction. Am J Sports Med 2002;30:167-173.