How does the knee age after ACL-surgery? The image is CC by Thomas Mues.

Nordenvall et al. [1] recently report in PLOS ONE an interesting study on cruciate ligament (CL) injuries where they could not find any protective effect on knee osteoarthritis (OA) from reconstructive surgery. It is a nation-wide study based on > 60,000 patients where they used the National Swedish Patient Register in order to find ICD-codes and surgical procedures code to identify patients with CL injury and those with a subsequent procedure. While the early results showed slightly less OA, there was an increased risk of 1.4 (95% confidence interval, 1.2 to 1.7) after > 10 years for those with surgery.

This finding is controversial in the orthopaedic community, there are plenty making the case for anterior cruciate ligament (ACL)-reconstructions being protective of later OA [2]. Some of the arguments have been that meniscal injuries are shown to increase risk of OA [3] and an intact ACL prevents further re-tears. This logic has always seemed strange to me as there has been little evidence for ACL to show any OA preventive capacity [4], [5] and as Wen and Lohmander point out there is plenty that we don’t know yet [6].

One of the areas that have interested me is the inflammatory response to the injured knee. There are several biomarkers currently being investigated [7] and there is an interesting case being made for the complement pathway being the bad guy. I find it intriguing that surgery/trauma could trigger an inflammatory response that causes the OA: (1) Can we stop the process early on? (2) Do different techniques elicit different biomarker response?

Study notes

A few things can of course be said about Nordenvall et al.’s study:

• “Knee abusers” are individuals with high-activity/risk behavior are more likely to injure their knee. Due to their high-activity they are also more likely to go through with ACL-reconstruction, a form of self-selection bias.
• Laterality is a problem in these studies. It is hard to believe that there is no left-right within the current ICD-system, but unfortunately this is the case. It is possible that patients with bilateral ACL injuries, or patients with contralateral meniscal injury correspond to a more severe trauma group, and that the surgery is simply an indicator of trauma severity.
• Time dependent cox regressions – there is obviously a change in how the ACL impacts the risk over time. The correct way to model this is to have a time-dependent variable. This would provide more precise estimates and allow for a pretty graph.
• Exposure time – early, in-between, and late reconstruction can be misleading, and there is a risk of immortal time bias. If we pose the hypothesis that the surgery triggers an immune response there may be interesting to have a variable indicating time without surgery and time after surgery. Granted this may be somewhat complicated, but right now the results indicate that late reconstruction is less risky. This could be an effect of less time for the post-surgical inflammation to impact the cartilage.

Summary

My belief is that you should have surgery if you experience symptoms (the title is a little provocative, I know 😉 ). I believe that this study supports this more restrictive approach to ACL-surgery – although I truly hope that some brilliant researcher looks into their old archives, dig up good RCT-studies, and looks at long-term results. There have been many RCTs reporting short-term outcomes, this shouldn’t be that difficult… one would think…

1. R. Nordenvall, S. Bahmanyar, J. Adami, V. M. Mattila, och L. Felländer-Tsai, “Cruciate Ligament Reconstruction and Risk of Knee Osteoarthritis: The Association between Cruciate Ligament Injury and Post-Traumatic Osteoarthritis. A Population Based Nationwide Study in Sweden, 1987–2009”, PLoS ONE, vol 9, num 8, s e104681, aug 2014.
2. P. N. Chalmers, N. A. Mall, M. Moric, S. L. Sherman, G. P. Paletta, B. J. Cole, och J., Bernard R. Bach, “Does ACL Reconstruction Alter Natural History?A Systematic Literature Review of Long-Term Outcomes”, J. Bone Jt. Surg., vol 96, num 4, ss 292–300, feb 2014.
3. M. Englund, E. M. Roos, och L. S. Lohmander, “Impact of type of meniscal tear on radiographic and symptomatic knee osteoarthritis: a sixteen-year followup of meniscectomy with matched controls”, Arthritis Rheum., vol 48, num 8, ss 2178–2187, aug 2003.
4. A. G. Sutherland, K. Cooper, L. A. Alexander, M. Nicol, F. W. Smith, och T. R. Scotland, “The long-term functional and radiological outcome after open reconstruction of the anterior cruciate ligament”, J Bone Jt. Surg Br, vol 92-B, num 8, ss 1096–1099, aug 2010.
5. M. A. Kessler, H. Behrend, S. Henz, G. Stutz, A. Rukavina, och M. S. Kuster, “Function, osteoarthritis and activity after ACL-rupture: 11 years follow-up results of conservative versus reconstructive treatment”, Knee Surg. Sports Traumatol. Arthrosc., vol 16, num 5, ss 442–448, maj 2008.
6. C. Wen och L. S. Lohmander, “Osteoarthritis: Does post-injury ACL reconstruction prevent future OA?”, Nat. Rev. Rheumatol., vol 10, num 10, ss 577–578, okt 2014.
7. S. Y. Ritter, R. Subbaiah, G. Bebek, J. Crish, C. R. Scanzello, B. Krastins, D. Sarracino, M. F. Lopez, M. K. Crow, T. Aigner, M. B. Goldring, S. R. Goldring, D. M. Lee, R. Gobezie, och A. O. Aliprantis, “Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues”, Arthritis Rheum., vol 65, num 4, ss 981–992, apr 2013.