Anterior cruciate ligament (ACL) injuries remain among the most feared and dreaded injuries an athlete can experience. Once known as a career ender among professional athletes and amateurs alike, ACL injuries often require somewhat lengthy periods of rehabilitation that commonly result in persistent weakness and muscle atrophy of the quadriceps muscles (quads) even after the athlete undergoes reconstruction surgery (ACL-R). In fact, there are several different studies suggesting that a 20% or more muscle weakness in the affected quadriceps may nag athletes after their surgeries for months to years. One of the most unfortunate aspects of this post-operative muscle weakness is that it not only delays an athlete’s return to sport and full-recovery, but it seems that it doesn’t matter which kind of ACL graft we attempt to use during reconstruction (patellar or hamstring autographs (from the patient’s own body) and allographs (cadaveric)), the weakness still seems to develop and persist in the post-operative period.
So besides delaying one’s return to sport, why is this such a big problem, medically speaking? Well, the answer to that question is several-fold. To begin with, the weakness that may persist post-repair not only predisposes an athlete to subsequent future injuries because it may change an athlete’s proprioception and knee mechanics/kinematics, but it has also been proposed that this change in knee mechanics may be one of the causal mechanisms in the development of osteoarthritis of the knee that many ACL-R patients seem to suffer from years down the road.
While the exact mechanism resulting in the persistent muscle atrophy/loss suffered after ACL-R is not fully understood, there are several hypotheses that have currently been proposed. Some readers may remember a piece I wrote regarding mouse ACLs and the inhibition inflammatory markers being studied to possibly reduce osteoarthritis. Though this is one thought, other researchers have pursued a slightly different thought process.
In a recent June 2013 paper published in the American Journal of Sports Medicine, Mendias et al. examined the role of a muscle growth signaling molecule called myostatin (GDF-8) as a possible explanation for the muscle loss and atrophy seen after ACL-R. It has been well documented that the role of myostatin in the body is to regulate muscle atrophy and limit muscle growth during development and repair. It can be thought of as a genetic brake so that we don’t all end up with out of control muscle growth. Furthermore, myostatin is a member of the TGF-B family of proteins which were previously touched upon in another article regarding the possible inflammatory mechanism that may lead to osteoarthritis after an ACL tear.
The researchers believed that they would see immediate and marked increases in both myostatin and TGF-B after ACL-R, which would remain elevated during the early post-operative period. In addition to these signaling molecules, several other atrophy-inducing signaling molecules were also measured (CCL2, CCL3, CCL4, CCL5, IL-1a, IL-1b, IL-1ra as well as IL-6 and TNF-a which were the cytokines of interest in the previous article I wrote).
The study examined 18 patients at the University of Michigan Medical School between the ages of 16-55 who had experienced a non-contact, athletic injury resulting in unilateral complete ACL tear. Each patient was required to participate in pre-operative rehabilitation to improve range of motion (ROM) for 6-8 weeks prior to their surgeries.
The researchers then evaluated each patient one-week prior to their surgery for a preoperative evaluation of knee strength and an assessment of subjective and objective knee functioning (IKDC and SF-12 surveys). Furthermore, blood was drawn pre-operatively as well for measurements of the various signaling markers that were previously described.
The patients then followed up 3 days post-operatively, and then at 2 weeks, 5 weeks, 12 weeks, 18 weeks and 26 weeks post-operatively in order to obtain measurements of strength and blood/cytokine markers. The patients underwent standardized, accelerated rehabilitation programs after their first post-operative clinic visit and were allowed to participate in full activities after their sixth post-operative visit.
The results of the study indicated that both myostatin and TGF-B significantly increased during the early post-operative period. Furthermore, they indicated that the patients perception of their knee strength and recovery were a bit premature based upon objective measurements of strength comparing the injured side to the non-injured side.
What was limited in this study is that, despite the fact that they were able to show the increases in myostatin and TGF-B in the immediate post-operative period, this does not necessarily show a cause and effect relationship. Furthermore, several of the other cytokines that were previously mentioned were not shown to change much in the plasma samples that were analyzed. Another limitation was the fact that muscle atrophy was not directly measured; that is to say that they were unable to measure muscle volume in the pre-operative and post-operative periods, which could have helped display the extent of atrophy and a possible connection between the level of myostatin and the subsequent extent of the muscle atrophy.
Despite the limitations of the study, this offers a somewhat promising advance in possibly helping to elicit the likely multi-factorial cause of muscle atrophy after ACL-R. Though it may appear as if no clear cause and effect could be documented, the fact that the myostatin and TGF-B demonstrated the expected changes allows us to further pursue possibly examining the effects of blocking such cytokines in an animal model which may lead to further investigation in humans if success is documented in preventing atrophy.
With around 250,000 ACL tears per year in the USA alone, it’s no surprise that reducing long-term morbidity such as muscle weakness and osteoarthritis would be something essential to help ameliorate and completely eliminate. Furthermore, as our procedures get less invasive and more personalized, it is the goal of every sports medicine specialist to try to reduce recovery time and get athletes back to their previous level of performance, if not better.
Hopefully, we will see more advances in the post-operative management of muscle atrophy and weakness in the near future. This study along with several other ongoing efforts show that we are likely heading in the right direction. As with all good science, proper analysis and attention to details takes some time, but recognizing a problem and documenting associated mechanisms is half the battle. Let’s be cautiously excited at what the near future may hold for any athlete suffering from an ACL tear.
Please feel free to leave me any comments, feedback, concerns, or insight on this page or email me at firstname.lastname@example.org Also, if you like what you’ve read subscribe to the feed to get my articles sent directly to your inbox!
1. Boden BP, Torg JS, Knowles SB, Hewett TE. Video analysis of anterior cruciate ligament injury: Abnormalities in hip and ankle kinematics. Am J Sports Med 2009;37(2):252-259.
2. Flemming BC, Hulstyn MJ, Oksendahl HL, Fadale PD. Ligament injury, reconstruction, and osteoarthritis. Curr Opin Orthop 2005;16:354-62.
3. Gelber AC, Hochberg MC, Mead LA, Wang NY Wigley FM, Klag MJ. Joint injury in young adults and risk for subsequent knee and hip osteoarthritis. Ann Intern Med 2000;133:321-8.
4. Mendias CL, Lynch EB, Davis ME, Sibilsky Enselman ER, Harning JA, DeWolf PD, Makki TA, Bedi A. Changes in circulating biomarkers of muscle atrophy, inflammation and cartilage turnover in patients undergoing anterior cruciate ligament reconstruction and rehabilitation. Am J Sports Med. 2013; 20(10): 1-8.
5. Murton AJ, Greenhaff PL. Physiological control of muscle mass in humans during resistance exercise, disuse and rehabilitation. Curr Opin Clin Nutr Metab Care. 2010;13(3):249-254.