As Goes the Meniscus Goes the Knee





The meniscus plays an important, complex role in maintaining the homeostasis and health of the knee. Meniscal tears are a risk factor for early chondral injury and eventually knee osteoarthritis. There is a growing body of evidence about the early biological changes associated with meniscal injury that likely start the process of joint degeneration. This review highlights the basic science, translational and clinical studies of the detrimental effects of meniscal injury and deficiency on the biology of the knee.


Key points








  • Meniscal injury has a negative effect on the biology of the knee within a very short period of time.



  • In patients with meniscus injuries, degenerative changes of the articular cartilage become apparent within a decade.



  • Over the long run, meniscal injury and deficiency increases the likelihood of severe osteoarthritis necessitating total knee arthroplasty, and these patients undergo total knee arthroplasty at a younger age compared with patients with an intact meniscus.




Introduction


Historically, the meniscus was thought of as vestigial remnant, with relatively little importance for the knee joint. In the mid-twentieth century, injuries to the meniscus were often treated with surgical resection of the entire meniscus. Later, intermediate and long-term follow-up studies demonstrated a high rate of osteoarthritis in these patients, suggesting the meniscus did have an important role in the knee. Subsequent studies have demonstrated that the meniscus plays an important, complex role in maintaining the homeostasis and health of the entire knee. Meniscal injury and deficiency can have a significant negative impact on knee mechanics and biology, often initiating a turn toward joint degeneration and ultimately knee osteoarthritis (OA).


The impact of meniscal injury on the biomechanics of the knee is well established. The purpose of this review is to highlight the basic science, translational and clinical studies emphasizing the detrimental effects of meniscal injury and deficiency on the biology of the knee. One important distinction is that this review focuses on meniscus tears rather than intrasubstance degeneration, which may be a distinct pathologic state as a precursor to further changes or an “incidental” finding with little or no clinical relevance.


Meniscal biology


The biology of the injured meniscus has been shown to be affected by several variables. Meniscal tears have traditionally been classified as traumatic, associated with longitudinal, bucket handle and radial patterns; or degenerative, associated with transverse, flap, and complex patterns. The cellularity of the injured meniscus is negatively affected by older age, more time from injury, and degenerative and radial tear types. A recent study demonstrated differential gene expression between traumatic and degenerative meniscus tears with higher expression of chemokines and matrix metalloproteinases (MMPs) and lower expression of COL1A1 in traumatic tears. Patient age seems to play an important role on the biological response of the meniscus to injury, whereas the relative significance of the other factors are unknown. Although degenerative tears have been associated with more diffuse and severe knee pathology, a recent review concluded that there is a lack of data on how tear morphology relates to OA both cross-sectionally and longitudinally.


Early changes


A meniscus tear can affect the knee within a couple of years. A study by Biswal and colleagues reviewed baseline and follow-up MRIs comparing patients with meniscus tears with those with intact menisci at a mean follow-up of 1.8 years. They found that patients with meniscal tears had a higher average rate of progression of cartilage loss than those with intact menisci (22% vs 14.9% progression of cartilage loss). They concluded that meniscal tears tended to accelerate the natural course of cartilage loss. It has been previously demonstrated that meniscal abnormalities alter articular forces and ultimately lead to enhanced chondromalacia.


It is known that injury to the meniscus, as well as subsequent surgery, is associated with an increased risk for OA. In a study by Rangger and colleagues, at an average follow-up of 4.5 years, degenerative changes were reported in 38% of patients after arthroscopic partial medial meniscectomy and in 24% of patients after arthroscopic partial lateral meniscectomy. The relationship between meniscal injury and development of chondral injury and OA has also been studied in a young cohort of National Football League (NFL) athletes. In a study by Nepple and colleagues, a large group of largely asymptomatic elite football players at the NFL combined with a mean age of 22.7 years underwent an MRI. It was found that a previous partial meniscectomy was associated with full-thickness cartilage lesions. It was also found that partial meniscectomies in the lateral compartment were associated with a higher rate of articular cartilage defects in the respective compartment (25%) compared with medial meniscectomies, suggesting that the lateral compartment may be more predisposed to chondral damage after partial meniscectomy. A separate analysis of the same NFL cohort demonstrated that meniscal surgery is also associated with an increased rate of knee OA in these athletes. This follow-up study looked at early evidence for OA rather than full-thickness cartilage defects. The rate of early OA after medial and lateral partial meniscectomies was similar between the 2 compartments (26% and 24% respectively), suggesting that meniscectomy in the medial compartment may be more likely to lead to OA than full-thickness cartilage defects. A case-control study showed that a history of a partial meniscectomy in elite college athletes is associated with a shorter career in professional football.


In a systematic review by Salata and colleagues, there was a significant increase in the development of OA with preexisting chondral damage. In addition, studies have reported worse patient outcomes after meniscectomy in patients with preexisting chondral damage. Another study examining patient-reported outcomes measurement information system (PROMIS) scores in the early postoperative period after partial meniscectomy found that patients with high-grade articular cartilage lesions did not have as much clinical improvement at 6 weeks post-op as measured by PROMIS physical function and pain interference as those with no or low-grade articular lesions. A study by Hunter and colleagues evaluated baseline and follow-up MRIs of patients with OA and determined that a substantial portion of the variance in joint space narrowing was associated with the position and degeneration of the meniscus. A study of the same cohort demonstrated that meniscal malposition and damage was associated with increased risk of cartilage loss; overall in this study each aspect of meniscal abnormality had a major effect on cartilage loss.


The association of meniscal injury in the setting of anterior cruciate ligament (ACL) reconstruction has been well studied. In a Multicenter ACL Revision Study (MARS) cohort of 725 knees undergoing revision ACL reconstruction, it was found that knees that had undergone previous partial meniscectomy were significantly more likely to have chondrosis than knees with previous meniscal repair or no history of meniscal surgery. The study concludes that at the time of ACL reconstruction it is preferable if possible to repair the meniscus when meniscal pathology is encountered. A 2016 study of the same cohort showed that previous medial and lateral meniscal pathology and treatment were found to be significantly associated with poorer patient reported outcomes at 2-year follow-up following revision ACL reconstruction. A study by Westermann in 2017 of the multicenter orthopedic outcomes (MOON) cohort, which evaluated outcomes 2 years after ACL reconstruction associated with meniscus surgery, showed that medial meniscectomy was associated with worse patient-reported outcomes and the greatest degree of joint space narrowing after surgery. Finally, in an MARS cohort of patients undergoing revision ACL reconstruction it was found that patients with intact meniscus had a 64% to 84% decrease odds of having chondrosis compared with those with meniscal injury. A study by Michalitsis and colleagues examining the articular cartilage 2 years after arthroscopic ACL reconstruction with MRI showed that patients who underwent medial meniscus surgery at the time of ACL reconstruction were found to have statically significant deterioration of cartilage lesions in the lateral and medial femoral condyles. A similar study by Li and colleagues found that at follow-up times ranging from 2 to 4.2 years ACL-associated meniscus injury treated with either partial meniscectomy or repair was associated with significantly higher T2 scores on MRI, which suggests cartilage degeneration.


Recent studies have also examined the biological impact of meniscal injury on synovial fluid and articular cartilage. One study demonstrated elevated MMP activity and prostaglandin E2 (PGE2) in the synovial fluid of patients with meniscus tears. These biomarkers are proinflammatory and may play a role in joint degeneration. MMP and PGE2 were found to be elevated nearly 25- and 290-fold in knees with meniscus tears compared with controls. Specifically, levels of MMP-2, MMP-3, sulfate glycosaminoglycan (sGAG), cartilage oligomeric matrix protein, interleukin 6 (IL-6), and PGE2 were higher in the synovial fluid than in the serum of the meniscus patients in this cohort. Complex meniscus tears were associated with higher levels of MMP-10 and lower levels of serum tumor necrosis factor alpha (TNF-α) and IL-8 compared with other tear patterns. A previous study from the same group demonstrated that total MMP activity in synovial fluid is positively correlated with increased cartilage strain at maximum knee flexion in patients with meniscus tears, suggesting the MMP levels are a biological marker for the mechanical effects of the meniscus tear on the joint. These markers are likely poor prognostic indicators both in terms of the healing potential of the injured meniscus as well as the initiation of changes that lead to the development of OA. Another study demonstrated elevated synovial fluid cytokines IL-1, IL-8, and TNF-α consistent with a proinflammatory state that last for several months following meniscal injury. Although these levels would likely contribute to the initiation and acceleration of degenerative change in the articular cartilage, this study did not find any association between the level of synovial fluid cytokines and the degree of chondral damage in the knee at the time of meniscectomy.


In contrast to the finding with regard to synovial fluid, there is some evidence for an association between gene expression in meniscus tears and the condition of the articular cartilage at the time of partial meniscectomy surgery. In one study, the torn menisci from knees with early degenerative changes on radiograph demonstrated higher expression of resistin compared with knees without any degenerative change. A couple of studies have demonstrated negative effects of resistin on the meniscus. Resistin has been shown to stimulate rapid and extensive catabolism of meniscus tissue, similar to IL-1, but not of articular cartilage. Another study demonstrated that resistin had the most significant negative effect out of several tested adipokines on the meniscus, inducing sGAG release and depleting sGAG content.


A study by Rai and colleagues demonstrated that macroscopically normal articular cartilage of patients undergoing partial meniscectomy demonstrated distinct patterns of gene expression exhibiting molecular signatures that reflect OA. Patients could be segregated by genetic risk alleles or by OA-associated gene transcripts, both of which identified subsets of patients with biological evidence for OA in the absence of macroscopic cartilage changes. The presence of a meniscus tear has been shown to alter the gene expression in ACL tear remnants. The combined injury pattern modulates genes and pathways that reflect a diminished healing capacity and elevated neurogenic signal compared with isolated ACL tears, demonstrating yet another biological effect of the injured meniscus on the rest of the knee.


Late changes


The natural history of meniscal injury eventually leads to late changes of OA. A study by Roos and colleagues established that open meniscectomy results in a high prevalence of OA at 21-year follow-up with a 14-fold increased risk for developing OA compared with age- and sex-matched controls. It has been shown that there is an inverse relationship between function of the knee and the amount of meniscal tissue resected. In a long-term follow-up study, 80% of knees demonstrated degenerative changes in patients who had undergone a partial lateral meniscectomy at a follow-up of 12.3 years. A study by Lohmander and colleagues showed that after meniscectomy about 50% of patients developed OA within 10 to 20 years. A study by Englund and Lohmander examined a cohort of 317 patients who had undergone a meniscal resection 15 to 22 years previously and determined that risk factors for progression of OA after meniscal injury was similar to risk factors for OA overall, including obesity, female gender, and preexisting early stage OA. They also found that after meniscectomy there was an increased risk of OA in patients with a body mass index of greater than 30 kg/m 2 . A 2017 meta-analysis demonstrated a 3.54-fold increase risk factor for developing OA after ACL reconstruction in patients who underwent partial meniscectomy compared with patients who did not. A systematic review by Paxton and colleagues showed that at long-term clinical follow-up meniscal injury treated with meniscal repair was associated with higher Lysholm scores and less radiographic deterioration than partial meniscectomies. However, at both short- and long-term follow-up, partial meniscectomies had a lower reoperation rate than meniscal repair.


Recent studies have shown an association between meniscal surgery and total knee arthroplasty (TKA). A 2014 study examining prevalence of TKA after previous knee surgery showed that after meniscectomy, men and women underwent TKA, 9.6 and 8.2 years younger, respectively, than patients without any history of knee surgery. After meniscectomy, patients underwent a TKA at an average interval of 12.6 years after meniscectomy. In addition, as many as 14% of patients underwent TKA within 1 year after meniscectomy. A matched case-control study of all TKAs in the United Kingdom from 1990 to 2011 by Khan and colleagues showed that patients with previous meniscal injury underwent TKA at 65.08 years compared with controls who underwent arthroplasty at 70.83 years. The adjusted odds ratio of TKA after a meniscal injury compared with patients without meniscal injury was 15.24.


Summary


Meniscal tears are known to be associated with a higher risk for knee OA. There is a growing body of evidence regarding the early biological changes associated with meniscal injury strongly implicating it as a cause of joint degeneration. Similarly, there are more studies demonstrating the intermediate and long-term clinical sequelae of meniscal injury in terms of chondral damage and ultimately OA.




References

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Aug 15, 2020 | Posted by in SPORT MEDICINE | Comments Off on As Goes the Meniscus Goes the Knee
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