PT Classroom - The Effects of Aspirin on Articular Cartilage ׀ by Chai Rasavong, MPT, MBA


Acetylsalicylic acid (ASA), commonly called aspirin, is a drug often used for the relief of pain and inflammation. It is a relatively inexpensive drug and is one of the most widely used peripherally acting analgesics in the world (1). In addition, ASA is often one of the major oral analgesics of choice for osteoarthritis (OA), a disease that is characterized by articular cartilage deterioration (1). In some other cases, however, additional research has indicated ASA might inhibit the synthesis materials required for the maintenance and repair of articular cartilage (AC). Although further research is required to warrant these findings one would now have to question the administration of ASA to individuals who have AC damage. The purpose of this review is to recognize and analyze the research that discusses the effects ASA has on AC.

Literature Review
Preliminary research in the past seems to support the use of ASA in the inhibition of cartilage deterioration. A study conducted by Simmons et al (2) showed that sodium salicylate (SS) was able to prevent a decrease in the viscosity of chondromucoprotein (CMP), a major macromolecular component of cartilage matrix. In their in vitro study 13 pairs of extracts of human AC were taken from three normal and nine patients with OA during surgery. These extracts were than homogenized in normal saline at 4 degrees C and centrifuged. After this process one half of each pair had SS added to them and all samples were than incubated with 1% CMP at pH 7 for 3 hours with frequent viscosity determinations. Results showed that the relative viscosity reduction of CMP was nearly always less in those mixtures containing SS (p<0.001). These are important findings, because in OA catabolic enzymes are often released that breakdown CMP which is needed for cartilage maintenance and growth (2). In interpreting these results one should realize that the CMP used was prepared from calf nasal cartilage which might not be similar enough to human CMP. In addition, it is left unclear from the article’s methods where the thirteenth pair of AC was obtained which makes one question if the authors were detailed enough in describing their study.

Similar results on the protective effects of ASA against degeneration of human AC was also found in a study conducted by Christman et al. (3). In this study the researchers hypothesized that salicylate can inhibit degradative enzymes in cartilage and allow for synthesis to catch up with degeneration. For this study they utilized individuals with recurrent lateral dislocations of the patella who are receiving surgical correction after the second or third occurrence. After the dislocation and 6-8 weeks before surgery the individuals were randomly divided into two groups with the individuals in one group instructed to take 3g of Bayer’s aspirin a day, everyday, before the surgery, while the individuals in the other group received no such instruction. During the surgical procedures the researchers were allowed to inspect the cartilage surface of the patella and rate it by the grading system developed by Bentley, which was not described in the article. The results of the study showed that of the 23 knees in the control group, only two showed no evidence for chondromalacia. Strongly contrasting with this, of the aspirin-treated group of 16 knees, 13 knees showed no signs of chondromalacia. Although the authors obtained significant statistical results, they did caution that a strict double blind study should have been implemented to increase reliability and validity. Other factors that the authors failed to mention that could have also affected the reliability and validity of the study was the adherence of taking the aspirin by the experimental group and the control of extraneous variables for both groups such as the amount of nutrition or rest each individual received. The number and severity of dislocations for each person could have affected the results as well.

A study by Roach et al (4) further supports the previously mentioned studies on the positive effects ASA has on the degradation of cartilage. In this study the authors compared the effects of steroid, ASA and SS on AC. Rabbit knee joints were compressed to produce cartilage degeneration in control and test animals who received intramuscular injections of prednisolone and ASA or SS by gavage, a technique of force feeding by a flexible tube and a force pump. The animals were then sacrificed after three weeks of compression and their AC was analyzed grossly and histologically. Similar to Simmons et al (2) and Christman et al (3), Roach et al. found from the gross and histological specimens from salicylate-treated rabbits that there was less degenerative changes compared to the control group and the steroid group.

Although the above studies have found positive results in the use of ASA for the protection of AC from degradation, other research warns of the use of ASA, because it could inhibit matrix components synthesis. In two such studies that were conducted by Henrotin et al (5) and Bassleer et al (6), chondrocytes from human femoral heads were cultivated in a three-dimensional culture which allowed chondrocytes to conserve their phenotype and produce matrix articular components such as type II collagen and proteoglycans (PG). NSAIDS which included etodolac and ASA were than added to the assays and incubated for 12 days for the Henrotin et al (5) study while NSAIDS which included tiaprofenic acid and ASA were added to the assays and incubated for 20 days for the Bassleer et al (6) study. In both studies radioimmunoassay were created so that the organic matrix could be examined. From the examination of these assays both studies concluded that PG synthesis was significantly decreased by ASA treatment while it was relatively not effected by etodolac or tiaprofenic acid. Both studies also found that neither ASA, etodolac, and tiaprofenic acid modified type-II collagen production, nor were they potent inhibitors of prostaglandins. These findings are important in AC management because we know PG and type II collagen help protect against high levels of stress and strain that could result from interfacial and fatigue wear.

Another study that supports the theory and identifies the source of how ASA suppresses cartilage PG synthesis was conducted by Hugenberg et al (7). In this study the researchers looked in depth at the effects of SS, ASA, and ibuprofen on enzymes required by chondrocytes for synthesis of chondroitin sulfate, the major glycosaminoglycan (GAG) constituent of cartilage PG. The enzymes looked at included UDP-glucose dehydrogenase (UDP-GD), glutamide-fructose-6-phosphate-aminotransferase (GFAT), and glucuronosyltransferase (GT). These enzymes were combined in assays with SS, ASA, and ibuprofen separately. At the end of the incubation for each case, enzymatic activity was then measured spectrophotometrically. The results showed that neither UDP-GD nor GFAT were inhibited by concentrations of SS, ASA, or ibuprofen. However, the results did show that GT activity was inhibited by SS, and ASA but not by ibuprofen. Therefore, the authors drew the conclusion that salicylates may suppress cartilage PG synthesis by inhibiting GT, a similar theme to findings of Henrotin et al (5) and Bassleer et al (6).

Similar results can again be drawn from another study conducted by Manicourt et al (8). Rather than focusing on enzyme inhibition, this study was directed at looking at the effects on the NSAIDs tenoxican and ASA on the metabolism of PG and hyaluronan (HA) in normal and osteoarthritic human AC. It should be noted that both PGs and HAs help provide articular tissue with its elasticity and stiffness in compression. Therefore, any decrease in the tissue concentration of PGs and HAs, as occurs in OA, compromises the functional properties of cartilage (8). In this study, cartilage was sampled from the medial femoral condyle of 30 subjects 24 hours postmortem. Of the 30 subjects, 10 had severe OA, 10 had moderate OA, and the other 10 had no signs of OA. Ninety cultures were made with 3 cultures from the cartilage of each individual. Tenoxicam and ASA were added to each individual’s culture while one culture remained the control. Results showed that ASA may produce OA-like changes in normal cartilage and is likely to worsen the disease process in OA tissue. With tenoxicam, however, results showed that it may reduce the HA content of normal cartilage, and in doing so may produce OA-like lesions, but this drug should not per se accelerate joint failure in OA. This is because tenoxicam uncouples HA synthesis from the loss of HA and produces a positive balance in HA metabolism (8).

From the review of literature we realize that ASA can have both a positive and negative effect on AC. The studies by Simmons et al (2), Chrisman et al (3), and Roach et al (4) all seem to conclude that ASA helps to prevent further deterioration of AC whether it be through the maintenance of chondromucoprotein or the inhibition of degradative enzymes present in damaged cartilage. These studies are advantageous because they were in vivo studies which are more practical than in vitro studies which simply treat samples outside the body with drugs and can not account for the many natural processes that could be occurring within the body. However, in the other studies conducted by Henrotin et al (5), Bassleer et al (6), Hugenberg et al (7) and Manicourt et al (8), an opposing view on the beneficial use of ASA exists. In these studies these researchers all drew the same conclusion that ASA suppresses PG synthesis and impairs the ability of the chondrocyte to repair its extracellular matrix. They also concluded that an inhibition of type II collagen production is not attributed to ASA and that the role of ASA as a potent inhibitor of prostaglandins is accurate. In addition, the study by Manicourt et al (8) also concluded that ASA can affect normal cartilage as well by reducing PG and HA synthesis. Unlike the first three studies, these four studies were conducted in vitro and can simply not mimic the environment, condition, and other factors that an in vivo study could obtain. The use of many different chemicals and procedures in creating the assays and cultures differ too greatly within each study and could even bias the results as well.

Physical therapists work with many patients with many different injuries, including injury to articular cartilage. With these injuries, patients often take medications such as ASA to relieve pain and inflammation. From the knowledge gained from the review of literature on the effects of ASA on AC we realize that there could be tradeoffs for using ASA, but more comprehensive research should be conducted and is warranted to further clarify the risks and benefits associated with the utilization of aspirin. Nevertheless, other treatment options are available to the patient in physical therapy which could contribute in not only improving function but decreasing pain as well.

Last revised: July 5, 2010
by Chai Rasavong, MPT, MBA


1) Dipiro J, et al. Pharmacotherapy: A Pathophysiologic Approach. Connecticut: Appleton and Lange. 1993;1745.
2) Simmons D, et al. Salicylate Inhibition of Cartilage Degeneration. Arthritis and Rheumatism. 1965;8:960-969.
3) Chrisman O, et al. The Positive Effect of Aspirin Against Degeneration of Human Articular Cartilage. Clinical Orthopaedics & Related Research. 1972;84:193-196.
4) Roach J, et al. Comparison of the Effects of Steriod, Aspirin, and Sodium Salicylate on Articular Cartilage. Clinical Orthopaedics & Related Research. 1975;106:350-356.
5) Henrotin Y, et al. In Vitro Effects of Etodolac and Acetysalicylic Acid on Human Chondrocyte Matabolism. Agents Actions. 1992;36:317-323.
6) Bassleer C, et al. Effects of Tiaprofenic Acid and Acetylsalicylic Acid on Human Articular Chondrocytes in 3-Dimensional Culture. The Journal of Rheumatology. 1993;20:1433-1438.
7) Hugenberg s, et al. Effect of Sodium Salicylate, Aspirin, and Ibuprofen on Enzymes Required by the Chondrocyte for synthesis of Chondroitin Sulfate. The Journal of Rheumatology. 1993;20:2128-2133.
8) Manicourt D, et al. Effects of Tenoxicam and Aspirin on the Metabolism of Proteoglycans and Hyaluronan in Normal and Osteoarthritic Human Articular Cartilage. British Journal of Pharmacology. 1994;113:1113-1120.

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