In Vitro Chondrotoxicity of Nonsteroidal Anti-inflammatory Drugs and Opioid Medications

Abrams, Geoffrey D.; Chang, Wenteh; Dragoo, Jason L.

doi:10.1177/0363546517724423

Cited by 24 publications

(18 citation statements)

References 58 publications

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“…Ketorolac increased inflammation and cartilage degradation in an experimental assay in rats, 29 and chondrocyte cell death in vitro. 30 Our observations (in vitro and in vivo) did not support COX-independent anti-inflammatory local effects of ketorolac on synovial cells, and probably local infiltration is of limited value.…”

Section: Discussioncontrasting

confidence: 76%

Randomized controlled trial of intra‐articular ketorolac on pain and inflammation after minor arthroscopic knee surgery

Solheim

Gregersen

Halvorsen

et al. 2018

Acta Anaesthesiol Scand

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Section: Discussioncontrasting

confidence: 76%

Randomized controlled trial of intra‐articular ketorolac on pain and inflammation after minor arthroscopic knee surgery

Solheim

Gregersen

Halvorsen

et al. 2018

Acta Anaesthesiol Scand

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“…Moreover, a higher mortality rate among KOA patients receiving tramadol for pain control has been reported [ 12 – 14 ]. In addition to known systemic adverse effects, chondrotoxicity of meperidine has been shown in cartilage specimens ex vivo [ 15 ]. Furthermore, a randomized trial that assessed treatment-related effects of opioids and non-steroidal anti-inflammatory drugs reported an association between the use of transdermal fentanyl and radiographic KOA progression over 12 weeks [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition to known systemic adverse effects, chondrotoxicity of meperidine has been shown in cartilage specimens ex vivo [ 15 ]. Furthermore, a randomized trial that assessed treatment-related effects of opioids and non-steroidal anti-inflammatory drugs reported an association between the use of transdermal fentanyl and radiographic KOA progression over 12 weeks [ 15 , 16 ]. However, most previous studies suffer from a low external validity, adherent to in vitro designs, and the aforementioned in-patient trial used radiographs to measure outcomes, which have been shown to be inferior to magnetic resonance (MR) imaging, in particular in early stages of the degenerative disease [ 17 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

Opioid users show worse baseline knee osteoarthritis and faster progression of degenerative changes: a retrospective case-control study based on data from the Osteoarthritis Initiative (OAI)

et al. 2021

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Background Opioids are frequently prescribed for pain control in knee osteoarthritis patients, despite recommendations by current guidelines. Previous studies have investigated the chondrotoxicity of different opioid subtypes. However, the impact opioids may have on progression of osteoarthritis in vivo remains unknown. The aim of this study was thus to describe the associations between opioid use and knee structural changes and clinical outcomes, over 4 years. Methods Participants with baseline opioid use (n=181) and who continued use for ≥1 year between baseline and 4-year follow-up (n=79) were included from the Osteoarthritis Initiative cohort and frequency matched with non-users (controls) (1:2). Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained, including a total summation score (WORMS total, range 0–96) and subscores for cartilage (0–36), menisci (0–24), and bone marrow abnormalities and subchondral cyst-like lesions (0–18, respectively). Knee Injury Osteoarthritis Outcomes score (KOOS) symptoms, quality of life (QOL), and pain were also obtained at baseline and follow-up (range 0–100; lower scores indicate worse outcomes). Using linear regression models, associations between baseline and longitudinal findings were investigated. As pain may modify observations, a sensitivity analysis was performed for longitudinal findings. All analyses were adjusted for sex, BMI, age, race, and Kellgren-Lawrence grade. Results Opioid users had greater structural degeneration at baseline (WORMS total: Coef. [95% CI], P; 7.1 [5.5, 8.8], <0.001) and a greater increase over 4 years (4.7 [2.9, 6.5], <0.001), compared to controls. Cartilage and meniscus scores increased greater in opioid users, compared to controls (P≤0.001), and findings withstood the adjustment for baseline pain (P≤0.002). All baseline KOOS scores were lower in opioid users compared to controls (P<0.001). QOL loss was greater, when adjusted for baseline KOOS pain (QOL −6.9 [−11.6, −2.1], 0.005). Conclusions Opioid users had worse baseline knee structural degeneration and faster progression. Opioid use was also associated with worse symptoms, pain, and QOL. Furthermore, QOL loss was greater in opioid users compared to controls, when adjusted for baseline KOOS pain, indicating that opioids may not be suited to prevent subjective disease progression in KOA patients.

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“…One in vitro study 42 reported that ketorolac has a dose-dependent cytotoxic effect on human chondrocytes whereas another in vitro study 43 reported increased chondrocyte viability. Furthermore, 4 in vivo studies found increased inflammation in the joint with histological examinations following NSAIDs administration.…”

Section: Resultsmentioning

confidence: 99%

“…Abrams et al . 42 investigated the effects of a single-dose ketorolac on mature healthy human chondrocytes in vitro . Chondrocytes were harvested from sixteen donors and a bioreactor was used to expose the chondrocytes to 0.3% and 0.6% ketorolac (more COX-1 selective NSAIDs).…”

Section: Resultsmentioning

confidence: 99%

Do Nonsteroidal Anti-Inflammatory Drugs Have a Deleterious Effect on Cartilage Repair? A Systematic Review

et al. 2019

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Objectives The purpose of this study was to systematically review the available evidence regarding any plausible deleterious effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on chondrocytes, chondrocyte differentiation, and allograft or autograft incorporation after cartilage repair procedures. Design Three databases (PubMed, Science Direct, and Cochrane Library) were screened for eligible studies: investigating the effects of NSAIDs on chondrocytes, chondrogenic differentiation, or allograft/autograft incorporation. This evaluation included studies of any level of evidence, written in English, reporting clinical or preclinical results, published in peer review journals and dealing with our topic. All articles evaluating the effects of NSAIDs on either osteoarthritic (OA) chondrocyte samples or OA chondrocyte models were excluded. Moreover, articles about bone healing in which allograft or autograft incorporation was not investigated were also excluded. Methodologic quality assessment was performed for in vivo animal studies according to ARRIVE guidelines, and risk of bias of each included study was identified using the ROBINS-I tool. Results Eighteen studies were included in the review: 4 in vitro studies, 13 animal studies, and 1 human study. According to these studies NSAIDs have no detrimental effect on healthy mature chondrocytes; however, these drugs influence chondrocyte differentiation and graft incorporation and therefore may interfere with chondrogenesis and incorporation after transplantation of chondrocytes or osteochondral grafts. Conclusion The use of NSAIDs, systemic or local, after cartilage repair procedures should be avoided unless a substantial clinical benefit would otherwise be withheld from the patient. More human studies are needed to analyze the effect of NSAIDs on cartilage repair.

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In Vitro Chondrotoxicity of Nonsteroidal Anti-inflammatory Drugs and Opioid Medications

Abstract: In vitro exposure of chondrocytes to single-dose equivalent concentrations of either ketorolac or meperidine demonstrated significant chondrotoxicity, while exposure to morphine or fentanyl did not lead to increased cell death.

Cited by 24 publications

References 58 publications

Randomized controlled trial of intra‐articular ketorolac on pain and inflammation after minor arthroscopic knee surgery

Randomized controlled trial of intra‐articular ketorolac on pain and inflammation after minor arthroscopic knee surgery

Opioid users show worse baseline knee osteoarthritis and faster progression of degenerative changes: a retrospective case-control study based on data from the Osteoarthritis Initiative (OAI)

Do Nonsteroidal Anti-Inflammatory Drugs Have a Deleterious Effect on Cartilage Repair? A Systematic Review

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