Single intra‐articular dexamethasone injection immediately post‐surgery in a rabbit model mitigates early inflammatory responses and post‐traumatic osteoarthritis‐like alterations

Abstract

Despite surgical reconstruction of the anterior cruciate ligament, a significant number of patients will still develop posttraumatic osteoarthritis (PTOA). Our objective was to determine if mitigating aspects of the acute phase of inflammation following a defined knee surgery with a single administration of a glucocorticoid could prevent the development of PTOA-like changes within an established rabbit model of surgically induced PTOA. An early and late post-surgical time-point was investigated in this study (48 h and 9 weeks post-surgery) in which the following groups were repeated (each n ¼ 6, for a total of 24 rabbits per time-point, and 48 rabbits used in the study): control (age/sex matched), sham (arthrotomy), drill injury (arthrotomy þ two drill holes to a noncartilaginous area of the femoral notch), and drill injury þ single intra-articular (IA) injection of dexamethasone (DEX). At 48 h postsurgery, DEX treatment significantly lowered the mRNA levels for a subset of pro-inflammatory mediators, and significantly lowered the histological grade. Nine weeks post surgery, DEX treatment significantly lowered the histological scores (presented as effect size) for synovium (3.8), lateral femoral condyle (3.9), and lateral tibial cartilage (5.1) samples. Thus, DEX likely acts to prevent injury induced inflammation that could contribute to subsequent joint damage. ß

Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing

“…Although this was not a major aim and this study was underpowered to demonstrate the absence of differences, effects of TAA bolus injections in OA joints compared to non‐treated joints, in contrast to the effects of the extended presence of TAA, are supported by various in vivo and clinical studies. Post‐surgical injection of the corticosteroid dexamethasone for inhibition of acute inflammation in a rabbit model of surgically induced OA showed no side effects (Heard et al, ; Huebner, Shrive, & Frank, ). In patients, corticosteroids have been intravenously administered perioperatively and post‐operatively during ACL repair surgery and orally afterwards to reduce inflammation and pain, without complications (Dahl, Spreng, Waage, & Raeder, ; Vargas & Ross, ).…”

Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis

“…It is well documented that the effects of glucocorticoids are dependent on the dose, frequency and duration of administration: large doses of corticosteroids have shown detrimental effects on cartilage structure, chondrocytes and subchondral bone (Wernecke et al , 2015). Only two reports were found that show chondroprotective effects with high Dex dose (Heard et al , 2015) and high frequency (Huebner et al , 2014) in a bone drill hole model of rabbit PTOA. A recent study by Flexion (Kumar et al , 2014) shows that intra-articular injection of clinically equivalent doses of triamcinolone in healthy beagle dogs (2, 6 and 19 mg) causes significant GAG loss that started 3 d after IA injection and peaked at 4–6 weeks.…”

Influence of Periostin on Synoviocytes in Knee Osteoarthritis

“…steroid-induced arthropathy (steroid arthropathy) (44). The principle of steroid-induced arthropathy has not been in vivo 31: 69-78 (2017) 74 elucidated in detail, but steroid therapy is very effective as a treatment of acute OA (44,45,46). However, steroid treatment should be used with care in terms of time, niche, and optimum dose.…”