Dexamethasone Enhances Achilles Tendon Healing in an Animal Injury Model, and the Effects Are Dependent on Dose, Administration Time, and Mechanical Loading Stimulation

Abstract

Background: Corticosteroid treatments such as dexamethasone are commonly used to treat tendinopathy but with mixed outcomes. Although this treatment can cause tendon rupture, it can also stimulate the tendon to heal. However, the mechanisms behind corticosteroid treatment during tendon healing are yet to be understood. Purpose: To comprehend when and how dexamethasone treatment can ameliorate injured tendons by using a rat model of Achilles tendon healing. Study Design: Controlled laboratory study. Methods: An overall 320 rats were used for a sequence of 6 experiments. We investigated whether the drug effect was time-, dose-, and load-dependent. Additionally, morphological data and drug administration routes were examined. Healing tendons were tested mechanically or used for histological examination 12 days after transection. Blood was collected for flow cytometry analysis in 1 experiment. Results: We found that the circadian rhythm and drug injection timing influenced the treatment outcome. Dexamethasone treatment at the right time point (days 7-11) and dose (0.1 mg/kg) significantly improved the material properties of the healing tendon, while the adverse effects were reduced. Local dexamethasone treatment did not lead to increased peak stress, but it triggered systemic granulocytosis and lymphopenia. Mechanical loading (full or moderate) is essential for the positive effects of dexamethasone, as complete unloading leads to the absence of improvements. Conclusion: We conclude that dexamethasone treatment to improve Achilles tendon healing is dose- and time-dependent, and positive effects are perceived even in a partly unloaded condition. Clinical Relevance: These findings are promising from a clinical perspective, as the positive effect of this drug was seen even when given at lower doses and in a moderate loading condition, which better mimics the load level in patients with tendon ruptures.

An immunohistochemical and biomechanical evaluation of the effect of fat graft on tendon healing

“…Previous studies investigating the tendon healing biomechanically found better results in early period only. 22,23 When these results were taken into consideration, the fact that no statistically significant difference was determined in the current study was thought to be due to the test having been performed in the 4th week. However, there are also studies in literature that have shown biomechanical healing with a test performed in the 4th week.…”

Increased expression of glutathione peroxidase 3 prevents tendinopathy by suppressing oxidative stress

“…In a recent clinical trial, local injections of steroids (maximum three times at 4-week intervals) combined with exercise showed better outcomes in the treatment of tendinopathy than with placebo injections and exercise at 6 months ( Johannsen et al, 2022 ). In the rat tendon injury model, tendon healing was enhanced, and their mechanical properties improved when dexamethasone was administered for 5 days ( Dietrich-Zagonel et al, 2022 ). In our analysis of fluoroquinolone-induced and age-related tendinopathy from the IBM MarketScan data, the median administration period of dexamethasone was 12 and 10 days in the fluoroquinolone and older adult cohort, respectively.…”

Achilles Tendon Tissue Turnover Before and Immediately After an Acute Rupture

“…Several previous studies have demonstrated an immediate response of tendon cell activity and matrix protein expression. 11,13,18,26,44 Therefore, it is very likely that a matrix-synthesizing process is begun right after a rupture and that this will lead to a rise in collagen synthesis. The present study showed that a marked rise in collagen synthesis did not seem to be an immediate phenomenon within the first 2 weeks after an ATR in patients.…”