Abstract
Summary Statement
The effects of local glucocorticoid on tendon appear broadly negative and this supports the emerging clinical evidence which points toward significant long term harms associated with this treatment modality.
Introduction
The use of locally administered glucocorticoid is widespread in the treatment of painful tendinopathy. Despite evidence of short term benefit, the emerging evidence points toward significant long term harms associated with this method of treatment, including an increased risk of recurrence, rupture and worsened clinical outcomes (1, 2). Our primary purpose was to summarise the known effects of locally administered glucocorticoid on tendon tissue and tendon cells.
Methods
We conducted a systematic review of the scientific literature using the PRISMA and Cochrane guidelines of the Medline database using specific search criteria. Only studies analysing the effects of locally administered glucocorticoid on tendon tissue or tendon cells with adequate controls were included. Specific attention was paid to histological and biomechanical findings. Inclusion was agreed upon by two independent researchers after review of abstracts or full text. The search yielded 4424 results, of which 42 met the inclusion criteria. The final 42 articles consisted of 13 human in vitro studies, 15 animal in vivo studies and 14 animal in vitro studies.
Results
Due to study heterogeneity, statistical pooling or meta-analysis of data was not possible. The results are therefore described qualitatively. Histologically, there was a loss of collagen structure (5 studies) and an increase in collagen necrosis (4 studies). The proliferation and viability of fibroblasts was reduced (11 studies). An increased inflammatory cell infiltrate was shown in 3 animal in vivo studies, while an increased fibroblast infiltrate was seen in 2 studies. Fibroblast migration was reduced in 2 in vitro studies. Collagen synthesis was reduced in 13 studies. An increased ratio of type 3 to type 1 Collagen was shown in 2 studies. Apoptosis was unaffected in 2 studies. 19 studies investigated the mechanical properties of tendon. Of these 7 showed deterioration in mechanical properties, 4 showed an improvement and 8 showed no difference.
Discussion/Conclusion
Overall it is clear that the local administration of glucocorticoid has significant negative effects on tendon cells in vitro, such as reduced cell viability, cell proliferation and collagen synthesis. There is increased collagen disorganisation and necrosis as shown by animal in vivo studies. The mechanical effects are equivocal. This review supports emerging clinical evidence showing significant long term harms associated with glucocorticoid injections. There is clearly a significant need for better designed human trials with appropriate blinding and control arms to investigate the effects of glucocorticoid on both clinical outcomes and characteristics of tendon tissue.