Cytotoxicity of drugs injected into joints in orthopaedics

P Busse, C Vater, M Stiehler, J Nowotny, P Kasten, H Bretschneider, S B Goodman, M Gelinsky, S Zwingenberger, P Busse, C Vater, M Stiehler, J Nowotny, P Kasten, H Bretschneider, S B Goodman, M Gelinsky, S Zwingenberger

Abstract

Objectives: Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro.

Methods: Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed.

Results: Using LA or GC, especially triamcinolone acetonide, a dilution of 1:100 resulted in only a moderate reduction of viability, while a dilution of 1:10 showed significantly fewer cell counts. TA and CA reduced viability significantly at a dilution of 1:2. Higher dilutions did not affect viability. Notably, HA showed no effects of cytotoxicity in all drug dilutions.

Conclusion: The toxicity of common intra-articular injectable drugs, assessed by cell viability, is mainly dependent on the dilution of the drug being tested. LA are particularly toxic, whereas HA did not affect cell viability.Cite this article: P. Busse, C. Vater, M. Stiehler, J. Nowotny, P. Kasten, H. Bretschneider, S. B. Goodman, M. Gelinsky, S. Zwingenberger. Cytotoxicity of drugs injected into joints in orthopaedics. Bone Joint Res 2019;8:41-48. DOI: 10.1302/2046-3758.82.BJR-2018-0099.R1.

Keywords: Chondrocytes; Intra-articular Drugs; Tenocytes; Toxicity.

Conflict of interest statement

ICMJE COI statement: The authors declare that there is no conflict of interest regarding the publication of this article.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6397327/bin/bonejointres-08-41-g001.jpg
Cell numbers of chondrocytes after 24-hour incubation with different dilutions of the different drugs determined by lactate dehydrogenase (LDH) assay. a) Dilution 1:2, b) Dilution 1:10, c) Dilution 1:100. Results are presented as mean and sd for each drug. For all dilutions, one-way analysis of variance (ANOVA) showed significant differences between the groups (p-value < 0.0001). For post hoc testing, * (p-value < 0.05), † (p-value < 0.01) and ‡ (p-value < 0.001) indicate statistical significance (non-paired t-test) towards normal saline.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6397327/bin/bonejointres-08-41-g002.jpg
Cell numbers of tenocytes after 24-hour incubation with different dilutions of the different drugs determined by LDH assay. a) Dilution 1:2, b) Dilution 1:10, c) Dilution 1:100 Results are presented as mean and sd for each drug. While for dilutions 1:2 and 1:10, one-way ANOVA showed significant differences between the groups (p-value < 0.0001), dilution 1:100 resulted in no significant difference (p-value = 0.4887). For post hoc testing, * (p-value < 0.05), † (p-value < 0.01) and ‡ (p-value < 0.001) indicate statistical significance (non-paired t-test) towards normal saline.
Fig. 3
Fig. 3
Haematoxylin and eosin (H&E) staining of chondrocytes. Cell nuclei are coloured blue/violet by haematoxylin. Cytoplasm is coloured red/pink by eosin. Normal saline serves as control.
Fig. 4
Fig. 4
Haematoxylin and eosin (H&E) staining of tenocytes. Cell nuclei are coloured blue/violet by haematoxylin. Cytoplasm is coloured red/pink by eosin. Normal saline serves as control.
Fig. 5
Fig. 5
Live staining of chondrocytes. Live cells are visible as green fluorescent cells and represented here in black. Normal saline serves as control.
Fig. 6
Fig. 6
Live staining of tenocytes. Live cells are visible as green fluorescent cells and represented here in black. Normal saline serves as control.

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