Summary

Arthrofibrosis after knee surgery is associated with significant healthcare cost and patient burden. Our systematic review identifies peri-operative oral medications which may influence rates of arthrofibrosis.

Abstract

Introduction

Arthrofibrosis is a condition characterized by the excessive production of collagen resulting in fibrous scar tissue within a joint. In the knee, the fibrous tissue forms adhesions within the capsule leading to reduced joint motion, stiffness and knee pain. Oral medication, such as non-steroidal anti-inflammatory drugs (NSAIDs), or steroids, may target this hyper exaggerated immune pathway. The aim of our systematic review is to report the existing evidence on whether the use of any oral medication, taken during the peri-operative period, may reduce the risk of arthrofibrosis after knee surgery.

Methods

Our review was registered on PROSPERO (CRD42024552252). A literature search using relevant terms of MEDLINE OVID, EMBASE, COCHRANE CENTRAL and AMED was performed on 24/06/2024. This yielded 691 papers to be reviewed. 9 other papers were found from screening of relevant previous studies, yielding a total of 700 papers that were title/abstract screened by two independent reviewers. Inclusion criteria included any study which reviewed peri-operative oral medication and rates of arthrofibrosis/stiffness/manipulation under anaesthetic (MUA) after any elective knee surgery studied in humans. Fracture related surgery was excluded. 17 full papers were subsequently screened, and 10 met our inclusion criteria. Data extraction included population type, sample size, study design, country of study, publication date and outcome measures reported.

Results

Ten studies have reviewed the use of peri-operative medication and rates of arthrofibrosis in elective knee surgery. Nine studies were retrospective cohort studies (seven used regression analysis, two used propensity score matching), and one was a randomised control trial. Publication dates ranged from 2005 to 2024. Nine studies reviewed patients who had elective TKR surgery, with only one reviewing ACL surgery. Sample sizes ranged from 95 to 216,147. Reported rates of arthrofibrosis ranged from 1.62% to 10.4%. Follow up times ranged from 90 days to eight years. Three studies report significantly reduced rates of arthrofibrosis with the peri-operative use of losartan [OR 0.80 (P=0.007), OR 0.94 (P<0.023) and OR 0.86 (P<0.009) respectively]. One study reports reduced rates with the use of NSAIDs [OR 0.67 (P=0.045)]. One study reports reduced rates with aspirin [OR 0.64 (P<0.001)]. One study reports reduced rates with COX-2 inhibitors [OR 0.88 (P=0.002)]. Warfarin was found to increase rates of arthrofibrosis in three studies [OR 4.20 (P<0.001), OR 1.53 (P<0.001) and OR 1.17 (P=0.03) respectively], whereas direct factor Xa inhibitors were wound to increase rates in two studies [OR 1.96 (P<0.001) and OR 1.42 (P<0.001) respectively]. Valsartan, Olmesartan, Vitamin C, ACE inhibitors, HMG-COA Reductase inhibitors and oral corticosteroids did not have any significant effect on rates of arthrofibrosis.

Conclusion

This study identifies oral medication which may play a role in either preventing or leading to arthrofibrosis in the knee. However, most of the evidence is currently retrospective, with focus being on knee arthroplasty populations. This highlights the need for prospective research particularly in arthroscopic surgery and the mechanisms involved in how these medications may cause arthrofibrosis.