Cartilage Repair Activity during Joint-Preserving Treatment May Be Accompanied by Osteophyte Formation

Mylène P Jansen,Roel J H Custers,Floris P J G Lafeber,Sander Spruijt,Ronald J Van Heerwaarden,Simon C Mastbergen,Elske J Willemse,Tonia L Vincent,Fiona E Watt,Pieter J Emans

doi:10.3390/app11157156

Abstract

Knee joint distraction (KJD) treatment has shown cartilage repair and clinical improvement in patients with osteoarthritis, as has high tibial osteotomy (HTO). Following KJD, TGFβ-1 and IL-6 were increased in synovial fluid (SF), factors related to cartilage regeneration, but also to osteophyte formation. As such, osteophyte formation after both joint-preserving treatments was studied. Radiographic osteophyte size was measured before, one year, and two years after treatment. Changes were compared with natural progression in patients from the CHECK cohort before undergoing total knee arthroplasty. An additional KJD cohort underwent SF aspiration, and one-year Altman osteophyte score changes were compared to SF-marker changes during treatment. After two years, both KJD (n = 58) and HTO (n = 38) patients showed an increase in osteophyte size (+6.2 mm2 and +7.0 mm2 resp.; both p < 0.004), with no significant differences between treatments (p = 0.592). Untreated CHECK patients (n = 44) did not show significant two-year changes (+2.1 mm2; p = 0.207) and showed significant differences with KJD and HTO (both p < 0.044). In SF aspiration patients (n = 17), there were significant differences in TGFβ-1 changes (p = 0.044), but not IL-6 (p = 0.898), between patients with a decrease, no change, or increase in osteophyte Altman score. Since KJD and HTO showed joint space widening and clinical improvement accompanied by osteophyte formation, increased osteophytosis after joint-preserving treatments may be a bystander effect of cartilage repair activity related to intra-articular factors like TGFβ-1 and raises questions regarding osteophyte formation as solely characteristic of the joint degenerative process.

Highlights

Osteoarthritis (OA) is characterized by articular cartilage loss, intra-articular inflammation, and osteophyte formation [1]
In CHECK, 30 patients received a total knee arthroplasty (TKA) during the 10-year follow-up, 14 of whom had a TKA in both knees, giving 44 knees to be compared to the Knee joint distraction (KJD) patients
The present study provides an indication that a rise in TGFβ1 might be a mediator in tissue repair activity upon KJD leading to osteophyte formation in addition to cartilage repair, but future studies would have to proof this concept

Summary

Introduction

Osteoarthritis (OA) is characterized by articular cartilage loss, intra-articular inflammation, and osteophyte formation [1]. Osteophytes are often formed at the joint margins, first as cartilage outgrowth and subsequently undergoing ossification [2]. While the exact purpose of osteophytes remains unknown, their presence and size in the knee are associated with joint space width (JSW) decrease, and they are an important radiographic feature used to define the severity of knee OA in classifications like the Altman score and Kellgren–Lawrence grade [3,4,5,6,7]. Osteophytes are frequently present in patients with end-stage knee OA receiving surgical treatment such as total knee arthroplasty (TKA) [8]. There is a demand for joint-preserving treatments for (severe) knee OA at a younger age. A joint-preserving alternative for patients with unicompartmental knee

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