Elsevier

Foot and Ankle Surgery

Volume 28, Issue 8, December 2022, Pages 1266-1271
Foot and Ankle Surgery

Histologic grading correlates with inflammatory biomarkers in tibialis posterior tendon dysfunction

https://doi.org/10.1016/j.fas.2022.05.004Get rights and content

Abstract

Background

It has been theorized that tibialis posterior tendon dysfunction (TPTD) is a degenerative process unrelated to inflammation. The purpose of this study was to determine if inflammatory cytokines, matrix metalloproteases (MMPs), and glutamate were elevated in diseased tibialis posterior tendons (TPTs).

Methods

Matched diseased TPT, TPT insertion, and flexor digitorum longus (FDL) samples were collected from 21 patients. The samples were individually incubated in media, which was analyzed for inflammatory cytokines, MMPs, and glutamate. Histology and statistical analyses were performed.

Results

Diseased TPT and TPT insertion were significantly elevated compared to transferred FDL in eight inflammatory markers (p < 0.005). Only the diseased TPT was significantly elevated compared to the transferred FDL tendons for glutamate (p < 0.01). Histologic grading correlated with inflammatory cytokine levels.

Conclusion

Diseased TPT and TPT insertion demonstrated significantly elevated levels of inflammatory markers compared to the transferred tendons used as controls, suggesting a role for inflammation in the disease process. The amount of inflammation correlated with increased tendon degradation.

Level of evidence

Level III

Introduction

Insufficiency of the tibialis posterior tendon (TPT) results in the painful clinical entity known as tibialis posterior tendon dysfunction (TPTD). Degeneration, biomechanical failure and potential rupture of the TPT leads to progressive deformity of the foot and ankle known as adult-acquired flat foot deformity (AAFD), or progressive collapsing foot deformity (PCFD) [1], [2], [3], [4]. The explicit etiology of the degeneration of the TPT, or of any tendinopathy, is currently unknown, but is likely to be multifactorial. There are a number of contributory factors including overuse, repetitive strain, abnormal alignment, hypovascularity, increased free radical damage, gender, and genetics [5]. Moreover, TPTD is known to be associated with obesity, diabetes mellitus, hypertension, steroid exposure, and previous trauma or surgery to the medial foot [1].

Currently, the most widely accepted theory of tendinopathy is the mechanical strain theory [5]. The theory suggests that heavy loading of the tendon may result in the initial microtrauma to tendon extracellular matrix or cells. Repetitive heavy loading then leads to progressive damage and microtearing as the excessive wear overwhelms the tendon’s ability to heal. The accumulation of microscopic injury leads to macroscopic injury, degeneration and tears, particularly in the region of tendon distal to the medial malleolus, which correlates to an area of hypovascularity as identified by Frey, Shereff and Greenidge [6], [7].

However, the link to painful symptoms from mechanical loading, microscopic injury and degeneration is currently unknown. While tendinopathy was once considered to be a non-inflammatory process, newer evidence suggest that pain-related inflammatory cytokines, matrix metalloproteases (MMPs), pain neurotransmitters and angiogenesis are highly associated with tendinopathy [5], [8], [9], [10]. Also of interest are numerous studies that have demonstrated increased expression of pain neurotransmitters or receptors, such as glutamate, N-methyl-D-aspartate receptor type 1 (NMDAr1), substance P (SP), and calcitonin-gene-related-peptide (CGRP) in Achilles, patellar, extensor carpi radialis brevis, and carpal tunnel tendons [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23].

There is still much unknown about tendinopathy, especially the TPT in TPTD. The objective of this study was to characterize a subset of inflammatory cytokines, MMPs, and pain neurotransmitters that may be involved in mediating the symptoms of TPTD in a cohort of patients presenting with symptomatic stage II TPTD undergoing FDL tendon transfer. Additionally, no prior information is available on a potential role for the tendon insertion in contributing to altered biochemistry with tendinopathy as the current literature is based on non-insertional tendinopathy. Thus, a secondary objective of this study was to test for involvement of the TPT insertion in the degenerative and pain processes of TPTD. Determining the etiology and pathophysiology of painful TPTD could lead to better non-operative treatments for TPTD and tendinopathy in general, such as better drug therapy or injections which are currently still in the investigational stages [24], [25].

Section snippets

Patients & sample collection

Institutional review board approval was obtained prior to prospectively enrolling patients. To be included in this study, patients had to have stage 2 TPTD, as defined by Bluman et al., that failed at least 6 months of conservative management prior to undergoing FDL tendon transfer surgery [26]. Patients with more advanced disease, underwent arthrodesis, rheumatological diseases, or were below the age of 18 were excluded. Trimmings from the mid-substance of the transferred FDL tendon, diseased

Results

Samples were obtained from 21 (15 female, 6 male) patients undergoing flexor digitorum longus (FDL) tendon transfer for stage 2 TPTD that failed non-operative management. The average subject age was 64.3 years with a range of 53–76. The average mass and range of the healthy FDL samples was 0.34 g, and 0.15–1.18 g respectively. Average mass and range for the diseased TPT samples was 0.45 g and 0.19–0.73 g respectively. The average mass and range for the insertional TPT were 0.46 g and

Discussion

The cytokines IL-1β, IL-6, IL-8, IL-10, and TNF-α and matrix metalloproteases MMP-1, MMP-2, and MMP-3 were all significantly elevated in diseased TPT and TPT insertion compared to the transferred FDL tendon. This data is consistent with much of the literature concerning tendinopathy. Significantly increased levels of inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α), have been found in other tendinopathic tendons, while the reported data on interleukin-6

Funding statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declarations of interest

None relevant.

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