Elsevier

Bone

Volume 51, Issue 3, September 2012, Pages 546-552
Bone

Original Full Length Article
RANKL in the osteolysis of AES total ankle replacement implants

https://doi.org/10.1016/j.bone.2012.05.007Get rights and content

Abstract

Peri-implant tissue reactions in failed total ankle replacement (TAR) are characterized by early developing peri-implant osteolysis. The hypothesis of the study was that this reaction is mediated by receptor activator of nuclear factor kappa B ligand (RANKL).

Samples of peri-prosthetic tissues from failed TAR implants were stained for macrophages, RANKL, its receptor RANK and osteoprotegerin (OPG), and compared to control samples.

The failed TAR implants were surrounded by implant capsule, synovial lining-like interface membrane or necrotic tissues. Infiltrating scavenger receptor I positive CD163+ macrophages were frequent, in particular around necrotic soft tissues or bone sequestrate, and possibly in part formed due to ischemia and mechanical factors. In contrast, implant-derived wear debris was scanty. Still many RANK+ macrophages were often seen in close contact with RANKL+ mesenchymal cells, whereas OPG was mostly located at a distance in vascular endothelial cells. Foreign body giant cells were frequent.

RANKL seems to stimulate locally accumulated CD163+ RANK-expressing cells to fusion, which leads to the local formation of multinuclear foreign body giant cells (and probably of osteoclasts). Therefore, peri-implant osteolysis in early TAR implant failure seems to be caused by the RANKL-driven chronic foreign body inflammation directed against, not implant-derived particles, but against necrotic autologous tissues.

Highlights

► The aseptic loosening of total ankle replacement (TAR) is characterized by infiltrates of CD163+ and RANK+ macrophages. ► The aseptic loosening of TAR is mediated via RANKL, expressed by mesenchymal cells, driving the fusion of multinuclear cell progenitors. ► Implant-derived wear debris and particles are rarely seen. ► Tissue necrosis is extensive and seems to drive the chronic foreign body reaction.

Introduction

TAR is nowadays a rather common orthopedic procedure in painful end-stage arthritis of the ankle and forms an alternative to ankle arthrodesis [1], [2], [3], [4]. In spite of technically successful implantation and satisfactory short-term results [1], [2], [3], [4], the intermediate and long-term results are compromised compared to joint replacements in other anatomical sites, such as the hip and knee, with an overall implant survival in register studies of only from 78% to 89% at 5 yrs [5], [6], [7], [8], [10]. Osteolysis in other joint replacements with relatively long life-in-service seems to be caused by wear debris-induced chronic foreign body reaction, so called particle disease.

In a recent report of 130 consecutive Ankle Evolutive System (AES) total ankle prosthesis series, revision operations were performed in several cases due to osteolysis [9]. Osteolytic lesions were prominent in computed tomography (CT) already early after the implantation, but scanning electron microscopy combined with an energy-dispersive X-ray elemental analysis disclosed only very few, singular Ti and Co–Cr particles in periprosthetic soft tissue.

The precise mechanism leading to rapidly progressive periprosthetic tissue reactions, including osteolysis, remains unknown [3], [9], [36], [37]. The hypothesis, which was raised, was that the receptor activator of nuclear factor kappa B ligand (RANKL, formerly also known as an osteoclastogenic factor) plays a key role, due to its involvement in the formation of both osteoclasts and foreign body giant cells [11], [12]. We therefore analyzed the components of the RANKL system in peri-prosthetic tissues obtained from early ankle implant revision operations.

Section snippets

Patients and surgery

Between 2008 and 2012, soft tissue samples were collected from multiple periprosthetic sites from ten patients undergoing revision operation of Ankle Evolutive System (Transystème, Nîmes, distributed by Biomet, Valence, France) TARs, performed for peri-implant osteolysis (Table 1). These patients were radiologically characterized by granulomatotic osteolytic areas, defined as discrete, well-circumscribed areas of lucency  2 mm wide, as seen in routine radiographs and CT images in peri-implant

Routine histology

Samples contained three different types of areas. Coagulative soft tissue necrosis (Fig. 1A) covered usually 5–15% of the tissue section area. Implant capsule was relatively dense collagenous tissue containing fibroblasts, mast cells and some histiocytes, and vascularized by microvessels. Finally, in some samples from such tissues, a synovial lining-like layer was also observed. The two last mentioned tissues contained often pieces of necrotic bone embedded in soft tissue matrix, but no

Routine histopathology

All the TAR implants studied were surrounded in part by implant capsule, often apparently covered by synovial membrane-like interface membrane (both are interface membranes), but in addition always by necrotic tissues. During mobilization and cyclic loading of the joint and upon expansion of the effective joint space fibrous implant capsule becomes in contact with pseudo-synovial fluid formed in the synovial-like lining of the prosthetic joint. This induces differentiation of the contact

Acknowledgments

This study was supported by grants from the HUS and TYKS evo funding, Sigrid Juselius Foundation, Finska Läkaresällskapet, ORTON Orthopedic Hospital, Wilhelm and Else Stockmanns Stiftelse, the National Doctoral Program of Musculoskeletal Disorders and Biomaterials, “Regenerative Medicine” RNP of the European Science Foundation, and “Individualized Musculoskeletal Medicine” of the Danish Council of Strategic Research.

References (49)

  • G. Labek et al.

    Revision rates after total ankle arthroplasty in sample-based clinical studies and national registries

    Foot Ankle Int

    (2011)
  • A. Henricson et al.

    10-year survival of total ankle arthroplasties. A report on 780 cases from the Swedish Ankle Register

    Acta Orthop

    (2011)
  • S.L. Haddad et al.

    Intermediate and long-term outcomes of total ankle arthroplasty and ankle arthrodesis. A systematic review of the literature

    J Bone Joint Surg Am

    (2007)
  • H. Koivu et al.

    Severe periprosthetic osteolytic lesions after the Ankle Evolutive System total ankle replacement

    J Bone Joint Surg Br

    (2009)
  • A. Kokkonen et al.

    High rate of osteolytic lesions in medium-term followup after the AES total ankle replacement

    Foot Ankle Int

    (2011)
  • J. Mandelin et al.

    Imbalance of RANKL/RANK/OPG system in interface tissue in loosening of total hip replacement

    J Bone Joint Surg Br

    (2003)
  • J. Mandelin et al.

    Interface tissue fibroblasts from loose total hip replacement prosthesis produce receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, and cathepsin K

    J Rheumatol

    (2005)
  • S.B. Goodman et al.

    Biocompatibility of total joint replacements. A review

    J Biomed Mater Res A

    (2009)
  • Y.T. Konttinen et al.

    The microenvironment around total hip replacement prostheses

    Clin Orthop Relat Res

    (2005)
  • S. Santavirta et al.

    Aggressive granulomatous lesions associated with hip arthroplasty. Immunopathological studies

    J Bone Joint Surg Am

    (1990)
  • S. Santavirta et al.

    Aggressive granulomatous lesions in cementless total hip arthroplasty

    J Bone Joint Surg Br

    (1990)
  • G. Mahendra et al.

    Necrotic and inflammatory changes in metal-on-metal resurfacing hip arthroplasties. Relation to implant failure and pseudotumor formation

    Acta Orthop

    (2009)
  • C. Brown et al.

    Characterisation of wear particles produced by metal on metal and ceramic on metal hip prostheses under standard and microseparation simulation

    J Mater Sci Mater Med

    (2007)
  • H.G. Willert et al.

    Metal-on-metal bearings and hypersensitivity in patients with artificial hip joints. A clinical and histomorphological study

    J Bone Joint Surg Am

    (2005)
  • Cited by (0)

    1

    Equal contribution.

    View full text