Original Full Length ArticleRANKL in the osteolysis of AES total ankle replacement implants
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.
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