Key pathogenetic components of aseptic loosening of joint prostheses

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Abstract

This review provides a comprehensive analysis of the pathogenetic mechanisms underlying aseptic loosening of joint prostheses and the associated periprosthetic osteolysis. Based on the systematization of current scientific evidence, the key factors contributing to the development of these complications are examined. A central focus is placed on debris-induced inflammation, in which prosthetic wear debris (metals, polyethylene, and bone cement) activates macrophages, leading to the release of pro-inflammatory cytokines (TNF-α, IL-1, IL-6). These mediators disrupt bone remodeling by stimulating osteoclastogenesis via activation of the RANKL/RANK/OPG signaling pathway and by suppressing osteoblast function. Particular attention is paid to the role of mechanical factors, including physiological implant micromotion, which, when exceeding the tolerance threshold (greater than 50–150 μm), impairs osseointegration and promotes the formation of a fibrous synovial-like interfacial membrane, as well as the phenomenon of stress shielding, resulting in bone resorption due to altered load distribution. The influence of pressurized fluid flow (up to 150 mmHg), which enhances bone destruction through direct effects on osteocytes, is also discussed. Specific immune responses to prosthetic components are analyzed in detail: the haptenic properties of metal ions (Co, Cr, Ti) and bone cement can initiate delayed-type hypersensitivity reactions with neoantigen formation and T cell activation. The local and systemic toxic effects of metallic particles are considered, including DNA damage and inhibition of osteoblast and mesenchymal stem cell proliferation. The contribution of bacterial endotoxins adsorbed onto wear particles, which can potentiate inflammation even in the absence of clinically evident infection, is highlighted. It is emphasized that aseptic loosening is a multifactorial process in which the combined action of these mechanisms shifts the balance toward osteolysis. Prospective strategies to reduce the risk of aseptic loosening include investigation of genetic susceptibility, development of biocompatible materials with improved tribological properties, and targeted suppression of inflammatory cascades. A systematic understanding of the underlying pathogenesis constitutes the basis for improving implant longevity and reducing the rate of revision interventions.

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Alexander D. Kamenskiy

Russian University of Medicine

Author for correspondence.
Email: alexkamenskiyvm@yandex.ru
ORCID iD: 0009-0007-3489-3555
SPIN-code: 9994-8149
Russian Federation, Moscow

Yurii V. Parakhin

Clinical Hospital "RZD-Medicine" named after N.A. Semashko

Email: parachinyuri@mail.ru
ORCID iD: 0009-0000-2591-0949
SPIN-code: 2524-0855

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Mikhail V. Parshikov

Russian University of Medicine

Email: parshikovmikhail@gmail.com
ORCID iD: 0000-0003-4201-4577
SPIN-code: 5838-4366

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

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