The Role of the Innate Immune System in Wear Debris-Induced Inflammatory Peri-Implant Osteolysis in Total Joint Arthroplasty

Abstract

Periprosthetic osteolysis remains a leading complication of total hip and knee arthroplasty, often resulting in aseptic loosening of the implant and necessitating revision surgery. Wear-induced particulate debris is the main cause initiating this destructive process. The purpose of this article is to review recent advances in understanding of how wear debris causes osteolysis, and emergent strategies for the avoidance and treatment of this disease. A strong activator of the peri-implant innate immune this debris-induced inflammatory cascade is dictated by macrophage secretion of TNF-α, IL-1, IL-6, and IL-8, and PGE2, leading to peri-implant bone resorption through activation of osteoclasts and inhibition of osteoblasts through several mechanisms, including the RANK/RANKL/OPG pathway. Therapeutic agents against proinflammatory mediators, such as those targeting tumor necrosis factor (TNF), osteoclasts, and sclerostin, have shown promise in reducing peri-implant osteolysis in vitro and in vivo; however, radiographic changes and clinical diagnosis often lag considerably behind the initiation of osteolysis, making timely treatment difficult. Considerable efforts are underway to develop such diagnostic tools, therapies, and identify novel targets for therapeutic intervention.

The Role of Receptor Activator of Nuclear Factor-κB Ligand/Osteoprotegerin Ratio in Synovial Fluid as a Potential Marker for Periprosthetic Osteolysis Following Total Ankle Arthroplasty

“…However, the precise mechanisms underlying osteolysis are obscured by the complex biological pathways and multitude of contributing factors. 13 15 18) Additionally, bone remodeling homeostasis is influenced not only by osteoclastic bone resorption but also by osteoblastic bone formation. 18) Koulouvaris et al 27) also indicated that osteogenic activity is suppressed by the presence of wear particles, as evidenced by in vitro studies.…”

“… 11 13 16) Macrophages, monocytes, lymphocytes, and fibroblasts (in tissues around osteolytic lesions) secrete numerous cytokines that promote bone resorption and inhibit bone formation. 13 17 18) The receptor activator of nuclear factor-κB ligand (RANKL) binds to RANK receptors on osteoclast precursor cells, upregulates osteoclast differentiation, and stimulates the production of proinflammatory cytokines. 18) …”

“… 13 17 18) The receptor activator of nuclear factor-κB ligand (RANKL) binds to RANK receptors on osteoclast precursor cells, upregulates osteoclast differentiation, and stimulates the production of proinflammatory cytokines. 18) …”

Mechanistic role of quercetin as inhibitor for adenosine deaminase enzyme in rheumatoid arthritis: systematic review

“…IL-17A plays a significant role in the development of RA by stimulating the synthesis of RANK-L through osteoblasts and synoviocytes leading to decreased bone development and increased bone degradation [ 39 ]. Also, facilitating the formation of matrix metalloproteinase (MMP-1) by synoviocytes [ 40 ] and promoting both endothelial cell migration and angiogenesis [ 41 ]. Inflammation and joint degeneration brought on by activated neutrophils are exacerbated by proinflammatory cytokines produced by synovial activated macrophages that attract and excite other innate immune cells [ 42 ].…”

Recent Advances in Bio-Tribology From Joint Lubrication to Medical Implants: A Review

“…It is of the utmost importance to comprehend the dimensions, makeup, and biological responsiveness of wear particles in order to forecast the enduring impacts on adjacent tissues and the operation of the implant. Recent research has investigated the relationship between wear debris and the immune system of the host, uncovering inflammatory pathways in the process [45,46]. Gaining insight into the biological reactions induced by wear can facilitate the formulation of approaches to alleviate the detrimental consequences and guarantee the effectiveness and safety of implants.…”