Mechanisms of Disease: molecular insights into aseptic loosening of orthopedic implants

Abstract

Despite the success of treating rheumatic disorders with biologic therapies, joint replacement surgery still remains the final treatment option in many cases. Approximately 1.5 million joint arthroplastic operations are performed annually worldwide. Implant failure due to massive bone loss and aseptic loosening of prostheses, however, is a major complication of joint replacement, which can lead to high socioeconomic burdens both for the individual patient and for health-care systems. To date, there is no approved drug therapy to prevent or inhibit periprosthetic osteolysis, and aseptic loosening of prostheses can only be overcome by surgical revision. Research during the past decade, however, has unravelled much of the pathogenesis of aseptic prosthesis loosening and preclinical studies have identified potential targets for pharmaceutical treatments. This article highlights the importance of a cooperative interaction between rheumatologists and orthopedic surgeons, and presents novel insights into the molecular mechanisms behind aseptic loosening of prostheses. In addition, we outline potential perspectives for the development of future therapeutic strategies for this devastating complication.

Dual effects and mechanism of TiO2 nanotube arrays in reducing bacterial colonization and enhancing C3H10T1/2 cell adhesion

“…6,7 The gap between the implant and the surrounding bone tissues, caused by an unsuitable prosthetic surface for cell adhesion and poor osseointegration, is one of the primary causes of aseptic loosening. 8,9 The physical and chemical properties of the surface are known to be crucial for the ultimate interaction between the prosthesis and the biological system; however, the precise role of the surface chemistry and topography in the early stages of dental implant osseointegration remain poorly understood. 10 Recent studies have indicated that a nanostructure surface can enhance the adhesion, growth, and proliferation of osteoblasts compared with a traditional microstructure surface.…”

Risk factors for accelerated polyethylene wear and osteolysis in ABG I total hip arthroplasty

“…This debris triggers multiple adverse host reactions that involve signalling pathways and finally result in osteoclast-mediated bone resorption [2]. Wear particles originate predominantly from motion between two opposing, articulating surfaces, but other mechanisms of particle generation are also possible [3].…”

Gender‐dependent association of the GNAS1 T393C polymorphism with early aseptic loosening after total hip arthroplasty

“…12,13 Third, Gas/cAMP are key regulators of interleukin-6 (IL-6) in osteoblasts 14 and in macrophages, 15 and IL-6 is a potent activator of osteoclasts and a promoter of aseptic loosening. 16 GNAS1, the gene coding for the stimulatory Gas subunit, is located on chromosome 20q13.2-13.3. and consists of 13 exons and 12 introns.…”