Effects of sequential treatment with intermittent parathyroid hormone and zoledronic acid on particle-induced implant loosening: Evidence from a rat model.

Particle-induced implant loosening is a major challenge to long-term survival of joint prostheses. Administration of intermittent parathyroid hormone (PTH) has shown potential in the treatment of cases of early-stage periprosthetic osteolysis, while sequential administration of intermittent PTH (iPTH) and bisphosphonates (Bps) has achieved significant effects on treatment of postmenopausal osteoporosis. The objective of this study was to determine whether sequential treatment could preserve bone mass and implant fixation during a pathological course of peri-implant osteolysis in a rat model. Ninety male Sprague Dawley rats were randomly divided into nine groups, four of which were used for confirmation of establishment of the peri-implant osteolysis model at two time points, while the other five were used to determine the efficiency of the sequential treatment on peri-implant osteolysis. Implant fixation and peri-implant bone mass were evaluated using biomechanical testing, micro-CT analysis, and histology at 6 and 12 weeks postoperative. The biomechanical test demonstrated that the maximum loading force during a push-out test was significantly elevated in the sequential treatment group compared to the osteolysis group and iPTH withdrawal group at 12 weeks. Peri-implant bone morphology also indicated a robust increase in bone volume in the sequential treatment group. Sequential administration of iPTH and Bps was effective in preventing experimental peri-implant osteolysis, resulting in improved implant fixation and increased peri-implant bone volume. Clinical significance: The innovative application of sequential treatment in peri-implant osteolysis could be used clinically to improve the prognosis of patients with early-stage periprosthetic osteolysis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1489-1497, 2019.

Topical zoledronic acid decreases micromotion induced bone resorption in a sheep arthroplasty model.

BACKGROUND: Initial micromotion of a total hip replacement is associated with aseptic loosening. The use of bisphosphonates could be one way to reduce peri-implant bone resorption induced by micromotion. Bisphosphonates compounds are inhibitors of bone resorption. The aim of this study was to investigate whether local treatment with bisphosphonate would reduce bone resorption and fibrous tissue around an experimental implant subjected to micromotion. METHODS: One micromotion implant were inserted into each medial femoral condyle in ten sheep. During each gait cycle the implant axially piston 0.5 mm. During surgery one of the femoral condyles were locally treated with 0.8 mg zoledronate. The other condyle served as control. Observation period was 12 weeks. RESULTS: Histological evaluation showed a fibrous capsule around both the control and bisphosphonate implants. Histomorphometrical analysis showed that 97% of the surface on both control and bisphosphonate implants were covered by fibrous tissue. However, the bisphosphonate was able to preserve bone in a 1 mm zone around the implants. CONCLUSION: This study indicates that local treatment with bisphosphonate cannot prevent the formation of a fibrous capsule around an implant subjected to micromotion, but bisphosphonate is able to reduce resorption of peri-prosthetic bone.

Scutellarin inhibits RANKL-mediated osteoclastogenesis and titanium particle-induced osteolysis via suppression of NF-κB and MAPK signaling pathway.

Aseptic prosthetic loosening is a major complication after hip joint replacement. Wear particle-induced periprosthetic osteolysis plays a key role in aseptic prosthetic loosening. Attempting to modulate receptor activator of nuclear factor-κB (RANKL) mediated signaling pathways is a promising strategy to prevent aseptic prosthetic loosening. In the present study, we determined the effect of scutellarin (SCU) on titanium (Ti) particle-induced osteolysis in a mouse calvarial model and RANKL-mediated osteoclastogenesis. We determined that SCU, the major effective constituent of breviscapine isolated from a Chinese herb, has potential effects on preventing Ti particle-caused osteolysis in calvarial model of mouse. In vitro, SCU could suppress RANKL-mediated osteoclastogenesis, the function of osteoclast bone resorption, and the expression levels of osteoclast-specific genes (tartrate-resistant acid phosphatase (TRAP), cathepsin K, c-Fos, NFATc1). Further investigation indicated that SCU could inhibit RANKL-mediated MAPK and NF-κB signaling pathway, including JNK1/2, p38, ERK1/2, and IκBα phosphorylation. Taken together, these results indicate that SCU could inhibit osteoclastogenesis and prevent Ti particle-induced osteolysis by suppressing RANKL-mediated MAPK and NF-κB signaling pathway. These results suggest that SCU is a promising therapeutic agent for preventing wear particle-induced periprosthetic osteolysis.

Inhibitory effect of icariin on Ti-induced inflammatory osteoclastogenesis.

BACKGROUND: Wear particle-induced periprosthetic osteolysis that results in aseptic loosening is the most common cause of long-term failure after total joint replacement. MATERIALS AND METHODS: Icariin (ICA), a flavonoid isolated from Epimedium pubescens, inhibits osteoclast formation, but its effects on wear particle-induced inflammatory osteoclastogenesis remains unclear. We investigated the role of ICA in the regulation of osteoclast differentiation in a murine macrophage cell line (RAW264.7), which is stimulated by titanium (Ti) particles and the receptor activator of NF-κB ligand. RESULTS: ICA effectively inhibited osteoclast formation and bone resorption in the differentiation medium. ICA (10(-7) mol/L) significantly reduced the number of tartrate-resistant acid phosphatase-positive cells compared with the control, and significantly reduced the percentage of the surface covered by resorption lacunae. Quantitative real-time polymerase chain reaction analysis showed that ICA inhibited messenger RNA expression for the receptor activator of nuclear factor-κB, cathepsin K, tartrate-resistant acid phosphatase-positive, and matrix metalloproteinase-9 in RAW264.7 cells stimulated by Ti particles and receptor activator of NF-κB ligand. ICA also reduced pro-inflammatory cytokine expression of interleukin-1ß and tumor necrosis factor-α in RAW264.7 cells cultured with Ti particles. In addition, incubation with cholecystokinin-8 showed that ICA had no toxic effects on RAW264.7 cells. CONCLUSIONS: ICA possibly elicited inhibitory effects on inflammatory osteoclastogenesis induced by Ti particles, indicating that ICA may be useful for the prevention and treatment of wear particle-induced osteolysis.

Prevention of voice prosthesis biofilms: current scenario and future trends in prolonging prosthesis lifetime.

Voice rehabilitation after a total laryngectomy is an important requisite for patients' rehabilitation. Oesophageal speech using tracheo-oesophageal-valved prostheses is now considered the state-of-art in postlaryngectomy voice rehabilitation. One of the major drawbacks of voice prostheses is their limited device lifetime. This is due to the deterioration of the silicone rubber material by different bacterial and yeast species, which are organised in the form of a biofilm resulting in internal leakage, increased airflow resistance, impeding speech, respiration and swallowing. The use of antimicrobials though easily applicable is associated with development of resistance if used on long-term basis. Other techniques in the form of modification of physicochemical properties of the silicon surface or covalent binding of antimicrobial agents to the silicon surface have been employed. This article reviews the different strategies investigated until now and the future trends in preventing biofilm formation for prolonging the lifetime of the silicon voice prostheses. Data was collected by conducting a computer aided search of the MED-LINE and PUBMED databases, supplemented by hand searches of key journals. Over 35 articles in the last two decades on the topic have been reviewed out of which 27 were found to be of relevant value for this article.