A novel bisphosphonate inhibits inflammatory bone resorption in a rat osteolysis model with continuous infusion of polyethylene particles.

Abstract

This study examined the inhibitory effect of a new bisphosphonate (TRK-530) on wear debris-mediated bone resorption in a rat osteolysis model involving continuous infusion of high density polyethylene (HDPE) particles. TRK-530 (TRK) is a novel synthetic bisphosphonate that has been shown to decrease the level of tumor necrosis factor alpha (TNF-alpha) in the bone marrow of rats with adjuvant arthritis. Forty Wistar rats were randomized to two groups (n = 20 each). In each rat, a Kirshner (K) wire was inserted into the femur and HDPE particles were continuously infused into the knee joint. Thereafter, the animals were subcutaneously injected with saline (control group) or 1 mg/kg of TRK (TRK group) every second day, and were sacrificed at 4 or 8 weeks after surgery. Radiographs obtained at the time of sacrifice were evaluated for periprosthetic osteolysis. We also examined the thickness of the reactive membrane as well as the number of osteoclast-like cells around the K-wire. In addition, we examined the expression of genes for bone-resorbing cytokines in the reactive membrane. Radiographic peri-implant osteolysis was more frequent in the control group compared with the TRK group at each time of assessment (p < 0.01). The interfacial membrane was significantly thinner in the TRK group compared with the control group (p < 0.01) and the average number of osteoclast-like cells around the K-wire was significantly fewer in the TRK group (p < 0.01). In addition, the expression of interleukin 1-alpha messenger ribonucleic acid (IL-1alpha mRNA) and TNF-alpha mRNA was suppressed in the TRK group at each time of assessment. We conclude that the TRK can inhibit the formation of inflammatory peri-implant osteolysis induced by HDPE particles.

• Authors: Miho Iwase, Kang Jung Kim, Yoshiro Kobayashi, Masatoshi Itoh, Tatsuo Itoh
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 20 Issue 3 Pg. 499-505 (May 2002) ISSN: 0736-0266 [Print] United States
• PMID: 12038623 (Publication Type: Journal Article)

Chemical References

• Diphosphonates
• Interleukin-1
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Polyethylene

Topics

• Animals
• Arthritis (drug therapy, etiology, pathology)
• Arthrography
• Bone Resorption (prevention & control)
• Diphosphonates (therapeutic use)
• Female
• Femur (diagnostic imaging, metabolism, pathology)
• Interleukin-1 (genetics)
• Knee Joint
• Microspheres
• Osteolysis (diagnostic imaging, drug therapy, etiology)
• Polyethylene
• Prostheses and Implants
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Tumor Necrosis Factor-alpha (genetics)