Polyethylene particle-induced bone resorption in substance P-deficient mice.

Aseptic loosening is the major cause of total joint replacement failure. Substance P (SP) is a neurotransmitter richly distributed in sensory nerve fibers, bone, and bone-related tissue. The purpose of this study was to investigate the potential impact of SP on bone metabolism in polyethylene particle-induced osteolysis. We utilized the murine calvarial osteolysis model based on ultrahigh molecular weight polyethylene (UHMWPE) particles in 14 wild-type mice (C57BL/J6) and 14 SP-deficient mice. Group 1 (C57BL/J 6) and group 3 (SP-knockout) received sham surgery, and group 2 (C57BL/J6) and group 4 (SP-knockout) were treated with polyethylene particles. Analytical methods included three-dimensional micro-computed tomographic (micro-CT) analysis and histomorphometry. Bone resorption was measured within the midline suture. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase-positive cells. UHMWPE-particle treated SP-deficient mice showed significantly reduced osteolysis compared to wild-type mice, as confirmed by histomorphometry (P < 0.001) and micro-CT (P = 0.035). Osteoclast numbers were significantly reduced in groups 3 and 4 compared to groups 1 and 2 (P < 0.001). Unexpectedly, SP-deficient mice (group 3) showed a significantly increased absolute bone mass compared to wild-type mice (group 1) (P = 0.02). The findings of our murine calvaria model lead to the assumption that SP is a promoter in particle-induced osteolysis. The pathophysiology of aseptic loosening is complex, and neuropeptides are not solely responsible for the progress of implant loosening; however, we conclude that there could be coherence between neurotransmitters and particle-induced osteolysis in patients with aseptic loosening.

[A comparison of the antiresorptive effects of bisphosphonates and statins on polyethylene particle-induced osteolysis]. / Ein Vergleich der antiresorptiven Effekte von Bisphosphonaten und Statinen auf Polyethylenpartikel-induzierte Osteolysen.

An ongoing unraveling of the molecular mechanisms in aseptic loosening of hip arthroplasty has opened up novel potential pharmacological interventions. In this study the antiresorptive effects of the bisphosphonate zoledronate and the statin simvastatin on ultra high molecular weighted polyethylene (UHMWPE) particle-induced osteolysis were compared. Two previous studies of our group based on the murine calvarial model of UHWMPE particle-induced osteolysis were pooled to form four study groups. Animals in group I (n=14) underwent sham surgery only. In groups II (n=14), III (n=7) and IV (n=7) UHMWPE particles were implanted on the calvariae. Animals in groups III and IV were additionally treated with zoledronate (single 25 microg/kg s.c. injection) and simvastatin (120 mg/day p.o. for 14 days), respectively. After two weeks, calvaria were processed for undecalcified histomorphometry. Bone resorption was measured using Giemsa staining. Osteoclast numbers were determined using TRAP-staining. UHMWPE particle implantation resulted in a grossly pronounced osteolytic activity with significantly increased values of bone resorption (p < 0.001) and osteoclast numbers (p < 0.001). Additional treatment with zoledronate or simvastatin counteracted the particle-induced effects. A comparison of the two medical treatments revealed no statistically significant differences in bone resorption (p = 0.63) and osteoclast numbers (p = 0.41). A single dose of the bisphosphonate zoledronate decreased UHMWPE particle-induced osteolysis in a murine calvarial model as effectively as a daily treatment with simvastin. Both drug groups may have a preventive and therapeutic role as antiresorptive agents in wear particle-induced bone resorption following total joint replacement.