RESUMO
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.
Assuntos
Reabsorção Óssea/induzido quimicamente , Nanopartículas/uso terapêutico , Osteonecrose/tratamento farmacológico , Polietilenos/uso terapêutico , Falha de Prótese , Substância P/genética , Animais , Reabsorção Óssea/diagnóstico por imagem , Osso e Ossos/anatomia & histologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Masculino , Teste de Materiais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteonecrose/patologia , Polietilenos/farmacologia , Crânio/diagnóstico por imagem , Crânio/efeitos dos fármacos , Crânio/patologia , Substância P/farmacologia , Tomografia Computadorizada por Raios XRESUMO
AIM: This study presents an overview of the general effects of bisphosphonates and in particular of their effects on different problems in joint arthroplasty. METHOD: First the chemical properties are described, then the biological effects. It is already known that bisphosphonates have effects on orthopaedic diseases and an increasing number of studies are investigating what effects can be achieved in joint arthroplasty with these substances. RESULTS: The bisphosphonates group was derived from industrial pyrophosphate which is used to prevent calcification. Bisphosphonates inhibit bone mineralisation and resorption. Several direct and indirect mechanisms are responsible for these effects. The inhibition of bone resorption is used to benefit patients suffering from various diseases causing increased bone resorption. Treatment with bisphosphonates results in greater bone density and improved mechanical bone quality. Indications for this treatment include osteoporosis, tumour-associated osseo-destruction, fibrous dysplasia and Paget's disease. Recent studies have shown that osseo-integration of metal implants is accelerated and periprosthetic bone loss, which is caused by various different mechanisms during the lifetime of an implant, can be reduced. CONCLUSION: Bisphosphonates have been an established element in the treatment of bone metabolic disorders for many years. Their use in joint arthroplasty could become increasingly important.