Abstract
Introduction: Activated matrix metalloproteinases (MMPs) are responsible for the osteolytic process in aseptic loosening. Fluvastatin has been shown in previous studies to inhibit MMPs. The purpose of this study was to investigate the potential pharmacological effect of fluvastatin on aseptic loosening.
Materials and methods: A radiolabelled mouse calvaria and human interface membrane cells culture system was used to study the effect of fluvastatin on bone resorption induced by interface membrane cells. The experimental conditions were: 1) test culture consisted of culturing a dead radiolabelled bone disc with cells from human interface membrane in culture medium containing fluvastatin for 14 days 2) control culture consisted of similar culture system without fluvastatin and 3) baseline control culture consisted of bone disc only. The bone discs from each test and control groups comparison were from the same parietal bone to ensure equal amount of radioactive calcium in the bone discs at the start of the experiment. Supernatant were sampled on day 7, 10 & 14 for scintillation counting. The total Ca45 remained in the bone discs at the completion of the culture were measured by scintillation counting. Eight sets of experiments were performed in this study. The results were expressed as the ratio of Ca45 in the fluvastatin exposed culture over culture containing bone disc only. In the control, the results were expressed as ratio of bone disc exposed to cells over culture containing bone disc only.
Results: In the supernatant Ca45, both the fluvastatin and control ratios increased with time confirming bone resorption in both culture. The fluvastatin culture consistently showed a lower ratio compared with control indicating an inhibitory effect. In the fluvastatin culture the mean ratios on day 7, 10 & 14 were 0.79, 1.53 and 2.55. The mean ratios in the control culture were 1.03, 1.81 and 3.20 (n = 8, p = 0.0001 ANOVA, General Linear Model). The mean ratio of total Ca45 remaining in the bone disc in the fluvastatin culture was 0.87 and the control was 0.70 (p = 0.01, t test). This implies 55% less bone resorption in the presence of fluvastatin.
Conclusions: In this in vitro study we found fluvastatin has the ability to inhibit osteolysis by cells from interface membrane of aseptically loosened hips. We believe fluvastatin inhibit bone resorption by MMPs inhibition. This may have therapeutic implication in the treatment of patients with aseptic loosening of total joint replacements.
Correspondence should be addressed to Carlos Widgerowitz, Honorary Secretary BORS, Division of Surgery and Oncology, Section of Orthopaedic and Trauma Surgery, Ninewells Hospital and Medical School, Tort Centre, Dundee DD1 9SY, Scotland.
