José Aguirre1, John M Bonvini, Barbara Rupnik, Claudio Camponovo, Andrea Saporito, Alain Borgeat. 1. From the Department of Anaesthesiology, Intensive Care and Pain Medicine, Balgrist University Hospital Zurich, Zurich (JA, JMB, BR, AB), Department of Anaesthesiology, Clinica Ars Medica, Gravesano (CC), Department of Anaesthesiology, Ospedale Regionale di Bellinzona e Valli, Bellinzona, Switzerland (AS) and Department of Surgery, University of Illinois at Chicago, Chicago, Illinois, USA (AB).
Abstract
BACKGROUND: Diclofenac and other NSAIDs are routinely used in the postoperative period. Their effect on fracture healing remains unclear and controversial. OBJECTIVE: The primary outcome was to assess the potential cytotoxicity of clinically relevant concentrations of diclofenac on human osteoblasts. DESIGN: Laboratory in vitro study. SETTING: Institute of Physiology, Zurich, Center for Integrative Human Physiology, University of Zurich. MATERIALS: Monolayers of human osteoblasts. INTERVENTIONS: Exposure of human osteoblast monolayers to several concentrations of diclofenac, for different periods of time, with and without an artificially induced inflammatory process. MAIN OUTCOME MEASURES: Cell count, cell viability, cell proliferation and apoptosis. RESULTS: A concentration-mediated, time and exposure dependent cytotoxic effect of diclofenac-mediated apoptosis was observed. Stimulated inflammatory conditions seemed to reduce toxic effects. CONCLUSION: Cytotoxic effects of diclofenac are exposure, time and concentration dependent. Simulating aspects of inflammatory conditions seems to increase resistance to diclofenac cytotoxicity, especially in the presence of higher concentration and longer exposure time.
BACKGROUND:Diclofenac and other NSAIDs are routinely used in the postoperative period. Their effect on fracture healing remains unclear and controversial. OBJECTIVE: The primary outcome was to assess the potential cytotoxicity of clinically relevant concentrations of diclofenac on human osteoblasts. DESIGN: Laboratory in vitro study. SETTING: Institute of Physiology, Zurich, Center for Integrative Human Physiology, University of Zurich. MATERIALS: Monolayers of human osteoblasts. INTERVENTIONS: Exposure of human osteoblast monolayers to several concentrations of diclofenac, for different periods of time, with and without an artificially induced inflammatory process. MAIN OUTCOME MEASURES: Cell count, cell viability, cell proliferation and apoptosis. RESULTS: A concentration-mediated, time and exposure dependent cytotoxic effect of diclofenac-mediated apoptosis was observed. Stimulated inflammatory conditions seemed to reduce toxic effects. CONCLUSION: Cytotoxic effects of diclofenac are exposure, time and concentration dependent. Simulating aspects of inflammatory conditions seems to increase resistance to diclofenaccytotoxicity, especially in the presence of higher concentration and longer exposure time.