[Modification of human osteoblasts by various analgesics]

Analgesia plays a major role in the therapy of fractures. This raises the question whether frequently used analgetics as Tramadol and Diclofenac have negative effects on the healing of fractures. Human osteoblasts were isolated from human spongiosa and incubated with Diclofenac, Tramadol and without analgetic substance in an in vitro experiment. After 9 days the absolute number of cells as a marker for proliferation and their mitochondrial activity were quantified. The mitochondrial activity was measured using the metabolisation of XTT (sodium-3'-(1-[phenylamino-carbonyl]-3,4-tetrazolium)-bis(4- methoxy-6-nitro) benzene-sulfonic acid hydrate). Both drugs led to a concentration-dependent decrease of cell proliferation. Tramadol showed a significant effect at a concentration of 20 micrograms/ml, which is much higher than the therapeutical concentration of 0.25 microgram/ml in serum. Diclofenac decreased cell proliferation at a concentration of 6 micrograms/ml, having a therapeutical concentration of 1.5 micrograms/ml in serum. Vitality of cells had constant correlation to absolute number of cells (R = 0.95). Our results don't suggest any negative effects of Tramadol on the osteoblast activities in vitro. Diclofenac significantly decreased the proliferation of human osteoblasts at concentrations probably reachable in vivo. A prolonged healing of fractures under treatment with Diclofenac may be possible in critical situations (pseudarthrosis revision, callus distraction).