Is there any impact of diclofenac on bone cells and their progenitors related to arthroplasty?

Introduction: Results of animal experiments have demonstrated that the osse ous integration of non-cemented prostheses can, at the very least temporari ly, be impaired by the application of nonsteroidal antiphlogistic agents (s uch as diclofenac). It is the objective of this study to examine whether th ere is a direct influence of diclofenac used in usual clinical dosages (3 t imes 50 mg daily) on bone cells and their progenitor cells which would expl ain the observed slow integration of the prostheses. Methods: To investigate this, cultivated human in vitro osteoblasts and str omal bone marrow cells were incubated with increasing doses of the medicati ons. Our study focused on the effect of diclofenac application on prolifera tion and functional metabolism in both cell lines. The measurable maximal p lasma concentration 2 h after the application of one tablet Voltaren 50 rea ched 1.6 mu g/ml. This correlated with diclofenac concentrations between 1 and 10 mi found in our experiments. The detected values were correlated to the control group (0 mu g/ml diclofenac). Results: The drug effect upon osteoblasts was higher than on progenitor cel ls. The proliferation of in vitro stromal bone marrow cells, compared to un treated cells, was found to be decreased. we observed a decrease to 82% at a diclofenac concentration of 1 mu g/ml, Osteoblasts exhibited a decrease t o 97.5% at the same concentration. The DNA synthesis increased to 118% in s tromal bone marrow cells, in osteoblasts to 144%. In contrast, we detected a neglectible decrease to 92% in the collagen synthesis of osteoblasts comp ared to untreated cells. The synthesis of osteocalcin by osteoblasts increa sed to 119%. The alkaline phosphatase activity was found to be decreased to 88% in stromal bone marrow cells and increased in osteoblasts to 111%, Conclusion: Temporary inhibiting effects on osseous integration in non-ceme nted prosthesis by diclofenac could be caused by a disturbance in the anabo lic bone metabolism, exhibited by an increase of osteoblastic osteocalcin e xpression. Osteocalcin as a known negative regulator of the osteoneogenesis is most likely inhibiting the collagen matrix deposition.