Influence of non-selective and cyclooxygenase-II-selective cyclooxygenase-inhibitors on primary human osteoblasts

Next to the correct treatment of a fracture itself the alleviation of pain is a conditio sine qua non. One central problem is a potential negative influence of the chosen analgesic on the fracture-healing. Especially non-selective COX-In are known to have an osteoblast-depressive effect. In the presented study we investigated the influence of a non-selective COX-In (Diclofenac) and a COX-II-selective COX-in (Celecoxib) in different concentrations (standard-dosage till 100x over-dosage) on the proliferation-rate, differentation and metabolism of primary human osteoblasts in vitro. We could demonstrate, that in the recommended standard plasma dosage neither Diclofenac nor Celecoxib showed any significant effect on these parameters. Celebrex showed in none of the tested dosages any significant effect on the above named parameters. Diclofenac lead to a significant reduction of the proliferation-rate of PHOst from the 5 x over-dosage, to a significant increase of the expression of alkaline Phosphatase from the 10x over-dosage and to a significant increase of the expression of Osteocalcin from the 50 x over-dosage. Non-selective COX-In simultaneously seem to lead to a reduction of the proliferation-rate and an increase of the osteoblast-differentation, while COX-II-selective COX-In do not show any of these effects. Due to the fact, that the effect of non-selective COX-In occurs in an over-dosage situation one may not recommend the renunciation of these analgesics during fracture treatment. In addition we do not know if the increase of osteoblast-differentation induced by non-selective COX-In may be advantageous for example during the callus formation, "modelling" and "remodelling".