G D Krischak1, P Augat, R Blakytny, L Claes, L Kinzl, A Beck. 1. Clinic for Traumatology, Hand, Plastic, and Reconstructive Surgery, Centre for Surgery, University of Ulm, Steinhoevelstr. 9, 89075 Ulm, Germany. gert.krischak@uniklinik-ulm.de
Abstract
INTRODUCTION: Non-steroidal anti-inflammatory drug (NSAID) is well known to significantly delay fracture healing. Results from in vitro studies implicate an impairment of osteoblast proliferation due to NSAIDs during the initial stages of healing. We studied whether diclofenac, a non-selective NSAID, also impairs appearance of osteoblasts in vivo during the early phase of healing (at 10 days). MATERIALS AND METHODS: Two defects (Ø 1.1 mm) were drilled within distal femurs of 20 male Wistar rats. Ten rats received diclofenac continuously; the other obtained a placebo until sacrificing at 10 days. Osteoblast proliferation was assessed by cell counting using light microscopy, and bone mineral density (BMD) was measured using pQCT. RESULTS: Osteoblast counts from the centre of bone defect were significantly reduced in the diclofenac group (median 73.5 +/- 8.4 cells/grid) compared to animals fed with placebo (median 171.5 +/- 13.9 cells/grid). BMD within the defect showed a significant reduction after diclofenac administration (median 111.5 +/- 9.3 mg/cm(3)) compared to the placebo group (median 177 +/- 45.4 mg/cm(3)). CONCLUSION: The reduced appearance of osteoblasts in vivo implicates an inhibiting effect of diclofenac on osteoblasts at a very early level of bone healing. The inhibition of proliferation and migration of osteoblasts, or differentiation from progenitor cells, is implicated in the delay of fracture healing after NSAID application.
INTRODUCTION: Non-steroidal anti-inflammatory drug (NSAID) is well known to significantly delay fracture healing. Results from in vitro studies implicate an impairment of osteoblast proliferation due to NSAIDs during the initial stages of healing. We studied whether diclofenac, a non-selective NSAID, also impairs appearance of osteoblasts in vivo during the early phase of healing (at 10 days). MATERIALS AND METHODS: Two defects (Ø 1.1 mm) were drilled within distal femurs of 20 male Wistar rats. Ten rats received diclofenac continuously; the other obtained a placebo until sacrificing at 10 days. Osteoblast proliferation was assessed by cell counting using light microscopy, and bone mineral density (BMD) was measured using pQCT. RESULTS: Osteoblast counts from the centre of bone defect were significantly reduced in the diclofenac group (median 73.5 +/- 8.4 cells/grid) compared to animals fed with placebo (median 171.5 +/- 13.9 cells/grid). BMD within the defect showed a significant reduction after diclofenac administration (median 111.5 +/- 9.3 mg/cm(3)) compared to the placebo group (median 177 +/- 45.4 mg/cm(3)). CONCLUSION: The reduced appearance of osteoblasts in vivo implicates an inhibiting effect of diclofenac on osteoblasts at a very early level of bone healing. The inhibition of proliferation and migration of osteoblasts, or differentiation from progenitor cells, is implicated in the delay of fracture healing after NSAID application.
Authors: Laura E Sidney; Thomas R J Heathman; Emily R Britchford; Arif Abed; Cheryl V Rahman; Lee D K Buttery Journal: Tissue Eng Part A Date: 2014-10-07 Impact factor: 3.845
Authors: Francisco Javier Manzano-Moreno; Javier Ramos-Torrecillas; Elvira De Luna-Bertos; Candela Reyes-Botella; Concepción Ruiz; Olga García-Martínez Journal: Clin Oral Investig Date: 2014-08-28 Impact factor: 3.573
Authors: I-H Song; K G Hermann; H Haibel; C E Althoff; D Poddubnyy; J Listing; A Weiss; B Freundlich; M Rudwaleit; J Sieper Journal: Ann Rheum Dis Date: 2011-05-08 Impact factor: 19.103