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The non-steroidal anti-inflammatory drug diclofenac reduces appearance of osteoblasts in bone defect healing in rats

  • Trauma Surgery
  • Published:
Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

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/cm³) compared to the placebo group (median 177 ± 45.4 mg/cm³).

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.

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Acknowledgments

We are grateful for the excellent technical assistance of Liselotte Mueller-Molenar, Patrizia Horny, Sonja Grueninger, and Marion Tomo. We would like to thank Novartis Pharma (Nuremberg, Germany) for their support.

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Authors and Affiliations

  1. Clinic for Traumatology, Hand, Plastic, and Reconstructive Surgery, Centre for Surgery, University of Ulm, Steinhoevelstr. 9, 89075, Ulm, Germany

    G. D. Krischak, L. Kinzl & A. Beck

  2. Trauma Centre Murnau, Prof. Küntscher Strasse 8, 82418, Murnau, Germany

    P. Augat

  3. Institute of Orthopedic Research and Biomechanics, University of Ulm, Helmholtzstr. 14, 89081, Ulm, Germany

    R. Blakytny & L. Claes

Authors
  1. G. D. Krischak
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  2. P. Augat
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  3. R. Blakytny
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  4. L. Claes
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  5. L. Kinzl
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  6. A. Beck
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Corresponding author

Correspondence to G. D. Krischak.

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Krischak, G.D., Augat, P., Blakytny, R. et al. The non-steroidal anti-inflammatory drug diclofenac reduces appearance of osteoblasts in bone defect healing in rats. Arch Orthop Trauma Surg 127, 453–458 (2007). https://doi.org/10.1007/s00402-007-0288-9

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  • DOI: https://doi.org/10.1007/s00402-007-0288-9

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