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


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)).


CONCLUSIONS
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.
Krischak
G D
GD
Clinic for Traumatology, Hand, Plastic, and Reconstructive Surgery, Centre for Surgery, University of Ulm, Steinhoevelstr. 9, 89075 Ulm, Germany. gert.krischak@uniklinik-ulm.de
Augat
P
P
Blakytny
R
R
Claes
L
L
Kinzl
L
L
Beck
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects; D004008:Diclofenac / Q000009:adverse effects*; D017102:Fracture Healing / Q000187:drug effects*; D008297:Male; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac