Flurbiprofen-induced stimulation of periosteal bone formation and inhibition of bone resorption in older rats.
The skeletal effects of flurbiprofen (Fb), a nonsteroidal anti-inflammatory drug, was studied by histomorphometry in 9-month-old retired female breeder, Sprague-Dawley rats. Flurbiprofen was given subcutaneously at 0, 0.2, 0.1, 0.5, 2.5, or 5 mg/kg/d for 21 days. Flurbiprofen had no effect on longitudinal growth, but stimulated radial growth (+200%) over controls. In the tibial shaft, Fb stimulated the mineral apposition rate (+25%), mineral bone formation rate (+100%), and periosteal labeling length (+64%) at the 2.5 and 5.0 mg Fb/kg dose levels, and had no effect on marrow cavity size compared to controls. However, these changes were insufficient to increase cortical bone mass. In the proximal tibial metaphysis, Fb suppressed osteoclasts/mm2 of metaphyseal tissue (-47%), osteoclasts/mm of bone surface (-46%), and the osteoclast/osteoblast ratio (-50%), increased the calcified cartilage core population (+100%), and had no effect on osteoblast numbers at all dose levels. There was an insignificant increase in metaphyseal cancellous bone mass. The current study leads to the conclusion that flurbiprofen-stimulated periosteal bone growth was due to direct stimulation of osteoblast recruitment and activity independent of longitudinal bone growth. Further, it confirms early findings in young rats that flurbiprofen induced depressed bone resorption without lowering bone formation. However, because of insufficient treatment time, the older rat did not accumulate bone as the young rats did.
Jee
W S
WS
Radiobiology Division, University of Utah School of Medicine, Salt Lake City 84112.
Li
X J
XJ
Li
Y L
YL
D000367:Age Factors; D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control*; D005260:Female; D005480:Flurbiprofen / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*; D010521:Periosteum / Q000187:drug effects*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011422:Propionates; D005480:Flurbiprofen