D. Guez et al., Impact of the timing of indomethacin treatment in a model of synchronized bone remodelling in rats, EXP PHYSIOL, 86(3), 2001, pp. 373-379
Prostaglandins (PGs) promote both bone resorption and formation ill vitro a
nd in vivo. In a synchronised model of bone remodelling, indomethacin, an i
nhibitor of PG synthesis, given from the start of the sequence, transiently
impaired bone resorption, In this study we further explored the involvemen
t of PGs in this model by treating rats,vith indomethacin (7.5 mg kg(-1) da
y(-1)) for 6 days from the peak of resorption (day 4 after activation in th
is model) or during reversal (day 6 after activation). In rats treated from
day 4, the resorption surface (Oc.S/BS) and the number of osteoclasts (N.O
c/BPm) were higher on day 10 (+69%, P < 0.01, and +60%, P < 0.02 compared w
ith controls, respectively); no effect on cell resorptive activity was obse
rved. The bone formation surface (OS/BS) was reduced (-50%, P < 0.01). The
inactive surface (ln/BS) was not modified. In rats treated from day 6, the
Oc.S/BS was also higher than in controls (P < 0.02), as was the N.Oc/BPm (P
< 0.05). Osteoclast activity appeared to be increased, as the osteoclast-b
one interface was larger (P < 0.02), but the mean lacuna area was reduced (
-23%, P < 0.05). Bone formation was also strongly affected: the OS/BS was d
ecreased (-66%, P < 0.01), as was the osteoid seam thickness (-24%, P < 0.0
5), The In/BS was increased 1.5-fold (P < 0.05). These data indicate that P
Gs intervene at various stages of tills remodelling sequence, as both resor
ption and formation were affected by indomethacin. Although resorption resu
med in the two treatment groups despite treatment continuation, the timing
of treatment was clearly important. Only inhibition of PG synthesis at the
peak of resorption delayed all phases of the remodelling sequence. In contr
ast, inhibition during the reversal phase prevented activation of a signifi
cant part of the bone surface usually involved at this stage of remodelling
; this treatment schedule reduced the resorptive capacity of the system, an
d depressed osteoblast activity.