Time-course of mast cell accumulation in rat bone marrow after ovariectomy

We previously reported that mast cells accumulate in the tibia bone marrow of ovariectomized (OVX) rats. In this study, the timing of mast cell accumu lation and osteoclast generation were compared to determine whether or not mast cell accumulation preceded osteoclast recruitment after ovariectomy. T his may be significant because of the number of cytokines released by mast cells that are potentially active on resorption. Sprague-Dawley rats (120) aged 12 weeks were OVX or sham-operated, and killed on days 4, 7, 14, 28, a nd 56 postsurgery. Ten additional intact rats were used as baseline control s. Ovariectomy was confirmed by a sharp and sustained fall in serum estradi ol. The loss in trabecular bone volume (BV/TV) began on day 7, reaching 80% on day 56 (P < 0.001 vs baseline controls). The number of osteoclasts (N.O C/TBPm) increased in the OVX rats between days 4 and 7 (+130%; P < 0.001), and continued rising to day 28. During the next month, it decreased greatly (-63%, P < 0.001 on day 56 vs day 28). In the sham-treated rats, few mast cells were scattered in the bone marrow (1.9 cells/mm(2) in the baseline co ntrols). Their number fluctuated during the experimental period, but at eac h time-point it was lower than in the OVX rats. They were predominantly (90 %) of the mucosal subtype. In the OVX rats, their number doubled between da ys 4 and 14 (P < 0.001), reached 8.6 cells/mm(2) on day 28 (a 5.4-fold incr ease compared with day 4 OVX rats), and plateaued for the next 4 weeks. OVX had no effects on mast cell subtypes. In conclusion, mast cell accumulatio n and osteoclast differentiation are precocious and concomitant; this does not support a direct role for mast cells in osteoclast recruitment. Rather, the two cell populations may derive from a common precursor or be targeted simultaneously by estrogen depletion through common stimulator(s). Mast ce ll hyperplasia appears to be a significant, and usually unknown, manifestat ion of ovariectomy in the bone marrow environment.