Cancellous bone of aged rats maintains its capacity to respond vigorously to the anabolic effects of prostaglandin E₂ by modeling-dependent bone gain

Abstract

The present study examined the early effects of prostaglandin (PG)E₂ on proximal tibial metaphyses of 20-month-old Wistar male rats. PGE₂ was given to intact rats for 10 and 30 days at 3 mg/kg/day. After multiple in vivo fluorochrome labeling, undecalcified longitudinal sections were subjected to analysis of bone histomorphometry and classification of the contour of the cement line in bone formation units. The latter was used to classify bone formation units into modeling, remodeling and uncertain units. After 10 days of treatment, there was a 2% increase in woven bone formation with the appearance of osteoprogenitor cells and increases in the number of osteoblasts (649%) and osteoid (375%) surfaces. Remodeling and modeling units increased by 56% and 429%, respectively. After 30 days of treatment, there was an increase of 212% of total trabecular bone mass, 60% of which was woven bone. In addition, there were increases in labeling surface (147%), mineral apposition rate (760%), bone formation rates tissue area (BFR/T.Ar, 1920%; BFR/B.Pm, 343%), and bone turnover (BFR/B.Ar, 426%). Osteoblasts and osteoid production at 30 days were 29% and 58% less than at 10 days post-treatment. Modeling and remodeling activity did not differ from that seen at 10 days. In addition, PGE₂ treatment tended to stimulate the closing of growth plates and decrease the fatty marrow area. We conclude that the aged skeleton was able to respond vigorously to PGE₂ treatment. Massive osteoprogenitors cells, and osteoid and osteoblast formations were observed within 10 days, and dramatic woven and lamellar bone formation was seen at 30 days post-treatment. The anabolic effects were driven mainly by modeling.