Decreased bone anabolic effect of basic fibroblast growth factor at fatty marrow sites in ovariectomized rats

Abstract

The purpose of the study was to compare the bone anabolic effects of basic fibroblast growth factor (bFGF) at hematopoietic (red) and fatty (yellow) marrow sites in ovariectomized (ovx) rats. Female Sprague Dawley rats were subjected to ovariectomy or sham surgery at 3 months of age and maintained untreated for 2 months after surgery. Three groups of ovx rats were then injected intravenously with bFGF for 14 days at a dose of 200 μg/kg body weight. One group of bFGF-treated OVX rats was killed at the end of the treatment period, whereas the other two groups were killed at 7 or 14 days after withdrawal of bFGF treatment. Another group of ovx rats and a group of sham-operated control rats were treated intravenously with vehicle alone for 14 days. The proximal tibia and first lumbar vertebra, bone sites with hematopoietic marrow, as well as the distal tibia and caudal vertebra, bone sites with primarily fatty marrow, were processed undecalcified for quantitative bone histomorphometry. At the hematopoietic marrow sites, bFGF treatment induced a marked accumulation of osteoid, which calcified during the withdrawal period to result in a significant increase in cancellous bone volume. Osteoblast and osteoid surfaces were increased by at least a factor of 10 at these sites in bFGF-treated ovx rats before declining rapidly during the withdrawal period. In contrast, osteoid volume was negligible in the fatty marrow sites of bFGF-treated ovx rats. Although these animals exhibited a nonsignificant trend for increased cancellous bone volume in the fatty distal tibia during the withdrawal period, no such trend was observed in the fatty caudal vertebra. Indices of bone formation (osteoblast and osteoid surfaces) were significantly increased by bFGF treatment in the fatty distal tibia, which retained some small pockets of hematopoietic cells, but not to the same great extent as in the skeletal sites with hematopoietic marrow. Furthermore, not even a trend for increased osteoblast and osteoid surfaces was observed in the fatty caudal vertebra of bFGF-treated ovx rats. These findings indicate that bFGF is a strong bone anabolic agent at skeletal sites with hematopoietic marrow, but the stimulatory effects of the growth factor on bone formation are greatly attenuated at fatty marrow sites.