1584 PARFITT except for its connection with the marrow sinusoids, there seems to be no pathway for marrow derived preosteoblasts to reach sites of bone formation, and any such pathway would breach the barrier between the inside and the outside of the marrow vessels. There is no evidence that circulating precursor cells contribute significantly to bone formation as they do to bone resorption.(18) The only way I can see out of this dilemma is that the canopy cells themselves are the origin of preosteoblasts, as Rasmussen and Bordier proposed (2) and as Hauge et al. discuss at length.(6) The BRC canopy cells have much stronger expression of the osteoblast phenotype than do the lining cells from which they began.(6) Because the area covered by a lining cell is much larger (by a factor of at least 5) than the area covered by an osteoblast,(1) and because neither BRC canopy cells nor lining cells have been observed to divide, there must be a flow of cells into the BRC canopy from another source. One such source has already been mentioned—the sinusoid endothelial cells involved in the genesis of the BRC—but it seems likely that marrow stromal cells, already known to be the major source of preosteoblasts,(27) make the largest contribution. Whatever the explanation, it seems that coupling of formation to resorption in cancellous bone depends on local signals within the BRC,(6) and not, as in cortical bone, on sequential changes in gene expression in the BMU capillary.(18)