Trabecular bone cell proliferation Ex vivo increases with donor age in the rat: It is correlated with the extent of bone loss and not with histomorphometric indices of bone formation

Morphometric parameters of bone formation are markedly depressed in senescent, 21-month old rats and even in middle-aged, 12-month-old animals when compared with mature, 4-month old adults. However, osteoblast-like cells obtained from the metaphyseal trabeculae of the distal femur of 21-month-old female and male rats proliferate more rapidly in primary and secondary cultures than cells from 4-month-old donors. In females the increase in proliferation is significant for donor ages from 4 to 12 months and from 12 to 21 months. Ex vivo cell proliferation is inversely correlated with trabecular bone volume and bone surface in females and with bone surface in males. The relationships are being maintained in females (not tested in males) when cells are grown in serum-free medium. We interpret age and bone loss-dependent stimulated cell proliferation as the in vitro response to an in vivo signal to proliferate resulting from higher strains on less trabeculae. The absence of response in vivo could result from the local deficiency of factors brought back to the cells by the serum-enriched culture medium, or from proliferation inhibitors developing with age.