TRABECULAR BONE CELL-PROLIFERATION EX-VIVO INCREASES WITH DONOR AGE IN THE RAT - IT IS CORRELATED WITH THE EXTENT OF BONE LOSS AND NOT WITHHISTOMORPHOMETRIC INDEXES OF BONE-FORMATION

Morphometric parameters of bone formation are markedly depressed in se nescent, 21-month old rats and even in middle-aged, 12-month-old anima ls when compared with mature, 4-month old adults. However, osteoblast- like cells obtained from the metaphyseal trabeculae of the distal femu r of 21-month-old female and male rats proliferate more rapidly in pri mary and secondary cultures than cells from 4-month-old donors. In fem ales 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 ma intained in females (not tested in males) when cells are grown in seru m-free medium. We interpret age and bone loss-dependent stimulated cel l proliferation as the in vitro response to an in vivo signal to proli ferate resulting from higher strains on less trabeculae. The absence o f response in vivo could result from the local deficiency of factors b rought back to the cells by the serum-enriched culture medium, or from proliferation inhibitors developing with age.