AGE-RELATED BONE LOSS - A HYPOTHESIS AND INITIAL ASSESSMENT IN MICE

The osteopenia associated with advanced age appears to be a universal phenomenon in humans and animals, but the mechanisms by which it occur s are understood incompletely. However, the explanation must lie in an absolute or relative diminution in the level of osteoblastic bone-for ming activity when compared with osteoclastic bone-resorbing activity. The authors postulated that with old age there would be a reduction i n the number or function or both of osteoblastic stem cells that could account for part of the diminution in bone formation. They further po stulated that there would be either no change or an increase in osteoc lastic potential and bone resorption. To test these concepts, bone mar row cells were isolated from 4- to 6-month-old or 24-month-old mice an d cultured in vitro under a variety of circumstances that permitted an assessment of the stromal osteogenic cells and marrow hemopoietic pro genitor cells belonging to the monocyte and osteoclast series. These d ata show a marked reduction in the number and in vitro activity of str omal osteogenic cells from old animals. There is an increase in old mi ce in the number of marrow cells capable of forming osteoclasts in coc ulture and responsive to the growth factors believed operational in th e monocyte and osteoclast series. The authors now are exploring the hy pothesis that an age-related diminution in transforming growth factor- beta levels is responsible for these changes in progenitor cell levels in marrow and their functional status as expressed in vitro. The data to date are consistent with age-related changes in osteoblast and ost eoclast precursor pools contributing to the loss of bone mass in Type II osteoporosis (osteopenia).