The roles of exercise and fall risk reduction in the prevention of osteoporosis.

In summary, the optimal model for the prevention of osteoporotic fractures includes maximization and maintenance of bone strength and minimization of trauma. Numerous determinants of each have been identified, but further work to develop preventative strategies based on these determinants remains to be undertaken. Physical activity is a determinant of peak BMD. There also is evidence that activity during growth modulates the external geometry and trabecular architecture, potentially enhancing skeletal strength, while during the adult years activity may reduce age-related bone loss. The magnitude of the effect of a 7% to 8% increase in peak BMD, if maintained through the adult years, could translate to a 1.5-fold reduction in fracture risk. Moreover, in the older population, appropriate forms of exercise could reduce the risk of falling and, thus, further reduce fracture risk. These data must be considered as preliminary in view of the paucity of long-term fracture outcome data from randomized clinical trials. However, current information suggests that the optimal form of exercise to achieve these objectives may vary through life. Vigorous physical activity (including weight-bearing, resistance, and impact components) during childhood may maximize peak BMD. This type of activity seems optimal through the young adult years, but as inevitable age-related degeneration occurs, activity modification to limit the impact component of exercise may become necessary. In the elderly, progressive strength training has been demonstrated to be a safe and effective form of exercise that reduces risk factors for falling and may also enhance BMD. In the frail elderly, activity to improve balance and confidence also may be valuable. Group activities such as Tai Chi may be cost-effective. Precise prescriptions must await the outcome of well-designed, controlled longitudinal studies that include fracture as an outcome. However, increased physical activity seems to be a sensible component of strategies to reduce osteoporotic fracture.

Modulation of human tumor colony growth in soft agar by serum.

The factors controlling the growth of human tumor cells in soft agar are poorly understood. However, it has been demonstrated that serum provides factors which promote anchorage-independent growth. We tested 58 tumor specimens, which were obtained from patients with adenocarcinoma of the lung, colon, ovary or squamous cell carcinoma, for their ability to form colonies in soft agar in serum-free or serum-supplemented media. The cells were unable to replicate, and none of the hormones or growth factors tested: insulin (I), transferrin (T), selenium (S), estradiol (E), hydrocortisone (H) or epidermal growth factor (EGF) could substitute for serum. Examination of the serum dose-response curves indicated that growth factors reduced the serum concentrations needed to support anchorage-independent growth. The addition of the supplements and the lowering of serum concentrations increased cloning efficiencies (C.E.) in 38/51 trials, when cells were able to grow initially. The addition of ITS increased C.E. in 18/21 cases, HITES in 15/17 cases and EGF in 12/18 cases as compared to controls. ITS and HITES increased the number of colonies only when serum was the limiting factor. EGF, however, increased the number of colonies even when serum was not the limiting factor. The ability of the supplements to enhance growth could not be correlated to tumor type or initial cloning efficiencies. However, in only 1/25 cases were cells that were unable to form colonies under standard conditions induced to form colonies in the presence of the growth factors. Normal and tumor-derived human fibroblasts did not form colonies in soft agar in the presence of these growth factors. The results suggest that human tumor cells may require the presence of serum-derived factors for growth in soft agar.