BONE DIMENSIONAL CHANGE WITH AGE - INTERACTIONS OF GENETIC, HORMONAL,AND BODY-SIZE VARIABLES

Changes in bony dimensions with age were assessed longitudinally from standardized X-ray films in 170 middle-aged Caucasian women, starting at age 40 years and with a median duration of observation of 21.125 ye ars. Consistent with earlier work, cortical area of the metacarpals an d radial shaft declined with age at rates ranging from 0.57 to 0.86%/y ear. As predicted, estrogen replacement therapy decreased this loss in a dose-dependent manner. Not previously reported is the fact that wei ght gain over the period of observation reduced upper extremity bone l oss. Moreover, this protection was independent of the estrogen effect. In contrast with bone loss in the upper extremity, both femur shaft d iameter and femur shaft cortical area increased significantly with age (0.23 and 0.26%/year, respectively). Estrogen replacement therapy inh ibited femur shaft expansion but had no effect on femur cortical area. Weight change, however, strongly influenced gain (or loss) of femur c ortical area: those in the highest weight change tertile gained 4 time s as much cortical area as those in the lowest weight change tertile. VDR genotype also significantly influenced femoral shaft changes: wome n with the bb genotype had both greater shaft expansion and a greater increase in cortical area. The VDR effects were independent of the eff ects of weight change and estrogen. Femoral shaft expansion was of suf ficient magnitude to suggest that the mechanical properties of the ent ire femur may change appreciably with age. Finally, contrary to widesp read belief, there was significant, if modest, expansion at the femora l neck with age.