ANALYSIS OF WHOLE SKELETON H-3 TETRACYCLINE LOSS AS A MEASURE OF BONE-RESORPTION IN MATURING RATS

Several modifications of the H-3-tetracycline bone labeling method for measuring whole skeleton bone resorption were tested. Under steady st ate conditions of whole skeleton resorptive activity, bone labeling fo r intervals longer than 2 weeks prior to experimentation did not signi ficantly alter the urinary H-3-tetracycline loss curve. The utilizatio n of nonlinear regression analysis showed that the urinary loss of H-3 -tetracycline was best described by double exponential equations, indi cating the loss of label from two distinct and independent exchangeabl e bone compartments. This conclusion was supported by the finding that soft tissues were effectively depleted of H-3-tetracycline by 24 hour s after the final injection of label. Hence, it was concluded that app roximately 40% of the H-3-tetracycline loss from skeletal bone is asso ciated with a ''fast'' compartment which is depleted within 6 or 7 day s after label loading. The size and rate of H-3-tetracycline loss from the fast compartment decreased (40%) with age such that the depletion time remained constant between 8 and 24 weeks of age in both male and female rats. The remaining 60% of H-3-tetracycline loss from a ''slow '' compartment which was depleted in about 70 days in young (8 week) r ats. This compartment, which is believed to reflect cell-mediated reso rption of calcified bone, decreased in size with age in both male (50% ) and female (30%) rats. The rate of label loss from this compartment, however, remained relatively high so that the depletion time decrease d (similar to 35%) between 8 and 24 weeks of age. By determining whole skeletal mass and calculating these parameters on the basis of skelet al mass, we were further able to demonstrate significantly higher reso rptive activity in female than in male rats by 24 weeks of age.