SHORT-TERM IMMOBILIZATION-INDUCED CANCELLOUS BONE LOSS IS LIMITED TO REGIONS UNDERGOING HIGH TURNOVER AND OR MODELING IN MATURE RATS/

Estrogen and calcium deficiencies increase both bone resorption and fo rmation, whereas immobilization mainly decreases bone formation. How t hese functionally different risk factors for bone loss interact in can cellous bone undergoing modeling or remodeling activity is not well un derstood. Mature (6-month-old) female rats were subjected to sham oper ation (sham), ovariectomy (ovx), dietary calcium deficiency (LoCa, 0.1 % Ca), and sciatic and femoral denervation (IM), ovx + IM, or LoCa + I M for 4 weeks. The primary spongiosa, the region of active modeling wi thin I mm of the growth plate, in ovx, LoCa, and IR?I groups showed a decrease in cancellous bone volume, trabecular number, and connectivit y when compared to sham controls. Groups combining two risk factors ex hibited additive changes when compared with single risk factor groups. In the secondary spongiosa, an area with little modeling activity, ov x and LoCa groups, as expected, lost bone. In contrast with the primar y spongiosa, IM alone did not induce bone loss in the secondary spongi osa, and the groups with a combination of IM and ovx or IM and LoCa sh owed a greater bone loss than either ovx or LoCa alone. Ovx and LoCa g roups showed increases in both bone formation rate and eroded surface in the secondary spongiosa, while IPI I groups showed a decrease in bo ne formation rate. Combining IM with either ovx or LoCa resulted in in creased eroded surface. The effects on cortical bone were assessed at the tibio-fibular junction. A trend toward decreased percentage of cor tical bone area and an increase in marrow cavity area mere observed in the combined deficiency groups only. These changes were the result of a statistically significant increase in endosteal eroded surface in I M + ovx and IM + LoCa groups. Our results demonstrate that immobilizat ion-induced bone loss is restricted to the primary spongiosa where mos t modeling events occur. However, the inhibitory effect of IM on bone formation in the secondary spongiosa is unmasked in remodeling sites w hen a high turnover state is provided by either estrogen or dietary ca lcium deficiency. These results suggest that the presence of a risk fa ctor, such as immobilization, which in the short term causes inhibitio n of bone formation, does not predispose the skeleton to rapid cancell ous bone loss except when accompanied by modeling or high turnover. (C ) 1997 by Elsevier Science Inc. All rights reserved.