Mechanical loading modifies ovariectomy-induced cancellous bone loss.

The object of this study was to determine the tissue level mechanism in which mechanical loading had an influence on ovariectomy-induced cancellous bone loss. Two experiments were performed: (1) 230 g female rats were divided into basal, age-related controls and right hindlimb immobilized (RHLI) group; (2) 250 g female rats were divided into basal, age-related, ovariectomized (OVX) controls and OVX combined with RHLI. The RHLI model immobilized (IM) or underloaded (UL) the right hindlimb and loaded (L) the left hindlimb compared to the right hindlimb. Both experiments lasted 60 days. Histomorphometric data was gathered from the secondary spongiosa of double fluorescent labeled proximal tibial metaphysis (PTM). The study confirmed that IM or UL induces cancellous bone loss, by decreasing bone formation, and increasing bone resorption and OVX results in cancellous bone loss, a higher bone turnover with bone resorption exceeding bone formation in the PTM. The OVX'd and immobilized (OVX + UL) PTM showed further decreased cancellous bone mass (-48%), decreased number (-43%), and decreased tissue-level bone formation rate (-54%) from that of OVX rats. However, the OVX'd and loaded (OVX + L) PTM partially prevented the OVX-induced cancellous bone loss. The cancellous bone area (+46%), number (+29%), and ratio of node to free end (+70%) were increased and percent eroded perimeter (-44%) and bone resorption rates (-30%) were decreased from OVX rats, but cancellous bone area and number were still significantly lower than those in age-related controls. We found that IM or UL accentuated cancellous bone loss in OVX rats by inhibiting bone formation and that loading partially prevented cancellous bone loss in OVX and RHLI rats by inhibiting bone resorption.