Response of the osteocyte syncytium adjacent to and distant from linear microcracks during adaptation to cyclic fatigue loading.

Cyclic loading induces fatigue in bone and initiates a complex, functionally adaptive response. We investigated the effect of a single period of fatigue on the histologic structure and biomechanical properties of bone. The ulnae of 40 rats were subjected to cyclic fatigue (-6000 microepsilon) unilaterally until 40% loss of stiffness developed, followed by 14 days of adaptation. The contralateral ulna served as a treatment control (n = 20 rats), and a baseline loaded/non-loaded group (n = 20 rats/group) was included. Bones from 10 rats/group were examined histologically and the remaining bones (10 rats/group) were tested mechanically. The following measurements were collected: volumetric bone mineral density (vBMD); ultimate force (Fu); stiffness (S); energy-to-failure (U); cortical area (Ct.Ar); microcrack density (Cr.Dn); microcrack mean length (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar and Ot.N/TV); bone volume fraction (B.Ar/T.Ar); resorption space density (Rs.N/Ct.Ar); and maximum and minimum area moments of inertia (IMAX and IMIN). Using confocal microscopy, the bones were examined for diffuse matrix injury, canalicular disruption, and osteocyte disruption. The adapted bones had increased B.Ar, IMAX, and IMIN in the mid-diaphysis. Fatigue loading decreased structural properties and induced linear microcracking. At 14 days, adaptation restored structural properties and microcracking was partially repaired. There was a significant nonlinear relationship between Ot.N/T.Ar and B.Ar/T.Ar during adaptation. Disruption of osteocytes was observed adjacent to microcracks immediately after fatigue loading, and this did not change after the period of adaptation. In fatigue-loaded bone distant from microcracks, diffuse matrix injury and canalicular disruption were often co-localized and were increased in the lateral (tension) cortex. These changes were partially reversed after adaptation. Loss of canalicular staining and the presence of blind-ends in regions with matrix injury were suggestive of rupture of dendritic cell processes. Taken together, these data support the general hypothesis that the osteocyte syncytium can respond to cyclic loading and influence targeted remodeling during functional adaptation. Changes in the appearance of the osteocyte syncytium were found in fatigue-loaded bone with and without linear microcracks. We hypothesize that the number of dendritic cell processes that experience load-related disruption may determine osteocyte metabolic responses to loading and influence targeted remodeling.