The purpose of this experimental work was to investigate whether apoptosis 
contributes to tissue remodelling during distraction bone healing. In a rabbit 
model of mandibular distraction osteogenesis, we quantitatively analysed the 
extent of apoptotic cell death in relation to differently applied mechanical 
loadings. Apoptotic cells were identified by means of an in situ detection assay 
for nuclear DNA fragmentation using a modified TUNEL procedure and by electron 
microscopical examination for typical morphological features of programmed cell 
death. TUNEL-positive cells were frequently detected in samples distracted at 
higher strain magnitudes. Ultrastructurally, these apoptotic cells displayed a 
condensed chromatin and fragmented nuclei, while the continuity of their plasma 
membranes remained intact. Our results clearly indicated that the discontinuous 
traction of osteotomized mandibles induced enhanced apoptosis. In contrast to 
non-distracted samples and mandibles distracted at low strain magnitudes, in 
which only minimal evidence of apoptotic cell death was detected, the 
application of hyperphysiological strain magnitudes resulted in an increased 
apoptosis rate. Thus, mechanical loading seems to be a triggering factor for 
apoptotic changes in osteoblastic cells. These findings suggest a 
pathophysiological role of apoptotic cell death in the control of tissue 
integrity during distraction osteogenesis.