TYPE-I COLLAGEN MUTATION ALTERS THE STRENGTH AND FATIGUE BEHAVIOR OF MOV13 CORTICAL TISSUE

Despite advances in understanding the molecular basis of Osteogenesis Imperfecta, the mechanisms by which type I collagen mutations compromi se whole bone function are not well understood. Previously, we have sh own that a heterozygous type I collagen mutation is associated with in creased brittleness of long bones from Mov13 transgenic mice, a model of the mild form of Osteogenesis Imperfecta. In the current study, we investigated tissue-level damage processes by testing the hypothesis t hat the fatigue properties of Mov13 tissue were significantly compromi sed relative to littermate controls. We also quantified tissue structu re and mineral content to explain variations in the fatigue behavior. Micro-beam specimens were machined from the anterior and posterior qua drants of Mov13 and control femurs and subjected to cyclic bending at one of four stress levels. Mov13 tissue exhibited a 22-25% reduction i n tissue bending strength and a similar reductions in fatigue life and the stress level at which damage was apparent. These results provided tissue-level evidence that damage accumulation mechanisms were signif icantly compromised in Mov13 cortical tissue. Given that significant a lterations in tissue structure were observed in Mov13 femurs, the resu lts of this study support the idea that Mov13 femurs were brittle beca use alterations in tissue structure associated with the mutation inter fered with normal damage processes. These results provide new insight into the pathogenesis of Osteogenesis Imperfecta and are consistent wi th bone behaving as a damaging composite material, where damage accumu lation is central to bone fracture. (C) 1997 Elsevier Science Ltd. All rights reserved.