Skeletal changes in type-2 diabetic Goto-Kakizaki rats

Abstract

We characterized appendicular and axial bones in rats with type-2 diabetes in five female Goto-Kakizaki (GK) rats, a strain developed from the Wistar rat showing spontaneous type-2 diabetes, and five age-and sex-matched nondiabetic Wistar rats. The humerus, tibia, metatarsals and vertebral bodies were analysed by peripheral quantitative computerized tomography (pQCT). In diabetic rats, the height of the vertebral bodies and length of the humerus were decreased while the length of the metatarsals was increased. A decreased cross-sectional area was found in the vertebral end-plate region and the tibial metaphysis. Notably, the diaphysis in all long bones showed expansion of periosteal and endosteal circumference. In tibia this resulted in increased cortical thickness, whereas in humerus and metatarsal it was unchanged. Areal moment of inertia was increased in all diaphyses suggesting greater bending strength. The most conspicuous finding in diabetic rats pertained to trabecular osteopenia. Thus, trabecular bone mineral density was significantly reduced in all bones examined, by 33-53%. Our pQCT study of axial and appendicular bones suggests that the typical feature of diabetic osteopathy in the GK rat is loss of trabecular bone and expansion of the diaphysis. The loss of metaphyseal trabecular bone if also present in diabetic patients may prove to underlie the susceptibility to periarticular fracture and Charcot arthropathy. The findings suggest that the risk of fracture in diabetes varies according to the specific sub-regions of a bone. The approach described may prove to be useful in the early detection of osteopathy in diabetic patients who may be amenable to preventive treatment.

Warfarin-induced impairment of cortical bone material quality and compensatory adaptation of cortical bone structure to mechanical stimuli

“…For example, type 2 diabetic patients have an increased fracture risk independently of areal BMD (Schwartz et al 2001, Strotmeyer et al 2005 and their circulating osteocalcin levels are low (Okazaki et al 1997). Consistent with our results, mid-shaft cortical bones of type 2 diabetic rats showed expansion of periosteal and endosteal circumferences (Ahmad et al 2003) and vitamin K treatment improved bone fragility by modifying minerals in these rats (Wada et al 2000).…”

Altered bone mass, geometry and mechanical properties during the development and progression of type 2 diabetes in the Zucker diabetic fatty rat

“…The estimated bending strength of the humeral and tibial diaphyses in Goto-Kakizaki rats has been reported to be higher relative to Wistar control animals (Ahmad et al 2003). The present study offers a more complete determination of bone strength changes with type 2 diabetes, with direct measurement of mechanical properties during the three stages of development and progression of type 2 diabetes.…”

“…By 20 weeks of age, these long bones were 7-8% shorter than bones of age-matched lean controls. Interestingly, the increase in long bone diameters and CSMI observed in Goto-Kakizaki rats, another rodent model of type 2 diabetes (Ahmad et al 2003), was not observed in the ZDF rats. In fact, data from the present study provide evidence for reduced radial growth as illustrated by smaller CSMI values in the long-term diabetic (20 weeks of old) rats.…”

Genetic loci for bone architecture determined by three-dimensional CT in crosses with the diabetic GK rat

“…Differences in bone structure, BMD and fragility phenotypes between inbred strains of rats have been identified including the non-diabetic F344 and the type-2 diabetic GK strain [8][9][10].…”