Bone loss in a rat model of non-insulin-dependent diabetes mellitus, the OLETF (Otsuka Long-Evans Tokushima fatty strain) rat

Abstract

A long-term investigation of bone metabolism was conducted in a newly developed strain, the OLETF (Otsuka Long-Evans Tokushima fatty strain) rat, which spontaneously develops non-insulin-dependent diabetes (NIDDM). The OLETF rats used in this study developed hyperglycemia before the age of 24 weeks and overt diabetes before 40 weeks. The bone mineral density (BMD) of the lumbar spine peaked at the age of 24 weeks in the OLETF rats, and declined rapidly after 40 weeks. In addition, the BMD of the tibial proximal metaphysis and diaphysis and the bone strength of the femoral diaphysis peaked at 40 weeks, then declined rapidly. In contrast, the BMD and the bone strength of the LETO (Long-Evans Tokushima Otsuka) rats, used as a control, peaked at 24 weeks, and did not change thereafter. The serum vitamin D metabolites [25-hydroxy vitamin D (25-OHD), 24,25-dihydroxyvitamin D (24,25(OH)2D), and 1,25-dihydroxy vitamin D (1,25(OH)2D)] levels for the OLETF rats declined with age, and were significantly lower than those of the control LETO rats. The level of serum bone-specific alkaline phosphatase (Alp) activity and serum tartrate-resistant acid phosphatase (Tr-Acp) activity in the OLETF rats increased remarkably with age from 24 weeks, and there were significant differences in the 56- and the 69-week values between the OLETF rats and the age-matched control LETO rats. These results suggested that this strain can serve as a useful model for NIDDM with osteopenia.