Osteoporosis and Diabetes: Lessons from the Diabetic BB Rat

Abstract

The spontaneously diabetic BB rat was used to study the effect of diabetes on bone. Short-term diabetes (3–4 weeks) resulted in a state of low bone turnover, characterized by a severe decrease in osteoblast/osteoid surface and bone mineral apposition rate on histology, and in serum osteocalcin concentrations. If diabetes was long-term (12 weeks), the parameters of low bone formation were associated with histological evidence of osteoporosis and a decreased bone strength; the relative bone calcium concentration remained normal in diabetes. We conclude that long-standing diabetes results in a low-turnover osteoporosis.

The Impact of Diabetes and Diabetes Medications on Bone Health

“…Verhaeghe et al (22) showed that serum osteocalcin (a marker of osteoblast function) levels were decreased in diabetic rats compared with those of nondiabetic controls. Recently, Achemlal et al (23) investigated biochemical markers of bone turnover in male patients with poorly controlled T2DM receiving treatment with metformin, or a sulfonylurea, or both.…”

Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues

“…Bone strength has also been shown to be diminished in T1DM rats at the femur and the femoral neck (16,48). In a number of T1DM animal studies, histomorphometric analyses have shown that, irrespective of the model used, insulindeficient rats may exhibit reduced or absent bone formation and this decline is appreciated in relation to all bone surfaces examined, i.e., trabecular, periosteal, and endocortical (132)(133)(134). The major deficits in these insulin-deficient models appear to be related to a deficit in mineralized surface area, a decrement in the rate of mineral apposition, deceased osteoid surface, depressed osteoblast activity, and decreased numbers of osteoclasts (34,104,112,135), leading to an overall depression in remodeling of bone in the untreated insulin-deficient state.…”

Characteristics of Diabetic Osteopenia in KK-Ay Diabetic Mice

“…However the time of its determination varied in each study so that the time of decreases was not clear, though there are a few studies using animal models that show that it decreases from the early stage of diabetes, which is within five weeks from onset. 18,36) The association with the time when BMD decreases has not been clarified, either. We found a lower blood osteocalcin level at 18 weeks old when the BMD of the proximal region was low, whereas there was no significant difference at 8 weeks old.…”

“…18,19,26,[35][36][37][38][39] But the time of its measurement was variable in each study and blood osteocalcin level has not been considered in its relationship with change in BMD or duration of diabetes. In the present study, we examined the BMD of the proximal region and the mid-diaphysis of the femur to clarify the characteristics of diabetic osteopenia using DXA and the relationship with blood osteocalcin or glucose level in KK-Ay mice, an animal model of type 2 diabetes.…”