The Hyperglycemia and Hyperketonemia Impaired Bone Microstructures: A Pilot Study in Rats

Though diabetes mellitus (DM) is one of the known causes of osteoporosis, it is also realized that ketogenic diet (KD), an effective regimen for epilepsy, impairs bone microstructures. However, the similarities and differences of effects between these two factors are still unknown. The purpose of this study is to identify different effects between hyperglycemia and hyperketonemia, which are manifestations of DM and KD, on bone in rats. Thirty male Sprague-Dawley rats were randomly divided into three groups: the sham, DM, and KD groups. Hyperglycemia was achieved by intravenous injection of streptozotocin in DM group, while hyperketonemia was induced by application of ketogenic diet (carbohydrates-to-fat as 1:3) in KD group. The body weight, blood ketone body, and blood glucose were recorded, and the bone turnover markers, bone length, bone microstructures, bone biomechanics and histomorphology were measured after 12 weeks intervention. Compared with the control and KD groups, a significant body weight loss was found in the DM group, and the bone lengths of tibia and femur of the group were shortened. The blood glucose and blood ketone were noticeably increased in the DM and KD rats, respectively. Microstructures and properties of cancellous bone were significantly deteriorated in both the DM and KD groups compared with the sham group, as the bone volumes were decreased and the bone trabecula structures were disturbed. Meanwhile, the thickness and strength of cortical bone was reduced more in the DM group than those in the sham and KD groups. The HE staining showed that bone trabecula was significantly decreased in both the DM and KD groups, and more adipose tissue was observed in the KD rats. The activity of osteoblasts was decreased more in both the KD and DM groups than that in the sham group, while the activity of osteoclasts of the two groups was remarkably increased. The present study indicates that both hyperglycemia and hyperketonemia have adverse effects on bone. Therefore, it is worth paying more attention to the bone status of patients with hyperglycemia and hyperketonemia in clinic.