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

Abstract

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.

Protective effects of low-magnitude high-frequency vibration on high glucose-induced osteoblast dysfunction and bone loss in diabetic rats

“…The morphological and microstructural character variations of the femur were examined. The measurement of the femur indicated that hyperglycaemia-induced bone showed a decrease in length and width in this study, which was consistent with previous studies [ 37 , 38 ]. Augmented length and width of the femur in the LMHFV group showed the protective effect of LMHFV in bone against diabetes.…”

The Comparative Study on the Status of Bone Metabolism and Thyroid Function in Diabetic Patients with or without Ketosis or Ketoacidosis

“…According to recent rat research, hyperketonemia, like hyperglycemia, harms bone microstructure and is linked to abnormal bone turnover indicators. 18 To the best of our knowledge, there have been few direct reports on the relationship between DKA, particularly recurrent DKA (RDK), and changes in bone parameters. According to one study, the observed severe negative calcium balance in DKA was caused by decreased bone formation independent of calciotropic hormones represented by OCN due to severe insulin deficiency and secondarily by metabolic acidosis.…”

Dietary Complex and Slow Digestive Carbohydrates Promote Bone Mass and Improve Bone Microarchitecture during Catch-Up Growth in Rats

“…In animals, catch-up growth was demonstrated to promote insulin resistance through dysfunction of the adipose tissue [ 41 ]. In addition, it has also been shown that hyperinsulinemia, together with an impaired control of the blood glucose levels, is associated with decreased bone mass and defective bone microarchitecture [ 14 , 42 ]. In this sense, studies conducted in streptozotocin-induced diabetic adult rats, which are characterized by induced hyperglycemia, have observed that diabetic animals display lower BMD and connection density along with compromised bone microstructure compared to control healthy rats [ 14 ].…”

“…In this regard, not only the quantity but also the quality of CHO presented in diets is important, since a nutrition consisting of carbohydrates with a high glycemic index, as a measure of their quality, elicits a higher glycemic response that could impair bone metabolism. Hence, rapid digestible carbohydrates (RDC), which deliver a faster glycemic response, might negatively affect bone health [ 13 , 14 ]. On the other hand, slow digestible carbohydrates (SDC) induce a more sustained glycemic response characterized by a less pronounced postprandial rise in blood glucose and insulin [ 15 , 16 ].…”

“…On the other hand, slow digestible carbohydrates (SDC) induce a more sustained glycemic response characterized by a less pronounced postprandial rise in blood glucose and insulin [ 15 , 16 ]. Notably, hyperglycemia has been linked to reduced osteoblast numbers and function along with inhibited osteoblast maturation and bone mineralization [ 13 , 14 ]. Thus, SDC might support bone growth and development during the catch-up period.…”