Effects of heparin and low-molecular-weight heparins on bone mechanical properties in rats

Abstract

Long-term administration of heparin can be associated with development of osteoporosis. The present study was carried out to compare the effects of standard heparin and two low-molecular-weight heparins (nadroparin and enoxaparin) on bone mechanical properties in rats. The experiment was conducted on 3-month-old female Wistar rats. Standard heparin was administered in doses of 1000 or 2000 IU/kg sc daily, nadroparin and enoxaparin were administered in doses of 1000 or 2000 anti-Xa IU/kg sc daily, for 28 days. Bone mass, length, diameter, mineral content and mechanical properties of the whole femur (extrinsic stiffness, ultimate and breaking load, deformation caused by the applied load) and the femoral neck (load at fracture) were examined. Standard heparin (2000 IU/kg sc daily) weakened the femoral neck. Enoxaparin and the higher doses of standard heparin and nadroparin induced similar unfavourable changes in mechanical properties of the whole femur; the changes were noticeable the most after administration of enoxaparin.

Effects of propranolol on the development of glucocorticoid-induced osteoporosis in male rats

“…The bone was prepared for measurement by fixing the diaphysis, which was cut at the mid-length of the femur, in a methacrylate plate [16]. The load was applied to the head of the femur along the long axis of the femur (preload of 1 N, displacement rate of 0.01 mm/s).…”

The influence of low molecular weight heparin on the expression of osteogenic growth factors in human fracture healing

“…However, the findings of in vivo animal studies of the effect of LMWHs on fracture healing remain contentious and no conclusive findings can be drawn from these studies [6,8,9]. Nevertheless, in vitro studies on bone cells [10][11][12] and in vitro studies on bone metabolism [6,[13][14][15][16][17] demonstrate that LMWHs decrease bone formation and, therefore, could potentially delay fracture healing. Evidence exists that LMWHs reduce cancellous bone volume [15,17,19] in a dose-dependent manner [15] and reduce the biomechanical strength of bone [14,15].…”

“…Nevertheless, in vitro studies on bone cells [10][11][12] and in vitro studies on bone metabolism [6,[13][14][15][16][17] demonstrate that LMWHs decrease bone formation and, therefore, could potentially delay fracture healing. Evidence exists that LMWHs reduce cancellous bone volume [15,17,19] in a dose-dependent manner [15] and reduce the biomechanical strength of bone [14,15]. In vitro studies have shown that the differentiation of osteoblasts from mesenchymal stem cells is inhibited by heparin and LMWHs, albeit to different extents [11].…”

Effects of Long-Term Low-Molecular-Weight Heparin on Fractures and Bone Density in Non-Pregnant Adults: A Systematic Review With Meta-Analysis

“…Some animal studies have suggested a dose-dependent effect of LMWH on bone, 78,79 but this relationship has not been fully explored or confirmed in humans. Qualitative analysis of the data suggests a slight trend towards dose-dependent effects of LMWH on bone.…”