Effects of alendronate in bone repair: A study in rat femur fractures treated with plates and screws

Background Alendronate (ALN) has direct action on bone metabolism, increasing osteogenesis and decreasing bone resorption. The study rated the effect of ALN on femoral fracture repair and the effect of different doses of the drug on the liver and kidneys. Methods Wistar rats were divided into groups: A1 (ALN 1 mg/kg), A2 (ALN 3 mg/kg), and C (saline solution). The drug/solution was applied intraperitoneally three times a week after femoral fracture until euthanasia 45 days later. Results Liver analysis from group A1 presented normal histological aspects, while hepatic steatosis was observed in group A2. In groups A1 and A2, kidneys showed amylocymile like cell degeneration. In femur bone callus, no difference was observed in collagens I and III or in number of trabeculae (p ≥ 0.05). Immunohistochemical evaluation showed positivity for the Transforming Grow Factor β-1 (TGFβ-1) marker in the control group, in spinal area and in small chondrocytes, but negativity for hypertrophy. In A1, an extensive area of cartilaginous expansion was observed, with positive hypertrophic TGFβ-1 cartilage, even in areas with bone matrix. A low positivity was observed in the medullar area, in contrast to the control. Group A2 presented a high number of chondroid matrices and a moderate number of TGFβ-1 cells, with little positivity in medullary area. Conclusions A dosage of ALN 1 mg/kg promotes cellular differentiation activity in the bone callus region, with mild damage in the liver and kidneys. A dosage of ALN 3 mg/kg became toxic without positive alterations in cell differentiation.

Biomechanical Assessment for Healing Progression of Fractured Long Bones: Numerical Investigations of Bending Stiffness and Resonant Frequency

Though biomechanical methods have been proposed to assess the healing status of fractured bones for more than two decades, the effective stiffnesses obtained theoretically never match the experimentally measured results for the healing progression. This paper proposed a novel numerical model, the simulation results of which are able to reflect the experimental observations. The callus is divided into 10 regions with different material properties and the gap-narrowing process of the fracture is simulated with the variations of the material properties during the healing progression. The variations of the effective bending stiffness and resonant frequency with the healing progression have been obtained. The bending stiffness and resonant frequency squared of the fractured bone show a substantial creeping part during gradual narrowing of the fracture gap. They start to increase rapidly during bridging of the fracture gap by a bony callus. When the Young’s modulus in the callus region calcified last (i.e., Region 10) reaches 5% that of the reference intact bone, the bending stiffness and resonant frequency squared rise up to 90% those of the reference intact bone. After that they increase slowly and get flat; they become less sensitive to bone growth in the late healing stages. It is the first time that the simulation results demonstrate three distinct stages like in the experimentally measured results. These results imply that the variations of the bending stiffness and resonant frequency squared are not linearly correlated with the healing progression; however, their fast growing phase does indicate bony bridging of the callus.

Ordering of the cellular arrangement and xylogenesis in wounded shoots of willow

Development of living organisms is characterized by self-organization, which results in ordered cell and tissue patterns. Xylem formation in callus tissue may serve as a model to study these phenomena. Applying auxin on the apical transverse cut surface of willow shoot segments stimulates the proliferation of callus with an unorganized cell arrangement. In some areas of callus, the cells form an ordered system and partly differentiate into tracheary elements. Below the cut surface a zone of initially unorganized parenchymatous cells is produced by the cambium. Later, some of the cells formed ordered arrangements giving rise to differentiation in xylem rays with a subsequent layer of normal wood. Digital image processing software based on a structure tensor revealed a more coherent orientation of the cellular pattern in the callus region close to the cambial zone in the cut shoot surface, compared with the areas at further distances near the outer parts of the callus ring. Differentiation of tracheary xylem elements occurs mostly in the regions where a higher degree of cellular ordering in parenchyma tissue is observed. Digital image analysis is a useful tool for the quantitative estimation of subtle changes of cellular ordering in various regions of regenerating tissue. Wider application of this tool may open new opportunities in studies of the complex mechanisms that control morphogenetic patterns in plants.