sirolimus and Femoral-Fractures

Blue rubber bleb nevus syndrome (BRBNS) is a rare condition with characteristic vascular malformations of the skin, most frequently lesions of the gastrointestinal tract and central nervous system, and less often, the musculoskeletal system. We report a 5-year case of BRBNS complicated with pathological femoral fracture that was successfully treated with sirolimus.. We report the case of a 1-week-old girl with a diagnosis of BRBNS who had multiple venous malformations over her body. She also presented with right lower-limb swelling and complicated with a pathological femoral fracture.. BRBNS with the complication of pathological femoral fracture.. Treatment with low-dose sirolimus as an antiangiogenic agent was administered, combined with hip spica protection.. The vascular lesion was reduced after about 6 months and the fracture site had healed around 2.5 years after initiation of sirolimus therapy. There were no drug adverse effects at the 5-year follow-up point. The patient showed excellent spirit and no obvious sequelae were found.. To the best of our knowledge, this is the first report of the successful use of sirolimus in a patient with a pathological femoral fracture related to BRBNS complications.

Topics: Female; Femoral Fractures; Gastrointestinal Neoplasms; Humans; Nevus, Blue; Sirolimus; Skin Neoplasms; Vascular Malformations

To investigate the changes in cell autophagy and the molecular mechanism of rapamycin affecting the fracture healing.. Sprague-Dawley (SD) rats were used to establish the right femoral shaft fracture models, and then underwent immunofluorescence assay to detect the autophagy level in bone tissues. After model establishment, SD rats were divided into two groups, the control group and the rapamycin group (1 mg/kg/d). Respectively, at the 2nd, 4th, and 6th week, rats were randomly selected from each group for X-ray and Micro-computed tomography (Micro-CT) examinations to determine callus growth, immunofluorescence assay to detect the protein expression of light chain 3 II (LC3 II), immunohistochemistry to evaluate the autophagy level through detecting the expression of Beclin1 in rats, Western blotting assay to detect cell apoptosis in tissues, hematoxylin and eosin staining (HE staining) to evaluate the osteoblastic activity through count of osteoblast in bone tissue at the end of fracture, and measure the expression of vascular endothelial growth factors (VEGF).. Significant increases were seen in protein expression of cells in bone tissues at the end of fracture. In rapamycin group, callus formation and calcification level in rats were all higher than those in control group; compared with control group, for rats in rapamycin group, cell autophagy was significantly elevated in bone tissues, while cell apoptosis at the end of fracture was reduced with a significant increase in osteoblastic activity. The expression of VEGF in rapamycin group was higher than that in control group.. Rapamycin can facilitate fracture healing through inducing cell apoptosis and suppressing cell apoptosis in bone tissues.

Topics: Animals; Apoptosis; Autophagy; Beclin-1; Bony Callus; Femoral Fractures; Fracture Healing; Male; Microtubule-Associated Proteins; Rats; Rats, Sprague-Dawley; Sirolimus; Vascular Endothelial Growth Factor A; X-Ray Microtomography

The immunosuppressive drug rapamycin (RAPA) prevents rejection in organ transplantation by inhibiting interleukin-2-stimulated T-cell division. Rapamycin has also been suggested to possess strong anti-angiogenic activities linked to a decrease in production of vascular endothelial growth factor (VEGF). Angiogenesis and VEGF are thought to play a crucial role in fracture healing and as osteoporotic and traumatic fractures are common complications in immunosuppressed, organ transplantation patients, we conducted this study to analyze the effect of rapamycin treatment on bone repair.. We investigated the effect of rapamycin treatment on bone repair in a murine closed femur fracture model using radiological, histomorphometric, immunohistochemical, biomechanical and protein biochemical analyses.. X-ray analyses demonstrated that rapamycin treatment inhibits callus formation after two weeks of fracture healing. The radiologically observed lack of callus formation was confirmed by histomorphometric analyses, which revealed a significantly diminished callus size and a reduced amount of bone formation when compared with vehicle-treated controls. Biomechanical testing further demonstrated that rapamycin significantly reduces torsional stiffness of the callus. Interestingly, this effect was associated with decreased vessel formation; a diminished proliferation of osteoblasts, endothelial cells and periosteal cells; and a reduced VEGF expression in hypertrophic chondrocytes. After five weeks treatment, however, the negative impact of rapamycin on fracture healing was overcome.. Thus, rapamycin initially delays fracture healing, most probably by inhibiting cell proliferation and neovascularization in the callus. These undesirable effects should be considered when rapamycin is administered to patients sustaining bone fractures.

Topics: Angiogenesis Inhibitors; Animals; Biomechanical Phenomena; Blotting, Western; Bony Callus; Cell Proliferation; Chondrocytes; Disease Models, Animal; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Femoral Fractures; Fracture Healing; Immunohistochemistry; Immunosuppressive Agents; Mice; Neovascularization, Physiologic; Osteoblasts; Osteogenesis; Sirolimus; Time Factors