Colchicine inhibits fracture union and reduces bone strength - In vivo study (original) (raw)
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The inhibitory effects of colchicine on cell proliferation and mineralisation in culture
The Journal of Bone and Joint Surgery, 2001
C olchicine is often used in the treatment of diseases such as familial Mediterranean fever (FMF) and gout. We have previously reported that patients with FMF who had colchicine on a daily basis and who had a total hip arthroplasty showed no heterotopic ossification after surgery. The mechanism by which colchicine causes this clinical phenomenon has never been elucidated. We therefore evaluated the effect of various concentrations of colchicine on cell proliferation and mineralisation in tissue culture, using rat and human cells with and without osteogenic potential. Cell proliferation was assessed by direct cell counts and uptake of ( 3 H)thymidine, and mineralisation by measuring the amount of staining by Alizarin Red.
Ectopic Bone Formation after Treatment with Colchicine
Folia Biologica, 2009
TWOREK K., SOLAK K., JANECZEK J., D¥BROWSKI Z., NIEDWIEDZKI T., TABAROWSKI Z., SCHOUTENS A., TWOREK S. 2010. Ectopic bone formation after treatment with colchicine. Folia biol. (Kraków) 58: 125-133. We followed changes occurring within bone tissue and marrow cells during the process of colchicine-induced ectopic bone development and its resorption inside the marrow cavity of the rat tibia. To stimulate ectopic bone formation male Wistar rats were i.p injected with 0.5 or 1 mg/kg b.w. of colchicine or with a 100 Fg intra-bone injection. Not all subjects responded to colchicine with ectopic bone formation in the marrow cavity, even among individuals belonging to the same strain. The kind of response in a given animal depended on the dose and site of colchicine administration. During 10 days of the experiment an increase in the occurrence of micronuclei in the polychromatic erythrocytes residing in the bone marrow (even 40-fold) was observed, indicating high genotoxicity of colchicine (at a dose of 1 mg/kg b.w. i.p. or 100 Fg intra-bone injection). An increase in the frequency of emperipolesis in megakaryocytes between the 4th and 8th days of the experiment was caused by the toxic action of colchicine and may indicate the labilisation of cell membranes and microtubule depolymerisation.
Pharmacological agents and bone healing
Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases, 2009
Osteoporosis is the most common alteration of bone metabolism. It derives from an increase in bone resorption with respect to bone formation and is characterized by microarchitectural alterations, decreased bone mass and increased risk of fracture. The coupling between bone formation and resorption is a fundamental concept in skeletal metabolism, and it explains how a certain amount of removed tissue can be replaced by the same amount of new bone. Various substances used to treat osteoporosis may also be used for orthopaedic conditions such as fracture healing, implant fixation, bone grafts and osteonecrosis. Fracture healing consists in the replacement of the lost bone by a tissue that has the same biomechanical properties as those preceding the fracture. The repair process is triggered by the local response to the tissue injury that damaged the continuity of bone. The duration of each phase of the healing process can vary significantly, depending on the site and characteristics of...
Journal of Bone and Mineral Research, 2009
In the rat tibia1 bone marrow cavity, following colchicine injection, there is a phase of osteogenesis in which bone trabeculae replace the necrotic bone marrow tissues and fill the marrow cavity. The newly formed bone is subsequently resorbed by osteoclasts and normal bone marrow is restored. In this study, we correlated these morphologic events with the pattern of gene expression of bone sialoprotein (BSP), an extracellular matrix protein in mineralized tissues, to elucidate the possible functions of BSP in bone formation and resorption in vivo. The expressions of osteopontin (OPN) and type I collagen were also examined. Northern hybridization of the tibia demonstrated that OPN mRNA was gradually increased and expressed a t a maximal level 10 days after colchicine injection (during the bone resorption process), while BSP mRNA expression already reached a maximal level at day 6 (during the initial process of bone formation). Its expression was, thus, quite temporary at the beginning of bone formation and different from that of type I collagen, which was continually elevated from days 6 to 10. In situ hybridization of the newly formed bone induced in the tibia revealed that BSP mRNA was evenly expressed in most osteoblasts and osteocytes, moreover in interconnecting colonies of spindle-shaped cells, possibly preosteoblasts, at day 6. At day 10, however, its expression became restricted to some cells on the bone surfaces, some osteoblasts, and most osteoclasts. These observations suggest that BSP may play an important role mainly in the initiation of bone formation and is also associated with the functions of osteoclast in vivo. (J Bone Miner Res 1995;10:1209-1217) Address reprint rcqucsts to: Nuoyu /hi Depurttnetit of Orul und Muxilktfirciiil Surgt~ry. Fuciilty of Dcvitistry 7bhyo Medicul und Detitul Uni\vt:vily 1-5-45 Yii.shimu, Bictikyo-hi 7 X y o 113. Juputi
An Overview of Drug Effects on Bone Healing on Animal Research Models
Vietnam Journal of Agricultural Sciences
Bone fracture is a common health problem in humans and animals, and the healing of the bone fracture is a complicated process. Several drugs may be used concurrently with the treatment of fractures, but they may interfere with the healing process of the bone. The present research reviewed previously published studies with the objective to enhance the understandings of the effects of different drugs on bone healing. There is clear evidence that antibiotics, corticosteroids, non-steroidal inflammatory drugs, and chemotherapeutic drugs all affect bone healing. By contrast, the effect of anticoagulants on bone healing is controversial, so more research is needed to determine its efficacy. In addition, there is no direct evidence to approve the effect of anesthetics on bone healing, so this is another area in need of further research.
A Comparison of effects of floroquinolones on fracture healing (An experimental study in rats)
2005
Çal›flman›n amac›, florokinolonlar›n oluflturulan femur k›r›klar› üzerine etkilerini histopatolojik olarak test etmek ve karfl›laflt›rmakt›r. GEREÇ VE YÖNTEM Her bir grupta befler denek olmak üzere toplam yirmi befl Wistar s›çan› befl gruba ayr›ld›. Tüm gruplarda manuel olarak bilateral femur k›r›¤› oluflturuldu. Kontrol (C) grubu olarak, ilk gruba herhangi bir ilaç verilmedi. ‹kinci grup norfloksas›nle (N), üçüncü grup ofloksasinle (O), dördüncü grup pefloksasinle (P) ve son grup da siprofloksasinle (C) tedaviye al›nd›. ‹ndüktlenen femur k›r›klar› sonras› yedinci günde antibiyotik tedavisine baflland›. Tüm gruplarda tedaviye yirminci gün son verildi. Femur k›r›klar›n›n indüksiyonundan dört hafta sonra tüm s›çanlar afl›r› doz eter ile feda edildi ve femurlar kallus dokusuyla birlikte blok halinde ç›kar›larak histopatolojik olarak de¤erlendirmeye al›nd›. BULGULAR Kontrol grubunda k›r›klar›n ortalama iyileflme derecesinin tüm di¤er antibiyotik gruplar›ndan yüksek oldu¤u bulundu. Grupl...
Osteoporosis International, 2007
The effect of cyclosporine A on bone turnover remains unclear. Using adult rats with vascularized bone transplantation, we show that long-term cyclosporine A administration increases bone turnover and zoledronic acid treatment enhances the reconstruction of cyclosporine Aadministered skeleton. Bisphosphonates might be efficacious in human bone repair under immunosuppression using cyclosporine A. Introduction Bisphosphonate treatment effectively prevents bone loss after transplantation. However, recent evidence from gain-and loss-of-function experiments has indicated that calcineurin inhibitors, such as cyclosporine A (CsA), reduce bone turnover, and severely suppressed bone turnover might delay the union of human fractured bone. The purpose of this study was to investigate the effects of bisphosphonate treatment on the repair of CsA-administered skeleton. Methods After skeletal reconstruction by vascularized tibial grafting, adult recipient rats were treated with intramuscular CsA (10 mg/kg/day) and low-dose (0.2 μg/kg/week) or high-dose (2 μg/kg/week) subcutaneous zoledronic acid alone or in combination for 8 weeks. Biochemical parameters were measured in blood and urine. The reconstructed skeleton was analyzed using soft X-ray, histology, dual energy X-ray absorptiometry, and three-point bending test. Results CsA induced mild renal dysfunction, hyperparathyroidism and high bone turnover. High-dose zoledronic acid delayed cortical bone union at the distal host-graft junction, but its combination with CsA did not cause such a delay. High-dose zoledronic acid prevented CsA-induced bone loss and bone fragility in the reconstructed skeleton. Conclusion In this rat model, long-term CsA administration increases bone turnover, at least partly, through hyperparathyroidism and high-dose zoledronic acid treatment does not impair the union of CsA-administered bone.
Brazilian Oral Research
The aim of this study was to assess the influence of cyclosporine administration on the repair of critical-sized calvaria defects (CSDs) in rat calvaria filled with diverse biomaterials. Sixty animals were divided into two groups: the control (CTR) group (saline solution) and the cyclosporine (CCP) group (cyclosporine, 10 mg/kg/day). These medications were administered daily by gavage, beginning 15 days before the surgical procedure and lasting until the day the animals were euthanized. A CSD (5 mm Ø) was made in the calvaria of each animal, which was allocated to one of 3 subgroups, according to the biomaterial used to fill the defect: coagulum (COA), deproteinized bovine bone (DBB), or biphasic calcium phosphate ceramics of hydroxyapatite and β-phosphate tricalcium (HA/TCP). Euthanasia of the animals was performed 15 and 60 days after the surgical procedure (n = 5 animals/period/ subgroup). Bone repair (formation) assessment was performed through microtomography and histometry, while the analyses of the expression of the BMP2, Osteocalcin, and TGFβ1 proteins were performed using immunohistochemistry. The CSDs not filled with biomaterials demonstrated lower bone formation in the CCP group. At 15 days, less bone formation was observed in the CSDs filled with DBB, a smaller volume of mineralized tissue was observed in the CSDs filled with HA/TCP, and the expression levels of BMP2 and osteocalcin were lower in the CCP group compared to the CTR group. The use of cyclosporine impaired bone repair in CSD, and this effect can be partially explained by the suppression of BMP2 and osteocalcin expression.