Indomethacin and Aspirin: Effect of Nonsteroidal Anti-Inflammatory Agents on the Rate of Fracture Repair in the Rat

Allen, Henry L.; Wase, Arthur W.; Bear, W. T.

doi:10.3109/17453678008990848

Cited by 274 publications

(204 citation statements)

References 10 publications

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“…In this study we did not find any delayed union of the trochanteric osteotomies which might have been expected, due to the treatment of ibuprofen (Tornkvist et al 1984). On the other hand, as soon as the administration of an anti-inflammatory drug ceases, experimental fractures usually heal (Allen et al 1980), which might explain the lack of delayed union of the osteotomies in the present study.…”

Section: Discussionsupporting

confidence: 42%

“…The presence of prostaglandins is probably of importance for bone formation, raised levels of prostaglandins have been found in surrounding muscle of tibial fracture from rabbits in vitro (Dekel et al 1981). It is therefore not surprising that indomethacin delays fracture healing in various experimental models (Allen et al 1980). Since inflammation is a dominant feature in and around the postoperative wound, treatment with anti-inflammatory drugs may inhibit the formation of heterotopic ossification after THR.…”

Section: Discussionmentioning

confidence: 99%

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Effect of ibuprofen on heterotopic ossification after hip replacement

Elmstedt

et al. 1985

Acta Orthopaedica Scandinavica

123

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Section: Discussionsupporting

confidence: 42%

Section: Discussionmentioning

confidence: 99%

Effect of ibuprofen on heterotopic ossification after hip replacement

Elmstedt

et al. 1985

Acta Orthopaedica Scandinavica

123

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“…The degree of fracture healing was evaluated using a five-point scale (grade 0-4) proposed by Allen et al 37 Samples were sectioned at siRNA targeting Lnk Y Kawakami et al 6-mm thickness on slides followed by fixation with 4% paraformaldehyde at 4 1C for 5 min. All morphometric studies were performed by two orthopedic surgeons blinded to the treatment.…”

Section: Histological Assessment Of Fracture Healingmentioning

confidence: 99%

A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization

Kawakami

Masaaki

Matsumoto

et al. 2013

Laboratory Investigation

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Lnk, an intracellular adapter protein, is expressed in hematopoietic cell lineages, which has recently been proved as an essential inhibitory signaling molecule for stem cell self-renewal in the stem cell factor-c-Kit signaling pathway with enhanced hematopoietic and osteogenic reconstitution in Lnk-deficient mice. Moreover, the therapeutic potential of hematopoietic stem/endothelial progenitor cells (EPCs) for fracture healing has been demonstrated with mechanistic insight into vasculogenesis/angiogenesis and osteogenesis enhancement in the fracture sites. We report here, Lnk siRNAtransfected endothelial commitment of c-kit þ /Sca-1 þ /lineage À subpopulations of bone marrow cells have high EPC colony-forming capacity exhibiting endothelial markers, VE-Cad, VEGF and Ang-1. Lnk siRNA-transfected osteoblasts also show highly osteoblastic capacity. In vivo, locally transfected Lnk siRNA could successfully downregulate the expression of Lnk at the fracture site up to 1 week, and radiological and histological examination showed extremely accelerated fracture healing in Lnk siRNA-transfected mice. Moreover, Lnk siRNA-transfected mice exhibited sufficient therapeutic outcomes with intrinstic enhancement of angiogenesis and osteogenesis, specifically, the mice demonstrated better blood flow recovery in the sites of fracture. In our series of experiments, we clarified that a negatively regulated Lnk system contributed to a favorable circumstance for fracture healing by enhancing vasculogenesis/angiogenesis and osteogenesis. These findings suggest that downregulation of Lnk system may have the clinical potential for faster fracture healing, which contributes to the reduction of delayed unions or non-unions.

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“…These drugs inhibit disordered osteoclast activity, retard woven-fibered bone tissue formation, and impair fracture healing [1,2,23,34,37,52,54,62,63]. COX inhibitors are, however, very efficient drugs in the treatment of postoperative inflammation and pain in orthopaedic trauma and surgery.…”

Section: Introductionmentioning

confidence: 99%

Parecoxib and Indomethacin Delay Early Fracture Healing: A Study in Rats

Dimmen

Nordsletten

Madsen

2009

Clinical Orthopaedics &Amp; Related Research

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Nonsteroidal antiinflammatory drugs (NSAIDs) are used to reduce inflammatory response and pain. These drugs have been reported to impair bone metabolism. Parecoxib, a specific COX-2 inhibitor, exerts an inhibitory effect on the mineralization of fracture callus after a tibial fracture in rats. Decreased bone mineral density (BMD) at a fracture site may indicate impairment of early healing, casting doubt on the safety of using COX-2 inhibitors during the early treatment of diaphyseal fractures. Fortytwo female Wistar rats were randomly allocated to three groups. They were given parecoxib, indomethacin, or saline intraperitoneally for 7 days after being subjected to a closed tibial fracture stabilized with an intramedullary nail. Two and 3 weeks after surgery, the bone density at the fracture site was measured using dual energy xray absorptiometry (DEXA). Three weeks after the operation the rats were euthanized and the healing fractures were mechanically tested in three-point cantilever bending.Parecoxib decreased BMD at the fracture site for 3 weeks after fracture, indomethacin for 2 weeks. Both parecoxib and indomethacin reduced the ultimate bending moment and the bending stiffness of the healing fractures after 3 weeks. These results suggest COX inhibitors should be avoided in the early phase after fractures.

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Indomethacin and Aspirin: Effect of Nonsteroidal Anti-Inflammatory Agents on the Rate of Fracture Repair in the Rat

Cited by 274 publications

References 10 publications

Effect of ibuprofen on heterotopic ossification after hip replacement

Effect of ibuprofen on heterotopic ossification after hip replacement

A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization

Parecoxib and Indomethacin Delay Early Fracture Healing: A Study in Rats

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