Pharmacological agents and impairment of fracture healing: What is the evidence?

Pountos, Ippokratis; Georgouli, T.; Blokhuis, Taco J.; Pape, Hans-Christian; Giannoudis, Peter V.

doi:10.1016/j.injury.2007.10.035

Cited by 141 publications

(79 citation statements)

References 112 publications

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“…Several studies have shown that the use of antiinflammatory or cytotoxic medications during the early stages of fracture healing may impair bone repair (Dimmen et al, 2008;Pountos et al, 2008;Simon and O'Connor, 2007). However, these studies have not established a direct relationship between inflammatory cells and bone fracture healing.…”

Section: Introductionmentioning

confidence: 99%

Multiple roles for CCR2 during fracture healing

Xing

et al. 2010

Disease Models &Amp; Mechanisms

162

170

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SUMMARYBone injury induces an inflammatory response that involves neutrophils, macrophages and other inflammatory cells. The recruitment of inflammatory cells to sites of injury occurs in response to specific signaling pathways. The CC chemokine receptor type 2 (CCR2) is crucial for recruiting macrophages, as well as regulating osteoclast function. In this study, we examined fracture healing in Ccr2-/-mice. We first demonstrated that the expression of Ccr2 transcripts and the filtration of macrophages into fracture calluses were most robust during the early phases of fracture healing. We then determined that the number of macrophages at the fracture site was significantly lower in Ccr2-/-mice compared with wild-type controls at 3 days after injury. As a result, impaired vascularization, decreased formation of callus, and delayed maturation of cartilage were observed at 7 days after injury in mutant mice. At day 14, Ccr2-/-mice had less bone in their calluses. At day 21, Ccr2-/-mice had larger calluses and more bone compared with wild-type mice, suggesting a delayed remodeling. In addition, we examined the effect of Ccr2 mutation on osteoclasts. We found that a lack of Ccr2 did not affect the number of osteoclasts within fracture calluses at 21 days after injury. However, Ccr2-/-osteoclasts exhibited a decreased ability to resorb bone compared with wild-type cells, which could contribute to the delayed remodeling of fracture calluses observed in Ccr2-/-mice. Collectively, these results indicate that a deficiency of Ccr2 reduces the infiltration of macrophages and impairs the function of osteoclasts, leading to delayed fracture healing.

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Section: Introductionmentioning

confidence: 99%

Multiple roles for CCR2 during fracture healing

Xing

et al. 2010

Disease Models &Amp; Mechanisms

162

170

View full text Add to dashboard Cite

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“…The means for neoformation and the respective standard deviations can be viewed in the graph of Figure 5. and stimulate tissue restoration. It is believed that interactions between these parameters promote bone regeneration (8,28,29) . To provide support for cell growth and osteogenic differentiation, use of scaffolds produced from different biomaterials is important.…”

Section: Radiographic and Histological Resultsmentioning

confidence: 99%

Estudo comparativo do uso isolado de plasma rico em plaquetas e combinado com cimento de alfa-fosfato tricálcico no reparo ósseo em ratos

Sebben¹,

Hoff²,

Klein³

et al. 2012

Rev. bras. ortop.

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Objectives: To evaluate the effect of alpha-tricalcium phosphate (α-TCP) cement combined with platelet-rich plasma (PRP) on osteogenesis, and to compare the results with use of PRP alone. Methods: A bilateral defect was produced in rat femurs and was filled with one of two types of treatments (PRP or α-TCP + PRP). The outcomes were evaluated after four and eight weeks. Radiographic images provided values for the lesion area, and histology (picrosirius staining) indicated the area of new bone formation. Results: The means relating to the lesion area of the α-TCP + PRP group (2.64 ± 2.07 and 1.91 ± 0.93 mm², after four and eight weeks, respectively) showed numerically better Rev Bras Ortop. 2012;47(4):505-12The authors declare that there was no conflict of interest in conducting this work this article is available online in Portuguese and English at the websites: www.rbo.org.br and www.scielo.br/rbort but non-significant results (p > 0.05) than those seen in the PRP group (5.59 mm ² ± 2.69 and 3.23 ± 1.46 mm ², after four and eight weeks, respectively). The mean new bone formation rates were 62.7% ± 12.1 and 79.01% ± 6.25 in the PRP group, and 73.3% ± 12.7 and 85.86% ± 10.45 in α-TCP + PRP group, after four and eight weeks, respectively (p > 0.05). Conclusion: The data from this study suggest that treatment with α-TCP cement combined with PRP does not show any significant difference in comparison with PRP alone. However, there is a possible early effect on bone regeneration when the two biomaterials are applied together.

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“…31,92 Cyclophosphamide causes diminished calcium and phosphate deposition in callus. 93 Doxorubicin, cyclophosphamide, adriamycin and methotrexate results in decreased bone formation and these effects might last up to three weeks after administration. 93 • Corticosteroids: The effect of long-term corticosteroid use on bone metabolism and fracture healing is well documented.…”

Section: Other Drugsmentioning

confidence: 99%