Functional Outcome After Treatment of Lower-Extremity Nonunions

Zlowodzki, Michael; Obremskey, William T.; Thomison, John B.; Kregor, Philip J.

doi:10.1097/01.ta.0000154302.23143.63

Cited by 30 publications

(29 citation statements)

References 54 publications

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“…Furthermore, even 3 years after the successful treatment of a nonunion, Short Form-36 scores, which measure general physical, mental, and emotional well-being, are significantly lower than in age-matched controls [6]. Patients with nonunions of the lower extremities also report significantly lower physical and mental health scores when compared to those with rheumatoid arthritis and osteoarthritis of the knee, hip, or shoulder [5].…”

Section: Introductionmentioning

confidence: 96%

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The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model

Hsu

Feeley

Krenek

et al. 2007

Eur J Nucl Med Mol Imaging

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Purpose-Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with 18 F-fluoride ion, which localizes in regions of high osteoblastic activity, and 18 F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. Methods-Fractureswere created in the femurs of immuno-competent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, 18 F-fluoride, and 18 F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery.Results-All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. 18 F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using 18 F-FDG PET imaging at any time point.Conclusion-This study suggests that 18 F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time point and may have a role in the assessment of longitudinal fracture healing. PET scans using 18 F-FDG were not helpful in differentiating metabolic activity between successful and delayed bone healing.

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Section: Introductionmentioning

confidence: 96%

“…Lower extremity nonunions have a significant negative impact on quality of life [5]. Fracture nonunions and delayed unions are associated with disability, pain, and prolonged rehabilitation periods.…”

Section: Introductionmentioning

confidence: 99%

The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model

Hsu

Feeley

Krenek

et al. 2007

Eur J Nucl Med Mol Imaging

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“…It has been estimated that nearly 10% of these fractures have delayed or disrupted healing resulting in significant morbidity and loss of productivity. Enhancing the quality and/or speed of fracture healing can translate into significant therapeutic benefit both in terms of patient outcomes and cost to society [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Gene Expression in Healing Fracture Callus Tissue by DNA Microarray

et al. 2008

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Fracture healing requires controlled expression of thousands of genes. Only a small fraction of these genes have been isolated and fewer yet have been shown to play a direct role in fracture healing. The purpose of this study was threefold: (1) to develop a reproducible open femur model of fracture healing that produces consistent fracture calluses for subsequent RNA extraction, (2) to use this model to determine temporal expression patterns of known and unknown genes using DNA microarray expression profiling, and (3) to identify and validate novel gene expression in fracture healing. In the initial arm of the study, a total of 56 wild-type C57BL/6 mice were used. An open, stabilized diaphyseal femur fracture was created. Animals were killed at 1, 5, 7, 10, 14, 21, and 35 days after surgery and the femurs were harvested for analysis. At each time point, fractures were radiographed and sectioned for histologic analyses. Tissue from fracture callus at all stages following fracture yielded reproducibly large amounts of mRNA. Expression profiling revealed that genes cluster by function in a manner similar to the histologic stages of fracture healing. Based on the expression profiling of fracture tissue, temporal expression patterns of several genes known to be involved in fracture healing were verified. Novel expression of multiple genes in fracture callous tissue was also revealed including leptin and leptin receptor. In order to test whether leptin signaling is required for fracture repair, mice deficient in leptin or its receptor were fractured using the same model. Fracture calluses of mice deficient in both leptin or leptin receptor are larger than wild-type mice fractures, likely due to a delay in mineralization, revealing a previously unrecognized role of leptin signaling in fracture healing. This novel model of murine fracture repair is useful in examining both global changes in gene expression as well as individual signaling pathways, which can be used to identify specific molecular mechanisms of fracture healing.

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“…Despite the current standards in internal fixation of human fractures and bone defects, delayed healing or nonunions occur with a frequency of 5% to 20%, resulting in high costs for the healthcare system [8,21,28]. Both biologic and mechanical factors affect the outcome and course of bone healing [10, 12-15, 19, 24].…”

Section: Introductionmentioning

confidence: 99%

Influence of Gender and Fixation Stability on Bone Defect Healing in Middle-aged Rats: A Pilot Study

Mehta

Duda

Perka

et al. 2011

Clinical Orthopaedics &Amp; Related Research

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Background Gender and stability of fixation independently influence bone regeneration but their combined effects are unclear. Questions/purposes In a pilot study we determined the combined influence of gender and fixation stability on the callus of middle-aged rats regarding (1) biomechanical properties; (2) bridging over time; (3) callus formation; and (4) callus size, geometry, mineralization, and microstructure. Methods We osteotomized the left femur of 32 SpragueDawley rats (12 months old). Femurs were externally fixed with a gap of 1.5 mm in four groups of eight animals each: female semirigid, male semirigid, female rigid, and male rigid. Qualitative and quantitative in vivo radiographic analyses were performed twice weekly. Six weeks postoperatively, harvested femora were evaluated using micro-CT and biomechanical testing. Results Torsional stiffness and maximum torque at failure were higher in male and in semirigidly fixed fractures. Radiographic analysis revealed earlier bridging and callus formation in both male groups. Micro-CT analysis showed a larger callus size, altered geometry, and microstructure in males and semirigidly fixed animals, whereas mineralization was similar in all animals. Conclusion Our data suggest female gender represents an independent risk factor for bone healing in middle-aged rats. Although healing in females was delayed compared with males, they exhibited a similar response (superior callus properties) to a more semirigid fixation. Clinical Relevance While female gender appears to reflect a risk for impaired bone healing in middle-aged female rats, clinical studies would be required to confirm the finding in humans.

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Functional Outcome After Treatment of Lower-Extremity Nonunions

Abstract: The results of this study can be used to guide patients' expectations regarding the functional outcome of treatment for a nonunion of the lower extremity.

Cited by 30 publications

References 54 publications

The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model

The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model

Identification of Novel Gene Expression in Healing Fracture Callus Tissue by DNA Microarray

Influence of Gender and Fixation Stability on Bone Defect Healing in Middle-aged Rats: A Pilot Study

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