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Experimental models for cancellous bone healing in the rat Comparison of drill holes and implanted screws
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
2015 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 6, 745-750 p.Article in journal (Refereed) PublishedText
Abstract [en]

Background and purpose - Cancellous bone appears to heal by mechanisms different from shaft fracture healing. There is a paucity of animal models for fractures in cancellous bone, especially with mechanical evaluation. One proposed model consists of a screw in the proximal tibia of rodents, evaluated by pull-out testing. We evaluated this model in rats by comparing it to the healing of empty drill holes, in order to explain its relevance for fracture healing in cancellous bone. To determine the sensitivity to external influences, we also compared the response to drugs that influence bone healing. Methods - Mechanical fixation of the screws was measured by pull-out test and related to the density of the new bone formed around similar, but radiolucent, PMMA screws. The pull-out force was also related to the bone density in drill holes at various time points, as measured by microCT. Results - The initial bone formation was similar in drill holes and around the screw, and appeared to be reflected by the pull-out force. Both models responded similarly to alendronate or teriparatide (PTH). Later, the models became different as the bone that initially filled the drill hole was resorbed to restore the bone marrow cavity, whereas on the implant surface a thin layer of bone remained, making it change gradually from a trauma-related model to an implant fixation model. Interpretation - The similar initial bone formation in the different models suggests that pull-out testing in the screw model is relevant for assessment of metaphyseal bone healing. The subsequent remodeling would not be of clinical relevance in either model.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD , 2015. Vol. 86, no 6, 745-750 p.
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-123812DOI: 10.3109/17453674.2015.1075705ISI: 000365484500019PubMedID: 26200395OAI: diva2:892904

Funding Agencies|Swedish Research Council [2031-47-5]; AFA insurance company; EU [279239]; Linkoping University; Eli Lilly and Company

Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2016-03-15
In thesis
1. Metaphyseal Fracture Healing
Open this publication in new window or tab >>Metaphyseal Fracture Healing
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Most of what is known about fracture healing comes from studies of shaft fractures in long bones. In contrast, patients more often have fractures closer to the ends (metaphyses). Here most bone tissue has a spongy, cancellous structure different from the compact bone of the shaft. There is an increasing awareness that metaphyseal fractures heal differently. However, the more easily studied shaft healing has usually been considered as good enough representative for fracture healing in general.

My work shows that the biology of metaphyseal healing is more different from shaft healing than was previously known and that this has implications on the effect of various commonly prescribed drugs.

First we studied biopsies of healing cancellous bone collected from human donors. We found that the most abundant new bone formation occurred freely in the marrow rather than on the surface of old trabeculae, as described in most literature. There was little cartilage, indicating that the dominant bone formation process is mostly membranous in nature. This is a contrast to the ample cartilage formation commonly found in the well-characterized shaft fracture models.

Next we characterized a model that allows for mechanical quantification of regenerating cancellous bone. By contrasting this cancellous healing model with the standard shaft healing model we could demonstrate that the NSAID indomethacin, the glucocorticoid dexamethasone, and the bisphosphonate alendronate all had different effects on the mechanical quality of bone regeneration in shaft and metaphysis; while anti-inflammatory drugs strongly impaired shaft healing, metaphyseal healing was not similarly affected. Alendronate had a positive effect on both models, though the effect was strongest in the metaphyseal model. Taken together these differences shed some light as to the differences in healing biology.

The last step (within the boundaries of this thesis) was a characterization of how healing in cortical and cancellous bone differs in terms of immune cell involvement. We could find little difference between the two bone types day 3. However, day 5 an increase in the number of granulocytes could be noted in the cancellous bone while the cortical bone had a higher number of lymphocytes.

To conclude, this work furthers our understanding of how metaphyseal healing differs from shaft healing. It has clinical implications as it motivates an increased attention to the site of fracture while contemplating treatment. I hope this thesis can be read as an argument for increased interest in metaphyseal fracture healing.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 22 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1502
National Category
Other Clinical Medicine Orthopedics Nursing
urn:nbn:se:liu:diva-126148 (URN)10.3384/diss.diva-126148 (DOI)978-91-7685-865-3 (Print) (ISBN)
Public defence
2016-04-26, Nils Holger salen, ing 71 pl 8, Campus US, Linköping, 14:00 (English)
Available from: 2016-03-15 Created: 2016-03-15 Last updated: 2016-08-31Bibliographically approved

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Bernhardsson, MagnusSandberg, OlofAspenberg, Per
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