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Glucocorticoids inhibit shaft fracture healing but not metaphyseal bone regeneration under stable mechanical conditions
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: BONE and JOINT RESEARCH, ISSN 2046-3758, Vol. 4, no 10, 170-175 p.Article in journal (Refereed) Published
Abstract [en]

Objectives Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors.

Methods We investigated the role of inflammation in three different models: a metaphyseal screw pull-out, a shaft fracture with unstable nailing (IM-nail) and a stable external fixation (ExFix) model. For each, half of the animals received dexamethasone to reduce inflammation, and half received control injections. Mechanical and morphometric evaluation was used.

Results As expected, dexamethasone had a strong inhibitory effect on the healing of unstable, but also stable, shaft fractures. In contrast, dexamethasone tended to increase the mechanical strength of metaphyseal bone regenerated under stable conditions.

Conclusions It seems that dexamethasone has different effects on metaphyseal and diaphyseal bone healing. This could be explained by the different role of inflammation at different sites of injury.

Place, publisher, year, edition, pages
BRITISH EDITORIAL SOC BONE JOINT SURGERY , 2015. Vol. 4, no 10, 170-175 p.
Keyword [en]
Bone; healing; fracture
National Category
Biomaterials Science
URN: urn:nbn:se:liu:diva-123157DOI: 10.1302/2046-3758.410.2000414ISI: 000364596200002OAI: diva2:877429

Funding Agencies|Swedish Research Council [VR 2009-6725]; Linkoping University; Ostergotland County Council; King Gustav V and Queen Victoria Mason Foundation; European Community [279239]

Available from: 2015-12-07 Created: 2015-12-04 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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Sandberg, OlofAspenberg, Per
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