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Experimental models for cancellous bone healing in the rat Comparison of drill holes and implanted screws
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
2015 (engelsk)Inngår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, nr 6, s. 745-750Artikkel i tidsskrift (Fagfellevurdert) Published
Resurstyp
Text
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.

sted, utgiver, år, opplag, sider
TAYLOR & FRANCIS LTD , 2015. Vol. 86, nr 6, s. 745-750
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-123812ISI: 000365484500019PubMedID: 26200395OAI: oai:DiVA.org:liu-123812DiVA, id: diva2:892904
Merknad

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

DOI does not work: 10.3109/17453674.2015.1075705

Tilgjengelig fra: 2016-01-11 Laget: 2016-01-11 Sist oppdatert: 2018-10-29
Inngår i avhandling
1. Metaphyseal Fracture Healing
Åpne denne publikasjonen i ny fane eller vindu >>Metaphyseal Fracture Healing
2016 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 2016. s. 22
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1502
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-126148 (URN)10.3384/diss.diva-126148 (DOI)978-91-7685-865-3 (ISBN)
Disputas
2016-04-26, Nils Holger salen, ing 71 pl 8, Campus US, Linköping, 14:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2016-03-15 Laget: 2016-03-15 Sist oppdatert: 2019-10-29bibliografisk kontrollert
2. Healing Processes in Cancellous Bone
Åpne denne publikasjonen i ny fane eller vindu >>Healing Processes in Cancellous Bone
2018 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Most of what is known about the biological response during fracture healing comes from numerous animal studies with shaft fractures in the long bone. However, most patients suffer from fractures closer to the ends of the long bones, in the hip, or in the vertebrae. These types of fractures mainly involve cancellous bone, while shaft fractures concern cortical bone. Compared to cortical bone whose structure is dense and compact, cancellous bone is of spongy and porous structure. A growing number of studies point towards that cortical and cancellous bone heal differently. To even this imbalance in knowledge between these two types of bone tissue, further studies in cancellous bone are justified.

In this thesis we delved into the quiet unknown processes behind cancellous bone healing.

In the first study we characterized and compared two models for cancellous bone healing in mice and rats: the first model can be used to analyze the morphology and morphometry of the regenerating bone; the second model can measure the mechanical properties of cancellous bone. The two models correspond in their developing patterns during the first week before they diverge. This suggests that these models can be utilized together to evaluate the initial healing in cancellous bone. Furthermore, we saw in the drill hole model that the bone formation is strictly restricted to the traumatized region, with a distinct interface to the adjacent uninjured tissue.

The second study characterized the cellular response during the initial healing phase in cancellous bone. The focus was to follow the spatial location of inflammatory and osteogenic cells over time in a cancellous bone injury. In contrast to shaft fractures (cortical bone), where healing is described as sequential events where inflammatory cells are the first to arrive to the trauma before osteogenic cells are recruited and initiate healing, we could see how inflammatory and osteogenic cells appeared early, simultaneously after a cancellous bone injury. This study showed that cancellous bone differs from how fracture healing is normally described.

In the third study we explored the role of a subpopulation of lymphocytes (CD8 positive cells), earlier studied in shaft fractures. We wanted to see how their absence would affect the healing in a cancellous bone injury. Without CD8+ cells, cancellous bone healing was impaired as expressed via poorer mechanical properties of the regenerated bone tissue.

The fourth and last study issued the influence of uninjured bone marrow on cortical bone healing. We developed a cortical defect model which blocked uninjured marrow from reaching the defect. Without the presence of marrow, the cortical defects ability to regenerate was significantly impaired. This implies that the marrow is important for cortical bone healing.

In conclusion, cancellous bone healing is different from its cortical counterpart and the general perception of fracture healing. We have briefly discerned healing mechanisms in cancellous bone that might be of clinical importance: the restricted cancellous bone formation is something to take into consideration when performing arthrodeses; and importance of marrow in skeletal defects (e.g. pseudarthroses). With this thesis, we hope to promote that further investigating on cancellous bone healing is necessary.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 2018. s. 24
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1652
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-152349 (URN)10.3384/diss.diva-152349 (DOI)9789176851777 (ISBN)
Disputas
2018-12-06, Belladonna, Campus US, Linköping, 13:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2018-10-30 Laget: 2018-10-29 Sist oppdatert: 2019-09-30bibliografisk kontrollert

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