A novel mouse model to study fracture healing of the proximal femur.


Journal

Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726

Informations de publication

Date de publication:
10 2020
Historique:
received: 09 10 2019
revised: 14 02 2020
accepted: 25 03 2020
pubmed: 2 4 2020
medline: 15 12 2020
entrez: 2 4 2020
Statut: ppublish

Résumé

The majority of fractures, especially in elderly and osteoporotic patients, occurs in metaphyseal bone. However, only a few experimental models exist to study metaphyseal bone healing in mice. Currently used mouse models of metaphyseal fracture healing are either based on drill hole defects, lacking adequate biomechanical stimulation at the site of fracture and therefore endochondral ossification in the fracture callus, or are introduced into the distal part of the mouse femur stabilized by a locking plate, which is challenging due to the small specimen size. Therefore, the aim of the current study was to develop a new mouse model to study metaphyseal fracture healing of the proximal femur. We chose a combination between an open osteotomy and a closed intramedullary stabilization. A 24 G needle was inserted into the femur in a closed manner, then an osteotomy was made with a 0.4-mm Gigli wire saw between the third and the lesser trochanter of the femur using an open approach. Fractured femurs were analyzed using microcomputed tomography and histology at days 14 and 21 after surgery. No animals were lost due to surgery or anesthesia. All animals displayed normal limb loading and a physiological gait pattern within the first three days after fracture. We found robust endochondral ossification during the fracture healing process with high expression of late chondrocyte and early osteogenic markers at day 14 (d14). By day 21 (d21), all fractures had a bony bridging score of 3 or more, indicating successful healing. Callus volume significantly decreased from d14 to d21, whereas high numbers of osteoclasts appeared at the fracture callus until d21, indicating that callus remodeling had already started at d21. In conclusion, we successfully developed a novel mouse model to study endochondral fracture healing of the proximal femur. This model might be useful for future studies using transgenic animals to unravel molecular mechanisms of osteoporotic metaphyseal fracture healing.

Identifiants

pubmed: 32232999
doi: 10.1002/jor.24677
doi:

Types de publication

Evaluation Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2131-2138

Informations de copyright

© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.

Références

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Auteurs

Melanie Haffner-Luntzer (M)

Institute of Orthopaedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany.
Department of Orthopaedic Surgery, Orthopaedic Trauma Institute, University of California, San Francisco, California.

Birte Weber (B)

Department of Orthopaedic Surgery, Orthopaedic Trauma Institute, University of California, San Francisco, California.
Department of Traumatology, Hand, Plastic, and Reconstructive Surgery, University Medical Center Ulm, Ulm, Germany.

Charles Lam (C)

Department of Orthopaedic Surgery, Orthopaedic Trauma Institute, University of California, San Francisco, California.

Verena Fischer (V)

Institute of Orthopaedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany.

Ina Lackner (I)

Department of Traumatology, Hand, Plastic, and Reconstructive Surgery, University Medical Center Ulm, Ulm, Germany.

Anita Ignatius (A)

Institute of Orthopaedic Research and Biomechanics, University Medical Center Ulm, Ulm, Germany.

Miriam Kalbitz (M)

Department of Orthopaedic Surgery, Orthopaedic Trauma Institute, University of California, San Francisco, California.
Department of Traumatology, Hand, Plastic, and Reconstructive Surgery, University Medical Center Ulm, Ulm, Germany.

Ralph S Marcucio (RS)

Department of Orthopaedic Surgery, Orthopaedic Trauma Institute, University of California, San Francisco, California.

Theodore Miclau (T)

Department of Orthopaedic Surgery, Orthopaedic Trauma Institute, University of California, San Francisco, California.

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