Animal models for studying metaphyseal bone fracture healing

Abstract

An estimated 2 million osteoporotic fractures occur annually in the US, resulting in a dramatic reduction in quality of life for affected patients and a high economic burden for society. Osteoporotic fractures are frequently located in metaphyseal bone regions. They are often associated with healing complications, because of the reduced healing capacity of the diseased bone tissue, the poor primary stability of the fracture fixation in the fragile bone, and the high frequency of comorbidities in these patients. Therefore, osteoporotic fractures require optimised treatment strategies to ensure proper bone healing. Preclinical animal models can help understanding of the underlying mechanisms and development of new therapies. However, whereas diaphyseal fracture models are widely available, appropriate animal models for metaphyseal fracture healing are scarce, although essential for translational research. This review covers large and small animal models for metaphyseal fracture healing. General requirements for suitable animal models are presented, as well as advantages and disadvantages of the current models. Furthermore, differences and similarities between metaphyseal and diaphyseal bone fracture healing are discussed. Both large- and small-animal models are available for studying metaphyseal fracture healing, which mainly differ in fracture location and geometry as well as stabilisation techniques. Most common used fracture sites are distal femur and proximal tibia. Each model found in the literature has certain advantages and disadvantages; however, many lack standardisation resulting in a high variability or poor mimicking of the clinical situation. Therefore, further refinement ofanimal models is needed especially to study osteoporotic metaphyseal fracture healing.

Antimicrobial Biomaterials for the Healing of Infected Bone Tissue: A Systematic Review of Microtomographic Data on Experimental Animal Models

“…Cancellous bone has a porous structure and a wider surface, which contribute to faster revascularization for new bone formation, further displaying a bone turnover that is higher than cortical bone [ 41 ]. Additionally, it is important to note that rats display the fastest cancellous bone healing, with rabbits presenting an intermediate time and sheep taking the longest healing time [ 42 ]. Therefore, attained differences—embracing the anatomical differences, defect size, and healing capabilities—may result in a potential challenge for the comparative analysis of the results.…”

Heterotopic ossification vs. fracture healing: Extracellular vesicle cargo proteins shed new light on bone formation

“…The long bone fractures included metaphyseal or diaphyseal part of the radius, ulna, humerus, femur, tibia or fibula. These types of fractures were selected for their presumed similarity to animal fracture models used in the existing studies ( Li et al, 2015 ; Haffner-Luntzer and Ignatius, 2020 ). Blood samples were drawn between the 7th and 21st day after fracture occurrence, a timeframe that was presumed to reflect the transition period from the inflammatory to the fibrocartilaginous phase of fracture healing: we therefore presumed that at this time the patients would have peak blood expression levels of growth and signaling factors ( Einhorn and Gerstenfeld, 2015 ; Morgan et al, 2014 ; Bahney et al, 2019 ; Hankenson et al, 2015 ).…”

“…The functionally relevant cargo dispatched in EVs can be efficiently delivered to neighbouring or remote cells receiving these molecular messages. This process has also been implicated in skeletal metabolism, in particular in bone formation and bone regeneration following trauma or disease ( Roy et al, 2018 ; Li et al, 2015 ; Haffner-Luntzer and Ignatius, 2020 ; Carnino et al, 2019 ; Rappsilber et al, 2007 ). Despite being researched extensively, to the best of our knowledge, there are no reports on the possible roles of EVs in HO or FOP.…”

A rat model of tibia fracture and recovery after plate fixation

“…The extent of injury and the di culty in healing the tibia is due to multiple biological and biomechanical factors such as the involvement of soft tissue damage, the di culty in wound coverage, the high incidence of periosteal damage and interruption of the intramedullary blood supply (8). These fractures are associated with postoperative pain that can signi cantly affect the patients' quality of life (9) and result in serious consequences such as loss of long-term income (10). Data from clinical studies have shown that severe postoperative pain is associated with an increased risk of complications, a slow recovery process, delayed return to normal function, prolonged hospital stay, increased readmission rates, and higher total costs (11).…”