A metaphyseal fracture rat model for mechanistic studies of osteoporotic bone healing

Abstract

Most osteoporotic fractures occur at metaphyseal regions of long bones. The present study proposed a clinically relevant animal model that satisfied: i) induction of osteoporosis, ii) unilateral complete osteotomy at metaphysis, iii) internal fixation. 6 months old female Sprague-Dawley rats (n = 64) were randomly divided into the ovariectomised-metaphyseal osteotomy (OVX, n = 32) and metaphyseal osteotomy (SHAM, n = 32) groups. The metaphyseal-osteotomy model was created with a plate-fixation of the osteotomy and assessed by X-ray, micro-computed tomography, histomorphometry and mechanical testing at weeks 1, 3 and 6. X-ray results showed complete healing of metaphyseal osteotomy at week 6. Histology showed 3 stages of metaphyseal healing. Stage 1 was characterised by fibrous tissue, consisting of disorganised orientation of collagen fibres, and infiltration of immune cells. At stage 2, a transitional zone consisting of maturing fibrous tissue and differentiating mesenchymal cells with early trabecular bone formation and disorganised woven bone were observed. During stage 3, cortical bone ends unified and woven bone underwent transformation to lamellar bone. OVX group healing was significantly delayed when compared to SHAM samples. The study demonstrated that healing of osteoporotic osteotomy at the metaphyseal region was delayed in terms of radiography, histomorphometry and mechanical strength. These quantitative evaluations, along with histological features, may provide key references for future studies. The animal model may provide additional clinical relevance as most osteoporotic fracture in humans occurs at metaphyseal regions.

Vibration treatment modulates macrophage polarisation and enhances early inflammatory response in oestrogen-deficient osteoporotic-fracture healing

“…Thaqif El Khassawna: Would the authors expect a deviant result if a more stable (rigid) fixation method was used? Authors: We have previously utilised a metaphyseal fracture model with complete osteotomy at the metaphysis unilaterally and rigid plate fixation (Wong et al, 2018;Wong et al, 2019;additional references). In addition, vibration treatment enhanced early phase fibrinolysis in a metaphyseal fracture model, which helped to accelerate the overall fracture healing by timely and more effectively removing fibrin from the fracture site (study submitted).…”

Inflammatory response in postmenopausal osteoporotic fracture healing

“…Different fracture regions such as the metaphyseal region could be examined as different fracture sites may show different inflammatory responses after injury. 77 , 78 In addition, parabiosis mice models could be used to investigate factors that are responsible for age-dependent tissue regeneration, as previous studies identified that a youthful circulation can rejuvenate aged-bone healing. 79 , 80 …”

Can we enhance osteoporotic metaphyseal fracture healing through enhancing ultrastructural and functional changes of osteocytes in cortical bone with low‐magnitude high‐frequency vibration?

“…To assess the healing processes, lateral X‐rays (UltraFocus DXA, Faxitron, IL) were taken weekly at 60 kVp and 3.0 s to monitor the fracture healing status. The metaphyseal osteotomy sites were manually selected and the radiopacity was quantified with image analysis software (ImageJ, USA) …”

“…The metaphyseal osteotomy sites were manually selected and the radiopacity was quantified with image analysis software (ImageJ, USA). 34…”