A new animal model of femoral head osteonecrosis: one that progresses to human‐like mechanical failure

Conzemius, Michael G.; Brown, Thomas; Zhang, Yongde; Robinson, Robert A.

doi:10.1016/s0736-0266(01)00108-5

Cited by 73 publications

(67 citation statements)

References 41 publications

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“…Genetic, environmental, and nutritional factors contribute to the development of osteoporosis in laying hens, with a 30% incidence of fracture reported for these animals (Fleming et al 2000). Osteonecrosis of the femoral head, including both the biological progression and the structural collapse, can be replicated in the emu hip by means of cryoinsult (Conzemius et al 2002). While avian species obviously are not full physiological counterparts of mammals, these many occurrences of familiar clinical disorders suggest potential utility of the emu in appropriately targeted experimental designs.…”

Section: Discussionmentioning

confidence: 99%

Hip joint contact force in the emu (Dromaius novaehollandiae) during normal level walking

Goetz

Derrick

Pedersen

et al. 2008

Journal of Biomechanics

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The emu is a large, (bipedal) flightless bird that potentially can be used to study various orthopaedic disorders in which load protection of the experimental limb is a limitation of quadrupedal models. An anatomy-based analysis of normal emu walking gait was undertaken to determine hip contact forces for comparison with human data. Kinematic and kinetic data captured for two laboratoryhabituated emus were used to drive the model. Muscle attachment data were obtained by dissection, and bony geometries were obtained by CT scan. Inverse dynamics calculations at all major lowerlimb joints were used in conjunction with optimization of muscle forces to determine hip contact forces. Like human walking gait, emu ground reaction forces showed a bimodal distribution over the course of the stance phase. Two-bird averaged maximum hip contact force was approximately 5.5 times body weight, directed nominally axially along the femur. This value is only modestly larger than optimization-based hip contact forces reported in literature for humans. The interspecies similarity in hip contact forces makes the emu a biomechanically attractive animal in which to model loading-dependent human orthopaedic hip disorders.

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Section: Discussionmentioning

confidence: 99%

Hip joint contact force in the emu (Dromaius novaehollandiae) during normal level walking

Goetz

Derrick

Pedersen

et al. 2008

Journal of Biomechanics

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“…Studies were done with various species such as dogs, rabbits, sheep and even nonstandard laboratory animals such as emus [Conzemius et al, 2002], however, mostly rats were used. Interrupting the blood circulation in the femoral head of rats mimics children's Legg-Calvé-Perthes disease more than it resembles adult osteonecrosis, due to the lifelong persisting physeal cartilage [Boss and Misselevich, 2003].…”

Section: Introductionmentioning

confidence: 99%

Changes in Bone Microarchitecture and Bone Mineral Density following Experimental Osteonecrosis of the Hip in Rabbits

Hofstaetter

Jin-Xi

Yan

et al. 2006

Cells Tissues Organs

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Background: Osteonecrosis of the femoral head is a common disorder which can lead to hip joint destruction usually necessitating total hip replacement. Methods: Quantitative micro-computed tomography, digital radiography and histology were used to characterize changes in bone microarchitecture and bone mineral density during the repair of the osteonecrotic femoral head as well as during the development of secondary osteoarthritis in the ipsilateral acetabulum. Osteonecrosis was induced surgically in 17 adult, male rabbits and the contralateral side was used as control. Results: At 4 weeks no changes in microarchitecture in the femoral head nor in the acetabulum were found. At 6 months the repair process led to an increase in bone mass in the trabecular region of the femoral head. However, a decrease in volumetric bone mineral density and an increase in apparent porosity were seen in the compact subchondral and cortical region of the osteonecrotic femoral head. At 6 months the subchondral bone of the osteoarthritic ipsilateral acetabulum was thicker, but had a lower volumetric bone mineral density and a higher apparent porosity. Conclusion: Resorption of necrotic compact bone may weaken the structural properties of the femoral head. Moreover, remodeling and resorption of subchondral bone may play a critical role in the disease process of osteoarthritis.

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“…This may be an important feature of the model as some animal models of osteonecrosis do not have collapse or deformity of the epiphysis develop. Development of bone deformity, which can lead to the early onset of osteoarthritis, is seen in patients and in some large animal models of ischemic osteonecrosis [7,22,25,33,35]. This feature also may be used to evaluate whether a potential treatment for osteonecrosis can prevent the development of the deformity.…”

Section: Discussionmentioning

confidence: 99%

Development of a Mouse Model of Ischemic Osteonecrosis

Kamiya

Yamaguchi

Aruwajoye

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Availability of a reliable mouse model of ischemic osteonecrosis could accelerate the development of novel therapeutic strategies to stimulate bone healing after ischemic osteonecrosis; however, no mouse model of ischemic osteonecrosis is currently available. Questions/purposes To develop a surgical mouse model of ischemic osteonecrosis, we asked, (1) if the blood vessels that contribute to the blood supply of the distal femoral epiphysis are cauterized, can we generate an osteonecrosis mouse model; (2) what are the histologic changes observed in this mouse model, and (3) what are the morphologic changes in the model. Methods We performed microangiography to identify blood vessels supplying the distal femoral epiphysis in mice, and four vessels were cauterized using microsurgical techniques to induce ischemic osteonecrosis. Histologic assessment of cell death in the trabecular bone was performed using terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) and counting the empty lacunae in three serial sections. Quantitation of osteoclast and osteoblast numbers was performed using image analysis software. Morphologic assessments of the distal femoral epiphysis for deformity and for trabecular bone parameters were performed using micro-CT. Results We identified four blood vessels about the knee that had to be cauterized to induce total ischemic osteonecrosis of the distal femoral epiphysis. Qualitative assessment of histologic sections of the epiphysis showed a loss of nuclear staining of marrow cells, disorganized marrow structure, and necrotic blood vessels at 1 week. By 2 weeks, vascular tissue invasion of the necrotic marrow space was observed with a progressive increase in infiltration of the necrotic marrow space with the vascular tissue at 4 and 6 weeks. TUNEL staining showed extensive cell death in the marrow and trabecular bone 24 hours after the induction of ischemia. The mean percent of TUNELpositive osteocytes in the trabecular bone increased from 2% ± 1% in the control group to a peak of 98% ± 3% in the ischemic group 1 week after induction of ischemia (mean difference, 96%; 95% CI, 81%-111%; p \ 0.0001). The mean percent of empty lacunae increased from 1% ± 1% in the control group to a peak of 78% ± 15% in the ischemic group at 4 weeks (mean difference, 77%; 95% CI, 56%-97%; p \ 0.0001). Quantitative analysis showed that the mean number of osteoclasts per bone surface was -015-4172-6 Clinical Orthopaedics and Related Research ® A Publication of The Association of Bone and Joint Surgeons® decreased in the ischemic group at 1, 2, and 4 weeks (p \ 0.0001, \ 0.0001, and p = 0.02, respectively) compared with the control group. The mean number of osteoclasts increased to a level similar to that of the control group at 6 weeks (p = 0.23). The numbers of osteoblasts per bone surface were decreased in the ischemic group at 1, 2 and 4 weeks (p \ 0.0001 for each) compared with the numbers in the control group. The mean number of osteoblasts also increased to a level...

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A new animal model of femoral head osteonecrosis: one that progresses to human‐like mechanical failure

Cited by 73 publications

References 41 publications

Hip joint contact force in the emu (Dromaius novaehollandiae) during normal level walking

Hip joint contact force in the emu (Dromaius novaehollandiae) during normal level walking

Changes in Bone Microarchitecture and Bone Mineral Density following Experimental Osteonecrosis of the Hip in Rabbits

Development of a Mouse Model of Ischemic Osteonecrosis

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