Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone

Qin, Ling; Zhang, G.; Sheng, Hui; Yeung, K.W.; Yeung, H.Y.; Chan, C.W.; Cheung, Wing-Hoi; Griffith, James F.; Chiu, Ka Lok; Leung, Kwok‐Sui

doi:10.1016/j.bone.2006.04.018

Cited by 113 publications

(190 citation statements)

References 26 publications

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“…The protein expression of BMP-2 in the control group (15 ± 2; 95% CI, 14-16) was lower (p \ 0.001) than in the LIPUS group (30 ± 3; 95% CI, 28-31). However, VEGF mRNA expression was not different (p = 0.114; Table 2) between the LIPUS group (28 ± 2; 95% CI, [26][27][28][29] and the control group (26 ± 3; 95% CI, [24][25][26][27][28]. VEGF protein expression also was not different (p = 0.0124, Fig.…”

Section: Bmp-2 and Vegf Expressionmentioning

confidence: 90%

“…Rabbits were fed a standard laboratory diet and water ad libitum. The steroid-associated osteonecrosis rabbit model was prepared using a previously published inductive protocol [26,37]. Briefly, the rabbits received intravenous injections of 10 lg/kg lipopolysaccharide followed by intramuscular injections of methylprednisolone (20 mg/kg) 24 hours later.…”

Section: Rabbit Modelmentioning

confidence: 99%

“…Two additional methylprednisolone injections then were administered at 24-hour intervals so that the rabbits received a total of three methylprednisolone injections. It has been reported that formation of osteonecrosis lesions can occur 2 weeks after methylprednisolone injection [26,39]. Four animals were randomly selected for MRI (T1-weighted image, TR 400 ms, TE 20 ms; T2-weighted image, TR 2000 ms, TE 106 ms) 2 weeks after methylprednisolone injection to test whether osteonecrosis was induced.…”

Section: Rabbit Modelmentioning

confidence: 99%

“…The structure of the trabecular bone in the volume of interest of the femoral head was evaluated with eXplore software [26,35]. The mean volumetric bone mineral density (BMD) (mg/cc) and trabecular architectural parameters, including the bone tissue volume density (bone volume/total volume, %), trabecular number (expressed as 1/mm), trabecular thickness (expressed as lm), and trabecular spacing (expressed as lm) to define the degree of plate-like and rodlike trabecular bone in the femoral head were measured.…”

Section: Micro-ct Analysismentioning

confidence: 99%

“…The mean of the two sections from each sample was taken as the value of that sample. The following parameters were assessed: (1) 200 osteocyte lacunae were counted in each established field at 9 200 magnification and then the percentage of the empty osteocyte lacunae was determined [33]; (2) the average diameter of the fat cells was measured in each field and the average diameter for fat cells of each animal was determined [26,33]; (3) the number and diameter of blood vessels were measured and averaged for each sample based on the a-SMA staining slides [3]. The number of blood vessels was expressed per area of tissue (/mm 2 ); (4) the mineralizing surface and bone surface and mineral apposition rate (lm/day) were calculated as described in previous studies [6,35].…”

Section: Histologic Evaluation and Immunohistochemistrymentioning

confidence: 99%

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Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Zhu

Cai

Lin

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Steroids are a leading cause of femoral head osteonecrosis. Currently there are no medications available to prevent and/or treat steroid-associated osteonecrosis. Low-intensity pulsed ultrasound (LIPUS) was approved by the FDA for treating delayed union of bone fractures. Some studies have reported that LIPUS can enhance bone formation and local blood flow in an animal model of fracture healing. However, whether the effect of osteogenesis and neovascularization by LIPUS can enhance the repair progress in steroid-associated osteonecrosis is unknown.Questions/purposes We hypothesized that LIPUS may facilitate osteogenesis and neovascularization in the reparative processes of steroid-associated osteonecrosis. Using a rabbit animal model, we asked whether LIPUS affects (1) bone strength and trabecular architecture; (2) blood vessel number and diameter; and (3) BMP-2 and VEGF expression. Methods Bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in 24 rabbits. The left femoral heads of rabbits received LIPUS therapy (200 mW/cm 2 ) for 20 minutes daily and were classified as the LIPUS group. The right femoral heads of the same rabbits did not receive therapy and were classified as the control group. All rabbits were euthanized 12 weeks after LIPUS therapy. Micro-CT, biomechanical testing, histologic evaluation, immunohistochemistry, quantitative realtime PCR, and Western blot were used for examination of the effects of LIPUS. Results Twelve weeks after LIPUS treatment, the loading strength in the control group was 355 ± 38 N (95% CI, 315-394 N), which was lower (p = 0.028) than that in the LIPUS group (441 ± 78 N; 95% CI, 359-524 N). The bone tissue volume density (bone volume/total volume) in the LIPUS group (49.29% ± 12.37%; 95 % CI, 36.31%-62.27%) was higher (p = 0.022) than that in the control group (37.93% ± 8.37%; 95 % CI, 29.15%-46.72%). The percentage of empty osteocyte lacunae in the LIPUS group (17% ± 4%; 95% CI, 15%-20%) was lower (p = 0.002) than that in the control group (26% ± 9%; 95% CI, 21%-32%). The mineral apposition rate (lm/day) in the LIPUS group (2.3 ± 0.8 lm/day; 95% CI, 1.8 2.8 lm/day) was higher (p = 0.001) than that in the control group (1.6 ± 0.3 lm/day; 95% CL, 1.4-1.8 lm/day). The number of blood vessels in the LIPUS group (7.8 ± 3.6/mm 2 ; 95% CI, 5.5-10.1 mm 2 ) was greater (p = 0.025) than the number in Hanxiao Zhu and Xunzi Cai contributed equally to this work and should be considered as co-first authors.The institution of the authors has received funding from the National Natural Science Foundation of China (Hangzhou, Zhejiang, China) (81101377, 81101345, 81171687, 81371954, 81201414, 81201416, 81401785, 81472113) 123Clin Orthop Relat Res (2015) 473:1830-1839 DOI 10.1007 Clinical Orthopaedics and Related Research ® A Publication of The Association of Bone and Joint Surgeons® the control group (5.7 ± 2.6/mm 2 ; 95% CI, 4.0-7.3 mm 2 ). Messenger RNA (mRNA) and protein expression of BMP-2 in the LIPUS group (75 ± 7, 95% CI, 70-7...

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Section: Bmp-2 and Vegf Expressionmentioning

confidence: 90%

Section: Rabbit Modelmentioning

confidence: 99%

Section: Rabbit Modelmentioning

confidence: 99%

Section: Micro-ct Analysismentioning

confidence: 99%

Section: Histologic Evaluation and Immunohistochemistrymentioning

confidence: 99%

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Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Zhu

Cai

Lin

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Continuous occurrence of both insufficient neovascularization and elevated vascular permeability in rabbit proximal femur during inadequate repair of steroid‐associated osteonecrotic lesions

Zhang¹,

Sheng²,

He³

et al. 2009

Arthritis & Rheumatism

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Objective. To examine the features of the intraosseous vasculature, the size of the marrow stem cell pool (MSCP), and expression of vascular endothelial growth factor A (VEGF) during inadequate repair of steroid-associated osteonecrotic lesions in rabbits.Methods. Steroid-associated osteonecrosis was induced in male rabbits. At 0, 1, 2, 4, and 6 weeks postinduction, vascularization and permeability indices were quantified by dynamic magnetic resonance imaging (MRI). In addition, the size of the MSCP in the hematopoietic and mesenchymal compartments was determined, and marrow mononuclear cells expressing specific surface markers for endothelial progenitor cells or periendothelial mural precursor cells were counted. At various time points after the rabbits were killed, the proximal femora were dissected to examine the intraosseous vasculature by angiography, histomorphometry, and ultramorphology. In addition, osteonecrotic lesion repair and marrow VEGF expression were evaluated.Results. Lesion formation without repair was observed at 2 weeks after induction of steroid-associated osteonecrosis. Rabbits displaying destructive repair (DR؉) and those displaying reparative osteogenesis (DR؊) from 4 weeks to 6 weeks postinduction were identified. From week 2 to week 6, the vascularization index was significantly lower in DR؉ rabbits compared with DR؊ rabbits, whereas the permeability index was significantly higher in DR؉ rabbits compared with DR؊ rabbits. The features of the intraosseous vasculature determined by angiography, histomorphometry, and ultramorphology were consistent with those determined by dynamic MRI. The MSCP size and number of marrow mononuclear cells expressing specific surface markers were all significantly lower in DR؉ rabbits than in DR؊ rabbits from week 1 to week 6. The increased VEGF expression at 2 weeks was maintained through week 6 in DR؉ rabbits, whereas VEGF expression decreased in DR؊ rabbits from week 2 to week 6.Conclusion. Continuous occurrence of both insufficient neovascularization and elevated vascular permeability is accompanied by a continuously lowlevel MSCP and uncontrolled VEGF expression during inadequate repair of steroid-associated osteonecrotic lesions.Pulsed steroids are frequently prescribed as lifesaving agents for serious infectious diseases such as severe acute respiratory syndrome and acquired immunodeficiency syndrome, or as disease-modifying agents for chronic autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. However, pulsed administration of steroids often results in osteonecrosis (also known as avascular necrosis). Orthopedic surgeons face the challenge of managing subchondral

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Promotion of bone repair by implantation of cryopreserved bone marrow–derived mononuclear cells in a rabbit model of steroid‐associated osteonecrosis

Xie

Wang

et al. 2012

Arthritis & Rheumatism

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Objective. Cytotherapy is an insufficient method for promoting bone repair in steroid-associated osteonecrosis (SAON), and this has been attributed to impairment of the bioactivity of bone marrow-derived stem cells (BMSCs) after pulsed administration of steroids. Cryopreserved autologous bone marrowderived mononuclear cells (BMMNCs), which contain BMSCs, might maintain their bioactivity in vitro. This study sought to investigate the effects of cryopreserved BMMNCs, before steroid administration, on the enhancement of bone repair in an established rabbit model of SAON.Methods. For in vitro study, bone marrow was harvested 4 weeks before SAON induction from the iliac crests of rabbits (n ‫؍‬ 10) to isolate fresh BMMNCs, and the BMMNCs were then cryopreserved for 8 weeks. Both the fresh and the cryopreserved BMMNCs were evaluated for their bioactivity and osteogenic differentiation capacity. In addition, BMMNCs were isolated 2 weeks after SAON induction and subjected to the same evaluations. For in vivo study, cryopreserved BMMNCs were implanted into the bone tunnel during core decompression of the femur (n ‫؍‬ 12 rabbits) after the induction of SAON, and tissue regeneration was evaluated by micro-computed tomography and histologic analyses at 12 weeks postoperation.Results. In vitro, there were no significant differences in the bioactivity or ability to undergo osteogenic differentiation between fresh BMMNCs and cryopreserved BMMNCs, but after SAON induction, both features were decreased significantly. In vivo, the bone mineral density, ratio of bone volume to total volume of bone, and volume and diameter of neovascularization within the bone tunnel were significantly higher in the BMMNC-treated group compared to the nontreated control group at 12 weeks postoperation.Conclusion. Cryopreserved BMMNCs maintained their bioactivity and promoted bone regeneration and neovascularization within the bone tunnel after core decompression in this rabbit model of SAON.

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Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone

Cited by 113 publications

References 26 publications

Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Continuous occurrence of both insufficient neovascularization and elevated vascular permeability in rabbit proximal femur during inadequate repair of steroid‐associated osteonecrotic lesions

Promotion of bone repair by implantation of cryopreserved bone marrow–derived mononuclear cells in a rabbit model of steroid‐associated osteonecrosis

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