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ABSTRACT: In order to enhance the corrosion resistance of the Ca(65)Mg(15)Zn(20) bulk metallic glass which has a too fast degradation rate for biomedical application, we fabricated the Ca(20)Mg(20)Zn(20)Sr(20)Yb(20) high entropy bulk metallic glass considering the unique properties of high entropy alloys. Our results showed that the mechanical properties and corrosion behavior were enhanced. The in vitro tests showed that the Ca(20)Mg(20)Zn(20)Sr(20)Yb(20) high entropy bulk metallic glass could stimulate the proliferation and differentiation of cultured osteoblasts. The in vivo animal tests showed that the Ca(20)Mg(20)Zn(20)Sr(20)Yb(20) high entropy bulk metallic glass didn't show obvious degradation after 4 weeks of implantation, and they can promote osteogenesis and new bone formation quickly after 2 weeks of implantation. The improved mechanical properties and corrosion behavior can be attributed to the different chemical composition as well as the formation of unique high entropy atomic structure with a maximum chaos and disorders.
Acta biomaterialia 02/2013; · 3.98 Impact Factor
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ABSTRACT: The aim of this randomized controlled trial was to determine whether whole body vibration (WBV) therapy was effective for treating osteopenia in adolescent idiopathic scoliosis (AIS) patients. Results showed that WBV was effective for improving areal bone mineral density (aBMD) at the femoral neck of the dominant side and lumbar spine BMC in AIS subjects. INTRODUCTION: AIS is associated with osteopenia. Although WBV was shown to have skeletal anabolic effects in animal studies, its effect on AIS subjects remained unknown. The objective of this study was to determine whether WBV could improve bone mineral density (BMD) and bone quality for osteopenia in AIS subjects. METHODS: This was a randomized, controlled trial recruiting 149 AIS girls between 15 and 25 years old and with bone mineral density (BMD) Z-scores <-1. They were randomly assigned to the Treatment or Control groups. The Treatment group (n = 61) stood on a low-magnitude high-frequency WBV platform 20 min/day, 5 days/week for 12 months. The Control group (n = 63) received observation alone. Bone measurement was done at baseline and at 12 months: (1) aBMD and BMC at femoral necks and lumbar spine using dual-energy X-ray absorptiometry (DXA) and (2) bone quality including bone morphometry, volumetric BMD (vBMD), and trabecular bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT) for nondominant distal radius and bilateral distal tibiae. RESULTS: The Treatment group had numerically greater increases in all DXA parameters with a statistically significant difference being detected for the absolute and percentage increases in femoral neck aBMD at the dominant leg (0.015 (SD = 0.031)g/cm(2), 2.15 (SD = 4.32)%) and the absolute increase in lumbar spine BMC (1.17 (SD = 2.05)g) in the Treatment group as compared with the Control group (0.00084 (SD = 0.026)g/cm(2), 0.13 (SD = 3.62)% and 0.47 (SD = 1.88)g, respectively). WBV had no significant effect for other bone quality parameters. CONCLUSIONS: WBV was effective for improving aBMD at the femoral neck of the dominant side and lumbar spine BMC in AIS subjects.
Osteoporosis International 09/2012; · 4.58 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the efficacy and safety of Cilnidipine tablets to treat Chinese patients with mild to moderate essential hypertension, and to examine the ability of Cilnidipine to lower blood pressure without eliciting unfavorable side effects. Medical databases and review articles were screened for randomized controlled trials that reported the effects of and adverse reactions to Cilnidipine and Amlodipine in treating Chinese patients with mild to moderate essential hypertension. The quality of the included studies was critically evaluated. A total of 547 articles were found, from which 11 articles met the inclusion criteria. The heterogeneity test, the efficacy analysis (Q statistic = 4.62, p = 0.91, I(2) = 0%) and safety analysis (Q statistic = 3.73, p = 0.93, I(2) = 0%) showed that Cilnidipine was equally effective and safe compared to Amlodipine. The funnel-plot displayed a symmetrical figure, indicating there was no publication bias, and all articles included described high quality trials. In conclusion, Cilnidipine is a useful agent to treat mild to moderate essential hypertension in China.
Cardiovascular & hematological disorders drug targets. 06/2012; 12(1):56-62.
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ABSTRACT: Introduction: Growth rate and pattern of girls with Adolescent idiopathic scoliosis (AIS) are proposed to be related to its occurrence and progression. The cross-sectional nature of previous studies did not allow a comprehensive understanding of the relationship. The current study aimed to use both cross-sectional and longitudinal anthropometric data to elucidate the growth pattern of AIS girls of different severities. Methodology: 611 AIS and 296 control girls aged between 12 and 16 were recruited. 194 AIS and 116 controls among the recruited subjects participated in the longitudinal study. The AIS girls were further divided into two groups according to their curve severity. Anthropometric parameters were measured at each visit. The differences in all parameters between AIS of different severities and control subjects were analyzed with one-way ANOVA in the cross-sectional study. While the growth patterns in terms of arm span were evaluated by linear mixed model in the longitudinal study. Results: In the cross-sectional study, severe AIS started with a shorter arm span than moderate AIS and control at age 12 but overtook at age 14-16. For the longitudinal analysis from age 12 to 16, moderate AIS had a longer arm span than control but with similar growth rate. While severe AIS had a higher growth rate than moderate AIS by 71% (p=0.001) and control by 30% (p=0.07) respectively. Discussion: Growth spurt during puberty is a key factor associated with the etiopathogenesis and curve progression in AIS. The current study showed that AIS of different severities and normal controls had different growth rate between age 12 and 16, revealing its possible association with scoliosis development and progression. The findings corroborated the hypothesis of abnormal skeletal growth in AIS which may contribute to its etiopathogenesis. The measurement of arm span growth could be an important clinical parameter in helping to predict the development of severe scoliosis in AIS.
Studies in health technology and informatics 01/2012; 176:474.
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Y-X He,
Z Liu,
X-H Pan,
T Tang,
B-S Guo,
L-Z Zheng,
X-H Xie,
X-L Wang,
K-M Lee,
G Li,
Y-P Cao,
L Wei,
Y Chen,
Z-J Yang,
L-K Hung, L Qin,
G Zhang
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ABSTRACT: This study examined the role of estrogen receptor (ER) beta during mouse femoral fracture healing by employing ER knockout (KO) mice. The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification.
This study was conducted to examine the role of ER beta during fracture healing.
Female ERbeta knockout (KO) mice (18 weeks old) and age-matched female wild-type (WT) mice underwent open osteotomy on the right femur. They were sacrificed at 1, 2, 4 and 6 weeks post-fracture. The sera and callus samples were subjected to the following analyses: micro-computed tomography (CT)-based angiography, micro-CT evaluation, histological examination, histomorphometry examination, real-time polymerase chain reaction (PCR) analysis, biochemical marker, and mechanical testing.
Micro-CT-based angiography showed that the total vessel volume at the fracture site was larger in the KO group than the WT group at 1 and 2 weeks post-fracture. Micro-CT analysis revealed that the callus volume was significantly higher in the KO group from week 2 to week 4 post-fracture when compared with the WT group consistent with the histological data. Analysis of biochemical markers indicated that circulating P1NP levels in the KO mice were significantly higher than in the WT mice from week 2 to week 4 and that temporal expression of circulating C-terminal telopeptide of type I collagen (CTX) levels was also higher in the KO mice than in the WT mice. These results were consistent with quantitative real-time PCR analysis. The ultimate load, stiffness, and energy to failure were significantly higher in the KO mice than in the WT mice at week 4.
The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification, but not by the end of healing. Blockade of ERbeta can be considered as another therapeutic strategy for osteoporotic fracture and non-union fracture.
Osteoporosis International 01/2012; 23(1):377-89. · 4.58 Impact Factor
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H Wang,
Y Wan,
K-F Tam,
S Ling,
Y Bai,
Y Deng,
Y Liu,
H Zhang,
W-H Cheung, L Qin,
J C-Y Cheng,
K-S Leung,
Y Li
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ABSTRACT: Countermeasures are desirable to retard bone loss during long-term space flight. We evaluated the effect of an intervention protocol on bed rest-induced bone loss.
We developed a resistive vibration exercise (RVE) platform to test if an intervention RVE protocol would be effective to protect bed rest-induced bone loss.
Fourteen male subjects were assigned randomly to either the RVE group (n = 7) that performed daily supervised resistive vibration exercise or to the no any exercise control (CON) group (n = 7). Both dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were used to monitor changes in bone mineral density.
RVE significantly prevented bone loss at multiple skeletal sites, including calcaneus, distal tibia, hip, and lumbar spine (L2-L4). The ratio of urinary calcium and creatinine was found higher after starting bed rest in CON group while no significant changes were observed in RVE group. No significant temporal change was found for osteocalcin-N during and after bed rest in CON group. However, a significant increase was shown after bed rest in RVE group. In both groups, the urinary concentration of bone resorption markers, such as C-telopeptide of type I collagen (CTX-I) and deoxypyridinoline (DPD), were significantly elevated after bed rest. In the CON group, no significant temporal effect was found for hydroxyproline (HOP), CTX-I, and DPD during bed rest and the serum concentration of HOP and TGF-β significantly increased about 52.04% and 24.03%, respectively only after bed rest. However, all these markers tended to decrease in the RVE group.
Our results might imply that the intervention of RVE retarded bone loss induced by simulated microgravity in humans that was mainly attributed to its anabolic effects.
Osteoporosis International 12/2011; 23(8):2169-78. · 4.58 Impact Factor
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ABSTRACT: A low density and high strength alloy, Ca65Mg15Zn20 bulk metallic glass (CaMgZn BMG), was evaluated by both in vitro tests on ion release and cytotoxicity and in vivo implantation, aimed at exploring the feasibility of this new biodegradable metallic material for potential skeletal applications. MTT assay results showed that the experimental CaMgZn BMG extracts had no detectable cytotoxic effects on L929, VSMC and ECV304 cells over a wide range of concentrations (0-50%), whereas for MG63 cells concentrations in the range ~5-20% promoted cell viability. Meanwhile, alkaline phosphatase (ALP) activity results showed that CaMgZn BMG extracts increased alkaline phosphatase (ALP) production by MG63 cells. However, Annexin V-fluorescein isothiocyanate and propidium iodide staining indicated that higher concentrations (50%) might induce cell apoptosis. The fluorescence observation of F-actin and nuclei in MG63 cells showed that cells incubated with lower concentrations (0-50%) displayed no significant change in morphology compared with a negative control. Tumor necrosis factor-α expression by Raw264.7 cells in the presence of CaMgZn BMG extract was significantly lower than that of the positive and negative controls. Animal tests proved that there was no obvious inflammation reaction at the implantation site and CaMgZn BMG implants did not result in animal death. The cortical thickness around the CaMgZn BMG implant increased gradually from 1 to 4 weeks, as measured by in vivo micro-computer tomography.
Acta biomaterialia 05/2011; 7(8):3196-208. · 3.98 Impact Factor
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ABSTRACT: Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis. In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.
Journal of Bone and Joint Surgery - British Volume 04/2011; 93(4):558-65. · 2.83 Impact Factor
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T Tang,
G Zhang,
Carol P Y Lau,
L Z Zheng,
X H Xie,
X L Wang,
X H Wang,
K He,
Y Patrick, L Qin,
Shekhar M Kumta
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ABSTRACT: Water-soluble phosphorylated chitosan (P-chitosan) and disodium (1 → 4)-2-deoxy-2-sulfoamino-β-D-glucopyranuronan (S-chitosan) are two chemically modified chitosans. In this study, we found that P-chitosan significantly promotes cell proliferation of both human primary osteoblasts (OBs) and the OB like stromal cell component of the giant cell tumor of bone (GCTB) cells at the concentration from 125 to 1000 µg ml⁻¹ at all time points of 1, 3, 5 and 7 days after treatment. Further investigation of the osteogenic effect of the P-chitosan suggested that it regulates the levels of osteoclastogenic factors, receptor activator of nuclear factor kappa B ligand and osteoprotegerin expression. An interesting finding is that S-chitosan at lower concentration (100 µg ml⁻¹) stimulates cell proliferation while a higher dose (1000 µg ml⁻¹) of S-chitosan inhibits it. The inhibitory effect of S-chitosan on human primary GCT stromal cells was greater than that of OBs (p < 0.05). Taken together, our findings elucidated the osteogenic effect of P-chitosan and the varying effects of S-chitosan on the proliferation of human primary OBs and GCT stromal cells and provided us the rationale for the construction of novel bone repair biomaterials with the dual properties of bone induction and bone tumor inhibition.
Biomedical Materials 02/2011; 6(1):015004. · 2.16 Impact Factor
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ABSTRACT: There have been few comprehensive studies on the age-related changes in bone mineral density (BMD) and bone structure in Chinese people. Using peripheral quantitative computed tomography (pQCT), we assessed volumetric BMD of both trabecular and cortical bone and their geometry at both radius and tibia in 620 Chinese men and 638 women, aged 20–98 years, in Hong Kong. Cortical BMD did not start declining until after the age of 50 years in women and the age of 60 years in men. In contrast, trabecular BMD declined with age starting from adulthood in both sexes, and the rates of decline accelerated after the age of 50 years only in women. The integral and trabecular bone area expanded with age in older men and women, primarily at the tibia. Cortical bone area decreased significantly in older women, particularly at the tibia, while it decreased only slightly with aging in men. The moment of inertia decreased with age at the radius in older men and women. At the tibia, age-related decline accelerated in older women, but not in older men. It was concluded that trabecularization of bone in response to declining BMD and mechanical loading may be maladaptive by reducing cortical bone area, if periosteal apposition cannot keep pace with it.
Journal of Bone and Mineral Metabolism 11/2010; 28(6):672-81. · 2.27 Impact Factor
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ABSTRACT: Animal models for the study of tendinopathy and bone-tendon (B-T) junction repair have been established in the past for sports medicine research. As healing at the B-T junction is difficult and sometimes delayed, establishing a delayed B-T healing experimental model is therefore essential to study the efficacy of potential biophysical and biological interventions for treatment of B-T junction healing.
To test the hypothesis that a delay in B-T healing could be modelled by shielding the B-T healing interface for the initial few weeks.
Using an established partial patellectomy model in rabbits, the B-T healing interface was shielded with a latex slice for the first 4 postoperative weeks in mature female rabbits. The characteristics of delay in B-T repair (n = 10) compared with controls (n = 10) were evaluated at 8 and 12 postoperative weeks.
Radiology showed consistent delay in osteogenesis at the healing interface in all samples in the delayed healing group; growth of new bone was only 25.8% and 50.1% of that in the control group at weeks 8 and 12, respectively. Bone mineral density was 56.0% lower in the delayed healing group at week 8, but this difference diminished at week 12. The quality of B-T healing was poor in the delayed healing group, with 22.9% and 24.2% lower failure load than the control group at weeks 8 and 12, respectively. The healing quality was also reflected by histological findings.
A delayed B-T healing experimental model was established for the first time for future sports medicine research.
British journal of sports medicine 02/2010; 44(2):114-20. · 2.55 Impact Factor
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ABSTRACT: We previously reported a noncontact ultrasound water jet indentation system for measuring and mapping tissue mechanical properties.
The key idea was to utilize a water jet as an indenter as well as the coupling medium for high-frequency ultrasound. In this
paper, the system was employed to assess articular cartilage degeneration, using stiffness ratio as an indicator of the mechanical
properties of samples. Both the mechanical and acoustical properties of intact and degenerated bovine patellar articular cartilage
(n=8) were obtained in situ. It was found that the stiffness ratio was reduced by 44±17% after the articular cartilage was treated by 0.25% trypsin
at 37°C for 4h while no significant difference in thickness was observed between the intact and degenerated samples. A significant
decrease of 36±20% in the peak-to-peak amplitude of ultrasound echoes reflected from the cartilage surface was also found
for the cartilage samples treated by trypsin. The results also showed that the stiffness obtained with the new method highly
correlated with that measured using a standard mechanical testing protocol. A good reproducibility of the measurements was
demonstrated. The present results showed that the ultrasound water jet indentation system may provide a potential tool for
the non-destructive evaluation of articular cartilage degeneration by simultaneously obtaining mechanical properties, acoustical
properties, and thickness data.
Annals of Biomedical Engineering 12/2008; 37(1):164-175. · 2.37 Impact Factor
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ABSTRACT: Swelling behavior is an electrochemical mechanical property of articular cartilage. It plays an important role in weight bearing and joint lubrication. In this study, the altered transient and inhomogeneous swelling behavior of the degenerated articular cartilage was observed and quantified in situ using ultrasound. Three groups of bovine patellar articular cartilage samples (n = 10 x 3) were obtained and digested by trypsin for 10, 20 and 30 min respectively to mimic different levels of degeneration. The osmotic-free shrinkage and swelling behavior induced by changing the concentration of the bathing saline solution from 0.15 M to 2 M and then back to 0.15 M were characterized using high-frequency ultrasound (central frequency = 35 MHz) before and after digestion. It was found that the degenerated cartilage specimens showed a weaker shrinkage-swelling behavior compared with the normal cartilage samples. However, no significant differences in the peak shrinkage or swelling strains were observed between different groups. The absolute values of the peak shrinkage strain significantly (p < 0.05) decreased by 45.4%, 42.1% and 50.6% respectively after the trypsin digestion for 10, 20 and 30 min, but such significance was not demonstrated for the peak swelling strains. Due to the potential alterations in the collagen-PG matrix during trypsin digestion, the correlation between the swelling strain and the shrinkage strain of the degenerated samples changed slightly in comparison with the normal samples. The proposed ultrasound method has been successfully used to measure the transient and inhomogeneous swelling behavior of the degenerated articular cartilage and has the potential for the characterization of osteoarthritis.
Physics in Medicine and Biology 05/2008; 53(10):2537-52. · 2.83 Impact Factor
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ABSTRACT: Adolescent idiopathic scoliosis (AIS) patients have lower bone mineral density (BMD) than their peers. Study showed that polymorphisms of type I collagen alpha 2 (COL1A2) gene was related to the spine BMD of adolescent female. It is hypothesize that COL1A2 gene may be associated with AIS and its related phenotypes. The polymorphism of COL1A2 gene in AIS girls was compared with control population and its association with the anthropometry and BMD of AIS patients was tested. Girls with AIS (n=522) and control (n=250) at age 12-16 were included with anthropometric data. The PvuII polymorphism of COL1A2 was characterized by PCR-RFLP. The spinal and femoral neck BMD were measured. The association of the gene polymorphism to the occurrence of AIS was tested by Chi-square. Standardized anthropometric parameters and BMD of AIS patients were compared between different genotypes. The genotype frequency of PP, Pp, and pp in AIS patients were 6.1%, 40.2%, and 53.6%, respectively. The distribution was significantly different from that of the control subjects (p=0.033). The BMC of the spine in AIS girls with pp was significantly lower than patients with P allele (PP and Pp) (p=0.008). The BMI of the AIS girls with pp genotypes had significantly lower BMI than others as well (p=0.035). AIS girls with pp genotype were shown to associate with the occurrence of AIS while this genotype also had significantly lower BMI, bone mineral status. It is suggested that COL1A2 gene might play an important role in the development of scoliosis and its related phenotypes.
Studies in health technology and informatics 02/2008; 140:328-9.
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ABSTRACT: Quantitative ultrasound (QUS) has found to be a useful tool in assessing the quality of bone non-invasively. Previous studies showed that a significant portion of AIS girls have low bone mineral density (BMD). However, studies in mechanical and structural properties of bone in AIS patients are limited. We aimed at to investigate the bone quality in AIS girls using radiation free calcaneal QUS. 528 AIS girls with initial Cobb angle >/=10 degrees and 240 age-matched normal control girls were recruited. QUS measurement was performed at the non-dominant side of calcaneum. Parameters measured by QUS included broadband ultrasound attenuation (BUA), velocity of sound (VOS) and stiffness index (SI). Independent t-test was used for analysis. Results showed that there were no significant difference in age and menarchal age between AIS and controls (p>0.05). The mean Cobb angle for AIS girls was 30 degrees +/-11. However, AIS had significantly lower in BUA, VOS and SI than those of the controls (BUA: 117.0+/-13.9 Vs 123.4+/-10.9; p<0.01; VOS: 1442.1+/-46.8 Vs 1447.9+/-53.8; p=0.037; SI: 353.2+/-69.3 Vs 379.6+/-69.3; p<0.01). The current study showed all the QUS parameters were found lower in AIS than those of age-matched controls. Results revealed poor bone quality may reflect the presence of abnormality in bone micro-architecture in AIS patients. Our previous study demonstrated that low BMD, measured by DXA, was found to be one of the risk factors in predicting curve progression. Further study in combining bone density and quality parameters for prognostication of curve progression in AIS could be of great clinical application.
Studies in health technology and informatics 01/2008; 140:354.
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ABSTRACT: The postoperative programmed muscle tension induced by functional electrical stimulation (FES) was evaluated for its potential efficacy on acceleration of osteotendinous junction healing using an established partial patellectomy model in rabbits. After immobilization of the operated knee for 6 weeks, daily FES was applied to quadriceps muscles for 30 minutes per day and 5 days per week for 6 weeks in the treatment group and compared with the non-treatment control group at postoperative week 12 and 18, radiologically, histologically and biomechanically. Results showed that FES-induced muscle tension significantly increased new bone formation, bone mineral density, and fibrocartilage zone restoration in the osteotendinous healing interface. The failure load and ultimate strength of the repairing osteotendinous complex were also improved significantly with healing over time. In conclusion, the postoperative programmed FES-induced muscle tension was favorable for acceleration of osteotendinous junction repair and therefore recommended for clinical trails in orthopedic sports medicine and rehabilitation.
International Journal of Sports Medicine 09/2007; 28(8):691-6. · 2.43 Impact Factor
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ABSTRACT: This study tested the effect of Epimedium-derived phytoestrogen (PE) on preventing steroid-associated osteonecrosis (ON) in rabbit model.
Thirty 28-week-old male New-Zealand white rabbits were divided into control group (CON; n=14) and PE group (PE; n=16; 5 mg/kg body weight/day) after receiving an established inductive protocol for inducing steroid-associated ON. Before and after inductive protocol, Dynamic-MRI was employed on bilateral femora for local intra-osseous perfusion, blood samples were examined for coagulation, fibrinolysis and lipid-transportation, and marrow samples were quantified for adipogenesis-gene mRNA expression. Six weeks later, bilateral femora were dissected for Micro-CT-based micro-angiography, and then ON lesion, intravascular thrombosis and extravascular fat-cell-size were examined histopathologically.
The incidence of ON in the PE group (31%) was significantly lower than that in the CON group (93%). Compared to the CON group, local intra-osseous perfusion was maintained in the PE group. Blocked trunk vessels were seldom found in micro-angiography of the PE-treated rabbits. Thrombosis incidence and fat-cell-size were both significantly lower in the PE group than those in the CON group. During the early period after induction, indicator of coagulation, fibrinolysis, lipid-transportation and adipogenesis-gene expression were found with significantly changing pattern in the PE group compared to the CON group.
PE was able to exert beneficial effect on preventing steroid-associated ON in rabbits with inhibition of both thrombosis and lipid deposition.
Bone 04/2007; 40(3):685-92. · 4.02 Impact Factor
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ABSTRACT: The present study employed both static and dynamic imaging modalities to study both intra- and extravascular events attributing to steroid-associated osteonecrosis (ON) using an experimental protocol with a single low-dose lipopolysaccharide (LPS) injection and subsequently three injections of high-dose methylprednisolone (MPS).
Fourteen 28-week-old male New Zealand white rabbits received one intravenous injection of LPS (10 microg/kg). 24 h later, three injections of 20 mg/kg of MPS were given intramuscularly at a time interval of 24 h. Additional 6 rabbits were used as controls. Dynamic MRI was performed on bilateral femora for local intraosseous perfusion before and after LPS injection. Blood samples were collected for hematological examinations before and after LPS injection. Bilateral femora were dissected and decalcified for microCT-based microangiography. ON lesion, intravascular thrombus and extravascular marrow fat cell size were examined histopathologically.
Intravascular thrombus was observed in all ON rabbits. Extravascular marrow fat cell size was significantly increased in ON rabbits than that of the controls (P<0.05). Compared to baseline, a significant decrease in ratio of tissue-type plasminogen activator/plasminogen activator inhibitor 1, activated partial thromboplatin time and a significant increase in ratio of low-density lipoprotein/high-density lipoprotein were only found in ON rabbits (P<0.05). Dynamic MRI showed a significant decrease in the perfusion index 'maximum enhancement' in the ON rabbits (P<0.05), and microCT-based microangiography showed blocked stem vessels in ON samples. Overall, 93% of the rabbits (13/14) developed ON, and no rabbits died throughout the experiment period.
Both intra- and extravascular events were found attributing to the steroid-associated ON based on our experimental protocol with a single low-dose LPS injection and subsequent three injections of high-dose MPS. Both high ON incidence and no mortality in rabbits treated with this inductive protocol suggested its effectiveness for future studies on evaluation of therapeutic efficacy of interventions developed for prevention of steroid-associated ON.
Bone 10/2006; 39(4):863-71. · 4.02 Impact Factor
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ABSTRACT: Growth factors potentially promote tendon healing. Understanding the right time to administer growth factors and the dosage of growth factors are prerequisites for designing effective cytokine therapy. We investigated the supplementation-time dependence of the effects of platelet-derived growth factor isoform B at various dosages on tendon healing, and the temporal responsiveness of healing tendon toward platelet-derived growth factor. Platelet-derived growth factor isoform B at various dosages (0, 10, 100, or 1000 ng) was delivered into the gap wound of rat patellar tendons via microsyringe injection on Day 3 or Day 7 after injury. Tendon specimens were harvested on Day 14 for measurement of cell proliferation, pyridinoline content, and mechanical properties. We found increased proliferative response only when the growth factor was supplemented on Day 3 after injury, whereas supplementation on Day 7 resulted in greater peak load, cross-sectional area, and pyridinoline content. The ultimate stress did not change. Our findings suggest supplementation of platelet-derived growth factor isoform B at Day 7 benefits the mechanical properties and maturation of healing tendons. We also found platelet-derived growth factor receptor beta expressing cells at the remodeling site as much as 6 months after injury, suggesting healing tendon also may be responsive to long-term delivery of platelet-derived growth factor.
Clinical Orthopaedics and Related Research 08/2006; 448:240-7. · 2.53 Impact Factor
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ABSTRACT: Factorial design was used to test our hypothesis whether a group of flavonoids (FE) derived from herbal Epimedium Brevicornum Maxim exerted its preventive effects on estrogen-deficiency-induced osteoporosis mainly through an enhancement in intestinal calcium absorption.
Forty-five 12-month-old female Wistar rats were used and randomly assigned into sham-operated group and four ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX group), OVX with FE (FE group), OVX with calcium supplement (CS group), and OVX with FE and CS (FE + CS group). Daily oral administration of FE (10 mg/kg/day) and/or CS (56 mg/kg/day) started on day 4 after OVX for 12 weeks. Before sacrificing the animals, urine and serum samples were collected for assaying indicators related to intestinal calcium absorption, regulator for calcium homeostasis, and markers of bone turnover. The left proximal femur was dissected for evaluation of the primary end-point (failure force), the second end-points (pQCT-quantified densitometry, geometry, and micro-CT-quantified 3-D trabecula micro-architecture), and pQCT-defined cross-sectional envelope.
FE was found to be able to prevent OVX-induced reduction in failure force as well as the above second end-points, without resulting in an increased uterus weight. CS had no preventive effect on OVX-induced reduction in failure force. Two-way factorial interaction analysis between FE and CS showed that the un-enhanced suppression of parathyroid hormone for calcium homeostasis did not provide link between the enhanced intestinal calcium absorption and the enhanced inhibition of bone resorption in the present study. Furthermore, the discrepancies between the enhanced intestinal calcium absorption and the un-enhanced end-point measures as well as anabolic effect were also revealed by the interaction analysis.
The present study suggested that FE inhibited bone resorption, stimulated bone formation, and accordingly prevented osteoporosis without hyperplastic effect on uterus in the OVX rat model, which was however independent of an enhancement in intestinal calcium absorption.
Bone 07/2006; 38(6):818-25. · 4.02 Impact Factor
