[Summary] _ Osteoporosis and diabetes mellitus are diseases which affect public heath severely, and osteoporotic fracture risk is increased in patients with diabetes. During recent years, new anti-diabetes drugs glucagon-like peptide-1(GLP-1) analogues and its receptor agonists had been used for diabetes treatment. As the research continues, besides of anti-diabetes, GLP-1 analogues are also found to play a role in bone metabolism and central nervous system by stimulating bone formation, inhibiting bone resorption, and nerve protection/nutrition, etc, suggesting that it may play an important role in the treatment of other diseases such as osteoporosis.

Periostin is preferentially expressed in the periosteum, which covers a large majority of bones.Periostin has been reported to promote osteoblast proliferation, adhesion, and differentiation, involving bone repair process, response to mechanical stimulation and parathyroid hormone (PTH), regulating bone development/ remodeling and bone strength.Circulating periostin may serve as a candidate of biological markers for bone metabolism.

Objective To explore the molecular mechanism of glucocorticoid (GC)-induced osteoporosis (GIOP). Methods Thirty-two female SD rats after matching body weight were divided randomly into three groups: baseline group (n = 10), control group (n = 11) and GC-treated group (n = 11). The administration time was 9 weeks. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry. A high resolution micro-CT was used to quantify the densitometric and microarchitectural properties of trabeculae in the proximal metaphysis of right tibia. In situ hybridization histochemistry and immunohistochemistry were used to detect the expression of cannabinoid type 1 receptor (CBI R) in the proximal metaphysis of left tibia. Results At the end of the experiment, whole-body BMD in vivo in the control group [(0. 156±0. 008) g/cm2]was higher than that in the baseline group [(0.147±0.006)g/cm2], while the whole-body BMD in vivo [(0.147±0.006) g/cm2]and total BMD in vitro at femurs in the GC-treated group [(0.220±0.011) g/cm2]was lower than those in the control group [(0. 240±0. 024)g/cm2]. Compared with the baseline group and control group, there was a remarkable decrease in the volumetric BMD, tissue BMD, trabecular number and trabecular connectivity (P<0.05) in the GC-treated group, while there was a significant increase in trabecular separation (P < 0. 05) and trabecular thickness also increased in the proximal metaphysis of tibiae in the GC-treated group. The expression level of CB1R mRNA and protein in osteoclasts in the GC-treated group was markedly higher than that in the baseline group and control group (P < 0. 05). There was a close correlation between the expression level of CB1R mRNA, protein in osteoclasts and some microarchitectural parameters in the proximal metaphysis in the GC-treated group (P<0.05). Conclusions The administration of GC is associated with a decrease in BMD and deterioration in microarchitecture of trabecular bone in rats tibiae. Glucocorticoid may up-regulate the CB1R expression level in osteoclasts and this may be a kind of molecular mechanism of GIOP.

Serum osteoprotegerin (OPG) concentration was measured in 647 healthy female adults (aged 20-81 years), and was compared with that of other races. The serum OPG was positively correlated with age (r = 0.276, P <0.01). The geometric mean value of serum OPG in premenopausal women was significantly lower than those in perimenopansal and postmenopausal women. The serum OPG in middle-aged Chinese women was signifieandy higher than those in middle-aged Austrian and Icelandic, but this was quite contrary to the results obtained in old-aged women.

Objective The aim of this study was to investigate the femoral head trabecular heterogeneity in Chinese male patients with osteoporotic fracture and their effects on osteoporotie fracture.Methods Human femoral heads were obtained from 11 male osteoporotie fracture (OP) patients ranged from 51 to 82 years old [average age (65±9 ) years old], and 7 male trauma ( TM ) patients ranged from 46 to 75 years old [average age (61±11 ) years old] who underwent total hip arthroplasty within two hours after either osteoporotic or trauma hip fracture.The OP was defined as having a fragility fracture.After laying femoral head as living body position and locating mark, nine trabecular specimens were obtained from femoral heads, each of 6 mm × 6 mm× 7 mm.The cortical shell was not included in each specimen.One cube was selected as the primary compressive trabecular region and the other 8 specimens as non-primary compressive trabecular region.These cubes were scanned using high-resolution microcomputed tomography scanner (μCT).After scanning, the data of total cubes, primary compressive trabecular region and noncompressive trabecular region were used for analysis by t test.Results In OP group volumetric bone mineral deosity(vBMD) [( 182.15±66.00) mg/mm3 vs (223.97±70.92) mg/mm3, t =3.041], tissue bone mineral density (tBMD) [(538.76±64.72) mg/mm3 vs (580.01±63.86 ) mg/mm3, t = 3.160],bone volume fraction (TV/BV) [(0.22 ± 0.06) % vs (0.26 ± 0.07 ) %, t = 2.821], trabecular thickness (Tb.Th.) [( 161.07 ±42.75 ) μm vs ( 205.47 ± 74.44 ) μm, t = 3.233] were significantly decreased while bone surface/bone volume ( BS/BV ) [( 13.75 ± 2.55 ) mm-1 vs ( 12.28 ± 2.70 ) mm-1, t =-2.777] was significantly increased in the non-primary compressive trabecular region than that in the primary compressive trabecular region ( P < 0.05 ).vBMD [( 182.15 ± 66.00) mg/mm3 vs ( 248.05 ±105.48) mg/mm3, t = - 3.598], tBMD [(538.76 ± 64.72) mg/mm3 vs ( 570.54 ± 100.32) mg/mm3,t=-2.108],TV/BV [(0.22±0.06) % vs (0.28±0.12) %, t= -3.466], Tb.Th.[(161.07±42.75) μm vs (200.31 ±96.63) μm, t= -2.866], trabecular number (Tb.N.)[(1.46±0.23)/mm3 vs ( 1.57 ± 0.29)/mm3, t = - 2.396] were significantly decreased while trabecular separation ( Tb.Sp.) [(780.82 ± 144.85 )μm vs ( 653.09 ± 119.64) μm, t = 5.470], degree of anisotropy (DA) ( 1.57±0.20 vs 1.47±0.18, t = 2.930 ) were significantly increased in OP than in TM in the non-compressive trabecular region( P < 0.05 ).No significant differents were found between OP and TM for any of the parameters measured in the primary compressive trabecular region.Tb.Th.[(199.37±68.22)μm vs (176.33 ±71.21 )μm, t = 2.060,P < 0.05] were significantly increased in the primary compressive trabecular region than that in the non-primary compressive trabecular region and no significant differences were found in the other parameters in the all 18 specimens.Conclusions The femoral head trabeculae had a heterogenic distribution in OP.Bone loss in OP primarily takes place in non-compressive trabecular region.Femoral neck fracture cannot be prevented though the bone microstructure do not loss in the primary compressive trabecular region.Tb.Th.in the femoral head could be an interesting parameter which is closely related to the femoral neck fracture.

Objective To investigate osteocyte density as a potential index of bone biomechanical property. Methods Forty 7-month-old female Sprague-Dawley rats were randomly group (EST) and sham operation group (SHAM). At 15 weeks postoperation, the compression test was performed on L5 vertebral body and micro-computed tomography (μ-CT) was used to estimate the three-dimensional bone mineral density (BMD) and three-dimensional microstructure parameters of L6 vertebral body. After fatigue damage testing, the L6 vertebral body was bulk-stained in 1% basic fuchsin and embedded in methylmethacrylate. Mounted bone slices were used to measure microcrack parameters and osteocyte density. Results At 15 weeks postoperation, osteocyte density (Ot. N/T. area) was significantly decreased in OVX group compared with SHAM group and EST group [(1268. 1 ±191.2)/mm2 vs. (1760. 8 ± 376.6)/mm2 and (1550. 9± 202.2)/mm2, F = 3.513,P<0. 05]. Maximum load (ML) was significantly decreased and the length of microcrack (Cr. Le) was significantly increased in OVX group compared with SHAM group, EST group and GEN group [(84. 4±16.9)N vs. (110.3±25.6),(103. 9±15. 8)and(110.1±4. 9)N; (58. 1±6.8) μm vs. (24.2±8. 1), (36. 5±9. 7)and(28.5±7. 5)μm, F=9. 561,3. 179, all P<0. 05]. Compared with SHAM group and EST group, bone trabecula connection density (Conn. D) was significantly decreased and trabecular separation (Tb. Sp) was significantly increased in OVX group [(47.4±7.4) m-3 vs. (71.8±16.0)and (74.0±12.7)m-3;(315.0±32.7)μm vs. (222. 5±21.7)and (273.3± 50.0)μm, F=7. 635,7. 007, all P<0. 05]. Bone mineral content (BMC) was lower in OVX group than that in SHAM group[(6.5±2. 2)g vs. (7. 9±1.2)g, P<0. 05]. When data in four groups were overall analyzed, Ot. N/T. Ar was positively correlated with ML, Conn. D and BMC (R2 = 0. 7874, 0. 1153, 0. 1309, all P<0. 05), but was negatively correlated with Cr. Le and Tb. Sp (R2 =0. 5738, 0. 3964, both P < 0.05). Conclusions Osteocyte plays a crucial role in maintaining bone biomechanical property and osteocyte density may be considered as a useful indicator for assessing bone biomechanical property.

Objective To observe and compare the changes of bone mass and microarchitecture in ovariectomized rat left tibia by dual energy X-ray absorptiometry(DXA)and microCT(μCT).Methods Forty seven-month-old SD rats were randomly divided into ovariectomized(OVX)and sham-operated(SHAM)groups,twenty in each group.After killed at 3 weeks and 15 weeks post-surgery,DXA scanning were performed in the left tibia in vitro.The images of left tibia were divided into seven isometric regions of interest(ROI1-7).When analysis finished,bone density(BD)of each ROI and the total bone were determined.The samples were fixed by 4% paraformaldehyde and then placed in the specimen holder filled with deionized water.The sensitive regions for bone mass changes were selected for scanning by Fluro.After scanning,the regions involving 0.4mm slice thickness and 2.5mm distance far end from tibial growth plate were selected as the ROI of cortical bone analysis.The regions selected as ROI of cancellous analysis,were involved in 1.2mm slice thickness and 0.7mm distance at the far end from tibial growth plate.After three dimension reconstruction.2D images of the maximum intensity projection and pictures of 3D microarchitecture were obtained.and BD and microarchitectural parameters were quantitatively identified.All data was statistically processed with SPSS for Windows.Results At the 3rd week,BD of ROI1 in rat left tibia in OVX(0.2346±0.0280)g/cm2 was much lower than that(0.2660±0.01990)g/cm2 in SHAM(P＜0.05).While at the 15th week,BD of ROI1(0.2527±0.0161)and ROI2(0.1862±0.0052)g/cm2 in OVX were both lower than SHAM(0.2793±0.0229)and(0.1986±0.0102)g/cm2 respectively,P＜0.01 for both).Compared wim SHAM rat[cortical area(Ct-Ar)=(0.3138±0.0621)mm2,marrow area(Ma-Ar)=(8.44±1.25)mm2,total area(T-Ar)=(8.75±1.26)mm2,moment of inertia(Mm)=(3.485±0.373)mm4],there were significant increases in Ct-Ar(0.4306±0.1308)mm2,Ma-Ar(10.31±1.98)mm2,T-Ar(10.74±2.05)mm2,and Mm(4.101±0.726)mm4 in OVX mice at the 3rd week(P＜0.05 for all).While at the 15th week,only cortical thickness(Ct-Th)(0.0235±0.0024)mm showed a decrease in OVX group(P＜0.05).In OVX group,Ct-Th(0.0235±0.0024)mm and Ct-Ar(0.2528±0.0367)mm at 15 weeks were lower than that[Ct-Th=(0.0377±0.0098)mm,Ct-Ar=(0.4306±0.1308)mm2 at 3 weeks(P＜0.01 for both)].In SHAM group,inner perimeter(In-Pm)(13.38±0.54)mm,outer perimeter(Ot-Pm)(13.59±0.56)mm and Mm(4.096±0.364)mm4 at 15 weeks were higher than that[In-Pm=(12.41±0.74)mm,Ot-Pm=(12.63±0.75)mm,Mm=(3.485±0.373)mm4 at 3 weeks(P＜0.01 for all)].OVX rats had much lower volume BD(vBD)(288.2±48.2)mg/mm3,tissue BD(tBD)(604.5±45.3)mg/mm3,bone volume fraction(BVF)(25.1±5.1)%,and trabecular mumeer(Tb-N)(6.04±2.94)mm-1(P＜0.01 for all),but higher structure model index(SMI)3.09±0.27 and trabecular separation(Tb-Sp)(0.186±0.129)mm than SHAM 2.63±0.21 and(0.078±0.038)mm respectively at the 3rd week(P＜0.01 and P＜0.05 respectively).At the 15th week,vBD(271.2±50.9)mg/mm3,BVF(21.6±5.2)%and Tb-N (3.21±1.92)mm-1 in OVX were still lower than SHAM[vBD=(389.8±77.0)mg/mm3,BVF=(30.9±6.0)%,Tb-N=(7.44±3.53)mm-1 respectively(P＜0.01 for all)],SMI 3.11±0.36 and Tb-Sp(0.370±0.215)mm in OVX were also higher than SHAM 2.58±0.36 and(0.141±0.104)mm(P＜0.01 for both),but no significant difference of tBD could be found.In OVX group.the scores of tBD(691.0±36.7)mg/mm,Tb-Th(0.040±0.009)mm,Tb-N(3.21±1.92)mm-1,Tb-Sp(0.370±0.215)mm in the 15th week were higher than that[tBD=(604.5±45.3)mg/mm,Tb-Th=(0.030±0.002)mm,Tb-N=(6.04±2.94)mm-1,Tb-Sp=(0.186±0.129)mm respectively]in the 3rd week (P＜0.05 for all),while there were no differences between the 3rd and the 15th week in SHAM group.Conclusions DXA is weak in detecting the tiny changes of BD though it is convenient and non-invasive.μCT is suitable to detect the changes of bone mass and microarchitecture.

OBJECTIVE: To explore the effect of methylprednisolone on bone mass, microarchitecture and microdamage in cortical bone of ulna in rats. METHODS: Twenty female Sprague-Dawley rats (3.5 months old) were randomly assigned to two groups: a treatment group and a control group (n=10 per group). The treatment group was subcutaneously injected with methylprednisolone 3.5 mg/(kg.d) while the control group was subcutaneously injected with same volume of vehicle (saline). Rats were sacrificed at 9 weeks after the treatments. Before the sacrifice, the body weight and total bone mineral density (BMD) were measured. The right forelimb was separated through humeral shoulder and then single axial fatigue loading was performed on the right ulna. After fatigue load, the middle ulna section was bulkstained in basic fuchsin. Bone histomorphometry and microdamage analysis were performed on the middle ulna section. RESULTS: Compared with the control group, the body weight, total bone BMD and ulnas BMD in the treatment group were decreased by 15%, 6.4% and 4.3% respectively (all P<0.05); the ulna inner perimeter and marrow area in the treatment group were increased by 23.3% and 32%, respectively (both P<0.05), while the outer perimeter were decreased by 3.1% (P>0.05). There was no significant difference in the cortical and total area between the 2 groups (both P>0.05). The number of microcrack, microcrack density and microcrack surface density in the treatment group were increased by 43%, 48% and 50%, respectively, compared with those in the control group (all P<0.05), but there was no significant difference in the mean length of microcrack between the 2 groups (P>0.05). CONCLUSION Methylprednisolone can significantly induce the bone loss and the deterioration of microarchitecture and microdamage in ulna of rats.
Animals ; Bone Density ; drug effects ; Female ; Methylprednisolone ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Ulna ; drug effects ; pathology

Having manufactured the bone fatigue damage testing device SL-2000, we applied it to research on bone fatigue damage and on the bone microdamage which can indicate bone biomechanical property. According to the general principle of industry fatigue machine and bone fatigue test, the strength, frequency and times of loading, temperature and degree of wetness were controlled in the SL-2000 Device for making the experiment condition stable. After the fatigue damage to SD rats' vertebrae, the models of bone microdamage in SD rat were established. 0-200 N of strength, 0-10 Hz frequency, and 0-999999 times of loading, ambient temperature 50 degrees C experiment, and approximately 99% of the ambient degree of wetness could be adjusted continuously. Three kinds of microdamage such as microcrack, cross-hatch staining, and diffuse staining were observed in the SD rats' vertebrae fatigue damaged by the device. The microcrack density was 19.76+/-15.05 #/mm2, the microcrack length was 36. 74+/-11. 51 microm, and the area ratio of diffuse staining was 0.4117%. Therefore the device is suitable for bone fatigue damage test and for establishment of the model of bone microdamage.
Animals ; Biomechanical Phenomena ; Compressive Strength ; Equipment Design ; Fractures, Stress ; diagnosis ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Spinal Fractures ; diagnosis ; physiopathology ; Spine ; pathology ; Weight-Bearing

In order to characterize the effects of 17β-estradiol (17β-E2) on the expression of IL-6,IL-11 and NF-κB in the human MG-63 osteoblast-likecell line, the expression of IL-6 was detected by RT-PCR, Northern blot and Western blot. The expression of IL-11 was determined by RT-PCR, and NF-κB by Western blot. The results showed that 17β-E2 down-regulated the expression of IL-6 mRNA and protein, IL-11 mRNA and NF-κB protein in MG-63 cells. It was suggested that the expression of NF-κB, IL-6 and IL-11 in MG-63 cells could be suppressed by 17β-E2, and this might lend support to estrogen replacement therapy in postmenopausal women.