Comparison of femoral neck geometric parameters between Chinese and Japanese females / 中南大学学报(医学版)

OBJECTIVES@#Femoral neck fracture is the most serious osteoporotic fractures that is responsible for high medical costs and high mortality. Femoral neck geometric parameters (FNGPs) are important parameters that reflect the geometrical characteristics of femoral neck, and are closely related to the strength of femoral neck and the risk of fragility fracture.There are differences in the incidence of femoral neck fractures among races. However, whether there is difference in FNGPs among races is unknown.Therefore, this study aims to compare the differences in FNGPs between Chinese and Japanese females.@*METHODS@#This study was a cross-sectional study, in which 3 859 healthy females aged 10-86 (45.7±17.1) years old were recruited from Changsha City of Hunan Province and surrounding areas. The weight and height were measured and recorded, and the body mass index (BMI) was calculated. A dual energy X-ray absorptiometry (DXA) bone densitometer was used to measure femoral neck projective bone area (BA) and bone mineral density (BMD). FNGPs were calculated using the BMD and BA, which included the outer diameter (OD), cross-sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), buckling ratio (BR), section modulus (SM), cross-sectional moment of inertia (CSMI), and compression strength index (CSI). The data of FNGPs in Japanese females was collected from literature. These subjects were grouped by 10-year age. The mean and standard deviation of height, weight, BMI, femoral neck BMD, and FNGPs of each group were calculated. The model with the best goodness-of-fit was selected from various mathematical regression models to analyze the distribution trend and the best fitting curve of FNGPs with age. The differences in FNGPs between Chinese and Japanese females were analyzed by using age-corresponding mean fitting curve for paired t-test, and the relative change rates of FNGPs were compared.@*RESULTS@#The mean values of FNGPs were significantly different among different years old healthy females (all P<0.01). The mean values of OD, CSA, CT, SM, and CSMI in femoral neck were high at 30 to 39 years old, and then they were gradually decreased with age. The CSI reached its peak at 20-29 years old, and it was decreased gradually after 30 years old. ED and BR were at a low level before 40 years old, they were gradually increased after 40 years old, and reached the maximum average value at 80-86 years old. The variations in FNGPs with age were fitted with the best goodness-of-fit by applying the cubic regression model and the determination coefficients of regression equations (R2: 0.062-0.404) were significant (all P<0.01). The distribution trend of FNGPs with age varied with the indices, among which CSA, CT, SM, CSMI and CSI were increased with age before 35 years old, and then they were decreased with age; BR was at a low level in the early stage, and then it was increased with age after about 40 years. There were significant differences in the fitting curves of FNGPs related to age between Chinese and Japanese females (all P<0.01). The fitting curves of OD, ED, BR and SM in Chinese females were significantly higher than those in Japanese females (all P<0.01), while those of CSA and CT in Chinese females were significantly lower than those in Japanese females (all P<0.01). Before the age of 50, the curves of CSMI and CSI of Chinese females were significantly higher than those of Japanese females (all P<0.01), while after the age of 60 the situation was reversed (all P<0.01). Except for SM and CSI, there were significant differences in the rate of OD, CSA, CT, ED, BR and CSMI with age (all P<0.01). By the age of 80 years old, the rates of change in OD, ED, and BR with the age in Chinese females were increased by 0.91%,3.94%, and 47.5%, respectively, while those in Japanese females were increased by 8.57%, 15.8% and 85.3%, respectively；the rates of change of CSA, CT, and CSMI with the age in Chinese females were declined 28.0%, 29.6%, and 25.2%, respectively, while those in Japanese females were declined 29.9%, 36.2%, and 10.9%, respectively. There were significant difference in the rates of change in FNGPs with the age between Chinese and Japanese females (all P<0.01).@*CONCLUSIONS@#The study reveals the variation of FNGPs with age in Chinese, and confirms that there are racial differences in FNGPs between Chinese and Japanese females, which may be one of the important reasons for the difference in the incidence of femoral neck fracture between Chinese and Japanese females.

Aromatase deficiency caused by mutation of CYP19A1 gene: A case report / 中南大学学报(医学版)

Aromatase deficiency (AD) is a rare autosomal recessive genetic disease caused by loss-of-function mutations in aromatase gene (CYP19A1), leading to congenital estrogen deficiency syndrome. Both mothers of AD patients during pregnancy and female AD fetus show virilization, while male patients are usually diagnosed in adulthood due to continued height increase and metabolic abnormalities. In 2019, a patient with AD was admitted in the Second Xiangya Hospital. The patient was a 37-year-old adult male who continued to grow linearly after adulthood. His estradiol was below the measurable line, the follicle-stimulating hormone (FSH) increased, bone age delayed, epiphysis unfused, and the bone mass reduced. CYP19A1 gene detection showed that c.1093C>T, p.R365W was homozygous mutation. This disease is rare in clinic. Clinicians need to raise awareness of the disease for early diagnosis and treatment to improve the long-term prognosis of patients.

The research of the effects of glucagon-like peptide-1 on bone metabolism and central nervous system and its mechanism / 中华内分泌代谢杂志

[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.

Effect of methylprednisolone on bone mass, microarchitecture and microdamage in cortical bone of ulna in rats / 中南大学学报(医学版)

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 P0.05). 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 P0.05).@*CONCLUSION@#Methylprednisolone can significantly induce the bone loss and the deterioration of microarchitecture and microdamage in ulna of rats.

Role of periostin in bone metabolism / 中华内分泌代谢杂志

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.

The trabecular heterogeneity of femoral head in male osteoporotic fracture / 中华放射学杂志

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.

The effects of glucocorticoid on expression of cannabinoid-1 receptors in osteoclasts from tibial proximal metaphysis of rats / 中华内科杂志

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.

Osteocyte density may be an important influencing factor for the bone biomechanical property / 中华老年医学杂志

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.

Age-related reference value of serum osteoprotegerin in female as compared with other races / 中华内分泌代谢杂志

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.

The analysis of bone mass and microarchitecture in ovariectomized rat by dual energy X-ray absorptiometry and microCT / 中华放射学杂志

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.

Manufacture and application of SL-2000 bone fatigue damage testing device / 生物医学工程学杂志

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.

Effects of 17β-Estradiol on the Expression of IL-6, IL-11 and NF-κB in Human MG-63 Osteoblast-like Cell Line / 华中科技大学学报（医学）（英德文版）

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.