BACKGROUND: Prevention of male osteoporosis is attracting more and more attention. OBJECTIVE: To study the effect of etidronate disodium on different skeletal sites by using bone histomorphometry through establishing a castrated rat model of osteoporosis. DESIGN, TIME AND SETTING: A completely randomized grouping controlled animal experiment was performed in the Animal Experimental Center and Department of Bone Biology Laboratory, Guangdong Medical College between October 2002 and September 2006. MATERIALS: Forty 3.5-month-old male Sprague Dawley rats, weighing (299+_22) g, were selected. Etidronate disodium was produced by Chengdu Chemical Pharmaceutical Factory with the batch number of 970101. Methyltestosterone was produced by Guangzhou Pharmaceutical Jacob with the batch number of 990701. METHODS: Rats were randomly divided into five groups: control group, sham operation group, castration group, castration with methyltestosterone group and castration with etidronate disodium group, eight rats in each group. Rats in the control group were sacrificed at the beginning of the study. Rats in the sham operation group underwent skin incision to expose the testis, but not removed. The remaining rats were treated to remove the testis by the method reported in the literature. Rats in the sham operation group and castration group were given normal saline, rats in the castration with methyltestosterone group were given methyltestosterone at 1.8mg/kg/d, rats in the castration with etidronate disodium group were given etidronate disodium at 36mg/kg/d. All of the rats were treated with intragastric administration at 5mL/kg for 90 days. MAIN OUTCOME MEASURES: Bone histomorphometric analysis of the proximal tibial metaphysis (PTM), tibial shaft (Tx) and the fifth lumbar vertebral body (LVB) were performed in undecalcified sections. RESULTS: Compared with the sham operation group, trabecular area percentage (%Tb.Ar), trabecular number (Tb.N) or trabecular thickness (Tb.Th) of PTM and LVB in the castration group were decreased (P < 0.05 and 0.01 ), while trabecular separation (Tb.Sp), percent labeled perimeter (%L.Pm), bone formation rate (BFR/BV) and osteoclast number per mm (Oc.N) were increased (P < 0.05 and 0.01 ). Tb.Ar of PTM and LVB were increased both in the etidronate disodium group and in the methyltestosterone group compared to those of the castration group, while bone formation indices and bone resorption perimeter were decreased. There was no significant difference between the etidronate disodium and methyltestosterone groups, and no significant change was in Tx in all groups. CONCLUSION: Etidronate disodium can prevent the cancellous bone loss of PTM and LVB in castrated rats, but has no effects on the cortical bone of Tx.

BACKGROUND:Fluoride treatment of osteoporosis has been controversial.Literatures addressing the effect of fluoride on bone bio-mechanical parameters of femur in young rats are few.OBJECTIVE:To study the effects of fluoride on bone biomechanical parameters of femur in young rats.METHODS:Ninety 2-month-old SPF Sprague Dawley rats,half male and female,were randomly divided into 9 groups:control group(young,adult and long-time)and drug-administered group(young high-fluoride,young low-fluoride,adult high-fluoride,adut low-fluoride,long-term high-fluoride and long-term low-fluoride).Rats in the control group were orally administered with physiological saline,while in the drug-administered group were given orally with different dose fluoride at the corresponding times.After experiment,rats were sacrificed under anaesthesia.Three-point bending test was performed at the left femur.The effects of fluoride on maximum load and rigidity of femur were measured.RESULTS AND CONCLUSION:Compared with young control group,the maximum load and the rigidity of femur in the young high-fluoride group were decreased by 13.18%and 13.61%,respectively(P＜0.05),which had no dramatically difference in the young low-fluoride group.Compared with long-term high-fluoride group,the maximum load and the rigidity offemur in the young high-fluoride were decreased by 17.22%and 17.17%(P＜0.05),which were obvious increased in the long.term low-fluoride grou by 18.33%and 19.15%,respectively(P＜0.05).The maximum load and the rigidity of femur were strengthened in the adult high-fluoride and adult low-fluoride groups(P＜0.05).The results suggested that young rats are more sensitive to high-dose fluoride,which can reduce bone quality in rats.The negative effects on bone quailty of rats were gradually displayed as the prolongation of the period of fluoride.

Aim To investigate the effects of retinoic acid (RA) on induction osteroporosis model rats andpreventive effects of Danshengubao.Methods 4-month-old female Sprague-Dawley rats were given RA at 70 mg·kg~(-1)·d~(-1) and were given Danshengubao at different doses at the same time.All rats were treated by oral gavaged for 28 days.The static and dynamic parameters in cancellous bone of the fifth lumbar vertebrae (LV5) were examined and the dynamic changes of the tibial shaft (Tx) were observed with histomorphometrical analyses; the forth lumbar vertebrae (LV4) was used to perform the compression test.Results Compared with control group, biomechanical properties of LV4, the static parameters ( total tissue area, trabecular area, trabecular perimeter) and the dynamic parameters of LV5 were significantly decreased in RA group.Compared with control group, bone formation of Tx was decreased in periosteal surfaces but enhanced in endocortical surfaces in RA group.Compared with RA group, the biomechanical properties of LV4 were increased significantly in low and medium dose of Danshengubao groups.Conclusion sRA can decrease the size and the biomechanical properties of LV, but it can not change the percentage trabecular area. The mechanism may be related to the act that RA can inhibit cancellous bone formation, decrease the modeling of cortical bone in periosteal surfaces and enhance the remolding of cortical bone in endocortical surfaces. Danshengubao can improve biomechanics of LV induced by RA in rats.

Aim To investigate the skeletal effects of ginseng flower bud(GF)on osteopenia induced by D-galactose using histomorphometry and biomechanical properties.Methods Fifty three-month-old male Sprague-Dawley rats were randomly divided into five groups.Rats in NS group(NS)were treated with NS(5 mL·kg-1·d-1)by subcutaneous injection and daily oral gavage with vehicle as control.Rats in the other four groups were given D-galactose at the dose of 100 mg·kg-1·d-1 by subcutaneous injection.Solvent control was performed between NS and DG: gastric irrigation with distilled water of 10 mL·kg-1·d-1.Other groups were: CP was gastric irrigated with integrated medicine(stanozolol 0.54 mg·kg-1·d-1+piracetam 432 mg·kg-1·d-1),GF(L)with ginseng flower bud of 0.486 g·kg-1·d-1 and GF(H)with ginseng flower bud of 2.43 g·kg-1·d-1 for 14 weeks.The longitudinal proximal tibial metaphyseal(PTM),the fifth lumbar vertebral body(LVB)and tibial shaft(Tx)sections were performed undecalcifiedly and used for bone histomorphometric analysis.858 Mini Bionix materials testing system was used to analyze the biomechanic properties of right femur via three-point bending test.The left femur was dried and assimilated,whose bone calcium(Ca),phosphate(P)content and bone hydroxyproline content were tested.Results Compared with D-glagatose group,in PTM of D-galactose treated rats,the％Tb.Ar was increased both in GF(L)and GF(H)treated groups.While the Tb.Sp was decreased.％Oc.S.Pm and Oc.N/mm decreased in GF(L),and those in GF(H)were decreased as well.In Tx,％Ct.Ar was raised,while％Ma.Ar was decreased in GF(L)and GF(H).The elastic load of femur was increased.Conclusions Compared with DG group,there are significant differences in bone histomorphometry of Tx and PTM in all doses of GF,but no significant changes are detected in hydroxyproline,Ca,and P content of femur.

Aim To investigate the effects of predni-sone on trabecular microstructure and biomechanical properties of femur in a rat model of type II collagen-induced arthritis (CIA ) using micro-CT and biome-chanics.Methods Forty 8-week-old male Lewis rats were randomly divided into 2 groups:control (CON ) group with 6 rats,and the remaining 34 rats were used to establish the CIA model.3 weeks after immunization screening CIA rats were randomly divided into CIA group,CIA plus prednisone 4.5 mg · kg-1 · d -1 group and CIA plus prednisone 9 mg · kg-1 · d -1 group.Rats in CON group were given vehicle as well as in CIA group.Rats in the other two groups were treated with prednisone at 4.5 mg·kg-1 ·d -1 or 9 mg ·kg-1 · d -1 .After 90 days treatment,all rats were euthanized,and the left femur was collected for biome-chanics,micro-CT scanning and three-dimensional re-construction.Results Micro-CT data showed that tra-becular thickness,trabecular number,bone volume/total volume,bone mineral density in CIA group were significantly lower than those in CON group.While tra-becular separation,structure model index were signifi-cantly higher than those in CON group.Compared with CON group,biomechanical properties (elastic load, maximum load,break load and stiffness)were signifi-cantly decreased in CIA group.Compared with CIA group,bone volume/total volume and trabecular num-ber were increased,while trabecular separation was significantly decreased in two prednisone groups.Com-pared with CIA group,there was no significant change in biomechanical properties in two prednisone groups. Conclusions Treatment with prednisone for 3 months can ameliorate the damage of trabecular microstructure of the femur in CIA rats,but it has no effect on biome-chanical properties and bone mineral density.

Objective To report the clinical,myopathological and genetic features of a patient with distal myopathy caused by caveolin-3 (CAV3) deficiency.Methods The patient was a 27-year-old female.She had an onset symptom of asymmetric lower extremities weakness.The proximal limb-girdle muscles were involved subsequently.Clinical data of this patient were collected.The leg muscle magnetic resonance imaging (MRI) and an open biopsy of left tibialis anterior muscle were performed.In addition to histological,enzyme histochemical staining and ultrastructural examination,immunohistochemical staining with antibody against CAV3 was done.CAV3 gene was analyzed in the patient and her parents.Results Tl-weighted enhanced skeletal muscle MRI of the lower limbs showed the abnormal signal in distal and proximal muscles.Muscle biopsy showed moderate dystrophic changes and immunostaining for CAV3 showed reduced plasmalemma in the muscle fibers.Gene analysis disclosed a heterozygous c.136G ＞ A (p.Ala46Thr)mutation in the CAV3 gene,and the patient's parents did not have this mutation.Conclusions We report a distal myopathy case caused by c.136G ＞ A (p.Ala46Thr) mutation in the CAV3 gene,who had an onset symptom of asymmetric lower extremities weakness.The proximal limb-girdal muscles were also involved.This would help clinical doctors to know more about this rare myopathy.

This investigation was directed to the effects of DanShenGuBao on biomechanical properties and bone mineral density (BMD) of femur induced by retinoic acid (RA) in rats. Forty 4-month-old virgin female Sprague-Dawley rats were randomly divided into 5 groups(8 rats each) control group, RA group and different doses of DanShenGuBao groups. Rats in control group were given vehicle, rats in other four groups were given RA at 70 mg x kg(-1) x d(-1) in the morning and given different drugs in the afternoon at the same time. Rats in RA group were given vehicle, rats in other groups were given different doses of DanShenGuBao which contained 10 mg x kg(-1) x d(-1), 5 mg x kg(-1) x d(-1), 2.5 mg x kg(-1) x d(-1) tanshinol, respectively. All of rats were treated at 5 ml x kg(-1) by oral gavaged for 28 days. In preparation for the determination of dynamic changes in bone tissues, all rats were given subcutaneous injections of 30 mg x kg(-1) tetracycline on the 14th, 13th day and 5 mg x kg(-1) calcein on the 4th, 3rd day before death. At the experimental endpoint, the rats were sacrificed by cardiac puncture under sodium pentobarbital anesthesia. Physical parameters, BMD and biomechanical properties of femur were assessed. Compared with those in control group, the physical parameters (cross-sectional diameter, wet and dry weight), BMD and biomechanical properties (max-load, elasticity-load, break-strain, rigid coefficient and bending-energe) were significantly decreased in RA group. Compared with that in RA group, the BMD of femur was increased significantly in medium and high dose of DanShenGuBao group, but there was no significant change in physical parameters and biomechanical properties of femur. RA could decrease the physical parameters, BMD and biomechanical properties of femur. DanShenGuBao could increase BMD, but it was found with no obvious effect on physical parameters and biomechanical properties.
Absorptiometry, Photon ; Animals ; Biomechanical Phenomena ; drug effects ; Bone Density ; drug effects ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Femur ; diagnostic imaging ; drug effects ; Osteoporosis ; chemically induced ; drug therapy ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry ; Tretinoin

Objective:To evaluate the feasibility and the application values of quantitative susceptibility mapping (QSM) for the assessment of meniscal injury and in distinguishing meniscus degeneration and tears.Methods:The clinical and imaging data of 70 patients suspected of meniscus injury and scheduled for arthroscopy in Shandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University from November 2019 to June 2020 were analyzed retrospectively. Thirty age-and sex-matched healthy subjects were also examined as controls. All subjects received knee joint QSM and routine MR imaging. According to the results of arthroscopy, the patients was divided into meniscus degeneration and meniscus tear groups, respectively. The conventional MR was evaluated by two radiologists. The meniscus injury area was delineated on the original QSM magnitude images (the central area of the posterior corner of the lateral meniscus was selected in the healthy controls) and mapped to the corresponding QSM maps, and the magnetic susceptibility values were measured. Kruskal-Wallis H test was used to analyze the magnetic sensitivity values of meniscal degeneration, meniscal tear and healthy control groups; and Bonferroni was used to correct the pairwise comparison. ROC curve was established to evaluate the threshold and efficacy of magnetic susceptibility value in the diagnosis of meniscal tear. The results were compared with those of conventional MRI. Results:The magnetic susceptibility values of meniscus of healthy controls, meniscal degeneration and meniscal tear groups were (0.035±0.016)ppm, -0.031(-0.040,-0.005)ppm, and(-0.122±0.115)ppm, respectively, with significant difference found among the three groups (χ2=44.419, P<0.05). The magnetic susceptibility values of meniscus of healthy controls was significantly higher than those of meniscus degeneration patients and meniscus tear patients (χ2=-23.843, -48.253, P<0.05). The magnetic susceptibility values of meniscus of meniscus tear group was significant lower than those of meniscus degeneration group (χ2=-24.410, P<0.05). Taking magnetic susceptibility values of -0.062 5 ppm as threshold, the area under the ROC curve for the diagnosis of meniscal tears was 0.949, with the sensitivity as 87% and the specificity as 100%. The sensitivity and specificity of conventional MRI in the diagnosis of meniscal tears were 86.8% and 87.5%, respectively. Conclusion:QSM can quantitatively evaluate meniscus injury and can be used as an effective supplement method to conventional MRI, which is helpful to improve the diagnosis of meniscus tear.

Objective To analyze the global research status,hotspots,and frontiers of proprotein convertase subtilisin/Kexin type 9(PCSK9)monoclonal antibodies,and to provide a reference for related scientific research and the rational drug use in clinical practice in China.Methods The research literature related to PCSK9 monoclonal antibody included in the Web of Science database was searched for the period from January 2011 to February 2022,and the literature included in the study was visually analyzed by the CiteSpace software.Results A total of 723 articles were included,and the annual number of publica-tions showed an overall upward trend.The top three countries were the United States,France,and the United Kingdom.Sanofi was the organization with the largest number of articles,and the organization with the highest citation of articles was Brigham and Women's Hospital.The hotspots of research mainly included the use of PCSK9 monoclonal antibody in the treatment of patients with hypercholesterolemia,patients who do not tolerate statins,patients with high cardiovascular risk,and the efficacy and safety of PCSK9 monoclonal antibody in lipid-lowering therapy combined statins;The frontiers of research in recent two years is the appli-cation of PCSK9 monoclonal antibodies in patients with acute coronary syndrome and the clinical benefits after reducing the level of lipoprotein(a).Conclusion A large number of studies have confirmed the efficacy and safety of PCSK9 monoclonal anti-bodies in reducing blood lipids,but there is still a lack of research on its economics and application in special populations,which should be the focus of future research.

Objective:To investigate the correlation of age with diffusion tensor imaging (DTI) values as fractional anisotropy (FA), apparent diffusion coefficient (ADC) and contrast to noise ratio (CNR) of three-dimensional nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation imaging (3D SHINKEI) of the brachial plexus in normal adults.Methods:A total of 54 adult healthy volunteers and 6 patients with Guillain-Barre syndrome were prospectively enrolled from October 2018 to April 2019. Healthy volunteers were divided into 3 groups according to age as 21-40 years old group ( n=20), 41-60 years old group ( n=20), and ≥61 years old group ( n=14). All of them underwent MRI examination of the brachial plexus, including DTI and 3D SHINKEI sequences. The average FA and ADC values of the brachial plexus were measured and calculated through the fusion of DTI and 3D SHINKEI by 2 physicians independently. The contrast to noise ratio (CNR) of brachial plexus nerve was measured in 3D SHINKEI sequence images. Intraclass correlation efficient (ICC) was used to analyze the consistency between the two physicians. A simple linear regression model and Pearson correlation analysis were used to detect the correlation between FA, ADC, CNR and age. One-way analysis of variance was used to compare the differences of FA, ADC and CNR in different age groups. The FA and ADC values in different genders were compared by independent sample t-test. Results:Inter-observer agreements of the 2 physicians were good for FA and ADC values with ICC values of 0.811 and 0.901, respectively. For different groups, FA values were 0.397±0.023, 0.368±0.023, and 0.334±0.018 and ADC values were (1.376±0.072) × 10 -3 mm 2/s, (1.466±0.086) × 10 -3 mm 2/s, (1.486±0.080) × 10 -3 mm 2/s, for 21-40, 41-60, and ≥61 years old groups, respectively with statistical significant difference ( F=25.311, P<0.001; F=9.948, P<0.001). The CNR of the brachial plexus were 510.583±192.846, 502.581±128.821, and 426.782±113.648 for 21-40, 41-60, and ≥61 years old group without statistical difference ( F=1.429, P=0.249). The FA value of brachial plexus was highly negatively correlated with age ( r=-0.745, P<0.001), while the ADC value was moderately positively correlated with age ( r=0.596, P<0.001). The CNR of 3D SHINKEI sequence was negatively correlated with age ( r=-0.292, P=0.033). There was no statistically significant difference in brachial plexus FA and ADC values between male and female subjects ( t=1.496, P=0.141; t=-1.557, P=0.126). The FA value of Guillain-Barre syndrome patients was lower than that of healthy volanteers in the same age group ( t=6.129, P<0.001), and the ADC value had no statistical diference ( t=-1.335, P=0.186). Conclusion:The values of FA, ADC and CNR of brachial plexus in normal adults change with age. Among them, FA value is more significant.