Occupational distribution and management strategies of occupational contact dermatitis / 环境与职业医学

Occupational contact dermatitis (OCD) is an occupational inflammatory skin disease. According to its pathogenesis, it can be divided into irritant contact dermatitis and allergic contact dermatitis. This review introduced the high-risk occupations of OCD, its incidence, common irritants and allergens, and corresponding treatments. Agriculture workers, construction workers, production workers, hairdressers, and medical workers are high-risk occupations of OCD who should be paid attention to.

Case-control study on fragility fractures in coal miners: A comparison between surface and underground workers / 环境与职业医学

Background The prevalence of osteoporosis and osteopenia is higher among underground coal miners than surface workers. The special underground work environment and unhealthy habits such as smoking, drinking, and a high-salt diet may lead to changes in bone metabolism, increasing the risk of fragility fractures and placing a heavy economic burden on individuals and society. Objective To identify potential factors influencing fragility fractures among coal miners in different working environments and to provide a basis for targeted preventive measures to reduce the occurrence of fragility fractures. Methods Male participants who attended at least one of the physical examinations in Kailuan Group between June 2006 and December 2020 were included in the study. The participants were divided into two groups based on their working environment: surface or underground. A case-control study was conducted, where patients with new fragility fractures served as the case group and participants without fragility fractures served as the control group. The two groups were matched with a case:control ratio of 1:4 by age (±1 year) and the same year of physical examination. The matching process was repeated twice, once for the surface working population and once for the underground working population. The analysis of risk factors was conducted using conditional logistic regression models. Results Among a total of 113138 employees in Kailuan Group, 82631 surface workers and 30507 underground workers were included, respectively. The number of individuals who suffered fragility fractures was 1375, accounting for 1.22% of the total population. The incidence of fragility fractures in underground workers was significantly higher than that in surface workers (1.63%>1.07%, P<0.001). The results of conditional logistic regression model showed that current smoking (OR=1.26, 95%CI: 1.05, 1.51), manual labor (OR=1.37, 95%CI: 1.06, 1.78), diabetes (OR=1.26, 95%CI: 1.04, 1.54), sinus tachycardia (OR=1.81, 95%CI: 1.23, 2.66), history of stroke (OR=1.51, 95%CI: 1.09, 2.09), education at college and above (OR=0.65, 95%CI: 0.45, 0.95), high income level (OR=0.69, 95%CI: 0.54, 0.90), elevated hemoglobin (OR=0.91, 95%CI: 0.85, 0.98), and elevated total cholesterol (OR=0.90, 95%CI: 0.82, 0.99) were associated with fragility fractures in the surface working population of coal mines; current smoking (OR=1.48, 95%CI: 1.17, 1.87), current drinking (OR=1.26, 95%CI: 1.01, 1.56), manual labor (OR=2.64, 95%CI: 1.41, 4.94), history of dust exposure (OR=1.28, 95%CI: 1.03, 1.58), and obesity (OR=0.72, 95%CI: 0.52, 0.96) were associated with fragility fractures in the underground working population of coal mines. Conclusion In preventing fragility fractures, special attention should be paid to the bone health of underground workers engaged in manual labor or having a history of dust exposure. It is important to correct their unhealthy behaviors in a timely manner, such as smoking and drinking, and to appropriately increase body weight to prevent fragility fractures. For surface workers, particular attention should be given to the high-risk group for fragility fractures, such as low family income per capita, manual labor, and having a history of stroke or diabetes; in addition, close monitoring of their resting heart rate, hemoglobin levels, and total cholesterol levels may help prevent fragility fractures.

Effect analysis of treating osteoporotic vertebral fracture combined reduction vertebroplasty with kyphoplasty / 中国综合临床

Objective:To compare postural reduction combined with percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCFs).Methods:From January 2019 to January 2020,68 patients with OVCFs who met the inclusion and exclusion criteria in the Second Hospital of Tangshan Hebei Province were included in the observation study. A prospective randomized controlled study was used. The matched groups were divided into PVP combined group (adjust the overextension of the operating table by 20°-30°, if the posture reduction fails, pry the puncture needle on both sides in reverse according to the compression degree of the end plate before operation, and inject bone cement) and PKP group (do not adjust the operating table before operation, insert a balloon and expand on both sides after operation, and inject bone cement), with 34 cases in each group. The Cobb angle of the injured vertebrae was measured by taking the anterior and lateral X-ray film of the patient's lumbar spine before operation. The degree of pain and low back function were evaluated by visual analogue scale (VAS) and Oswetry disability index (ODI). The operation time and fluoroscopy times were recorded during the operation. On the second day after operation, the anterior and lateral X-ray of lumbar spine were taken to measure the Cobb angle of injured vertebrae. All patients were underwent computed tomography (CT) check the bone cement for leakage, record the VAS score, and record the ODI 3 months after operation to evaluate the patient's function. Follow up at the end of 12 months after operation to count the treatment cost and re-fracture of the patient. The data analysis and measurement data were compared by independent sample t-test between the two groups, paired sample t-test was used for intra-group comparison before and after operation. χ 2 test was used for counting data comparison between two groups. Results:All patients were followed up for 12 months. The operation time ((42.7±5.9) min), fluoroscopy times ((20.0±3.6) times) and treatment cost ((19 153±601) yuan) in the PVP combined group were better than those in the PKP Group ((67.4±7.3) min, (30.1±5.9) times, (27 496±669) yuan), and the difference was statistically significant ( t values were 15.39, 8.46, 54.12; all P<0.001). Cobb angle: Postoperative Cobb angle of injured vertebrae in the two groups (PVP combined group (10.7±4.5)°) and (PKP group (13.4±3.8)°) decreased compared with preoperative (PVP combined group (17.0±5.1)°) and (PKP group (16.7±5.1)°) ( t values were 10.61, 5.61; all P=0.001), and PVP combined group recovered better than PKP group, with statistically significant difference ( t=2.70, P=0.009). VAS score: Postoperative (PVP combined group (3.9±1.5) points) and (PKP group (4.1±1.6) points) was lower than preoperative the scores of (PVP combined group (6.9±1.1) points) and (PKP group (7.1±0.9) points), and the difference was statistically significant ( t values were 8.63, 8.88; all P=0.001). There was no significant difference in VAS scores between the two groups ( t=0.48, P=0.630). ODI scores: The scores of (PVP combined group (0.315±0.068)) and (PKP group (0.319±0.077)) after operation were lower than preoperative (PVP combined group (0.574±0.066), (PKP group (0.553±0.075)), and the difference was statistically significant ( t values were 18.54, 14.16, all P=0.001). There was no significant difference in ODI between the two groups ( t=0.25, P=0.803). There was no statistical significance in the two groups of postoperative bone cement leakage (χ 2=0.22, P=0.642). In PVP combined group, 1 case was re-fractured due to trauma, and there was no re-fracture in PKP group. Conclusion:Postural reduction combined with percutaneous needle prying reduction of PVP and PKP can alleviate the pain, improve the postoperative function and restore kyphosis in patients with OVCFs. Postural reduction combined with needle prying reduction of PVP has more advantages in operation time, radiation injury to doctors and patients, treatment cost, and the effect of correcting deformity is more significant.

Long-term imiquimod stimulation induces psoriasiform dermatitis and bone loss in mice / 中华皮肤科杂志

Objective To establish a mouse model of psoriasis complicated by bone loss by long-term topical application of imiquimod. Methods Twelve 10-week-old Kunming mice were randomly and equally divided into 2 groups:experimental group topically treated with 50 mg/d imiquimod cream every day on the shaved back, and control group topically treated with equivalent vaseline ointment every day on the shaved back. Skin manifestations were observed on the mouse back every day. The mice were sacrificed 10 weeks later. Before the sacrifice, the degree of erythema, scaling and skin thickening was evaluated, psoriasis area severity index(PASI)was calculated, mouse weight was measured, and eyeball blood was obtained. After the sacrifice, skin lesions on the back were resected and subjected to hematoxylin-eosin staining, so as to evaluate histological changes. Then, the left tibia was obtained from the mice, immunohistochemical staining was performed to observe the expression and distribution of osteoprotegerin(OPG)and receptor activator of nuclear factor kappa-β ligand(RANKL)in bone tissues, and micro-computerized tomography was conducted to determine the bone mass of spongy bone, and the bone volume-to-total volume ratio, number, thickness, spacing and connectivity density of the trabecular bone in the proximal tibia. The left femur was also obtained from the mice, and subjected to three-point bending test for evaluating its biomechanical properties. Enzyme-linked immunosorbent assay(ELISA)was performed to detect serum levels of tumor necrosis factor(TNF)-αand interleukin(IL)-17. RNA was extracted from the right tibia, and real-time PCR was conducted to determine the mRNA expression of OPG and RANKL. Two-independent-sample t test was used to compare the above indices between two groups. Results Ten-week topical stimulation with imiquimod could lead to psoriasiform dermatitis on the mouse back, presenting as erythema, scales and skin thickening. The PASI score was significantly higher in the experimental group(9.167 ± 1.722)than in the control group(0, t=13.31, P<0.001). Hematoxylin-eosin staining showed thickened spinous layer, extended rete ridges, infiltration of inflammatory cells in the superficial dermis, spongiosis, vasodilatation and increased hair follicles in the experimental group. Immunohistochemical staining revealed that the expression of OPG and RANKL was significantly higher in the experimental group(16021.33 ± 1954.61, 35433.33 ± 1197.95 respectively)than in the control group(3307.00 ± 1158.72, 13644.67 ± 4764.61, respectively;t=9.692, 7.682 respectively, both P < 0.01). Micro-computerized tomography showed that the bone volume-to-total volume ratio and thickness of trabecular bone in the proximal tibia were significantly lower in the experimental group than in the control group, but the spacing of trabecular bone was significantly higher in the experimental group than in the control group(P<0.01 or<0.05). There were no significant differences in the elastic modulus and fracture energy of the femur between the experimental group and control group(both P>0.05). Moreover, no significant differences in the serum levels of TNF-αand IL-17 were observed between the two groups(both P>0.05). Real-time PCR revealed that the mRNA expression of OPG and RNAKL was significantly higher in the experimental group than in the control group(P<0.05,<0.01 respectively). Conclusions Long-term topical application of imiquimod can not only induce psoriasiform dermatitis in mice, but also lead to bone loss of spongy bone and micro-architectural deterioration in the proximal tibia. Thus, mouse models of psoriasis complicated by bone loss can be established by long-term imiquimod stimulation.

Long-term imiquimod stimulation induces psoriasiform dermatitis and bone loss in mice / 中华皮肤科杂志

Objective@#To establish a mouse model of psoriasis complicated by bone loss by long-term topical application of imiquimod.@*Methods@#Twelve 10-week-old Kunming mice were randomly and equally divided into 2 groups: experimental group topically treated with 50 mg/d imiquimod cream every day on the shaved back, and control group topically treated with equivalent vaseline ointment every day on the shaved back. Skin manifestations were observed on the mouse back every day. The mice were sacrificed 10 weeks later. Before the sacrifice, the degree of erythema, scaling and skin thickening was evaluated, psoriasis area severity index (PASI) was calculated, mouse weight was measured, and eyeball blood was obtained. After the sacrifice, skin lesions on the back were resected and subjected to hematoxylin-eosin staining, so as to evaluate histological changes. Then, the left tibia was obtained from the mice, immunohistochemical staining was performed to observe the expression and distribution of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-β ligand (RANKL) in bone tissues, and micro-computerized tomography was conducted to determine the bone mass of spongy bone, and the bone volume-to-total volume ratio, number, thickness, spacing and connectivity density of the trabecular bone in the proximal tibia. The left femur was also obtained from the mice, and subjected to three-point bending test for evaluating its biomechanical properties. Enzyme-linked immunosorbent assay (ELISA) was performed to detect serum levels of tumor necrosis factor (TNF) -α and interleukin (IL) -17. RNA was extracted from the right tibia, and real-time PCR was conducted to determine the mRNA expression of OPG and RANKL. Two-independent-sample t test was used to compare the above indices between two groups.@*Results@#Ten-week topical stimulation with imiquimod could lead to psoriasiform dermatitis on the mouse back, presenting as erythema, scales and skin thickening. The PASI score was significantly higher in the experimental group (9.167 ± 1.722) than in the control group (0, t = 13.31, P < 0.001) . Hematoxylin-eosin staining showed thickened spinous layer, extended rete ridges, infiltration of inflammatory cells in the superficial dermis, spongiosis, vasodilatation and increased hair follicles in the experimental group. Immunohistochemical staining revealed that the expression of OPG and RANKL was significantly higher in the experimental group (16 021.33 ± 1 954.61, 35 433.33 ± 1 197.95 respectively) than in the control group (3 307.00 ± 1 158.72, 13 644.67 ± 4 764.61, respectively; t = 9.692, 7.682 respectively, both P < 0.01) . Micro-computerized tomography showed that the bone volume-to-total volume ratio and thickness of trabecular bone in the proximal tibia were significantly lower in the experimental group than in the control group, but the spacing of trabecular bone was significantly higher in the experimental group than in the control group (P < 0.01 or < 0.05) . There were no significant differences in the elastic modulus and fracture energy of the femur between the experimental group and control group (both P > 0.05) . Moreover, no significant differences in the serum levels of TNF-α and IL-17 were observed between the two groups (both P > 0.05) . Real-time PCR revealed that the mRNA expression of OPG and RNAKL was significantly higher in the experimental group than in the control group (P < 0.05, < 0.01 respectively) .@*Conclusions@#Long-term topical application of imiquimod can not only induce psoriasiform dermatitis in mice, but also lead to bone loss of spongy bone and micro-architectural deterioration in the proximal tibia. Thus, mouse models of psoriasis complicated by bone loss can be established by long-term imiquimod stimulation.

Effects of simvastatin on bone loss in vertebrae and intervertebral disc degeneration in ovariectomized rats / 医学研究生学报

Objective Simvastatin, as a widely used lipid-lowering drug, exhibits a potential effect of promoting bone forma-tion. The present study aimed to investigate the effect of oral simvastatin on lumbar vertebral bone mass and intervertebral disc ( IVD) degeneration in ovariectomized ( OVX ) rats. Methods Thirty female Sprague-Dawley rats were subjected to dual OVX ( n=20) or sham surgery ( n=10) and the OVX rats were treated orally with either saline vehicle (OVX+V, n=10) or simvastatin (OVX+SIM, n=10 ) at 5 mg per kg of the body weight per day. After 6 months of intervention, the microstructure of the L3 vertebra was ob-served by micro-CT, the bone mineral density ( BMD) in the L5-6 ver-tebrae determined by dual-energy X-ray absorptiometry, and histo-logical changes of the L5-6 vertebrae analyzed by van Gieson stainingand semi-quantitative evaluation. Results Compared with the sham-operation group, both the OVX+V and OVX+SIM groups showed significantly decreased BMD in L5([0.2933±0.0110] vs [0.2423±0.0081] and [0.2598±0.0249] g/cm2, P<0.05), L6 ([0.2907±0.0150] vs [0.2395±0.0061] and [0.2572±0.0121] g/cm2, P<0.05), and L5-6([0.2860±0.0115] vs [0.2380± 0.0059] and [0.2528±0.0126] g/cm2, P<0.05), but all the 3 parameters were remarkably higher in the OVX+SIM than in the OVX+V group (P<0.05). Micro-CT analysis manifested significantly lower BV/TV and Tb.N but higher Tb.Sp in the OVX+V than in the sham operation group ( P<0.05) . Abundant notochordal cells and extracellular matrix in the nucleus pulposus with well-arranged outer annulus fibrosus were observed in the rats of the sham operation group. The animals of the OVX+V and OVX+SIM groups displayed de-generation of the nucleus pulposus, annulus fibrosus, reduced notochordal cells and their replacement by chondrocyte-like cells in the nucleus pulposus, mucoid degeneration in the matrix, and disruption of the nuclear-annular border in the annulus fibrosus. The disc de-generation scores were significantly higher in the OVX+V and OVX+SIM than in the sham operation group (4.35±0.9 and 3.53±0.42 vs 2.48±0.92, P<0.05). Conclusion OVX induces not only bone loss in vertebrae but also IVD degeneration in rats, while simvasta-tin can partly prevent bone loss in lumbar vertebrae without aggravating IVD degeneration in OVX rats.

Morphology of the intervertebral disc in high fat combined with streptozotocin-induced type Ⅱ diabetic rats / 中国组织工程研究

BACKGROUND:Rat models of diabetes mellitus type 2 (T2DM) are usually induced by the combination of high-fat diet and low-dose streptozotocin, but their effects on the intervertebral disc have not yet been reported. Endplate sclerosis is an important factor contributing to intervertebral disc degeneration. OBJECTIVE:To evaluate whether the rat T2DM model induced by high-fat diet combined with low-dose streptozotocin is suitable for the study of T2DM related intervertebral disc degeneration. METHODS:Thirty-two 3-month-old female Sprague-Dawley rats were divided into four groups (n=8 per group), including sham, bilateral variectomy, DM, and bilateral variectomy plus DM groups, followed by subjected to bilateral ovariectomy and/or high-fat diet combined with low-dose streptozotocin, respectively. The blood glucose level, body mass and glucose tolerance were determined. The bone mineral density of the lumbar spine was measured after 8-week streptozotocin treatment. The L5-6 segments were removed and cut through midst sagittal plane after decalcification, and then underwent Von Gieson staining and histological degeneration scoring, and the disc height and endplate thickness were measured. RESULTS AND CONCLUSION:Fasting blood glucose and random blood glucose levels in the DM and bilateral variectomy plus DM groups were significantly higher than those in the other two groups, and the insulin sensitivity in the DM and bilateral variectomy plus DM groups were significantly lower than that in the other groups (P<0.05). L4-6 vertebral bone mineral density in the bilateral variectomy group was significantly lower than that in the sham group (P<0.05);L5-6 vertebral bone mineral density in the DM and bilateral variectomy plus DM groups was significantly lower than that in the sham group (P<0.05). L5-6 vertebral histological scores in the DM and bilateral variectomy plus DM groups were significantly higher than those in the other groups (P<0.05). Similar with the bilateral variectomy group, there were chondrometaplasia and mucoid degeneration of nucleus pulposus cells in the bilateral variectomy plus DM group, and the histological scores were significantly higher than those in the sham and DM groups (P<0.05). Compared with the sham group, the intervertebral disc height in the bilateral variectomy and bilateral variectomy plus DM groups was significantly decreased (P<0.05). While, there was no significant difference in the endplate thickness among groups. These results indicate the combination of high-fat diet and low-dose streptozotocin-induced rat T2DM models possess diabetic characteristics, but the rat intervertebral disc tissues show no significant differences from the normal ones;therefore, this model may be unsuitable for the study on T2DM-related intervertebral disc degeneration.

Effect of simvastatin on bone mass recovery in rats with reloading after tail-suspension / 中国比较医学杂志

Objective To observe the changes of bone mass in reloaded rats after tail-suspension,and the effect and mechanism of simvastatin on this process.Methods Twenty-four 5-month old rats were divided into 4 groups of 6 animals in each group: Control (CL) group without tail-suspension,unloaded (UL) group with tail-suspension for 6 weeks,other 12 rats received tail-suspension for 3 weeks,then reloaded for subsequent 3 weeks (UL+RL) or combined with simvastatin treatment (UL+RL+SIM) at a dose of 10 mg/kg/d.All rats were sacrificed 6 weeks later,and the left femur was used for examination of bone mineral density,left tibia was used for bone histomorphometry analysis,the right femur and tibia were harvested for biomechanical test,and expression levels of type I collagen by real-time PCR and Western blot,respectively.Results 1.BMD of the CL group was significantly higher than those of the other three groups (P<0.05),and was markedly lower than those in the UL+RL and UL+RL+SIM groups (P<0.05).2.The bone histomorphometry showed that BV/TV in the CL group was significantly higher than those in the other 3 groups,and the UL+RL and UL+RL+SIM groups showed a significantly higher BV/TV than that of UL group (P<0.05).The Tb.Th was significantly higher in the CL group than in the UL group.The Tb.Sp in the CL group was significantly lower than those in the other 3 groups (P<0.05).The UL+RL and UL+RL+SIM groups showed significantly lower Tb.Sp than that of the UL group (P<0.05).3.Biomechanical test showed that the maximal load and elastic modulus in the CL groups were significantly higher than those of the other three groups (P<0.05).4.Real-time PCR showed that no significant difference in the mRNA expression level of Col I was found between any two groups.5.Western blot showed that the IOD of Col I is significantly lower than that in the CL group.Conslusions Bone loss,destruction of trabecular bone micro-architecture and biomechanical properties and reduction of type 1 collagen are present in tail-suspension treated rats,which are partially restored after reloading,and this recovery process is not enhanced by simvastatin treatment.

Effects of simvastatin versus alendronate on bone loss and biomechanical property deterioration in ovariec-tomized rats / 医学研究生学报

Objective Alendronate is widely used as an anti-osteoporosis agent , while simvastatin , as a lipid-lowering drug , is being considered beneficial for bone formation .The present study aims to compare the effects of simvastatin and alendronate on bone loss in ovariectomized ( OVX) rats. Methods Thirty-two female SD rats were equally randomized into a sham operation , an OVX mod-el, a simvastatin ( OVX +S), and an alendronate ( OVX +A) group.All the rats but those in the sham operation group underwent dual ovariectomy .The animals of the OVX model and OVX +S groups were treated intragastrically with vehicle and simvastatin at 5 mg per kg of the body weight per day , respectively , while those of the OVX+A group injected subcutaneously with alendronate at 70μg per kg of the body weight per week .After 12 weeks of intervention , all the rats were sacrificed for detection of the serum concentrations of PINP and ICTP by ELISA, analysis of bone mineral density and bone histo-morphometry parameters of L 4 vertebrae , determination of the maximum loading and elastic modulus of L 5 vertebrae by compression test. Results The serum concentrations of P1NP and ICTP were significantly lower in the sham operation than in the other three groups (P0.05).Bone histomorphometry showed significantly lower BV /TV in the OVX model than in the sham operation and OVX +A groups ([19.9 ±1.69]%vs [29.03 ±2.59]%and [27.05 ±1.91]%, P<0.05), but markedly higher Tb.Sp in the former than in the latter two groups ([357.33 ±26.55] μm vs [211.17 ±16.56] μm and [252.50 ±19.35] μm, P<0.05).The maximum load and elastic modulus of L5 vertebrae were significantly lower in the OVX model rats than in the other three groups (P <0.05). Conclusion Both simvastatin and alendronate can inhibit bone loss in OVX rats , with comparable effects of preventing the deteriora-tion of biomechanical properties , but the latter is evidently more effective in maintaining bone mineral density .

Effect of simvastatin on bone mineral density and biomechanical properties of ovariectomized rats / 中国组织工程研究

BACKGROUND:Osteoporosis and its complications severely threaten the elder’s health. Simvastatin, widely accepted as a lipid-lowering drug, is reported to potentialy promote bone formation, but it is in debate when oraly administered, and there is no evidence to support whether this is due to the region difference. OBJECTIVE:To investigate the effect of oraly administered simvastatin on bone mass and biomechanical properties of the femur and vertebrae in osteopenia rats induced by ovariectomy (OVX). METHODS: Twenty-four 6-month-old female Sprague-Dawley rats were subjected to OVX+oraly administered saline vehicle (OVX group,n=8), OVX+oraly administered simvastatin (5 mg/kg/d; intervention group,n=8) or sham surgery (sham group,n=8). After 8 weeks of treatment, al rats were sacrificed and the level of procolagen type I N-terminal propeptide in blood serum was assessed by ELISA. Bone mineral density was determined in the L5 vertebra and left femur using dual-energy X-rays. Furthermore, the biomechanical properties of the L4 vertebra and right femur, including maximum load and elastic modulus, were detected by compression testing and three-point bending test, respectively. RESULTS AND CONCLUSION: The serum level of procolagen type I N-terminal propeptide in the sham group was significantly lower than that in the other two groups. OVX rats showed significantly lower bone mineral density in both the L5 vertebra and left femur than sham rats (P < 0.05). Rats in the intervention group showed higher bone mineral density than those in the OVX group, with statisticaly significant difference in the L5 vertebra (P < 0.05), but insignificant difference in the femur. Maximum load and elastic modulus of the L4 vertebra in the OVX group were significantly lower than those in the sham and intervention group. Markedly lower elastic modulus of the femur was found in the OVX group than the sham and intervention groups. These findings demonstrate that simvastatin treatment can partialy prevent bone loss in OVX rats with more notable effect on the vertebrae than the femur, and for this model, the vertebra is superior to the femur used in biomechanical test.

Effects of simvastatin treatment with different intervention programs on the bone quality of osteoporotic rats / 中国比较医学杂志

Objective To investigate the effects of simvastatin on the bone loss and deterioration of bone quality with different intervention programs. Methods Thirty two 3?month?old female Sprague?Dawley ( SD ) rats were randomized into 4 groups of 8 animals in each: All rats but those in the sham group ( A) received bilateral ovariectomy, and treated by vehicle (B), simvastatin (5 mg/kg/day) at first half period (C) or at latter half period (D). The rats in group C received simvastatin by a gavage after the OVX operation immediately, and stopped at 10 weeks after OVX. The rats in group D began to receive simvastatin treatment from 10 weeks after OVX and ended at 20 weeks after OVX. At week 20, all rats were sacrificed and the concentrations of serum PINP and ICTP were detected by ELISA, L3 vertabra was used to detect the bone mineral density, L4 vertebra was used to analyze the maximum loading and elastic modulus by compression test, and the microstructure of the L5 vertebra was detected by micro?computed tomography. Results 1. ELISA analysis:the concentrations of serum P1NP and ICTP in the groups A, B and C were significantly higher than that of group A (P<0?05). 2. BMD test showed that the rats in group B had significantly lower BMD than the other 3 groups (P<0?05), while the BMD of groups C and D were markedly lower than that of group A (P<0?05). 3. Biomechanical test:the maximum load and elastic modulus of L4 vertebrae in the group B were significantly lower than the other 3 groups ( P<0?05), and those of the groups C and D were markedly lower than that in the group A (P<0?05). 4. micro?CT:BV/TV and Tb. N in the sham operated rats were significantly higher than those of the other 3 groups, while the opposite trends was found in Tb. Sp (P<0?05), and the Tb. Sp in the groups C and D were significantly lower than that of group B (P<0?05). Conclusions Our data demonstrate that bone loss and deterioration of bone micro?structure and biomechanical properties occurred at 20 weeks after ovariectomy, both the first?half?period and latter?half?period treatment by simvastatin may partially prevent these changes, but can not restore the BMD to normal level.

Comparison of the Effects of Strontium Ranelate and PTH (1-34)on Bone Quality of Ovariectomized Rats / 中国药房

OBJECTIVE:To compare the effects of strontium ranelate and PTH(1-34)on bone quality of ovariectomized rats. METHODS:80 SD rats were randomly divided into sham operation group(group A,n=10)and dual ovariectomy(group B,n=70). 3 months after operation,group B were randomly divided into 7 groups,with 10 rats in each group. B0 group were given nor-mal saline [0.9 g/(kg·d)] subcutaneously;B1-B3 groups were given low-dose,medium-dose and high-dose of strontium ranelate [0.45,0.9,1.35 g/(kg·d)] intragastrically;B4-B6 groups were given low-dose,medium-dose and high-dose of PTH(1-34)[30, 60,90 μg/(kg·d),treated for 5 days,rested for 2 days] subcutaneously. Group A was same to group B0 in therapy regimen. All rats were sacrificed 8 weeks later. The contents of P1NP and CTX-1 in serum of rats were determined by ELISA assay;bone densi-ty of 4th lumbar vertebrae was detected by bone densitometer;BV/TV,Tb.Th,Tb.N and Tb.Sp were detected by CT;maximal load and elastic modulus of 5th lumbar vertebrae were measured by compression test. RESULTS:Compared with group A,the se-rum levels of P1NP and CTX-1 in B0-B6 groups increased significantly,while bone density of 4th lumbar vertebrae,maximal load and elastic modulus of 5th lumbar vertebrae decreased significantly in B0-B3 groups(P0.05). CONCLUSIONS:PTH(1-34) is better than strontium ranelate in inhibiting bone loss,improving vertebral bone micro-structure and biomechanical properties of ovariectomized rats.

Simvastatin effects on the expressions of specific osteogenic genes in bone marrow stromal stem cells / 中国组织工程研究

BACKGROUND:Previous studies have demonstrated that simvastatin that can promote osteogenic differentiation of bone marrow stromal stem cel s in vitro, is likely to be a new osteogenic drug. While it is stil unknown whether there is time-dependent stimulation of simvastatin on the expressions of bone morphogenetic protein 2 and col agen type I. OBJECTIVE:To investigate the expressions of bone morphogenetic protein 2 and col agen type I in rat bone marrow stromal stem cel s in vitro stimulated by simvastatin at different time points. METHODS:Passage 1 bone marrow stromal cel s were divided into control and simvastatin group, fol owed by cultured in osteogenic differetiation medium with or uithout 10-7 mol/L simvastatin. After 7-day intervention, expression of alkaline phosphatase was detected in passage 3 cel s. Passage 4 cel s were divided and cultured as described above, and afterwards, RNA and proteins were extracted at 12 and 36 hours to detect the expressions of bone morphogenetic protein 2 and col agen type I using real-time PCR and western blot assay. RESULTS AND CONCLUSION:Both two groups could express alkaline phosphatase, while the rate of positive cel s significantly increased in the simvastatin group compared with the control group (P<0.05);at 12 and 36 hours after intervention, mRNA expressions of bone morphogenetic protein 2 and col agen type I in the simvastatin group were significantly higher than those in the control group (P<0.05). Besides, western blot assay showed:at both 12 and 36 hours, simvastatin significantly enhanced the expression of bone morphometric protein 2, while the expression of col agen type I significantly increased at 12 hours (P<0.05), but not at 36 hours. In conclusion, simvastatin can promote the expressions of bone morphometric protein 2 and col agen type I in rat bone marrow stromal cel s, with more favorable outcomes after 12-hour treatment.

Expression of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase 1 in knee articular cartilage / 中国组织工程研究

BACKGROUND:Tissue inhibitor of matrix metaloproteinase 1 (TIMP-1) is the corresponding antagonist of matrix metaloproteinase 13 (MMP-13), and their balance between expression and functional activity exerts an important role in the metabolic state of the extracelular matrix. During the development of osteoarthritis, however, TIMP-1 and MMP-13 expressions and their expression ratio show unclear changes in DH guinea pigs. OBJECTIVE:To explore the expression levels of MMP-13 and TIMP-1 in DH guinea pigs with different ages, and to analyze the relationship between the ratio of MMP-13 to TIMP-1 and the age-dependent degenerative changes in the articular cartilage. METHODS:Twenty-four female Dunkin Hartley guinea pigs were sacrificed at age of 2, 4, 8, 12 months separately, with six animals at each time point. The knee joints were colected and gross visual appearance of the articular cartilage was observed, then were decalcified and prepared for paraffin sections. VG staining and Mankin score were used to analyze the histological changes. Immunohistochemistry was conducted to assess the expression levels of MMP-13 and TIMP-1 in the cartilage. Integrated absorbance values were used as the quantitive analysis calculated by Image pro-Plus 6.0. Linear regression analysis was done to analysis the relationship between Mankin score and the ratio of MMP-13/TIMP-1. RESULTS AND CONCLUSION:Normal appearance in the articular cartilage was observed in 2-month-old DH guinea pigs, while degenerative changes in the articular cartilage were shown in 4-month-old animals, which became severer with age. Significant difference was found in Mankin score between any two groups (P < 0.05). The ratio of MMP-13 to TIMP-1 increased with age, and the ratio was positively correlated to the Mankin score (P < 0.05). Age-related articular cartilage degeneration occurred in Dunkin Hartley guinea pigs at 4 months of age, and devoloped with age, which is related with the imbanlance of the expression ratio of MMP-13 to TIMP-1.

Effect of Strontium ranelate on stress-absence induced osteoporosis / 天津医药

Objective To investigate the preventive effect of Strontium ranelate on stress-absence induced osteoporo?sis in tail-suspended rat. Methods A total of 30 SD rats with average age of 6 month were randomly divided into 3 groups (n=10 in each group):Group A was normal control group while rats in group B and C were subjected to tail suspension test to establish stress absence models. Rats in group C were administered with Strontium ranelate [1 g/(kg·d)]. All rats were sacri?ficed 4 weeks later. Left femurs were harvested for bone mineral density (BMD) test and prepared for undecalcified tissue sec?tion and thereby bone histomorphometry assessment. Bone marrow from right femurs and tibias were cultured and induced to?wards osteogenic-differentiation. The expression levels of osteocalcin in the fourth-passage cultured bone marrow cells and in blood serum were detected separately. Results Rats in group B showed markedly decreased BMD comparing to those in group A and C(P<0.05). Trabecular volume (BV/TV), number (Tb.N) and thickness (Tb.Th) in group B were lower than those in group A and C;erosion percentage (Er.Pm) and osteoclast number (Oc.N) in group B and C were higher than those in group A;comparing to those in group B, bone formation rate (BFR/BV), labeled percentage (L.Pm), were higher in group C, coupled with decreased Er.Pm and Oc.N(P<0.05). mRNA expression levels of OCN in group B and C were higher than those of group A. But its level in plasma were lower in group B than those in group A and C(P<0.05). Conclusion Tail suspension could induce osteosporosis. Strontium ranelate prevent bone loss in stress-absence osteoporosis in rat induced by tail-suspension for 4 weeks, which might be partially through upregulating the expression of OCN, thereby promoting bone formation.

The Effect of Lovastatin Combined with Calcitonin on Fracture Repair in Osteoporotic Rats / 天津医药

Objective To investigate the effects of lovastatin alone or combined with calcitonin on fracture repair in osteoporotic rats. Methods Forty 4-month-old female SD rats were randomized into 5 groups(8 rats in each group):normal fractured group (A), osteoporotic fractured group (B), lovastatin treatment group(C), calcitonin treatment group (D) and lovastatin combined with calcitonin treatment group. All rats except group A received bilateral ovariectomy. The midshaft femur fracture model was established in all rats 8 weeks after operation. The serum level of procollagen amino-terminal propeptide (PINP) was assessed by ELISA. X-ray and bone mineral density detection was used to observe the fracture healing process. The maximal loading of femoral fractures was analyzed by biomechanical method. Results (1) The serum level of PINP was significantly lower in group A than that of other groups. There was a significantly higher level of PINP in group C and group E than that of group B, and the level of PINP was significantly lower in group D than that of group C. (2) The X-ray showed more progressed fracture healing in group A and group E. The accordingly score indicated that there was a markedly higher score in groups A and group E compared to that of other three groups. (3) There was a highest bone mineral density in the full-length and in the middle of femur bone in group A, followed by group E, group D and group C. The lowest bone mineral density was found in group B. (4) The biomechanical test showed that the maximal loading in femur fracture side was significantly higher in group A than that of other four groups, in which it was higher in group E than that of group B. Conclusion The osteoporosis decreased bone mass and delayed fracture healing process in rat model. The treatment of lovastatin combined with calcitonin showed more positive effect on preventing bone loss and promoting fracture repair than lovastatin alone.

Effect of calcitonin on vascular endothelial growth factor in osteoporotic fracture callus / 重庆医学

Objective To study the effect of calcitonin on the expression of vascular endothelial growth factor in femoral fracture healing in ovariectomized rats .Methods 80 female rats of 3 months old were randomly divided into four groups :Sham operation group(Sham ,10 cases);Ovariectomized operation group(OVX ,10 cases);Ovariectomy+ fracture+ salinegroup(Control ,30 cases) and Ovariectomy+ fracture +calcitonin group(Experimental ,30 cases) .Rats in Sham group and OVX group were performed ovari-otomy and killed after 4 weeks ,femoral bone mineral density was measured .For rats in Control group and Experimental group ,right middle femoral facture was performed 4 weeks later after ovariectomy .Calcitonin(16 IU/kg)were injected subcutaneously once per 2 days in Experimental group ,while those in Control group were given equal volume of normal saline .Rods in these two groups were killed after 3 ,6 ,9 weeks(10 at a time) ,femoral bone mineral density(BMD)was measured;hematoxylin-eosin staining and im-munohisto-chemical staining were performed at the 3th ,6th and 9th week after fracture ,respectively .Results Compared with Sham group ,rats weight in OVX group gained more(P0 .05)in BMD .At the 6th week after fracture ,bone trabecula in both groups arranged in order ,compared with the control group ,BMD in experimental group increased significantly(P0 .05) .Con-clusion The results suggest that calcitonin treatment could enhance the bone mineral density significantly after fracture ,but it has no impact on the expression of VEGF in osteoporotic fracture healing .

Research progress of subchondral bone in osteoarthritis / 医学研究生学报

Osteoarthritis ( OA) is a chronic joint disease characterized by degeneration of articular cartilage and changes of subchondral bone play an important role in the occurrence and development of OA .Recent studies have found that change in the struc-ture and mechanical properties of subchondral bone is one of the main pathological processes in OA .To confirm the role of subchondral bone in OA process can provide not only more details about the pathogenesis of OA , but also new targets for treatment .Early diagnosis and treatment of OA may be possible by detecting radiographic and genomics of subchondral bone .We review subchondral bone chan-ges andits role in OA process in aspects of biomechanics , biology, radiological and genomics .

Effects of internal fixation with simvastatin coating on healing of rat osteoporotic fractures at late period / 中国组织工程研究

BACKGROUND:As a lipid-lowering drug, simvastatin has been proved to be effective in promoting bone formation. Previous studies have demonstrated that local y applied simvastation accelerated fracture healing at middle phase in osteoporotic rats, while no study focuses on the influence of local y applied simvastatin on fracture healing at late period in an osteoporotic rat. OBJECTIVE:To investigate the effect of simvastatin local y applied from a bioactive polymer coating of implants on osteoporotic fracture healing at late period. METHODS:Female Sprague-Dawley rats were divided into sham group, osteoporotic fracture group and simvastatin group. In the sham group, the abdominal cavity was exposed without ovariectomy. Six weeks later, femur fracture models were established in normal or osteotoporotic Sprague-Dawley rats, and intramedul ary stabilization was achieved with uncoated titanium Kirschner wires in normal rats (sham group),with polylactic acid coated titanium Kirschner wires (osteoporotic fracture group) and with simvastatin/polylactic acid coated titanium Kirschner wires (simvastatin group). Femurs were harvested after 12 weeks, bone mineral density was determined with dual X-ray absorptiometry, and then radiographic and histological analysis was performed for analysis of fracture healing. Immunohistochemical evaluation was employed for bone morphogenetic protein 2 expression. RESULTS AND CONCLUSION:The bone mineral densities of both the total fractured femur and fractured site 12 weeks after fracture in the osteoporotic fracture group and simvastatin group were markedly decreased compared to normal fractured rats. The bone mineral density of the fractured site was significantly higher in the simvastatin group than the osteoporotic fracture group. Radiographic results demonstrated completely finished cal us remodeling in the sham group;poor healing, pale cal us density and blurred fracture line were seen in the osteoporotic fracture group;disappearance of fracture line, bone defects fil ed with cal us, and deep periosteal reaction were found in the simvastatin group. X-ray scores in the sham and simvastatin groups were significantly higher than that in the osteoporotic group (P<0.05). Hematoxylin-eosin staining showed a delayed healing process in the osteoporotic group, and revealed a significantly processed cal us with regular-shaped newly formed bone trabeculae in the simvastatin group. Immunohistochemical evaluation showed no significant difference in the bone morphogenetic protein 2 expression between any two groups. These findings suggest an improved fracture healing under local application of simvastatin in osteoporotic rats.

Effect of simvastatin on bone formation and osteogenic differentiation of bone marrow stromal cells in young rats / 中国组织工程研究

BACKGROUND: Recently simvastatin has been shown to stimulate osteogenic differentiation and bone formation, but there is no report about the effect of simvastatin on the bone development of young rats.OBJECTIVE: To evaluate the effects of simvastatin on osteogenic relative genes of proximal tibia trabecular bone and osteogenic differentiation of bone marrow stromal cells (BMSCs).METHODS: Twenty 1-week-old Spragua-Dawley young rats were randomly and equally divided into simvastatin and control groups. Rats in the simvastatin group were treated with a subcutaneous injection of simvastatin[5 mg/(kg·d)] for 2 weeks, while rats in the control group were treated with placebo for 2 weeks. The expressions of bone morphogenetic protein-2 (BMP-2), matrix metalloproteinase-13 (MMP-13), and vascular endothelial growth factor (VEGF) of trabecular bone in the tibia were analyzed by mmunohistochemicel staining. BMSCs harvested from the rat femur were osteogenic-differentiation cultured. Alkaline phosphatase (ALP) staining was performed on day 14, real-time PCR analysis was applied to investigate the BMP2, RUNX2,Osterix, MSX2, DLX3, DLX5 mRNA expressions during osteogenic differentiation in vitro on day 21, and von Kossa staining was detected on day 28.RESULTS AND CONCLUSION: ① There was no significant difference in the expressions of BMP-2, MMP-13, and VEGF between simvastatin and control groups. ② The percentages of ALP positive-stained cells were about 30% and there was no significant difference between the two groups (P ＞ 0.05). ③There was no significant difference in the expressions of BMP-2,RUNX2, Osterix, MSX2, DLX3, DLX5 mRNA in osteoganic differentiation-induced BMSCs. ④ von Kossa staining demonstrated that dark brown calcified spots in various sizes were observed, but there was no significant difference in size and density between simvastatin and control groups. A subcutaneous injection of simvastatin[5 mg/(kg·d)] for 2 weeks could not remarkably affect osteogenic relative genes of bone trabecula and osteogenic differentiation of BMSCs.