[Analysis of the causes of residual back pain in the early and late stages after percutaneous vertebral augmentation].

OBJECTIVE: To explore the influencing factors of the residual back pain in patient with osteoporotic vertebral compression fractures(OVCFs) in the early and late stages after percutaneous vertebral augmentation(PVA), and analyze the correlation between these factors and the residual back pain after PVA. METHODS: From March 2018 to December 2019, 312 patients with OVCFs who treated with PVA were collected. According to the inclusion and exclusion criteria, a total of 240 patients were included in this retrospective study. There were 59 males and 181 females, aged from 50 to 95 years old with an average of (76.11±10.72) years old, and 50 cases of fractures located in the thoracic region (T5-T10), 159 cases in the thoracolumbar region (T11-L2), and 31 cases in the lumbar region (L3 and below). The first day after PVA was regarded as the early postoperative period, and the seventh day was regarded as the late postoperative period. According to the visual analogue scale (VAS), the patients were divided into 4 groups:early postoperative pain relief group(group A, VAS≤4 scores), there were 121 patients, including 29 males and 92 females, aged from 50 to 90 years with an average of (75.71±11.00) years;early postoperative pain relief was not an obvious group (group B, VAS >4 scores), there were 119 patients, including 30 males and 89 females, aged from 53 to 95 years with an average of (76.51±10.46) years; late postoperative pain relief group (group C, VAS≤ 4 scores), there were 172 patients, including 42 males and 130 females, aged from 50 to 95 years with an average of (76.20±10.68) years; late postoperative pain relief was not obvious group (group D, VAS>4 scores), there were 68 patients, including 17 males and 51 females, aged from 53 to 94 years old with an average of (75.88±10.91) years old. The age, gender, bone mineral density(BMD), injured vertebral segment, preoperative thoracolumbar fascial condition, surgical methods, single or bilateral puncture, the amount of bone cement injection, anterior vertebral height recovery rate and central vertebral height recovery rate in the 4 groups were analyzed by univariate analysis. The statistically significant factors were put into a Logistic regression to analyze the correlation between these factors and residual back pain after PVA. RESULTS: Univariate analysis showed that the residual back pain in the early stage after PVA was correlated with BMD, preoperative thoracolumbar fascial injury, single or bilateral puncture, the amount of bone cement injection, anterior vertebral height recovery rate and central vertebral height recovery rate(P<0.05). The residual back pain in the late postoperative period was related to BMD, injured vertebral segment, surgical methods, the amount of bone cement injection, anterior vertebral height recovery rate and central vertebral height recovery rate(P<0.05). Multivariate Logistic regression analysis showed that thoracolumbar fascial injury(OR=4.938, P=0.001), single or bilateral puncture(OR=5.073, P=0.002) were positively correlated with the residual back pain in the early stage after PVA(B>0), which were risk factors;the BMD (OR=0.211, P=0.000) and anterior vertebral height recovery rate (OR=0.866, P=0.001) were negatively correlated with the residual back pain in the early stage after PVA(B<0), which were protective factors. In the late stage after PVA, the BMD(OR=0.448, P=0.003), the amount of bone cement injection (OR=0.648, P=0.004) and anterior vertebral height recovery rate (OR=0.820, P=0.000) were negatively correlated with residual back pain(B<0), which were protective factors. CONCLUSION: The decrease of BMD, injury of the thoracolumbar fascia, single or bilateral puncture, poor recovery of anterior vertebral height and insufficient injection of bone cement are closely related to the occurrence of residual back pain after PVA, which affect the relief of residual back pain in the early and late postoperative periods.

USF2 reduces BMP3 expression via transcriptional activation of miR-34a, thus promoting osteogenic differentiation of BMSCs.

INTRODUCTION: Osteoporosis is the most susceptible disease for people over 60. The main cause of osteoporosis is the decreased osteogenic differentiation of mesenchymal stem cells (MSCs). Here we showed that upstream stimulatory factor 2 (USF2)/microRNA-34a (miR-34a)/bone morphogenetic protein 3 (BMP3) axis regulated osteogenic differentiation of BMSCs. MATERIALS AND METHODS: USF2 and miR-34a expression were examined using qPCR. Protein levels of BMP3 and osteogenic markers expression were evaluated using both western blot and qPCR. Activity of ALP was determined by ALP assay kit. Mineralization capacity of hBMSCs was assessed using ARS. Besides, CHIP assay was employed to verify whether USF2 could bind to miR-34a promoter. Finally, RIP assay and dual-luciferase reporter assay were employed to verify whether miR-34a directly bound to BMP3. RESULTS: Our results suggested that miR-34a was upregulated during osteogenic differentiation of BMSCs, and miR-34a overexpression could enhance osteogenic differentiation of BMSCs. USF2 could positively regulate miR-34a expression by interacting with its promoter. USF2 overexpression enhanced osteogenic differentiation of BMSCs, while miR-34a inhibition reversed the effect. Besides, BMP3 was the target of miR-34a. MiR-34a overexpression enhanced osteogenic differentiation of BMSCs, which was abolished by BMP3 overexpression. CONCLUSION: Taken together, USF2 enhanced osteogenic differentiation of BMSCs via downregulating BMP3 by interacting with miR-34a promoter.

[Mechanism action of Chinese herbal compound and target network pharmacology of Yougui (YG) pill for the treatment of osteoporosis].

OBJECTIVE: To explore compounds, targets and mechanism of Yougui (YG) pill in treating osteoporosis based on systemic pharmacology of traditional Chinese medicine. METHODS: The known effective Chinese herbal compound of YG pill was searched from traditional Chinese medicine integrated database(TCMID). Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN-TCM) was used to predict target of components;DisGeNET and artificial literature reading were used to obtain targets of osteoporosis and bone remodeling;Cytoscape 3.7.1 software and its plug-ins BiN-GO and ClueGO were used to enrich the GO annotation and pathwaysof the related targets, and validation of the predicted target of YG pill were validated by 87 differentially expressed proteins in postmenopausal osteoporosis and postmenopausal osteoporosis disease models in postmenopausal patients with normal bone mass from the previous serum proteomics data. RESULTS: Totally 392 compounds were retrieved from YG pill, including 83 sovereign drugs (monkshood, cinnamon, deerhorn gelatin), 127 ministerial drugs (prepared rehmannia root, dogwood, wolfberry fruit and Chinese yam) and 182 supplementary drugs (cuscuta chinensis, eucommia ulmoides and Chinese angelica). Among them, there were 4 same compounds between sovereign drug and ministerial drug, 1 same compound between sovereign drug and supplementary drug, and 14 same compounds between ministerial drug and supplementary drug. Totally 2 112 trusted targets were identified, included 775 sovereign drugs, 1 483 ministerial drugs and 1 491 supplementary drugs;227 targets were selected from YG pill for treating osteoporosis, which participate in nearly 20 process of metabolic process, cell differentiation and biology, and data mining revealed that the process involved bone remodeling and bone mineralization. Acting site of cell mainly inclded 9 kinds of cell which had 13 molecular function. Results of KEGG metabolic pathway enrichment analysis showed 137 signal passages were obviously enriched. Among them, classical osteoclast differentiation signal passages and relative estrogen regulates signaling pathways of menopause were widely distributed in 27 signal passages. Sixtargets were screened by target validation, such as AGT, FGA, APOE, DKK3, P4HB and RAB7A. CONCLUSION: The characteristics of multi-targets and multi-pathways of YG pill for the treatment of osteoporosis were clarified, which provided a clear direction for the in-depth research. The pharmacodynamic components of YG pill include 36 compounds, and their main action targets include FGA, AGT, APOE, DKK3, P4HB and RAB7A.

Artesunate promotes osteoblast differentiation through miR-34a/DKK1 axis.

BACKGROUND: Osteoporosis is characterised by impairment of microarchitecture and bone mass. Therapeutic strategy promoting osteoblast differentiation is considered as a promising direction for the treatment of osteoporosis. Artesunate (ART) is related to osteoporosis, but the relationship between ART and osteogenic differentiation is still unknown. METHODS: Cells proliferation were measured by MTT, ALP activity assay and Alizarin Red S staining were used to assess osteogenic differentiation of hBMSCs. Western blotting and qRT-PCR were applied for measuring expression of protein and mRNA, respectively. The relationship between miR-34a and Dickkopf-1 (DKK1) was detected by dual luciferase reporter assay. RESULTS: The expression of osteoblasts differentiation related proteins (Runx2, OCN, and OPN) were significantly increased by ART. And ART accelerates the osteoblasts differentiation of hBMSCs through promoting Wnt signaling pathway by DKK1 inhibition. Significant higher expression of miR-34a and lower expression of DKK1 could be induced by ART. We firstly proved that miR-34a could bind DKK1 specifically. CONCLUSION: ART could promote osteoblast differentiation through miR-34a/DKK1/Wnt pathway. Therefore, our findings may provide a new thought for the treatment of osteoporosis by ART through osteoblast differentiation promotion.

[Analysis of the related factors of fever of unknown causes before operation of intertrochanteric fracture in the elderly].

OBJECTIVE: To explore the related factors of fever of unknown causes before operation of intertrochanteric fracture of femur in the elderly. METHODS: From August 2015 to August 2018, 156 cases of intertrochanteric fracture of femur were treated by intramedullary nail fixation. According to the preoperative measurement, whether there was fever was divided into fever group and non fever group. There were 80 cases in fever group, 26 males and 54 females, aged 60 to 93 (75.063±13.082) years; 76 cases in non fever group, 39 males and 37 females, aged 60 to 96 (74.763±13.692) years. All patients' sex, age, basic diseases, WBC, NE%, Hb, CRP, D dimer and ALB were observed for single factor analysisand multi factor analysis. RESULTS: Single factor analysis showed that gender, Hb, CRP had influence on preoperative fever, but other indexes had no influence; multi factor analysis showed that gender and CRP might have influence on fever. The probability of fever increased by 1.2%(P=0.050) for every increase of CRP, and there was no significant difference between female and male in the probability of fever (P=0.061). CONCLUSION: CRP is an independent risk factor of preoperative fever in the elderly patients with intertrochanteric fracture of femur. The abnormality of CRP indicates that patients are more likely to have preoperative fever. Perioperative management should pay attention to the monitoring of CRP and early intervention.

Study on Zoledronic Acid Reducing Acute Bone Loss and Fracture Rates in Elderly Postoperative Patients with Intertrochanteric Fractures.

OBJECTIVE: To observe the effect of zoledronic acid on the reduction of acute bone loss and fracture rate in elderly postoperative patients with intertrochanteric fracture. METHODS: From August 2012 to January 2015, a total of 482 patients with senile osteoporotic femoral intertrochanteric fracture, who accepted proximal femoral intramedullary fixation under anesthesia were analysed. The patients were divided into two groups. Treatment group (353 cases) were treated with 100 mL/5 mg of zoledronic acid injection in 1 week after operation, as well as orally taken 600 mg/d of calcium carbonate and active vitamin D3 400 IU/d. Control group (129 cases) were given the same dose of calcium carbonate and active vitamin D3 orally. Efficacy evaluation were conducted during different periods of medication RESULTS: Compared with pre-medication, indexes of bone metabolism (TARP-5b, CTX) in the treatment group were brought down, especially significantly statistically different after 12 months of medication. The treatment group performed superior to control group in alleviating the pain of back and posture changing (P < 0.05), improving bone density (P < 0.05), depressing re-fracture rate (P < 0.01) after 24 months of medication. In addition, BP, PF and MH dimension scores were demonstrated with statistical significance (P < 0.05). CONCLUSIONS: The application of zoledronic acidin elderly postoperative patients with intertrochanteric fracture can not only relieve acute bone loss, reduce the incidence rate of re-fracture, alleviate osteoporosis pain and the pain from osteoporotic fracture, but also improve bone metabolism and quality of life, which may offer an acceptable clinical opinion.

[Micro-CT evaluating inhibitory effect of zoledronic acid on polyethylene particle-induced periprosthetic osteolysis model].

OBJECTIVE: To observe inhibitory effect of zoledronic acid on polyethylene particle-induced periprosthetic osteolysis model. METHODS: Thirty male adult specific-pathogen-free SD rats (weighted 250 to 300 g) were randomly divided into sham group, model group, and zoledronic acid group, 10 in each group. Modeling were building by titanium screws and polyethylene particles implanted into right femur of rats, sham group and model group were performed hypodermic injection by 0.9% saline with 2 ml/kg, zoledronic acid with 0.1 ml/mg were injected into zoledronic acid group, once a week for 8 weeks. After 8 weeks, right femur specimens were drawn and used to san microstructure of femoral cancellous bone in rats model was examined by Micro-CT, and the images were treated with three-dimension reconstruction and analysis software BMD, BV/TV, Tb.N, Tb.Th, SMI, BS/BV, Tb.Sp and Tb.Pf and other parameters include. RESULTS: According to Micro-CT three-dimensional imaging, BMD in model group was significantly decreased than sham group, bone microstructure damage was serious, bone trabecula changed thinning continuity; while bone microstructure was obviously improved compared with model group and zoledronic acid group. After analyzing Micro-CT parameters of femur microstructure, BMD in model group(0.081±0.020) was significantly decreased than control group(0.160±0.018) and zoledronic acid group(0.125±0.012); BV/TV in model group (10.563±1.070) was obviously lower than control group(27.935±1.834) and zoledronic acid group(14.559±1.258); Tb.N in model group (1.005±0.165) was lower than control group(2.058±0.108) and zoledronic acid group(1.515±0.126); while Tb.Th in model group (0.075±0.016) was decreased than control group(0.158±0.016) and zoledronic acid group(0.124±0.011). Meanwhile, SMI in model group(1.817±0.127) was significantly higher than control group(1.104±0.120) and zoledronic acid group(1.547±0.122); BS/BV in model group(35.784±1.650) was higher than control group(21.506±2.771) and zoledronic acid group(30.399±2.730); Tb.Sp in model group(0.735±0.107) was higher than control group(0.423±0.057) and zoledronic acid group(0.577±0.082), TB.Pf in model group(9.088±1.283) was higher than control group(2.447±0.703) and zoledronic acid group(5.862±1.042). CONCLUSIONS: Zoledronic acid could change bone microstructure of rats to inhibit polyethylene particle-induced bone solution, which provides a scientific basis for prevent bone solution by zoledronic acid as a therapeutic intervention.

[Clinical observation of improved proximal femoral locking plate in treating osteoporotic intertrochanteric fractures].

OBJECTIVE: To investigate the effects of proximal femoral locking plate (PFP) in treating osteoporotic intertrochanteric fractures and to analyze the failure cases. METHODS: Totally 32 patients with osteoporotic intertrochanteric fractures of Evans I and II were treated with improved locking PFP, including 17 males and 15 females with an average age of 77.3 years old ranging from 70 to 86 years old. After operation, according to Harris hip scores, the hip function and therapeutic effects were evaluated. RESULTS: The observed 32 patients' operative time was (60.5±15.7) min, intraoperative blood loss was (128.8±73.6) ml;perioperative blood transfusion was (224.0±72.7) ml. Hospitalization time was from 14 to 20 d with an average of 17.2 d. All patients were followed up from 6 to 18 months with an average of 14.1 months. The fracture healing time was from 3 to 6 months with an average of 3.1 months. One patient occurred internal fixation loosening and screw backward, 4 cases occurred urinary tract infection, 1 patient died of cardiovascular disease for 6 months postoperative, 2 patients died of a stroke for 1 year postoperative. No incision deep infection, peri internal fixation fractures, lower extremity deep venous thrombosis, internal fixation breakage, nonunion, severe coax vara and coax valgus occurred. The final Harris score was 89.74±6.84, the result was excellent in 10 cases, good in 16 cases, fair in 4 cases, and poor in 2 cases. CONCLUSIONS: Locking PFP can provide relative stable fixation to proximal end of osteoporotic femoral fractures, which is a good choice for the treatment of intertrochanteric fractures. It could provide stableness of fractures and bone union, even avoid screws loose or slide out.

[Research progress on wear particles and periprosthetic osteolysis after artificial joint replacement].

It is an important influencing factor that the generated wear particles lead to periprosthetic osteolysis after artificial joint replacement. Current research suggests that the primary cause of wear particles results in periprosthetic osteolysis is relate to the prosthetic materials and the stimulations because of these materials generated wear particles to relevant cells such as macrophage, osteoblast, osteoclast. Induced a variety of inflammatory cytokines, activating and openning the cell signal and channels, producing the long term chronic inflammation leads to periprosthetic osteolysis. Therefor, the paper mainly studies the different types of wear particles influence on periprosthetic osteolysis, and the wear particles around the periprosthetic osteolysis mechanism in the process of progress, moreover, to explore how to reduce the occurrence of wear particles and blocking its role in the periprosthetic osteolysis, in order to achieve the purpose of prevention and treatment of periprosthetic osteolysis.

[Inhibitory effect of zoledronate sodium on periprosthetic osteolysis induced by polyethylene particles].

OBJECTIVE: To observe the effect and mechanisim of zoledronate sodium on periprosthetic osteolysis in rat induced by polyethylene particles. METHODS: Total 30 adult male SD rats, weighting from 250 to 300 g, were selected and randomly divided into three groups: blank control group, model control group and zoledronate sodium group respectively, 10 animals for each group. No treatment was performed in the blank control group. In model control group and zoledronate sodium group, the modle of periprosthetic osteolysis in rats were made by implanting polyethylene particles and titanium rods into their right femurs. After operation, rats in zoledronate sodium group were administered with zoledronate sodium (0.1 mg/kg each week) through subcutaneous injection for 8 weeks, then the blood was obtained and all experimental animals were sacrificed to get the right femur specimens. The femur BMD, IL-1ß, IL-6, TNF-α, serum TRACP5b and CTX-I were detected. RESULTS: Compared with the model control group, the femur BMD was increased, while IL-1ß, IL-6 and TNF-α were all decreased in zoledronate sodium group; the serum TRACP5b and CTX-I level were both reduced in zoledronate sodium group. CONCLUSION: The zoledronate sodium could effectively inhibit periprosthetic osteolysis in rats induced by polyethylene particles, which might be realized by inhibiting the activity of osteoclasts and the expression of IL-1ß, IL-6 and TNF-α. It provides a new method to treat periprosthetic osteolysis of the artificial joint prosthesis.

Interventional value of total flavonoids from Rhizoma Drynariae on Cathepsin K, a potential target of osteoporosis.

Osteoporosis, the sixth most common disease in the world, is bringing increasingly serious harm to people's health. Cathepsin K, which plays an important role in bone resorption, is a potential target in the treatment of osteoporosis. Total flavonoids, the active ingredients in Rhizoma Drynariae, have shown obvious, therapeutic effect on osteoporosis. In previous studies, it was presumed that the mechanism for the therapeutic effect was through inhibiting the expression of Cathepsin K. However, there are still no detailed reports on some key issues such as the specific inhibitory results of total flavonoids on Cathepsin K and the pathway of inhibition and so on. Based on previous studies on total flavonoids from Rhizoma Drynariae, the pathway for the effect of, total flavonoids inhibiting Cathepsin K and their interventional value on Cathepsin K were analyzed in this paper, so as to explore the interventional feasibility and value of total flavonoids in Rhizoma Drynariae on Cathepsin K.

[Effect of qianggu drink ([Chinese characters: see text]) on bone histomorphometry of lumbar vertebrae in ovariectomized rats].

OBJECTIVE: To observe the effect of Chinese herbal medicine Qianggu drink ([Chinese characters: see text]) on bone histomorphometry of lumbar vertebrae in ovariectomized rats and to explore its mechanism. METHODS: Sixty female SD rats (weight 230 to 280 gram) were randomized into three groups: Qianggu drink ([Chinese characters: see text]) group (treatment group), Miacalcic group (control group) and blank group. The osteoporosis model was established successfully after all rats were ovariectomized for 10 weeks. The treatment group was used intragastric infusion with Qianggu drink ([Chinese characters: see text]) 0.001 ml/kg once a day. The control group was used hypodermic injection once a day with Miacalcic 0.72 U/kg. Five rats were killed respectively and the lumbar specimens were taken and cut for bone histomorphometric analysis at 45, 90, 135 and 180 days after the treatment. RESULTS: The thickness of trabecular bone in treatment group had the statistical significance with control group at 135 days after ovariectomized rats were given the medicine. The data of BV/TV and the thickness and space of trabecular bone had statistical significance compared with control group and blank group 180 days later. CONCLUSION: Qianggu drink ([Chinese characters: see text]) could effectively improve the histomorphometry indexes. The mechanism probably plays by stimulating osteogenesis and inhibiting the cytoactive of osteoclast and the trend of bone transform.