Research progress of strontium and pregnancy and pregnancy diseases / 基础医学与临床

Strontium(Sr)is a trace element naturally found in the human skeletal system.In recent years,the po-tential impact of strontium on bone and cardiovascular health has called significant attention,particularly during pregnancy,when alterations in mineral metabolism may affect the health of both the mother and the fetus.This com-prehensive review assesses the current understanding of the role of strontium as a nutritional substance during preg-nancy,its effects on maternal health and fetal development,and its potential associations with pregnancy complica-tions such as preeclampsia,gestational hypertension,and lactation-induced osteoporosis.The review also summarizes the possible effects of strontium deficiency,excess,and supplementation,and provides information for developing prenatal nutrition supplementation guideline.

Angiogenesis mechanism of metal ions and their application in bone tissue engineering / 中国组织工程研究

BACKGROUND:Owing to excellent angiogenesis activity and their participation in the physiological processes such as angiogenesis in osteogenesis,the researches and applications of a variety of metal ions are getting deeper in the field of bone tissue engineering. OBJECTIVE:To systematically explain the mechanism of angiogenesis of different metal ions such as copper ion(Cu2+),magnesium ion(Mg2+),strontium ion(Sr2+),zinc ion(Zn2+),cobalt ion(Co2+)and their current research situation as well as application in the treatment of diseases in the field of bone tissue engineering. METHODS:The two authors used PubMed and CNKI to search the literature published between 2017 and 2022 with the search terms"copper ion,magnesium ion,strontium ion,zinc ion,cobalt ion,bone,angiogenesis"in Chinese and"copper,cuprum,Cu,magnesium,Mg,strontium,Sr,zinc,Zn,cobalt,Co,metal ion,angiogenesis,bone"in English.After reading titles and abstracts,the articles were initially screened,and irrelevant articles were excluded.Finally,114 articles were included for review. RESULTS AND CONCLUSION:(1)Metal ions can regulate angiogenesis by acting on vascular endothelial growth factors,hypoxia-inducible factors,angiogenesis-related genes,endothelial cells and conducting immune regulation of macrophages.(2)Metal ions such as copper,magnesium,strontium,zinc and cobalt are often used to improve the performance of tissue engineering scaffolds due to their significant angiogenic effect.Among them,hydrogels,bioceramics and synthetic polymer materials are widely used at present,and magnesium and its alloys also have advantages due to their excellent bearing capacity.However,these materials all have some defects.Currently,there is no ideal bone replacement material.(3)Various metal ions show different application potentials in bone replacement materials:Copper has antibacterial,angiogenic and osteogenic properties,and is mainly used for bone defects caused by infection and tumors.Magnesium and zinc have strong biodegradability,so the degradation rate should be controlled.Magnesium is corrosive and is mainly used as an alloy.The angiogenesis mechanism of zinc is less involved.Magnesium and strontium are effective in treating osteoporotic bone defects.(4)The above five metal ions(copper,magnesium,strontium,zinc and cobalt)have a significant role in promoting angiogenesis and then promote osteogenesis through angiogenesis.Some ions,such as copper ions,have a bactericidal effect.These ions can be used as a new strategy for the treatment of bone defects caused by tumors,osteoporosis,infection and trauma,but the current clinical trials and application studies of products are relatively insufficient.

Strontium ranelate-loaded sodium alginate/collagen hydrogel promotes bone defect repair in osteoarthritis / 中国组织工程研究

BACKGROUND:Cartilage degeneration and subchondral bone damage are the main pathological features of osteoarthritis,and treatment based on this pathological feature will be a promising improvement for osteoarthritis. OBJECTIVE:To design and study an annotated strontium ranelate-loaded drug delivery system and to observe its therapeutic effect on promoting cartilage repair and improving subchondral bone structure in osteoarthritis. METHODS:(1)In vitro experiment:Strontium ranelate was loaded into sodium alginate/collagen hydrogel matrix to construct in situ drug delivery system,and the in vitro slow release performance of the system was characterized.Strontium ranelate-loaded sodium alginate/collagen hydrogel(experimental group)and alginate sodium/collagen hydrogel(control group)were co-cultured with bone marrow mesenchymal stem cells,respectively,and cultured cells were used as a blank control group to detect cell proliferative activity.After chondroblast-induced differentiation,saffron O staining,Alcian blue staining and RT-qPCR were performed respectively.The two hydrogels were co-cultured with osteoblasts,and the cultured cells were used as a blank control group for immunofluorescence staining and RT-qPCR.(2)In vivo experiment:A total of 18 adult SD rats were selected and the model of right posterior knee osteoarthritis was established by the method of medial meniscectomy.After 1 week,the rats were divided into three groups by the random number table method:The blank group did not receive any treatment.The control group was injected with sodium alginate/collagen hydrogel in the knee,and the experimental group was injected with strontium ranelate-loaded sodium alginate/collagen hydrogel,with 6 rats in each group.After 6 weeks,the samples were subjected to Micro-CT scanning,hematoxylin-eosin staining,saffron O-solid green staining and immunofluorescence staining. RESULTS AND CONCLUSION:(1)In vitro experiment:Strontium ranelate-loaded sodium alginate/collagen hydrogel had porous microstructure and sustainable release of strontium ranelate.At 21 days,the cumulative release reached(60.89±0.58)%.Bone marrow mesenchymal stem cell staining showed that both hydrogels had good cytocompatibility.The results of the CCK-8 assay demonstrated that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote the proliferation of bone marrow mesenchymal stem cells.The results of Safranin O staining,Alcian blue staining,immunofluorescence staining and RT-qPCR exhibited that strontium ranelate-loaded sodium alginate/collagen hydrogel could promote chondrogenic differentiation of bone marrow mesenchymal stem cells.Immunofluorescence staining and RT-qPCR revealed that strontium ranelate-loaded sodium alginate/collagen hydrogel could decrease bone resorptivity by increasing the ratio of osteophosphorin/nuclear factor κB receptor activator ligand.(2)In vivo experiment:Micro-CT scan verified that compared with the blank group and control group,the subchondral bone volume fraction and bone mineral density of the knee of rats were increased in the experimental group(P<0.05,P<0.01).Histological staining displayed that compared with the blank group and control group,the knee cartilage injury was significantly reduced;the expression of type II collagen was promoted,and the expression of matrix metalloproteinase 2 protein was inhibited in the experimental group(P<0.05,P<0.01).(3)These results confirm that the strontium ranelate-loaded sodium alginate/collagen hydrogel can promote the repair of cartilage defects in osteoarthritis and reconstruct the complex interface between cartilage and subchondral bone.

Strontium-containing mesoporous bioactive glass nanoparticles loaded with bisphosphonates ameliorate bone loss in ovariectomized mice / 中国组织工程研究

BACKGROUND:Inhibition of osteoclast activity by bisphosphonates slows the progression of osteoporosis.However,serious complications of bisphosphonates,such as osteonecrosis of the jaw and atypical femur fracture,limit the clinical application of bisphosphonates.Effective alternative therapies need to be sought to improve existing clinical dilemmas. OBJECTIVE:To prepare strontium-containing mesoporous bioactive glass nanoparticles loaded with bisphosphonates(BPS@Sr-MBG)and analyze its activity against bone loss. METHODS:Strontium-containing mesoporous bioactive glass nanoparticles(Sr-MBG)were prepared by sol-gel method and added to alendronate saturated solution for the preparation of BPS@Sr-MBG.(1)Cell experiment:Mouse bone marrow macrophages were inoculated in 96-well plates and supplemented with ɑ-MEM complete culture medium containing macrophage colony stimulating factor and activator-ligand of nuclear factor κB receptor for osteoclast induced differentiation experiment.Meanwhile,they were cultured in three groups.The blank group was added with PBS.The control group was added with bisphosphonate,and the experimental group was added with BPS@Sr-MBG.After 5 days of culture,the differentiation of osteoclasts was observed by F-actin ring staining.(2)Animal experiments:Twenty-four female C57/BL mice were randomly divided into four groups with six mice in each group.Except sham operation group,ovariectomy group,BPS group and BPS@Sr-MBG group were used to construct osteoporosis model.One week after model establishment,mice in BPS group and BPS@Sr-MBG group were intraperitoneally injected with bisphosphonate solution and BPS@Sr-MBG solution,respectively.Mice in the sham operation group and ovariectomy group were intraperitoneally injected with PBS once a week.After 8 weeks of continuous injection,mouse femurs were taken for Micro-CT scanning and hematoxylin-eosin staining. RESULTS AND CONCLUSION:(1)Cell experiment:F-actin ring-formation staining demonstrated that compared with blank group,the area proportion and number of osteoclasts in the control group were decreased(P<0.01).Compared with the control group,the area proportion of osteoclasts and the number of osteoclasts in the experimental group were decreased(P<0.01).(2)Animal experiments:Micro-CT scanning results of femur showed that compared with the sham operation group,bone density,trabecular bone volume fraction,trabecular thickness and trabecular number of mice in the ovariectomy group were decreased(P<0.05,P<0.01),while trabecular distance and structural model index were increased(P<0.01).Compared with the ovariectomy group,the above bone parameters in the BPS group and BPS@Sr-MBG group were significantly improved(P<0.01),and the improvement in the BPS@Sr-MBG group was more obvious.The Micro-CT scanning results were further confirmed by hematoxylin-eosin staining of the femur.(3)The results show that BPS@Sr-MBG can exert anti-osteoporosis activity through anti-osteoclastic effect and promoting bone formation.

Application of strontium polyphosphate with both radiopaque and osteogenic functions in calcium phosphate cement / 中国组织工程研究

BACKGROUND:Our previous studies found that adding barium sulfate could improve the mechanical and radiopaque properties of calcium phosphate cement.However,with the degradation of calcium phosphate,the remaining radiopaque agent is difficult to degrade,and the space-occupying and osteoclast effects at the implantation site affect the bone repair process.Therefore,it is necessary to develop a new biodegradable radiopaque material. OBJECTIVE:To discuss the radiopaque ability of bioactive degradable material strontium polyphosphate(SrPP)and its impact on the physicochemical properties and osteogenic effect of calcium phosphate cement. METHODS:(1)Calcium phosphate cement(CPC),starch modified calcium phosphate cement(CPS)and starch modified calcium phosphate cement(20%SrPP-CPN)containing SrPP(20%mass fraction of bone cement powder)were prepared respectively,and the physicochemical properties of the three groups of bone cements were characterized.(2)The three groups of bone cement extracts were co-cultured with rat bone marrow mesenchymal stem cells,respectively,to detect cell proliferation,energy metabolism,and osteogenic differentiation.(3)Bone defects with a diameter of 5 mm were made on each side of the top of the skull of 24 SD rats,and they were randomly divided into control group(without any intervention),CPC group,CPS group,and 20%SrPP-CPN group for intervention,with 6 rats in each group.Relevant tests were performed after 4 and 12 weeks of intervention. RESULTS AND CONCLUSION:(1)Compared with the other two groups of bone cement,20%SrPP-CPN had enhanced radiopaque ability,increased compressive strength and degradation rate,and prolonged curing time,and 20%SrPP-CPN could release Sr2+ stably during degradation.(2)CCK-8 assay showed that 20%SrPP-CPN did not affect the proliferation of bone marrow mesenchymal stem cells.Cell starvation test(serum-free culture)showed that 20%SrPP-CPN could promote the proliferation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.Compared with the other two groups of bone cements,20%SrPP-CPN increased adenosine triphosphate concentration in bone marrow mesenchymal stem cells.Alkaline phosphatase and alizarin red staining showed that 20%SrPP-CPN could promote osteogenic differentiation of bone marrow mesenchymal stem cells compared with the other two groups of bone cement.(3)In the rat skull defect experiment,Micro-CT scanning and histological observation(hematoxylin-eosin and Masson stainings)showed that bone cement in 20%SrPP-CPN group was significantly degraded compared with that in CPC and CPS groups,and a large number of new bone tissues were dispersed in degraded bone cement.Immunohistochemical staining showed that Runx2 protein expression was increased in 20%SrPP-CPN group compared with CPC group and CPS group(P＜0.01).(4)These results show that 20%SrPP-CPN has good radiopaque ability and osteogenic properties.

Biological and physicochemical properties of bioactive ion modified brushite cements / 中国组织工程研究

BACKGROUND:As a bone replacement and filling material,calcium phosphate stone bone cement has good biocompatibility,bone conductivity,and other advantages,especially its better biodegradability compared to other calcium phosphate bone cements.It has important application value in bone repair.However,due to its limitations such as insufficient mechanical properties,fast solidification reaction,and poor injection performance,it is currently only suitable for the repair of non weight-bearing bone. OBJECTIVE:To explore the modification of brushite cements with bioactive ions(metal and non metal ions)to expand its application range. METHODS:The author used PubMed,ScienceDirect,CNKI,and WanFang to search the literature published between 2018 and 2023 with the search terms"metal ion,iron,copper,strontium,magnesium,zinc,non-metal ion,modification,bone,brushite cements"in Chinese and"metal ion,iron,Fe,copper,Cu,strontium,Sr,magnesium,Mg,zinc,Zn,non-metal ion,modification,bone,brushite cements"in English.After reading titles and abstracts,the articles were initially screened,and irrelevant and duplicate articles were excluded.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Bioactive ions affect the hydration process of calcium phosphate bone cement.Different ions are substituted by ions and incorporated into the crystal structure of calcium phosphate bone cement,changing the crystal morphology of the cement and causing changes in physical and chemical properties such as setting time,injectability,and compressive strength.(2)Ionic modified calcium phosphate bone cement produces different ion release effects due to different crystal structures.Different types of ions have properties such as promoting angiogenesis/osteogenesis,antibacterial,anti-tumor,etc.In addition,calcium phosphate bone cement has good biodegradability,which has great advantages for the performance of various ions.(3)The physicochemical properties of calcium phosphate bone cement modified with different ions are as follows:iron,copper,strontium,magnesium,zinc,silver,and cobalt can prolong the setting time.Strontium,and magnesium can improve injection performance.Copper,strontium,magnesium,silver and silicon can enhance compressive strength.The ions that can simultaneously improve the three physical and chemical properties of calcium phosphate bone cement include strontium and magnesium.Good physical and chemical properties are a prerequisite for clinical application,so improving the setting time,injectability,compressive strength,and other properties of calcium phosphate bone cement with ions is of great significance for the research and application of bone cement.(4)The biological properties of calcium phosphate bone cement modified with different ions are as follows:copper,strontium,magnesium,zinc,cobalt,lithium,selenium,and silicon have promoting angiogenesis/osteogenic effects.Iron,copper,magnesium,zinc,and silver have antibacterial properties.Magnesium ions have anti-inflammatory properties.Copper and selenium have anti-tumor properties.(5)In summary,magnesium ions can improve the setting time,injectability,and compressive strength of calcium phosphate bone cement,while also promoting neovascularization/osteogenesis,antibacterial properties,and have good application prospects for the treatment of bone defects with concurrent infections.In addition,copper also has anti-tumor properties,so copper ions have great potential in the treatment of bone defects caused by infections and tumors.However,relevant research is still in the basic research stage,and the effects of different ion doping concentrations and synthesis conditions on the physicochemical properties of calcium phosphate bone cement need to be further explored.At the same time,the impact of biological properties also needs to be studied and observed for a longer period of time.

Titanium micro-nano textured surface with strontium incorporation improves osseointegration: an in vivo and in vitro study*

Abstract Objectives This study aimed to investigate the osseointegration of titanium (Ti) implants with micro-nano textured surfaces functionalized with strontium additions (Sr) in a pre-clinical rat tibia model. Methodology Ti commercially pure (cp-Ti) implants were installed bilaterally in the tibia of 64 Holtzman rats, divided into four experimental groups (n=16/group): (1) Machined surface - control (C); (2) Micro-nano textured surface treatment (MN); (3) Micro-nano textured surface with Sr2+ addition (MNSr); and (4) Micro-nano textured surface with a higher complementary addition of Sr2+ (MNSr+). In total, two experimental euthanasia periods were assessed at 15 and 45 days (n=8/period). The tibia was subjected to micro-computed tomography (μ-CT), histomorphometry with the EXAKT system, removal torque (TR) testing, and gene expression analysis by PCR-Array of 84 osteogenic markers. Gene expression and protein production of bone markers were performed in an in vitro model with MC3T3-E1 cells. The surface characteristics of the implants were evaluated by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and laser scanning confocal microscopy. Results SEM, confocal, and EDS analyses demonstrated the formation of uniform micro-nano textured surfaces in the MN group and Sr addition in the MNSr and MNSr+ groups. TR test indicated greater osseointegration in the 45-day period for treated surfaces. Histological analysis highlighted the benefits of the treatments, especially in cortical bone, in which an increase in bone-implant contact was found in groups MN (15 days) and MNSr (45 days) compared to the control group. Gene expression analysis of osteogenic activity markers showed modulation of various osteogenesis-related genes. According to the in vitro model, RT-qPCR and ELISA demonstrated that the treatments favored gene expression and production of osteoblastic differentiation markers. Conclusions Micro-nano textured surface and Sr addition can effectively improve and accelerate implant osseointegration and is, therefore, an attractive approach to modifying titanium implant surfaces with significant potential in clinical practice.

Effect of pH on the chelation between strontium ions and decellularized small intestinal submucosal sponge scaffolds / 北京大学学报(医学版)

OBJECTIVE@#To investigate the preparation of decellularized small intestinal submucosa (dSIS) sponge scaffolds with chelated strontium (Sr) ions at different pH values, and to select the appropriate pH values for synthesizing Sr/dSIS scaffolds using the physicochemical properties and biocompatibility of the scaffolds as evaluation indexes.@*METHODS@#(1) Sr/dSIS scaffolds preparation and grouping: After mixing dSIS solution and strontium chloride solution in equal volumes, adjusting pH of the solution to 3, 5, 7, and 9 respectively, porous scaffolds were prepared by freeze-drying method after full reaction at 37℃, which were named Sr/dSIS-3, -5, -7, and -9 respectively, and the dSIS scaffolds were used as the control group. (2) Physicochemical property evaluation: The bulk morphology of the scaffolds was observed in each group, the microscopic morphology analyzed by scanning electron microscopy, and the porosity and pore size determined, the surface elements analyzed by energy spectroscopy, the structure of functional groups analyzed by infrared spectroscopy, the chelation rate determined by atomic spectrophotometry, the water absorption rate detected by using specific gravity method, and the compression strength evaluated by universal mechanical testing machine.(3) Biocompatibility evaluation: The cytotoxicity and proliferative effect to bone mesenchymal stem cells (BMSCs) of each group were evaluated by Calcein-AM/PI double staining method.@*RESULTS@#Scanning electron microscopy showed that the scaffolds of each group had an interconnected three-dimensional porous structure with no statistical difference in pore size and porosity. Energy spectrum analysis showed that strontium could be detected in Sr/dSIS-5, -7 and -9 groups, and strontium was uniformly distributed in the scaffolds. Functional group analysis further supported the formation of chelates in the Sr/dSIS-5, -7 and -9 groups. Chelation rate analysis showed that the Sr/dSIS-7 group had the highest strontium chelation rate, which was statistically different from the other groups (P < 0.05). The scaffolds in all the groups had good water absorption. The scaffolds in Sr/dSIS-5, -7 and -9 groups showed significantly improved mechanical properties compared with the control group (P < 0.05). The scaffolds in all the groups had good biocompatibility, and the Sr/dSIS-7 group showed the best proliferation of BMSCs.@*CONCLUSION@#When pH was 7, the Sr/dSIS scaffolds showed the highest strontium chelation rate and the best proliferation effect of BMSCs, which was the ideal pH value for the preparation of the Sr/dSIS scaffolds.

Research progress on surface modification of titanium implants by strontium ions / 口腔疾病防治

@#Traditional titanium implants do not completely meet the clinical requirements because they are bioinert. The surface of titanium implants, modified by strontium ions, can enhance osseointegration and reduce peri-implantitis. In this paper, the biological properties of titanium implant surfaces modified by strontium ions were reviewed. Strontium ions can be coated on the implant surface by hydrothermal treatment, electrochemical deposition, phosphate chemical conversion, flame-spraying, supramolecular self-assembly, magnetron sputtering, laser deposition and alkali etching. Implant surfaces modified by strontium ions can not only promote osteogenesis and early osseointegration but also inhibit bacterial growth and reduce postoperative infections. Even better osseointegration and antibacterial effects can be achieved when strontium ions are incorporated with other elements, such as silver, zinc, gallium, and calcium. However, most of the studies on the use of strontium ion-modified titanium implants are animal experiments and in vitro experiments, and the observation time is short compared with the actual service life of the implants. Thus, the conclusions obtained may be different from the actual clinical application, and the long-term effects need to be studied. In addition, the osteogenic effects of various modification methods also need to be compared. Future research can focus on the following points: ① to find efficient modification methods that can be widely used in the clinic; ②to study how to control the concentration of strontium ions near the implant to exert their biological function and reduce their toxic side effects; and ③ to conduct long-term follow-up clinical trials to observe their osteogenic and antibacterial effects.

Clinical value of CT-guided 125I seeds combining with 89SrCl 2 in relieving pain of patients with bone metastases from prostate cancer after failure of external irradiation / 中华核医学与分子影像杂志

Objective:To evaluate the clinical value of CT-guided 125I seeds implantation combining with 89SrCl 2 to relieve pain after failure of external irradiation in patients with bone metastases from prostate cancer. Methods:Clinical data of 48 patients (age 56-85 years) with bone metastases from prostate cancer admitted to General Hospital of the Northern Theater Command from January 2019 to June 2021 were retrospectively analyzed. Patients were treated with 125I seeds implantation combining with 89SrCl 2 (group A) and 89SrCl 2 alone (group B), respectively. Independent-sample t test and repeated measures analysis of variance were used to evaluate the differences of pain level (most severe pain, least pain, mean pain and current pain) scores and bone pain interference scores between 2 groups before and after treatment (before treatment, 3 d, 4 weeks, 8 weeks and 12 weeks after treatment). Prostate specific antigen (PSA), free PSA (fPSA) and alkaline phosphatase (ALP) 12 weeks after treatment of 2 groups were also compared by using independent-sample t test. Results:In group A, a total of 722 seeds were implanted in 39 bone metastases in 23 patients, and the implantation successful rate was 97.44%(38/39). There were 25 patients in group B. In group A, the most severe pain, mean pain and current pain scores decreased with time ( F values: 3.71-22.47, all P<0.05). Except for the scores at 3 d posttreatment, most severe pain, mean pain, and current pain scores at different times showed significant differences with those before treatment (all P<0.05). There were also differences in the most severe pain, mean pain, and current pain scores in group B before and after treatment ( F values: 2.45-2.52, P values: 0.044-0.049), with scores decreasing first (till 8 weeks after treatment) and increasing later. The most severe pain, mean pain, and current pain scores 8 week after treatment were lower than those before treatment (all P<0.05), but all the four scores at 12 weeks were not significantly different from those before treatment ( P values: 0.057-0.693). At 12 weeks after treatment, the differences in the most severe pain, mean pain and current pain scores between 2 groups were statistically significant ( t values: 2.04-3.41, P values: 0.001-0.047). Bone pain interference scores 12 weeks after treatment in group A were higher than those in group B ( t values: 2.04-3.16, P values: 0.022-0.047), and PSA, fPSA and ALP 12 weeks after treatment in group A were significantly lower than those in group B ( t values: 4.38-6.82, P values: 0.012-0.042). Conclusion:CT-guided 125I seeds implantation combined with 89SrCl 2 is feasible and effective for the treatment of bone pain after failed external irradiation in patients with prostate cancer bone metastases, especially for the combination of fulminant pain.

Enfoques terapéuticos de la osteoporosis / Therapeutic approaches to osteoporosis

La finalidad del tratamiento de la osteoporosis es la prevención primaria y secundaria de fracturas. Las indicaciones para las intervenciones terapéuticas en la osteoporosis deben derivarse de la determinación del riesgo absoluto de fractura, que tiene en cuenta la evaluación de los factores de riesgo y la densidad ósea. El propósito de este estudio es comentar algunos enfoques terapéuticos empleados en la osteoporosis, destacando el mecanismo de acción del ranelato de estroncio que aumenta la formación de hueso y disminuye la resorción. La causa más común de osteoporosis en las mujeres es la disminución de los niveles de estrógeno durante la menopausia, lo que lleva a un aumento significativo en el recambio de masa ósea y el consiguiente desequilibrio entre la formación y reabsorción ósea con un aumento de la pérdida ósea y el deterioro de la estructura y fuerza óseas. El ranelato de estroncio sigue siendo una opción farmacológica eficaz y viable en la prevención de las fracturas vertebrales y del cuello femoral en mujeres posmenopáusicas y hombres adultos con osteoporosis, en cuanto a indicaciones, contraindicaciones y una cuidadosa evaluación de sus efectos y riesgos. Representa una alternativa a los medicamentos antirresortivos en caso de contraindicación, intolerancia o fracaso(AU)

The purpose of the treatment of osteoporosis is the primary and secondary prevention of fractures. The indications for therapeutic interventions in osteoporosis should be derived from the determination of the absolute risk of fracture, which takes into account the evaluation of risk factors and bone density. To comment on some therapeutic approaches used in osteoporosis, highlighting the mechanism of action of strontium ranelate that increases bone formation and reduces resorption. The most common cause of osteoporosis in women is the decrease in estrogen levels during menopause, which leads to a significant increase in the turnover of bone mass and the consequent imbalance between bone formation and resorption with an increase in bone loss and deterioration of bone structure and strength. Strontium ranelate continues to be an effective and viable pharmacological option in the prevention of vertebral and femoral neck fractures in postmenopausal women and adult men with osteoporosis, in terms of indications, contraindications and a careful evaluation of its effects and risks. It represents an alternative to antiresorptive drugs in case of contraindication, intolerance or failure(AU)

Comparative evaluation of remineralisation potential of bioactive glass, casein phosphopeptide-amorphous calcium phosphate and novel strontium-doped nanohydroxyapatite paste: An In-Vitro study

Background: Many studies explained the importance of remineralisation of early carious lesions with various remineralising agents. In the present study, we incorporated the remineralising agents in a dentifrice, applied that in artificial enamel caries and evaluated their remineralising potential and compared the efficacy among the three. Aim: To evaluate and compare the remineralisation potential of a dentifrice containing bioactive glass, casein phosphopeptide?amorphous calcium phosphate and novel laboratory synthesised strontiumdoped nanohydroxyapatite paste in artificial enamel caries. Methods and Materials: 120 enamel specimens were divided into 4 groups of 30 specimens each, based on the type of dentifrice applied: GI ? conventional toothpaste (control group), GII ? calcium sodium phosphosilicate (Novamin), GIII ? casein phosphopeptide?amorphous calcium phosphate (GC tooth mousse) and GIV? Novel strontiumdoped nanohydroxyapatite paste (SrnHAp paste). Specimens in all the groups were subjected to demineralisation, and calcium/phosphorous ratio was analysed followed by remineralisation and the mean calcium–phosphorus ratio was assessed using a scanning electron microscope and energy dispersing X?ray analysis. Statistical Analysis: Data were analysed using IBM SPSS Statistics for Windows Software, version 22 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used to calculate the mean and standard deviation. Kruskal?Wallis, ANOVA and Mann–Whitney tests were used. The level of significance was set at 5%. Results and Conclusion: All except the control group showed a net increase in calcium and phosphorous values after application of the respective remineralising agents in respective groups. Inter?group comparison revealed that Group IV ? SrnHAp paste yields higher net calcium and phosphorous values than other groups. Hence, novel SrnHAp can be considered as the material of choice in remineralising early enamel carious lesions

Absence of medication-related jaw osteonecrosis after treatment with strontium ranelate in ovariectomized rats

Abstract This study aimed to evaluate the potential of strontium ranelate (SR) in medication-related jaw osteonecrosis (MRONJ) after tooth extraction in ovariectomized rats. Thirty ovariectomized rats were divided into three groups (n = 10): bisphophonate (BP) group (zoledronic acid; 0.4 mg/kg/week), SR group (625 mg/kg/day), and control group (saline solution). The lower first molars were extracted after 60 days of drug therapy. Drug administration was continued for another 30 days after tooth extraction. The mandibles were subjected to clinical, histological, radiographic, and microtomographic evaluations. Only the BP group showed clinical changes, characterized by the presence of 70% (n = 7) and 20% (n = 2) of ulcers and extraoral fistulas. Radiographic evaluation demonstrated bone sequestration only in the BP group (n = 7, 70%). Microtomographic analysis revealed increased bone porosity after ovariectomy, particularly in the the control group (p < 0.05). The BP group showed a higher bone surface density, bone volume, and trabecular number than SR and control groups, but with less trabecular separation (p < 0.05). All the animals in the BP group demonstrated histological osteonecrosis. There was no evidence of osteonecrosis in the control and SR groups, which was characterized by the absence of empty osteocyte gaps and associated with the gradual healing of the extraction area. Also, an increased number of blood vessels and a reduced number of osteoclasts were observed in the SR group (p < 0.05). Therefore, SR treatment increased angiogenesis and osteoclastogenesis in the healing socket and was not associated with MRONJ development after tooth extraction in ovariectomized rats.

Impacto clínico del estroncio y del zinc en los procesos de regeneración ósea y del cartílago, aproximación desde la biología hacia la clínica. Revisión de literatura / Clinical impact of strontium and zinc on bone and cartilage regeneration processes, an approach from biology to the clinic. Literature review

Muchos trastornos sistémicos como la artritis o la osteoporosis son patologías responsables de las alteraciones crónicas de la articulación temporomandibular, creando así un problema a largo plazo que afectan la calidad de vida de aquellas personas que las padecen. Actualmente no existe tratamiento curativo para dichas patologías, aunque sí de tipo paliativo, que en muchas ocasiones tienen efectos secundarios en el tiempo o una limitación en su efectividad y eficacia, por lo que se hace necesario buscar alternativas con la implementación de terapias regenerativas para el tratamiento de aquellas enfermedades que afectan el sistema musculoesquelético. En muchos estudios se discute sobre el papel fundamental que cumple el zinc y el estroncio en la génesis de tejido tanto cartilaginoso como óseo, así como la relevancia de incorporarlos con diversos biomateriales en procedimientos de regeneración, sin embargo, este tema no es claro aún y requieren más aten- ción por parte del clínico. El objetivo de este artículo es determinar la función cumplen el zinc y el estroncio en los procesos de regeneración del hueso y el cartílago desde una visión molecular y celular aplicada a la práctica clínica, con el fin de obtener nuevas alternativas en el tratamiento de diversas patologías y alteraciones musculoesqueléticas que mejoren las condiciones de salud oral de los pacientes, además de, contar con la revisión que nos aproxime a comprender los mecanismos de acción de diferentes moléculas que incorporadas a los biomateriales compatibles con el tejido duro y blando mejoren las condiciones biológicas para la regeneración.

Many systemic disorders such as arthritis or osteoporosis are pathologies responsible of temporomandibular joint chronic dysfunctions, thus creating a long-term problem that affects life ́s quality of those who suffer from them. Currently there is no curative treatment for these pathologies, although there is a palliative treatment, which in many cases have side effects over time or a limitation in their effectiveness and efficacy, so it is necessary to look for alternatives with the implementation of regenerative therapies for treatment of those diseases that affect musculoskeletal system. In many studies the fundamental role of zinc and strontium in genesis of both cartilaginous and bone tissue is discussed, as well as the relevance of incorporating them with various biomaterials in regeneration procedures, however, this issue is not clear yet and requires more attention from the clinician. The objective of this article is to determine function of zinc and strontium in regeneration processes of bone and cartilage from a molecular and cellular perspective applied to clinical practice, in order to obtain new alternatives in the treatment of various pathologies and musculoskeletal alterations that improve the oral health conditions of patients. In addition, this review brings us closer to understanding the mechanisms of action of different molecules that when incorporated into biomaterials compatible with hard and soft tissue improve the biological conditions for the regeneration.

Application of 90Sr application in the treatment of cutaneous hemangioma / 中华核医学与分子影像杂志

Cutaneous hemangioma is a kind of benign skin vascular tumor caused by congenital abnormal vascular development. The rays emitted by 90Sr has a good effect on it. Meanwhile, 90Sr application is easy to operate, effective, with less side effects and painless. It is a method worthy of promotion in the treatment of skin hemangioma. This article reviews the application of 90Sr application in cutaneous hemangioma treatment.

Therapeutic effect of 90Sr application on infantile hemangioma in hair area and its influence on hair volume / 中华核医学与分子影像杂志

Objective:To investigate the clinical effect of 90Sr application on superficial hemangioma in hair area and its effect on the volume of hair. Methods:A total of 136 pediatric patients (55 males, 81 females, 1-30 months old; 136 lesions) with head hemangioma in the First Affiliated Hospital of Guangxi Medical University between February 2018 and October 2019 were enrolled. They were divided into 3 groups according to the hair density of tumor sites. Group A ( n=63, 3(2, 6) months old, male/female=27/36): the hair in tumor sites was as thick as the surrounding hair. Group B ( n=40, 3(2, 5) months old, male/female=17/23): the hair in tumor sites was thinner than the surrounding area. Group C ( n=33, 3(2, 6) months old, male/female=11/22): there was no hair growth in the tumor sites. All groups were treated with 90Sr application, and the total absorbed dose of each course was 10-30 Gy, which was divided into 8 times. Three to four months after the treatment, the efficacy and adverse reactions were evaluated and the volume of hair was divided into 3 grades according to the hair density of the tumor sites: flourishing, good growth and no growth. If the clinical effect was unsatisfied, a second course of treatment was conducted. Kruskal-Wallis rank sum test or χ 2 test was used for data analysis. Results:The differences of age ( H=0.01), gender ( χ 2=0.92) among group A, group B and group C were not significant (both P>0.05). The total recovery rates of 3 groups after two-course treatment were 88.9%(56/63), 95.0%(38/40) and 93.9%(31/33) respectively ( χ 2=1.49, P>0.05). Besides, the incidences of adverse reactions were 6.3%(4/63), 7.5%(3/40) and 9.1%(3/33) respectively ( χ 2=0.24, P>0.05). Three to four months after treatment, the hair on tumor sites in group A and B was rated as flourishing, 28 children in group C were rated as flourishing, 5 children were rated as good growth, and none of the children showed no growth. Conclusions:The 90Sr application has a good treatment effect on the small superficial hemangioma in the hair area of infants, and the amount of hair in the affected area can be restored to normal after treatment. This treatment is worthy of clinical application.

Avaliação da morfologia hepática em ratos após administração do ranelato de estrôncio / Evaluation of hepatic morphology in rats after administration of strontium ranelate

Introdução: o fármaco ranelato de estrôncio (RE) é muito utilizado na terapêutica profilática e no controle da osteoporose. Age sistemicamente diminuindo a reabsorção e aumentando a formação óssea, apresentando eventos adversos pouco esclarecidos na literatura, à exemplo a síndrome DRESS com envolvimento hepático. Objetivo: avaliar a morfologia hepática em ratos norvegicus albinus após administração do RE. Metodologia: estudo experimental com 10 ratos, divididos aleatoriamente em dois grupos, Grupo Controle (GC), sem administração do RE, e Grupo Ranelato de Estrôncio (GRE), ambos acompanhados durante 15 dias, e, em seguida, sacrificados e o fígado de cada animal colocado para fixação no solução de formaldeído a 4% durante 48 horas. Após essa etapa, foram realizados os procedimentos necessários à análise pela microscopia óptica, com lâminas coradas pela hematoxilina e eosina, e picrosirius red.Resultados: nos GC e GRE foram encontradas alterações similares, como reação ductular, dilatação sinusoidal e fibrose perissinusoidal, com intensidades distintas entre os grupos, sendo a reação ductular mais proeminente no GC, e a dilatação sinusoidal e fibrose perissinusoidal mais pronunciada no GRE. Além disso, no GC foram evidenciados achados inflamatórios, como presença de infiltrado inflamatório misto e hiperplasia de células de Kupffer, não visualizados no GRE, implicando numa possível ação anti-inflamatória do RE. Conclusão: pode-se concluir que foram visualizadas diferenças nos achados morfológicos do parênquima hepático dos ratos tratados com o RE em comparação aos não tratados, ainda que esses achados não sejam suficientes para inferir a incidência de um processo patológico característico, como cirrose ou hepatite.

Introduction: the drug strontium ranelate (SR) is widely used in prophylactic therapy and in the control of osteoporosis. It acts by reducing reabsorption and increasing bone formation systemically, presenting unclear adverse events in the literature, such as the DRESS syndrome with hepatic involvement. Objective: to evaluate hepatic morphology in norvegicus albinus rats after SR administration. Methodology: experimental group with 10 rats, divided into two groups, randomly distributed, five from the Control Group (CG), without SR administration, and the other five from the Strontium Ranelate Group (SRG), both followed for 15 days, and then sacrificed and the liver of each animal placed for fixation in 4% formalin for 48 hours. After this step, the procedures necessary for the analysis by optical microscopy were performed, with blades stained by hematoxylin e eosin, and picrosirius red. Results: in CG and SRG, similar alterations were observed, such as ductular reaction, sinusoidal dilatation and perissinusoidal fibrosis, with distinct intensities between the groups, being the ductular reaction more prominent in the CG, and sinusoidal dilation and a perissinusoidal fibrosis more pronounced in the SRG. In addition, in the CG were evidenced inflammatory findings such as the presence of mixed inflammatory infiltrate and Kupffer cell hyperplasia, not visualized in the SRG, implying a possible anti-inflammatory action of SR. Conclusion: it can be concluded that differences were observed in the morphological findings of the hepatic parenchyma of rats treated with SR compared to untreated rats, although these findings are not sufficient to infer the incidence of a characteristic pathological process, such as cirrhosis or hepatitis.

Preliminary development and manufacturing of radioactive sewage purification device / 中国职业医学

OBJECTIVE: To develop a radioactive sewage purification device that can effectively filter the nuclides in low-level nuclide-contaminated wastewater. METHODS: The radioactive sewage purification device was composed of lifting pump, stack filter, multi-medium filter, security filter, tubular ultrafiltration membrane, high-pressure pump and reverse osmotic membrane. The combined process of adsorption-ultrafiltration-reverse osmosis was used to separate radioactive elements from wastewater by reverse osmosis membrane separation system. Through two-stage multi-medium filter circulation system circulation treatment, radioactive sewage was purified. The flow rate of water treatment is 20 L/min. The filtration efficiency and purification efficiency of the device were tested by filtration experiments on elements containing radionuclide and purification experiments on radionuclide.RESULTS: The filtration efficiency on iodine, potassium, strontium and cesium, that are the common elements in radioactive sewage samples were 97.88%, 98.38%, 99.99% and 99.80%, respectively. The single purification efficiency of radionuclide ~(40)K in low-level radioactive sewage was over 90.00%. CONCLUSION: The device has high filtering efficiency for common elements such as iodine, potassium, strontium and cesium in sewage and high removal rate of radioactive activity for sewage containing ~(40)K. It can be further optimized and transformed into a suitable radioactive sewage water purifier.

Research progress on trace elements-modified titanium implant surfaces / 口腔疾病防治

@#Traditional titanium implants are bioinert, and some biological properties, such as osteogenic and antibacterial properties, can be obtained by adding different trace elements to their surfaces. These trace elements can help enhance implant-bone binding and effectively prevent peri-implantitis. Different trace elements have different advantages, and different modification methods can also affect the biological properties. In this paper, the biological properties of titanium implant surfaces modified by trace elements were reviewed. The results of a literature review show that implant surfaces modified by fluoride, silver, zinc, manganese, etc. can inhibit the growth of bacteria and reduce the negative impact on normal cells from bacteria. Other elements, such as strontium, tantalum and cobalt, can promote the differentiation of osteoblasts on the surface of titanium implants, improve the activity of alkaline phosphatase, and improve the expression of osteogenic genes, thus increasing the amount of bone formation and enhancing the strength of implant-bone integration. Most elements have multiple properties, and the combined application of two or more elements can yield more biological properties than a single element. Since there are many trace elements in the human body, there is still a wide research space available in the field of the surface modification of dental implants by trace elements.

Calcium hydrogen phosphate dehydrate combined with gelatin and recombinant human bone morphologic protein 2/7 for repair of bone defects in rabbits / 中国组织工程研究

BACKGROUND: Studies have shown that the osteogenic ability of 10% strontium-doped calcium hydrogen phosphate dihydrate is higher than that of calcium hydrogen phosphate dihydrate and 5% strontium-doped calcium hydrogen phosphate dihydrate, but also found that the pore structure of 10% strontium-doped calcium hydrogenphosphate dihydrate is not ideal, and the early osteogenic effect is not satisfactory. OBJECTIVE: To investigate the osteogenic effect of the composite of 10% strontium-doped calcium hydrogenphosphate dehydrate and gelatin and recombinant human bone morphogenetic protein 2/7 (rhBMP2/7). METHODS: Gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate and gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate material containing 0.04 g/L and 1 g/L rhBMP2/7 were prepared respectively. Forty-five rabbit models of bilateral mandibular defects were prepared and then divided into five groups. In the blank control group, no material was implanted. 10% strontium-doped calcium hydrogen phosphate dihydrate (control group) and gelatin-10% strontium-doped calcium hydrogen phosphate dihydrate (gelatin group), 0.04 g/L rhBMP2/7-gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate (0.04 g/L rhBMP2/7 group), and 1 g/L rhBMP2/7-gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate (1 g/L rhBMP2/7 group) were implanted in the remaining four groups, respectively. Bone defect specimens were taken at 4, 8 and 12 weeks after surgery, and were examined by cone beam CT and immunohistochemistry. This study was approved by the Animal Ethics Committee of North China University of Science and Technology, China. RESULTS AND CONCLUSION: Cone beam CT examination revealed that at 8 weeks after surgery, bone repair was basically completed and the new bone tissue was almost fused with the surrounding tissue in the 1 g/L rhBMP2/7 group. Most of defect area was repaired, and the edge of new bone was unsmooth in the 0.04 g/L rhBMP2/7 and gelatin groups. Bone defect in the control group partially repaired. At 12 weeks after surgery, bone repair was completed in the gelatin, 0.04 rhBMP2/7 and 1 g/L rhBMP2/7 groups. Immunohistochemistry revealed that at 4 and 8 weeks after surgery, type I collagen expression in the 1 g/L rhBMP2/7 group was significantly higher than that in the other four groups (P 0.05). These results suggest that the addition of gelatin and 1 g/L rhBMP2/7 to 10% strontium-doped calcium hydrogenphosphate dihydrate can promote the repair of bone defects.