Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-...Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.展开更多
Objective:To investigate the effect of alendronate on bone mass and organ pathology of ovariectomized mice.Methods:Thirty SPF grade C57 female mice were randomly divided into three groups(n=10):Sham operation group(Sh...Objective:To investigate the effect of alendronate on bone mass and organ pathology of ovariectomized mice.Methods:Thirty SPF grade C57 female mice were randomly divided into three groups(n=10):Sham operation group(Sham),ovariectomized group(OVX)and ovariectomized+alendronate group(ALN).The sodium alendronate was injected subcutaneously at 400μg/kg twice a week in the ALN group.The equal volume of normal saline was injected subcutaneously twice a week in the SHAM group and OVX group.After 12 weeks of drug administration,the samples were taken.The organ coefficients,main organ pathological sections,and bone histopathological sections were observed,and the micro CT,L4 biomechanics and serum biochemical indicators were analyzed.Results:The uterine coefficient of Sham group was(0.0054±0.0007)significantly higher than that of OVX group(0.0026±0.0009)and ALN group(0.0025±0.0007),and the difference was statistically significant(P<0.05).No obvious lesions or toxic or side effects were observed in the main organs.Compared with the OVX group,the ALN group with decalcified sections of bone tissue had compact trabecular structure and fewer adipocytes.Micro-CT results showed that the Tb.BMD,Tb.N,Tb.Th and Tb.BV/TV values of the ALN group were significantly increased compared with those of the OVX group,but the Tb.Sp value was significantly decreased,and the difference was statistically significant(P<0.05).In L4 vertebral body biomechanics,the elastic modulus(50.29±13.43)and maximum load number(29.83±4.92)of ALN group were significantly higher than those of OVX group(14.77±3.12)and maximum load number(11.57±3.18),and the difference was statistically significant(P<0.05).Compared with the OVX group,the serum OCN and PINP indicators of bone formation in the ALN group were increased,while the bone resorption indicators TRACP-5b and CTX-I were decreased,with statistical significance(P<0.05).Conclusion:Alendronate sodium improves bone quality by increasing bone density,improving bone microstructure,increasing bone strength,promoting bone formation and inhibiting bone resorption,without obvious toxic and side effects on organs.展开更多
BACKGROUND Osteoporosis is a global disease affecting 6.6%of the total population.Osteoporosis complications include fractures,increased bone fragility,and reduced bone strength.The most commonly affected parts are th...BACKGROUND Osteoporosis is a global disease affecting 6.6%of the total population.Osteoporosis complications include fractures,increased bone fragility,and reduced bone strength.The most commonly affected parts are the vertebral body,hip,and wrist.AIM To examine the effect of alendronate sodium combined with InterTan for osteoporotic femoral intertrochanteric fractures on bone and fracture recurrence METHODS In total,126 cases of osteoporotic femoral intertrochanteric fractures were selected and divided into two groups according to the 1:1 principle by the simple random method.They were admitted to the Department of Orthopedics,First Affiliated Hospital of Xingtai Medical College,from January 2018 to September 2020.The control group was treated with InterTan fixation combined with placebo,and the observation group with alendronate sodium based on InterTan fixation.Operation-related indicators,complications,and recurrent fractures were compared between the groups.Changes in bone metabolism markers,t value for hip bone mineral density,and Harris Hip Score were observed.RESULTS Operation time,intraoperative blood loss,postoperative ambulation time,and complications were compared between the groups,and no significant difference was found.The fracture healing time was significantly shorter in the observation group than in the control group.β-Collagen-specific sequence(β-CTX)and total aminoterminal propeptide of type I procollagen(T-PINP)in the control group at 3 mo after operation were compared with those before operation,and the difference was not significant.Six months after the operation,theβ-CTX level decreased and T-PINP level increased.β-CTX level at 3 and 6 mo in the observation group after operation was lower,and TPINP level was higher,than that before operation.Compared with the control group,T-PINP level of the observation group was significantly higher andβ-CTX level was significantly lower at 3 and 6 mo after operation.The t value of hip bone mineral density was compared in the control group before and 1 mo after operation,and significant difference was not found.Compared with the control group,the t value of hip bone mineral density in the observation group was significantly higher at 1,3,6,and 12 mo after operation.Compared with the control group,the Harris score of the observation group was significantly higher at 1,3,6,and 12 mo after operation.The recurrence rate of fractures in the observation group within 12 mo was 0.00%,which was significantly lower than 6.35%in the control group.CONCLUSION Alendronate sodium combined with InterTan in the treatment of osteoporotic femoral intertrochanteric fractures can increase bone mineral density,improve hip joint function,promote fracture healing,and reduce fracture recurrence.展开更多
As a mono-sodium salt form of alendronic acid,alendronate sodium presents multi-level ionization for the dissociation of its four hydroxyl groups.The dissociation constants of alendronate sodium were determined in thi...As a mono-sodium salt form of alendronic acid,alendronate sodium presents multi-level ionization for the dissociation of its four hydroxyl groups.The dissociation constants of alendronate sodium were determined in this work by studying the piecewise linear relationship between volume of titrant and p H value based on acidbase potentiometric titration reaction.The distribution curves of alendronate sodium were drawn according to the determined p Ka values.There were 4 dissociation constants(pKa_1=2.43,pKa_2=7.55,pKa_3=10.80,pKa_4=11.99,respectively) of alendronate sodium,and 12 existing forms,of which 4 could be ignored,existing in different p H environments.展开更多
Objective To evaluate the effect of alendronate on osteoprotegerin(OPG)and receptor of activator of nuclear factor κB-ligand(RANKL)expression in human marrow stroma cells(hMSCs)in vitro.Methods hMSCs were isolated fr...Objective To evaluate the effect of alendronate on osteoprotegerin(OPG)and receptor of activator of nuclear factor κB-ligand(RANKL)expression in human marrow stroma cells(hMSCs)in vitro.Methods hMSCs were isolated from human marrow,cultured in vitro,and randomly divided into two groups:alendronate group,hMSCs culture fluid containing 1×10-7mol/L alendronate;control group,no special treatment but culturing hMSCs in DMEM.Two weeks after treatment,the expressions of OPG and RANKL were evaluated by RT-PCR and Western blot.Results hMSCs became uniform spindle-shaped fibroblasts.As cells proliferated,they formed colonies and showed whirlpool arrangement.After one week's treatment,hMSCs in alendronate group had reduced processes and gradually showed disc shape,which did not happen in control group but kept fibroblast shape and just increased in density.In RT-PCR,the ratio of OPG/RANKL in alendronate group and control group was 8.77±1.16 and 4.58±1.27,respectively.In Western blot,the ratio of OPG/RANKL in alendronate group and control group was 2.58±0.47 and 1.52±0.32,respectively.The ratio of OPG/RANKL was higher in alendronate group than in control group(P<0.01).Conclusion Alendronate enhances OPG expression and inhibits RANKL expression of hMSCs in vitro.展开更多
Bisphosphonates are among the most frequently used antiresorptive drugs for the management of postmenopausal osteoporosis. We review here two of the commonly used bisphosphonates zoledronate and alendronate.
BACKGROUND The epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone.Despite the abovementioned atractive reasons for alendronate’s use,few data on the effect of alendronate ...BACKGROUND The epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone.Despite the abovementioned atractive reasons for alendronate’s use,few data on the effect of alendronate during epiphyseal growth exist.AIM Verify the effect of alendronate on the growth epiphyseal plate,and compare its effect with the size of the femur during the double-staining of the immunolocalization of transforming growth factor-β1(TGF-β1)and bone morphogenetic protein-2(BMP2)in endochondral ossifing in specimens that have received alendronate.METHODS Forty newborn rats were randomly divided into two groups:a control group(were given applications of 1 mg/kg physiologic saline)and a group that received Alendronate(a dose of 2.5 mg/kg).These groups were then divided into two subgroups for euthanasia in two and 12 d of life.After euthanasia,the femurs were removed,and the femoral bones were measured linearly between the apex of the greater trochanter until the lower intercondylar midlle face to verify the probable bone growth between 3 and 12 d in control and alednroanto treated rats.Posteriorly,the surgical pieces were also sent to the histopathology laboratory to produce histological slides.The obtained slides were stained with hematoxylin and eosin to measure each of the cartilage zones in endochondral development.and other slides were immunohistochemically tested for anti-TGF-β1 and BMP-2 antibodies to investigate the immunolocalization of these proteins in the epiphyseal plaque area.RESULTS On the third day,some diferences between the control group and specimens treated with alendronate were verified.Macroscopiccaly,we found similarities in size between the femoral bones when we compared the control group with the specimens that received alendronate.On the 12^th day,the bone size of the mice receiving the drug was significantly smaller than those of the control group.These results coincide with changes in the TGF-β1 and BMP-2 expression.In the specimens that received alendronate,the TGF-β1 was expressed in some sites of trabecular bone that was neoformed,peripherally to the bone marrow area.The BMP-2 was also positive in proliferative chondrocytes and hypertrofic chondrocytes.On the 12^th day,all layers of chondrocytes exhibited positivity for BMP-2 in the specimens that received alendronate.In the interface between the trabecular bone and cartilage,an area of disorganized bone deposition was evident.Neoformed bone also appeared to be different at 12 d.In the control group,BMP-2 was positive in an intense area of bone trabeculae,whereas the alendronate-treated group showed TGF-β1 positive trabeculae and a greater bone area.CONCLUSION Alendronate alters the immunolocalization of TGF-β1 and BMP-2 simultaneously,a condition that changes the usual histological aspects of the cartilage zone and impairs epiphysis growth and femur growth.展开更多
AIM To evaluate the effects of sodium alendronate on bone repair in fractures created in appendicular bones. METHODS Wistar rats(n = 36) were allocated into three distinct groups: group C(control), group B1(received 1...AIM To evaluate the effects of sodium alendronate on bone repair in fractures created in appendicular bones. METHODS Wistar rats(n = 36) were allocated into three distinct groups: group C(control), group B1(received 1 mg/kg of alendronate), and group B2(received 3 mg/kg of alendronate). The rats underwent femoral transversal linear fracture surgery using stable internal fixation with a 2.0 mm plate and screw system. Each animal randomly received intraperitoneal applications of sodium alendronate at a dose corresponding to group B1 or B2 three times a week, while the control group received a 0.9% saline solution. Drug administration was performed until euthanasia at 45 d. The femurs were removed and each surgical piece was sent for radiographic, tomographic and microtomographic analysis. Data were submitted to descriptive and inferential statistical analysis(95% confidence interval).RESULTS Quantitative evaluations of bone neoformation did not show differences among the groups in the radiographic(P = 0.341), microtomographic(P = 0.581) and tomographic evaluations(P = 0.171). In the qualitative microtomographic analysis, a smaller distance was observed between the internal bone trabeculae in the groups that used alendronate(P = 0.05). On the other hand, group B2 had a higher amount of bone trabeculae per unit length when compared to the other groups(P = 0.04).CONCLUSION It is likely that the use of alendronate did not have a direct influence on the amount of bone neoformation, however it did influence the bone quality in a dosedependent manner, ultimately affecting the distance and quantity of the trabeculae.展开更多
Intrinsic osteoinductivity—the ability to induce bone formation in ectopic sites without addition of osteogenic factors has been reported in various porous materials. Tartrate-resistant acid phosphatase (TRAP)-positi...Intrinsic osteoinductivity—the ability to induce bone formation in ectopic sites without addition of osteogenic factors has been reported in various porous materials. Tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells are thought to play an important role in material-induced osteoinduction. To investigate the influence of osteoclastic activity on intrinsic osteoinduction, we loaded alendronate (10–2 , 10–4 , and 10–6 M) onto porous β-tricalcium phosphate (β-TCP) blocks to inhibit osteoclastic activity, and evaluated osteoinductivity by implantation of the blocks into the dorsal muscles of adult beagle dogs. Alendronate-loaded porous β-TCP blocks increased both speed and amount of osteoinduction, as measured 4 weeks after implantation, with the 10–4 M alendronate-loaded β-TCP being especially active. This finding indicates that β-TCP loaded with 10–4 M alendronate might prove crucial in providing the desirable balance between the degradation rate of bone scaffolds and their osteoinductive replacement. Thus, material-induced osteoinduction may be controlled by local application of alendronate, establishing alendronate loading as a promising therapeutic approach.展开更多
Background: Adipocyte and osteoblast derive from the same mesenchimal progenitor. Age-related decrease in bone mass is accompanied by an increase in marrow adipose tissue. Vitamin D3 (VD3) inhibits adipogenesis in 3T3...Background: Adipocyte and osteoblast derive from the same mesenchimal progenitor. Age-related decrease in bone mass is accompanied by an increase in marrow adipose tissue. Vitamin D3 (VD3) inhibits adipogenesis in 3T3-L1 preadipocytes. Recently it has been demonstrated that alendronate (ALN) inhibits adipogenesis while promoting osteoblast differentiation of mesenchimal stem cells. Aim of the Study: To evaluate the role of ALN on adipocyte differentiation in vitro and the potential synergic role of VD3 co-treatment. Procedures: Murine 3T3-L1 and 3T3-F442A preadipocytes were routinely differentiated in presence of ALN and VD3 10-9 - 10-7 M for 7 days and then stained with Oil Red O. The effect of these treatments on mRNA expression of the main molecular markers of adipocyte differentiation (PPARγ and C/EBPα) and VD Receptor (VDR) were analyzed through RT-PCR. Results: Both ALN and VD3 showed a marked anti-adipogenic effect on 3T3-L1 cells. Co-incubation of ALN 10-8 M and VD3 10-9 M displayed no synergic effect on inhibition of adipogenesis. PPARγ mRNA expression was significantly reduced by ALN and VD3. mRNA expression of C/EBPα was reduced only by VD3 treatment. An increase in VDR mRNA expression of 3T3-L1 cells was observed with both ALN and VD3. On the contrary, 3T3-F442A cells, which are in a more advanced adipogenic differentiation stage compared to 3T3-L1, did not express detectable levels of VDR. Interestingly, adipose differentiation of 3T3-F442A was not affected by ALN nor VD3. These results suggest that VDR may represent the molecular target of the anti-adipogenic effect of ALN. Conclusion: VDR plays a critical role in mediating the anti-adipogenic effect of ALN. Further studies to clarify this mechanism are warranted.展开更多
Osteoporosis is commonly seen in aged people, but not much attention is paid to it. Patient compliance is challenged by many factors, including long-time treatment and high rates of fatality and disability caused by f...Osteoporosis is commonly seen in aged people, but not much attention is paid to it. Patient compliance is challenged by many factors, including long-time treatment and high rates of fatality and disability caused by fragility fractures. With age-related changes, the treatment will last for a lifetime. A clinical case of postmenopausal patient who had received incontinuous treatment of alendronate for 20 years was studied in this article. As the level of compliance varied in different treatment phases, the curative outcome of this patient was altered. This study also presented a literature review to discuss the current situation, treatment and compliance of osteoporosis in China and the corresponding influences on bone mineral density (BMD) and prognosis. Hopefully, this study can increase physicians’ awareness of osteoporosis in clinical treatment and its pharmacotherapy and treatment course.展开更多
Growing rates of osteoporosis in the whole world is a serious health problem. As the “expected lifetime” is prolonged, population of elderly women with chronic diseases who require long-term treatment increases. Thi...Growing rates of osteoporosis in the whole world is a serious health problem. As the “expected lifetime” is prolonged, population of elderly women with chronic diseases who require long-term treatment increases. This study aimed to compare antiresorptive treatment—that has become a classic treatment in the light of Canadian Guideline for osteoporosis—with the antiresorptive plus osteoblastic activity inducing treatment modality. The clinical and laboratory results of patients treated with a single dose of 2 mg Strontium ranelate sachet (Protelos ®) or alendronate sodium used weekly 70 mg tablet (Fosamax ® once a week tablet) for 12-months were compared. Treatment compliance has been questioned. A hundred women in post-menopausal period were included in this study. Patient satisfaction survey among the group of strontium ranelate was unsatisfactory. Among patients using alendronate sodium the ease of use in this sense obtained a rate of 91% satisfaction from patients.展开更多
Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the ...Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine(PORCN) that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159(ETC-159) had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably,simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family,mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN inhibitors.Mitigation of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.展开更多
Objective. To evaluate the effects of alendronate on the structural properties of trabecular bone.Methods. Alendronate was administered at a daily p.o. Dose of 0. 5 mg/kg over a 12-week period in hound dogs (n = 8 for...Objective. To evaluate the effects of alendronate on the structural properties of trabecular bone.Methods. Alendronate was administered at a daily p.o. Dose of 0. 5 mg/kg over a 12-week period in hound dogs (n = 8 for both the control and treated group), and the structural indices of the lumbar vertebral (L1 and L2) trabecular bone were assessed directly from 3-D images.Results. Treatment with alendronate increased bone volume fraction by 9. 5% and 7.7% in L1 and L2 respectively. Trabecular thickness significantly increased after alendronate treatment, whereas trabecular separation remained constant. The degree of anisotropy for the alendronate- treated group was decreased compared with that of the control group. Bone surface to volume ratio declined significantly in the alendronate-reated group, whereas alendrenate induced a higher bone surface density.Conclusion. Alendronate increased the structural properties of canine trabecular bone after short-term treatment at a dose of 0. 5 mg @ kg-1@day-1.展开更多
Unexpected benefits to the catalytic performance of materials often originate from the presence of surface defects.Here,novel Dpenicillamine modified molybdenum oxide nanodots,with abundant oxygen vacancy defects,were...Unexpected benefits to the catalytic performance of materials often originate from the presence of surface defects.Here,novel Dpenicillamine modified molybdenum oxide nanodots,with abundant oxygen vacancy defects,were fabrication by a mild,simple,and cost-effective method.Ultraviolet–visible(UV–Vis)absorption spectra analysis showed that the nanodots had peroxidaselike and catalase-like activities.The reactive oxygen species were probed by electronic paramagnetic resonance technique and spectroscopic methods,demonstrating that the nanodots also had oxidase-like activity.Interestingly,the peroxidase-like activity of nanodots was synergistically enhanced in the presence of ferrous ions or ferric ions.Remarkably,less than nanomolar levels of ferrous ions were required to display this phenomenon,meaning Fenton reagent acted as leverage.Based on this,a sensitive colorimetric and fluorescent dual-mode sensor for alendronate sodium was developed.The linear ranges for colorimetric and fluorescence analysis were 0.2–2.5 and 0.2–2.0μM,with detection limits of 31.21 and 71.84 nM,correspondingly.The method has a simple large-scale material preparation process with higher sensitivity and shorter reaction time,which can inspire and enlighten the design of nanozyme sensors.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81673996,81904220)the Jiangmen Association for Science and Technology-Youth science and technology talent lifting project(Grant No.2022-2023).
文摘Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.
基金General program of National Natural Science Foundation of China(81770879)Gansu Youth Science and Technology Fund Program(20JR5RA589)Joint Service Support Force 940 Hospital Laboratory Cultivation Project(2021yxky081)。
文摘Objective:To investigate the effect of alendronate on bone mass and organ pathology of ovariectomized mice.Methods:Thirty SPF grade C57 female mice were randomly divided into three groups(n=10):Sham operation group(Sham),ovariectomized group(OVX)and ovariectomized+alendronate group(ALN).The sodium alendronate was injected subcutaneously at 400μg/kg twice a week in the ALN group.The equal volume of normal saline was injected subcutaneously twice a week in the SHAM group and OVX group.After 12 weeks of drug administration,the samples were taken.The organ coefficients,main organ pathological sections,and bone histopathological sections were observed,and the micro CT,L4 biomechanics and serum biochemical indicators were analyzed.Results:The uterine coefficient of Sham group was(0.0054±0.0007)significantly higher than that of OVX group(0.0026±0.0009)and ALN group(0.0025±0.0007),and the difference was statistically significant(P<0.05).No obvious lesions or toxic or side effects were observed in the main organs.Compared with the OVX group,the ALN group with decalcified sections of bone tissue had compact trabecular structure and fewer adipocytes.Micro-CT results showed that the Tb.BMD,Tb.N,Tb.Th and Tb.BV/TV values of the ALN group were significantly increased compared with those of the OVX group,but the Tb.Sp value was significantly decreased,and the difference was statistically significant(P<0.05).In L4 vertebral body biomechanics,the elastic modulus(50.29±13.43)and maximum load number(29.83±4.92)of ALN group were significantly higher than those of OVX group(14.77±3.12)and maximum load number(11.57±3.18),and the difference was statistically significant(P<0.05).Compared with the OVX group,the serum OCN and PINP indicators of bone formation in the ALN group were increased,while the bone resorption indicators TRACP-5b and CTX-I were decreased,with statistical significance(P<0.05).Conclusion:Alendronate sodium improves bone quality by increasing bone density,improving bone microstructure,increasing bone strength,promoting bone formation and inhibiting bone resorption,without obvious toxic and side effects on organs.
基金Supported by Special Projects for Social Development Areas.
文摘BACKGROUND Osteoporosis is a global disease affecting 6.6%of the total population.Osteoporosis complications include fractures,increased bone fragility,and reduced bone strength.The most commonly affected parts are the vertebral body,hip,and wrist.AIM To examine the effect of alendronate sodium combined with InterTan for osteoporotic femoral intertrochanteric fractures on bone and fracture recurrence METHODS In total,126 cases of osteoporotic femoral intertrochanteric fractures were selected and divided into two groups according to the 1:1 principle by the simple random method.They were admitted to the Department of Orthopedics,First Affiliated Hospital of Xingtai Medical College,from January 2018 to September 2020.The control group was treated with InterTan fixation combined with placebo,and the observation group with alendronate sodium based on InterTan fixation.Operation-related indicators,complications,and recurrent fractures were compared between the groups.Changes in bone metabolism markers,t value for hip bone mineral density,and Harris Hip Score were observed.RESULTS Operation time,intraoperative blood loss,postoperative ambulation time,and complications were compared between the groups,and no significant difference was found.The fracture healing time was significantly shorter in the observation group than in the control group.β-Collagen-specific sequence(β-CTX)and total aminoterminal propeptide of type I procollagen(T-PINP)in the control group at 3 mo after operation were compared with those before operation,and the difference was not significant.Six months after the operation,theβ-CTX level decreased and T-PINP level increased.β-CTX level at 3 and 6 mo in the observation group after operation was lower,and TPINP level was higher,than that before operation.Compared with the control group,T-PINP level of the observation group was significantly higher andβ-CTX level was significantly lower at 3 and 6 mo after operation.The t value of hip bone mineral density was compared in the control group before and 1 mo after operation,and significant difference was not found.Compared with the control group,the t value of hip bone mineral density in the observation group was significantly higher at 1,3,6,and 12 mo after operation.Compared with the control group,the Harris score of the observation group was significantly higher at 1,3,6,and 12 mo after operation.The recurrence rate of fractures in the observation group within 12 mo was 0.00%,which was significantly lower than 6.35%in the control group.CONCLUSION Alendronate sodium combined with InterTan in the treatment of osteoporotic femoral intertrochanteric fractures can increase bone mineral density,improve hip joint function,promote fracture healing,and reduce fracture recurrence.
基金the support of Key Laboratory of Chinese Medicine Preparation of Solid Dispersion,Gansu Longshenrongfa Pharmaceutical Industry Co.,Ltd.,Gansu Province,China
文摘As a mono-sodium salt form of alendronic acid,alendronate sodium presents multi-level ionization for the dissociation of its four hydroxyl groups.The dissociation constants of alendronate sodium were determined in this work by studying the piecewise linear relationship between volume of titrant and p H value based on acidbase potentiometric titration reaction.The distribution curves of alendronate sodium were drawn according to the determined p Ka values.There were 4 dissociation constants(pKa_1=2.43,pKa_2=7.55,pKa_3=10.80,pKa_4=11.99,respectively) of alendronate sodium,and 12 existing forms,of which 4 could be ignored,existing in different p H environments.
基金supported by the National Natural Science Foundation of China(No.30600624)
文摘Objective To evaluate the effect of alendronate on osteoprotegerin(OPG)and receptor of activator of nuclear factor κB-ligand(RANKL)expression in human marrow stroma cells(hMSCs)in vitro.Methods hMSCs were isolated from human marrow,cultured in vitro,and randomly divided into two groups:alendronate group,hMSCs culture fluid containing 1×10-7mol/L alendronate;control group,no special treatment but culturing hMSCs in DMEM.Two weeks after treatment,the expressions of OPG and RANKL were evaluated by RT-PCR and Western blot.Results hMSCs became uniform spindle-shaped fibroblasts.As cells proliferated,they formed colonies and showed whirlpool arrangement.After one week's treatment,hMSCs in alendronate group had reduced processes and gradually showed disc shape,which did not happen in control group but kept fibroblast shape and just increased in density.In RT-PCR,the ratio of OPG/RANKL in alendronate group and control group was 8.77±1.16 and 4.58±1.27,respectively.In Western blot,the ratio of OPG/RANKL in alendronate group and control group was 2.58±0.47 and 1.52±0.32,respectively.The ratio of OPG/RANKL was higher in alendronate group than in control group(P<0.01).Conclusion Alendronate enhances OPG expression and inhibits RANKL expression of hMSCs in vitro.
文摘Bisphosphonates are among the most frequently used antiresorptive drugs for the management of postmenopausal osteoporosis. We review here two of the commonly used bisphosphonates zoledronate and alendronate.
文摘BACKGROUND The epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone.Despite the abovementioned atractive reasons for alendronate’s use,few data on the effect of alendronate during epiphyseal growth exist.AIM Verify the effect of alendronate on the growth epiphyseal plate,and compare its effect with the size of the femur during the double-staining of the immunolocalization of transforming growth factor-β1(TGF-β1)and bone morphogenetic protein-2(BMP2)in endochondral ossifing in specimens that have received alendronate.METHODS Forty newborn rats were randomly divided into two groups:a control group(were given applications of 1 mg/kg physiologic saline)and a group that received Alendronate(a dose of 2.5 mg/kg).These groups were then divided into two subgroups for euthanasia in two and 12 d of life.After euthanasia,the femurs were removed,and the femoral bones were measured linearly between the apex of the greater trochanter until the lower intercondylar midlle face to verify the probable bone growth between 3 and 12 d in control and alednroanto treated rats.Posteriorly,the surgical pieces were also sent to the histopathology laboratory to produce histological slides.The obtained slides were stained with hematoxylin and eosin to measure each of the cartilage zones in endochondral development.and other slides were immunohistochemically tested for anti-TGF-β1 and BMP-2 antibodies to investigate the immunolocalization of these proteins in the epiphyseal plaque area.RESULTS On the third day,some diferences between the control group and specimens treated with alendronate were verified.Macroscopiccaly,we found similarities in size between the femoral bones when we compared the control group with the specimens that received alendronate.On the 12^th day,the bone size of the mice receiving the drug was significantly smaller than those of the control group.These results coincide with changes in the TGF-β1 and BMP-2 expression.In the specimens that received alendronate,the TGF-β1 was expressed in some sites of trabecular bone that was neoformed,peripherally to the bone marrow area.The BMP-2 was also positive in proliferative chondrocytes and hypertrofic chondrocytes.On the 12^th day,all layers of chondrocytes exhibited positivity for BMP-2 in the specimens that received alendronate.In the interface between the trabecular bone and cartilage,an area of disorganized bone deposition was evident.Neoformed bone also appeared to be different at 12 d.In the control group,BMP-2 was positive in an intense area of bone trabeculae,whereas the alendronate-treated group showed TGF-β1 positive trabeculae and a greater bone area.CONCLUSION Alendronate alters the immunolocalization of TGF-β1 and BMP-2 simultaneously,a condition that changes the usual histological aspects of the cartilage zone and impairs epiphysis growth and femur growth.
文摘AIM To evaluate the effects of sodium alendronate on bone repair in fractures created in appendicular bones. METHODS Wistar rats(n = 36) were allocated into three distinct groups: group C(control), group B1(received 1 mg/kg of alendronate), and group B2(received 3 mg/kg of alendronate). The rats underwent femoral transversal linear fracture surgery using stable internal fixation with a 2.0 mm plate and screw system. Each animal randomly received intraperitoneal applications of sodium alendronate at a dose corresponding to group B1 or B2 three times a week, while the control group received a 0.9% saline solution. Drug administration was performed until euthanasia at 45 d. The femurs were removed and each surgical piece was sent for radiographic, tomographic and microtomographic analysis. Data were submitted to descriptive and inferential statistical analysis(95% confidence interval).RESULTS Quantitative evaluations of bone neoformation did not show differences among the groups in the radiographic(P = 0.341), microtomographic(P = 0.581) and tomographic evaluations(P = 0.171). In the qualitative microtomographic analysis, a smaller distance was observed between the internal bone trabeculae in the groups that used alendronate(P = 0.05). On the other hand, group B2 had a higher amount of bone trabeculae per unit length when compared to the other groups(P = 0.04).CONCLUSION It is likely that the use of alendronate did not have a direct influence on the amount of bone neoformation, however it did influence the bone quality in a dosedependent manner, ultimately affecting the distance and quantity of the trabeculae.
文摘Intrinsic osteoinductivity—the ability to induce bone formation in ectopic sites without addition of osteogenic factors has been reported in various porous materials. Tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells are thought to play an important role in material-induced osteoinduction. To investigate the influence of osteoclastic activity on intrinsic osteoinduction, we loaded alendronate (10–2 , 10–4 , and 10–6 M) onto porous β-tricalcium phosphate (β-TCP) blocks to inhibit osteoclastic activity, and evaluated osteoinductivity by implantation of the blocks into the dorsal muscles of adult beagle dogs. Alendronate-loaded porous β-TCP blocks increased both speed and amount of osteoinduction, as measured 4 weeks after implantation, with the 10–4 M alendronate-loaded β-TCP being especially active. This finding indicates that β-TCP loaded with 10–4 M alendronate might prove crucial in providing the desirable balance between the degradation rate of bone scaffolds and their osteoinductive replacement. Thus, material-induced osteoinduction may be controlled by local application of alendronate, establishing alendronate loading as a promising therapeutic approach.
文摘Background: Adipocyte and osteoblast derive from the same mesenchimal progenitor. Age-related decrease in bone mass is accompanied by an increase in marrow adipose tissue. Vitamin D3 (VD3) inhibits adipogenesis in 3T3-L1 preadipocytes. Recently it has been demonstrated that alendronate (ALN) inhibits adipogenesis while promoting osteoblast differentiation of mesenchimal stem cells. Aim of the Study: To evaluate the role of ALN on adipocyte differentiation in vitro and the potential synergic role of VD3 co-treatment. Procedures: Murine 3T3-L1 and 3T3-F442A preadipocytes were routinely differentiated in presence of ALN and VD3 10-9 - 10-7 M for 7 days and then stained with Oil Red O. The effect of these treatments on mRNA expression of the main molecular markers of adipocyte differentiation (PPARγ and C/EBPα) and VD Receptor (VDR) were analyzed through RT-PCR. Results: Both ALN and VD3 showed a marked anti-adipogenic effect on 3T3-L1 cells. Co-incubation of ALN 10-8 M and VD3 10-9 M displayed no synergic effect on inhibition of adipogenesis. PPARγ mRNA expression was significantly reduced by ALN and VD3. mRNA expression of C/EBPα was reduced only by VD3 treatment. An increase in VDR mRNA expression of 3T3-L1 cells was observed with both ALN and VD3. On the contrary, 3T3-F442A cells, which are in a more advanced adipogenic differentiation stage compared to 3T3-L1, did not express detectable levels of VDR. Interestingly, adipose differentiation of 3T3-F442A was not affected by ALN nor VD3. These results suggest that VDR may represent the molecular target of the anti-adipogenic effect of ALN. Conclusion: VDR plays a critical role in mediating the anti-adipogenic effect of ALN. Further studies to clarify this mechanism are warranted.
文摘Osteoporosis is commonly seen in aged people, but not much attention is paid to it. Patient compliance is challenged by many factors, including long-time treatment and high rates of fatality and disability caused by fragility fractures. With age-related changes, the treatment will last for a lifetime. A clinical case of postmenopausal patient who had received incontinuous treatment of alendronate for 20 years was studied in this article. As the level of compliance varied in different treatment phases, the curative outcome of this patient was altered. This study also presented a literature review to discuss the current situation, treatment and compliance of osteoporosis in China and the corresponding influences on bone mineral density (BMD) and prognosis. Hopefully, this study can increase physicians’ awareness of osteoporosis in clinical treatment and its pharmacotherapy and treatment course.
文摘Growing rates of osteoporosis in the whole world is a serious health problem. As the “expected lifetime” is prolonged, population of elderly women with chronic diseases who require long-term treatment increases. This study aimed to compare antiresorptive treatment—that has become a classic treatment in the light of Canadian Guideline for osteoporosis—with the antiresorptive plus osteoblastic activity inducing treatment modality. The clinical and laboratory results of patients treated with a single dose of 2 mg Strontium ranelate sachet (Protelos ®) or alendronate sodium used weekly 70 mg tablet (Fosamax ® once a week tablet) for 12-months were compared. Treatment compliance has been questioned. A hundred women in post-menopausal period were included in this study. Patient satisfaction survey among the group of strontium ranelate was unsatisfactory. Among patients using alendronate sodium the ease of use in this sense obtained a rate of 91% satisfaction from patients.
基金supported by an NIH grant to BOW (R01AR053293)the Van Andel Research Institutesupported in part by the National Research Foundation Singapore
文摘Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine(PORCN) that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159(ETC-159) had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably,simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family,mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN inhibitors.Mitigation of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.
文摘Objective. To evaluate the effects of alendronate on the structural properties of trabecular bone.Methods. Alendronate was administered at a daily p.o. Dose of 0. 5 mg/kg over a 12-week period in hound dogs (n = 8 for both the control and treated group), and the structural indices of the lumbar vertebral (L1 and L2) trabecular bone were assessed directly from 3-D images.Results. Treatment with alendronate increased bone volume fraction by 9. 5% and 7.7% in L1 and L2 respectively. Trabecular thickness significantly increased after alendronate treatment, whereas trabecular separation remained constant. The degree of anisotropy for the alendronate- treated group was decreased compared with that of the control group. Bone surface to volume ratio declined significantly in the alendronate-reated group, whereas alendrenate induced a higher bone surface density.Conclusion. Alendronate increased the structural properties of canine trabecular bone after short-term treatment at a dose of 0. 5 mg @ kg-1@day-1.
基金National Natural Science Foundation of China(No.21603276)Fundamental Research Funds for the Central Universities(Nos.19CX02060A and 22CX03024A)the Natural Science Foundation of Shandong Province(No.ZR2022MB148).
文摘Unexpected benefits to the catalytic performance of materials often originate from the presence of surface defects.Here,novel Dpenicillamine modified molybdenum oxide nanodots,with abundant oxygen vacancy defects,were fabrication by a mild,simple,and cost-effective method.Ultraviolet–visible(UV–Vis)absorption spectra analysis showed that the nanodots had peroxidaselike and catalase-like activities.The reactive oxygen species were probed by electronic paramagnetic resonance technique and spectroscopic methods,demonstrating that the nanodots also had oxidase-like activity.Interestingly,the peroxidase-like activity of nanodots was synergistically enhanced in the presence of ferrous ions or ferric ions.Remarkably,less than nanomolar levels of ferrous ions were required to display this phenomenon,meaning Fenton reagent acted as leverage.Based on this,a sensitive colorimetric and fluorescent dual-mode sensor for alendronate sodium was developed.The linear ranges for colorimetric and fluorescence analysis were 0.2–2.5 and 0.2–2.0μM,with detection limits of 31.21 and 71.84 nM,correspondingly.The method has a simple large-scale material preparation process with higher sensitivity and shorter reaction time,which can inspire and enlighten the design of nanozyme sensors.
