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International Journal of Oral and... Jul 2017There is controversy regarding whether locally delivered alendronate enhances osseointegration. The aim of this systematic review was to assess the role of local... (Meta-Analysis)
Meta-Analysis Review
There is controversy regarding whether locally delivered alendronate enhances osseointegration. The aim of this systematic review was to assess the role of local alendronate delivery (topical, or as a coating on implant surfaces) in the osseointegration of implants. The focused question was, "Does the local delivery of alendronate affect osseointegration around implants?". To address this question, indexed databases were searched, without time or language restriction, up to and including January 2017. Various combinations of the following key words were used: "alendronate", "bisphosphonates", "osseointegration", and "topical administration". letters to the editor, historic reviews, commentaries, case series, and case reports were excluded. In total, 18 experimental studies were included: alendronate-coated implants were used in 13 of these studies and local delivery in five studies. The results of 11 of the studies showed that alendronate coating increased new bone formation, the bone volume fraction, or bone-to-implant contact (BIC) and biomechanical properties. Results from two studies in which alendronate was administered topically indicated impaired BIC and/or biomechanical fixation around implants. On experimental grounds, local alendronate delivery seems to promote osseointegration. From a clinical perspective, the results in animal models support phase 1 studies in healthy humans (without co-morbidities other than edentulism).
Topics: Administration, Topical; Alendronate; Dental Implantation, Endosseous; Dental Implants; Diphosphonates; Humans; Osseointegration
PubMed: 28366449
DOI: 10.1016/j.ijom.2017.03.009 -
Human & Experimental Toxicology Jul 2021Osteoarthritis (OA) is a disease with significant degenerative changes of articular cartilage, which is reported to be closely related to the integrity of chondrocytes...
BACKGROUND AND PURPOSE
Osteoarthritis (OA) is a disease with significant degenerative changes of articular cartilage, which is reported to be closely related to the integrity of chondrocytes extracellular matrix (ECM). Alendronate belongs to the family of bisphosphonates with promising cartilage repair function. In the present study, the effects of Alendronate on the gene expression of chondrocytes ECM and the potential mechanism will be investigated to explore the potential therapeutic property of Alendronate on OA.
METHODS
Human SW1353 chondrocytes were stimulated with 1 and 2 μM Alendronate for 12 h. The gene expression of , and in the treated chondrocytes was determined by qRT-PCR. QRT-PCR and western blot analysis were used to evaluate the expression level of SOX-9 in the treated chondrocytes. The expression level of SP-1 was checked by qRT-PCR and immunostaining. SiRNA against SP-1 was transfected into chondrocytes to knockdown the expression of SP-1. The levels of p-ERK1/2 and total ERK1/2 were examined using western blot analysis. TNF-α was used to induce an OA-like model in the chondrocytes for therapeutic evaluations.
RESULTS
Treatment with Alendronate increased the levels of ECM related genes (, and ) in a dose-dependent manner through increasing the expression of SOX-9, a central regulator of ECM genes. Additionally, our findings demonstrate that the effects of Alendronate in the expression of SOX-9 are mediated by SP-1 as silencing of SP-1 abolished these effects. Notably, Alendronate increased the phosphorylation of ERK1/2 and inhibition of ERK1/2 using its specific inhibitor U0126 blocked the expression of SP-1. Finally, we found that treatment with Alendronate could rescue TNF-α-induced reduction of , and SOX-9.
CONCLUSION
Our data indicated that Alendronate might promote the gene expression of extracellular matrix through SOX-9 mediated by the ERK1/2/SP1 signaling pathway.
Topics: Alendronate; Bone Density Conservation Agents; Cells, Cultured; Chondrocytes; Extracellular Matrix; Gene Expression; Humans; Osteoarthritis
PubMed: 33522294
DOI: 10.1177/0960327120988875 -
Journal of Basic and Clinical... Jun 2021Alendronate are widely used in the treatment of bone disorders characterized by inhibit osteoclast-mediated bone resorption such as Paget's disease, fibrous dysplasia,...
OBJECTIVES
Alendronate are widely used in the treatment of bone disorders characterized by inhibit osteoclast-mediated bone resorption such as Paget's disease, fibrous dysplasia, myeloma, bone metastases and osteoporosis. In recent studies alendronate improves proliferation and differentiation of osteoblasts, thereby facilitating for bone regeneration. The disadvantages of this class are their poor bioavailability and side effects on oral and intravenous application such as stomach irritation and osteonecrosis in jaw. Thus, local treatment of alendronate is needed in order to achieve high concentration of drug. Bovine hydroxyapatite-gelatin scaffold with alendronate was studied. Glutaraldehyde was used as cross-linking agent, increase the characteristics of this scaffold. The objectives of this study were to manufacture and characterize alendronate scaffold using bovine hydroxyapatite-gelatin and crosslinked by glutaraldehyde.
METHODS
Preparation of cross-linked bovine hydroxyapatite-gelatin and alendronate scaffold with different concentration of glutaraldehyde (0.00, 0.50, 0.75, and 1.00%). The scaffolds were characterized for compressive strength, porosity, density, swelling ratio, degradation, and cytotoxicity (the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, shorted as MTT assay).
RESULTS
Bovine hydroxyapatite-gelatin-alendronate scaffold cross-linked with glutaraldehyde showed lower density than without glutaraldehyde. As glutaraldehyde concentration increased, porosity also increased. Eventually, it reduced compressive strength. Swelling ratio and degradation was negatively dependent on glutaraldehyde concentration. In addition, the scaffold has a good safety by MTT assay.
CONCLUSIONS
Bovine hydroxyapatite-gelatin-alendronate scaffold was fabricated with various concentrations of glutaraldehyde. The presence of glutaraldehyde on bovine hydroxyapatite-gelatin-alendronate is safe and suitable candidate scaffold for bone regeneration.
Topics: Alendronate; Animals; Bone Regeneration; Cattle; Durapatite; Gelatin; Glutaral; Tissue Scaffolds
PubMed: 34214349
DOI: 10.1515/jbcpp-2020-0422 -
Journal of Clinical Densitometry : the... 2022Osteoporosis is a chronic disease with an increasing prevalence. Anti-sclerostin antibodies are being investigated for the treatment of osteoporosis. The aim of this... (Meta-Analysis)
Meta-Analysis Review
Osteoporosis is a chronic disease with an increasing prevalence. Anti-sclerostin antibodies are being investigated for the treatment of osteoporosis. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of antis-sclerostin antibodies compared to placebo and conventional therapies (alendronate and teriparatide) in the treatment of osteoporosis. Randomized controlled trials were searched from PubMed, EMBASE and Cochrane Central Register of Controlled Trails (CENTRAL) from their inception up to June 2021 by using Medical Subject Headings terms "anti-sclerostin antibody", "romosozumab", "blosozumab", "AMG 785″, "LY2541546", and "osteoporosis". Two investigators independently screened eligible studies, assessed the risk of bias and extracted the data from each study. The I index was used to assess heterogeneity. Meta-analysis was conducted using the Review Manager Software (RevMan, Version 5.4). The GRADE approach was used to rate the quality of evidence for all the pooled outcomes. 8 RCTs with 12,416 patients met the inclusion criteria. Anti-sclerostin antibodies significantly increased lumbar spine, total hip and femoral neck bone mineral density compared to placebo, alendronate and teriparatide at both 6 and 12 mo. Adverse events were comparable between anti-sclerostin antibodies and other treatments, except for the incidence of injection-site reactions that was higher in the anti-sclerostin antibody groups. Anti-sclerostin antibodies represent a valid theurapeutic option in the treatment of osteoporosis. Further studies with longer duration and follow-up are needed to confirm the results of this meta-analysis.
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Teriparatide
PubMed: 34920938
DOI: 10.1016/j.jocd.2021.11.005 -
Transplantation Proceedings Apr 2022In this study, we aimed to investigate the effect of long-term administration of alendronate to treat bone loss in renal transplant patients.
PURPOSE
In this study, we aimed to investigate the effect of long-term administration of alendronate to treat bone loss in renal transplant patients.
METHODS
Eighty-two renal transplant recipients were divided into 3 groups. Group 1 included patients who were treated with calcium, vitamin D3, and alendronate; group 2 included patients who were treated with calcium and vitamin D3; and group 3 included patients who did not receive these medications. All patients' sociodemographic data, biochemical parameters, and bone mineral density (BMD) measurements were recorded.
RESULTS
There were no significant differences between sociodemographic and laboratory findings at the beginning of study in all groups. The BMD of lumbar spine and femoral neck was significantly less in group 1 at the beginning, 12 and 24 months of the study when compared with other group. At 12 and 24 months of the study, the BMD levels were decreased both group 2 and group 3, whereas in group 1, it was stable at 12 months and increased thereafter. In group 1, the initial femoral neck BMD was negatively correlated with parathormone, sex, and body mass index, and positively correlated with creatinine level. While there was a positive correlation between basal body mass index and femur neck BMD in group 2, there was no correlation between baseline parameters, demographic data, and bone mineral density in group 3 patients.
CONCLUSIONS
In conclusion, bone loss is inevitable despite calcium and vitamin D replacement. However, bone loss can be stopped and even reversed with alendronate therapy.
Topics: Alendronate; Bone Density; Bone Diseases, Metabolic; Calcium; Cholecalciferol; Humans; Kidney Transplantation; Minerals
PubMed: 35272880
DOI: 10.1016/j.transproceed.2022.01.016 -
Circulation Jun 2021Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic differentiation of valvular interstitial cells are important contributory mechanisms. We aimed to establish whether inhibition of these pathways with denosumab or alendronic acid could reduce disease progression in aortic stenosis.
METHODS
In a single-center, parallel group, double-blind randomized controlled trial, patients >50 years of age with calcific aortic stenosis (peak aortic jet velocity >2.5 m/s) were randomized 2:1:2:1 to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly), or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and F-sodium fluoride positron emission tomography and computed tomography. The primary end point was the calculated 24-month change in aortic valve calcium score.
RESULTS
A total of 150 patients (mean age, 72±8 years; 21% women) with calcific aortic stenosis (peak aortic jet velocity, 3.36 m/s [2.93-3.82 m/s]; aortic valve calcium score, 1152 AU [655-2065 AU]) were randomized and received the allocated trial intervention: denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25; pooled for analysis). Serum C-terminal telopeptide, a measure of bone turnover, halved from baseline to 6 months with denosumab (0.23 [0.18-0.33 µg/L] to 0.11 µg/L [0.08-0.17 µg/L]) and alendronic acid (0.20 [0.14-0.28 µg/L] to 0.09 µg/L [0.08-0.13 µg/L]) but was unchanged with placebo (0.23 [0.17-0.30 µg/L] to 0.26 µg/L [0.16-0.31 µg/L]). There were no differences in 24-month change in aortic valve calcium score between denosumab and placebo (343 [198-804 AU] versus 354 AU [76-675 AU]; P=0.41) or alendronic acid and placebo (326 [138-813 AU] versus 354 AU [76-675 AU]; =0.49). Similarly, there were no differences in change in peak aortic jet velocity or F-sodium fluoride aortic valve uptake.
CONCLUSIONS
Neither denosumab nor alendronic acid affected progression of aortic valve calcification in patients with calcific aortic stenosis. Alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with this potentially fatal condition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.
Topics: Aged; Aged, 80 and over; Alendronate; Aortic Valve Stenosis; Bone Density Conservation Agents; Denosumab; Disease Progression; Double-Blind Method; Female; Humans; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Treatment Outcome; Vascular Calcification
PubMed: 33913339
DOI: 10.1161/CIRCULATIONAHA.121.053708 -
Pharmacoepidemiology and Drug Safety Jun 2023Osteoporotic vertebral compression fracture (OVCF) is a common fragile fracture resulting from osteoporosis. We compared the efficacy and safety of romosozumab and... (Meta-Analysis)
Meta-Analysis
Evaluation of the efficacy and safety of romosozumab (evenity) for the treatment of osteoporotic vertebral compression fracture in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials (CDM-J).
PURPOSE
Osteoporotic vertebral compression fracture (OVCF) is a common fragile fracture resulting from osteoporosis. We compared the efficacy and safety of romosozumab and commonly used osteoporosis drug treatments for the treatment of OVCF in postmenopausal women.
METHODS
Through searching and screening five databases, we included randomized controlled trials (RCTs) published through June 18, 2021 comparing different treatments. Following the Preferred Reporting Items for Systematic Reviews statement, the main objective was to evaluate the mean difference and risk ratio of the treatment effect. The primary measures of romosozumab efficacy used in this study were vertebral, non-vertebral, and clinical fracture events, and secondary outcomes were bone mineral density (BMD) changes at the lumbar spine, total hip, and femoral neck and the incidence of adverse events (AEs), RESULTS: Nine RCTs including 12 796 participants were included in the analysis, and romosozumab was compared with placebo, alendronate, and teriparatide in the treatment of osteoporosis in postmenopausal women. The incidence of fractures, low BMD, and AEs was analyzed. Compared with the controls, three doses of romosozumab were linked to evident advantages in the treatment of low BMD and fractures but associated with increased hypersensitivity and injection site reaction risks. Furthermore, fewer AEs were observed in the romosozumab arms (210 mg: risk ratio = 0.96, 95% confidence interval = 0.93-0.99; 140 mg: risk ratio = 0.28, 95% confidence interval = 0.08-0.98) than in the alendronate and placebo arms.
CONCLUSIONS
Our meta-analysis revealed the evident advantages of romosozumab in the treatment of osteoporosis and low BMD in postmenopausal women and increased risks of hypersensitivity and injection site reactions.
Topics: Female; Humans; Bone Density Conservation Agents; Alendronate; Osteoporosis, Postmenopausal; Fractures, Compression; Postmenopause; Randomized Controlled Trials as Topic; Osteoporosis; Bone Density
PubMed: 36703260
DOI: 10.1002/pds.5594 -
Acta Odontologica Scandinavica Oct 2016Due to accumulation in the bone matrix and a half-life of at least 10 years, it is important to understand the cellular impact of bisphosphonates (BPs). This study...
OBJECTIVE
Due to accumulation in the bone matrix and a half-life of at least 10 years, it is important to understand the cellular impact of bisphosphonates (BPs). This study assessed the effects of alendronate (ALN) on human primary osteoblasts.
MATERIAL AND METHODS
Osteoblasts were incubated with ALN (5, 20 and 100 μM), and both cells and cell culture media were harvested after d 1, 3, 7 or 14. Proliferation was evaluated by H-thymidine incorporation and tetrazolium dye (MTT) colorimetric assay, and viability by the lactate dehydrogenase (LDH) activity in the medium. Differentiation was evaluated using protein Luminex multiplex assays and RT-PCR.
RESULTS
ALN had no significant effects on cell viability. The lower concentrations enhanced the proliferation, whereas 100 μM diminished the proliferation. mRNA expression of osteocalcin (OC), alkaline phosphatase (ALP) and α-1 type 1 collagen were reduced, whereas ALN enhanced the expression of leptin mRNA and the secretion of interleukin-8 (IL-8) and regulated on activation normal T cell expressed and secreted (RANTES).
CONCLUSIONS
ALN enhanced the secretion of immune factors from human osteoblasts. Combined with a lower rate of proliferation and a decline in differentiation, this indicates that higher dosages or accumulation may cause undesirable local changes in bone.
Topics: Alendronate; Alkaline Phosphatase; Bone Density Conservation Agents; Bone and Bones; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cell Survival; Cells, Cultured; Chemokine CCL5; Collagen Type I; Collagen Type I, alpha 1 Chain; Humans; Interleukin-8; L-Lactate Dehydrogenase; Leptin; Osteoblasts; Osteocalcin
PubMed: 27546224
DOI: 10.1080/00016357.2016.1217041 -
Acta Odontologica Scandinavica Nov 2022Bisphosphonates like alendronate mainly exert their effects on osteoclasts. However, osteoblasts are also affected, but exposed to a much lower concentration than the...
OBJECTIVE
Bisphosphonates like alendronate mainly exert their effects on osteoclasts. However, osteoblasts are also affected, but exposed to a much lower concentration than the osteoclasts. Given that the effects are dose-dependent, the intention of the study was to identify a therapeutically relevant concentration of alendronate for studies on osteoblasts.
MATERIALS AND METHODS
Primary human osteoblasts were incubated with alendronate (5, 20 and 100 µM) for 1, 3, 7 and 14 days. Proliferation and viability were assessed, and the effects on cellular growth and function were evaluated by multianalyte profiling of selected proteins in cell culture media using the Luminex 200.
RESULTS
The viability was not affected by any of the dosages. Exposure to 5 µM alendronate had a neutral effect on osteoblast proliferation, and on secretion of osteogenic and inflammatory markers, while enhancing synthesis of a marker of angiogenesis. 20 µM alendronate induced a decline in proliferation and affected angiogenic and osteogenic biomarkers adversely. 100 µM alendronate reduced proliferation dramatically, and this dosage was excluded from further experiments.
CONCLUSION
A concentration of 5 µM alendronate exerted effects on human osteoblasts that may translate to those observed and could therefore be relevant for studies.
Topics: Humans; Alendronate; Osteoblasts; Diphosphonates; Osteoclasts; Osteogenesis; Cells, Cultured
PubMed: 35605138
DOI: 10.1080/00016357.2022.2072522 -
BioMed Research International 2019Periodontal bone regeneration relies on coupled and cooperative bone formation and resorption. Accordingly a novel strategy on concurrent use of platelet-rich fibrin... (Meta-Analysis)
Meta-Analysis Review
Periodontal bone regeneration relies on coupled and cooperative bone formation and resorption. Accordingly a novel strategy on concurrent use of platelet-rich fibrin (PRF) (anabolic agent) and 1% alendronate (ALN) (anticatabolic agent) was proposed recently in regenerative periodontal treatment. It was supposed to enhance bone formation and reduce bone resorption simultaneously. However, there is a lack of evidence-based studies to answer whether this concurrent application was superior to single application until now. Besides, concerns on ALN lead to some reservation on this synergistic way. ALN may impair new bone formation and necrotize jaws. Thus, in order to compare the clinical efficacy between PRF plus 1%ALN and PRF alone on periodontal bone regeneration, we performed present systematic review and meta-analysis. Because it is the prerequisite for measuring the combined efficacy of PRF plus 1%ALN, firstly we evaluated the effectiveness of 1%ALN. Our data indicated that adjunctive 1%ALN was effective in promoting periodontal bone repair. Further, PRF plus 1%ALN showed a greater capacity for periodontal regeneration than PRF alone with statistical significance. The findings of this study revealed the promising prospects on synergistic application of bone anabolic agents (PRF) and antiresorption medications (1%ALN) in regenerative periodontal treatment.
Topics: Alendronate; Bone Regeneration; Fibrin; Guided Tissue Regeneration, Periodontal; Humans; Osteogenesis; Platelet-Rich Fibrin
PubMed: 31531371
DOI: 10.1155/2019/9148183