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International Journal of Molecular... May 2024Aminobisphosphonates (NBPs) are the first-choice medication for osteoporosis (OP); NBP treatment aims at increasing bone mineral density (BMD) by inhibiting the activity...
Aminobisphosphonates (NBPs) are the first-choice medication for osteoporosis (OP); NBP treatment aims at increasing bone mineral density (BMD) by inhibiting the activity of farnesyl diphosphate synthase (FDPS) enzyme in osteoclasts. Despite its efficacy, inadequate response to the drug and side effects have been reported. The A allele of the rs2297480 (A > C) SNP, found in the regulatory region of the gene, is associated with reduced gene transcription. This study evaluates the variant rs2297480 (A > C) association with OP patients' response to alendronate sodium treatment. A total of 304 OP patients and 112 controls were enrolled; patients treated with alendronate sodium for two years were classified, according to BMD variations at specific regions (lumbar spine (L1-L4), femoral neck (FN) and total hip (TH), as responders (OP-R) ( = 20) and non-responders (OP-NR) ( = 40). We observed an association of CC genotype with treatment failure ( = 0.045), followed by a BMD decrease in the regions L1-L4 (CC = -2.21% ± 2.56; = 0.026) and TH (CC = -2.06% ± 1.84; = 0.015) after two years of alendronate sodium treatment. Relative expression of the gene was also evaluated in OP-R and OP-NR patients. Higher expression of the gene was also observed in OP-NR group (FC = 1.84 ± 0.77; = 0.006) when compared to OP-R. In conclusion, the influence observed of expression and the rs2897480 variant on alendronate treatment highlights the importance of a genetic approach to improve the efficacy of treatment for primary osteoporosis.
Topics: Humans; Alendronate; Bone Density; Female; Geranyltranstransferase; Male; Osteoporosis; Aged; Treatment Failure; Middle Aged; Polymorphism, Single Nucleotide; Bone Density Conservation Agents; Genotype; Alleles; Case-Control Studies
PubMed: 38891810
DOI: 10.3390/ijms25115623 -
BMC Oral Health Jan 2022This systematic review and meta-analysis aimed to investigate the role of alendronate combined with step 2 of periodontal therapy in reducing probing pocket depth,... (Meta-Analysis)
Meta-Analysis
Added effect of 1% topical alendronate in intra-bony and inter-radicular defects as part of step II periodontal therapy: a systematic review with meta-analysis and trial sequential analysis.
BACKGROUND
This systematic review and meta-analysis aimed to investigate the role of alendronate combined with step 2 of periodontal therapy in reducing probing pocket depth, improving clinical attachment level, and reducing bone defect depth in intra-bony and inter-radicular defects.
METHODS
RCTs with more than 6 months follow-up were included in this study. Risk of bias assessment was performed using the Cochrane collaboration tool. In addition, meta-analysis and trial sequential analysis were used to aggregate the available evidence.
RESULTS
Seven studies met the inclusion criteria and were included in the systematic review. Topical application of alendronate during second step of periodontal therapy significantly improved PD and CAL.
CONCLUSION
Local application of alendronate may confer a beneficial effect when applied during step II of periodontal therapy even if long term studies are needed to confirm these results.
CLINICAL RELEVANCE
Considering the emerging role of host-inflammatory response in treatment of periodontitis and the antiresorptive and osteostimulative properties of bisphosphonates, several studies are focusing on the role of alendronate as an addition to non-surgical periodontal therapy.
Topics: Alendronate; Alveolar Bone Loss; Diphosphonates; Humans; Periodontal Attachment Loss; Periodontitis
PubMed: 35062940
DOI: 10.1186/s12903-022-02044-1 -
Acta Biochimica Polonica Jun 2020The aim of the current research work was to develop sonophoresis-assisted transdermal patches for the treatment of osteoporosis. In the present investigation, we...
The aim of the current research work was to develop sonophoresis-assisted transdermal patches for the treatment of osteoporosis. In the present investigation, we formulated alendronate-chitosan nanoparticles by ionotropic external gelation method. The prepared nanoparticles were found to be smooth and free-flowing. The optimized formulation showed 82.7% of drug release over a period of 12 hours with 99.54% EE, the particle size of 250 nm, PDI 0.22 and zeta potential of 28 mV. The solvent casting evaporation method was used for the development of the patches using HPMC as rate-controlling polymer and dibutyl phthalate as the plasticizer. The optimized patch formulation was found acceptable in terms of physical characteristics (appearance, thickness, folding endurance, weight variation, moisture loss and uptake). The drug content was found to be 99.66±0.9 % with 69.44% of drug permeation through the rat skin. The TP3 formulation had drug content of 99.96% which was the highest among all of the formulations and showed relatively controlled skin permeation of 69.44% over the period of 12 hours. Nearly six-time enhancement of bioavailability was observed when alendronate was used in the nanoparticulate form in transdermal patches used with sonophoresis. Over the period of seven days, the plasma calcium concentration in the rat model was decreased from 16 mg/dl to 4 mg/dl (4 times) in rat groups treated with the transdermal patches containing CS-ALN-NP while the concentration dropped only to 12 mg/dl in case of the transdermal patches containing pure Alendronate. These findings (enhanced skin permeation, enhanced bioavailability and suppression of the plasma calcium level) regarding the transdermal delivery system suggest a promising approach for the treatment of osteoporosis.
Topics: Administration, Cutaneous; Alendronate; Animals; Biological Availability; Bone Density Conservation Agents; Calcium; Chitosan; Disease Models, Animal; Drug Delivery Systems; Drug Liberation; Male; Nanoparticles; Osteoporosis; Particle Size; Permeability; Rats; Rats, Sprague-Dawley; Skin; Transdermal Patch; Treatment Outcome; Ultrasonic Waves
PubMed: 32558528
DOI: 10.18388/abp.2020_5162 -
Medicina Oral, Patologia Oral Y Cirugia... Mar 2014Bisphosphonates is a group of inorganic pyrophosphates analogues that suppress bone resorption by inducing osteoclast inactivation, being frequently used for management... (Review)
Review
Bisphosphonates is a group of inorganic pyrophosphates analogues that suppress bone resorption by inducing osteoclast inactivation, being frequently used for management of diseases affecting bone metabolism, bone metastases and bone tumors. However, since 2003 many cases describing the presence of necrotic bone exposures in the jaws have been described in patients receiving these drugs, what represent a significant complication of bisphosphonates treatment. The overall incidence of bisphosphonate-related osteonecrosis of the jaws is low, ranging from 0.7% to 12%, mainly observed in those patients receiving intravenously treatment. Osteonecrosis of the jaws associated to oral bisphosphonate, particularly alendronate, has also been reported by a number of authors. Considering that alendronate is one of the most used drug worldwide, specially for treatment of osteoporosis, a better understanding of osteonecrosis of the jaws related to its use and how to manage these patients is extremely important. Therefore, in the current manuscript the authors aim to review the most important topics related to this pathological presentation.
Topics: Alendronate; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Humans
PubMed: 23986020
DOI: 10.4317/medoral.19094 -
Calcified Tissue International Nov 2023Buffered and effervescent alendronate (ALN-EFF) increases gastric pH and is reported to decrease the risk of gastrointestinal side effects compared to conventional... (Randomized Controlled Trial)
Randomized Controlled Trial
Buffered and effervescent alendronate (ALN-EFF) increases gastric pH and is reported to decrease the risk of gastrointestinal side effects compared to conventional formulations of alendronate (ALN). The clinical effectiveness of ALN-EFF, however, has not been investigated. This study aims to investigate if ALN-EFF is non-inferior to ALN in suppressing bone turnover markers (BTM). We conducted a 16-week prospective, randomized, open-label study comprising 64 postmenopausal women with BMD T-score < -1 naïve to osteoporosis treatment. Participants were randomized 1:1 to ALN or ALN-EFF. We collected blood samples at 0, 4, 8, and 16 weeks. Non-inferiority margin was determined as 12% (80% of efficacy retained), and an SD of 15% on change in CTx. CTx decreased by 58.2% ± 24.1% in the ALN group and by 46.9% ± 23.3% (CI - 38.42:- 55.35) in the ALN-EFF group (p = 0.08). The non-inferiority limit was 46.6%. With ALN-EFF the CI crosses the non-inferiority limit thus the test for non-inferiority was indeterminate. PINP decreased by 45.7 ± 22.6% in the ALN group and by 35.1 ± 20.7% in the ALN-EFF group (p = 0.07). Changes over time in the BTMs were not significantly different between the groups, p > 0.10 for both CTx and PINP. There was no difference in frequency of AEs or compliance between the two groups, but rate of discontinuation was lower with ALN-EFF. In conclusion, suppression of BTMs was not significantly different between the groups but formal non-inferiority could not be established.
Topics: Female; Humans; Alendronate; Osteoporosis, Postmenopausal; Prospective Studies; Bone Density; Bone Remodeling; Bone Density Conservation Agents
PubMed: 37803182
DOI: 10.1007/s00223-023-01140-w -
Medicine Mar 2017Low bone mineral density (BMD) is a frequent complication of inflammatory bowel disease (IBD), particularly in patients with Crohn disease (CD). The aim of our study is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Low bone mineral density (BMD) is a frequent complication of inflammatory bowel disease (IBD), particularly in patients with Crohn disease (CD). The aim of our study is to determine the efficacy and safety of different drugs used to treat low BMD in patients with CD.
METHODS
PUBMED/MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched for eligible studies. A random-effects model within a Bayesian framework was applied to compare treatment effects as standardized mean difference (SMD) with their corresponding 95% credible interval (CrI), while odds ratio (OR) was applied to compare adverse events with 95% CrI. The surface under the cumulative ranking area (SUCRA) was calculated to make the ranking of the treatments for outcomes.
RESULTS
Twelve randomized controlled trials (RCTs) were eligible. Compared with placebo, zoledronate (SMDs 2.74, 95% CrI 1.36-4.11) and sodium-fluoride (SMDs 1.23, 95% CrI 0.19-2.26) revealed statistical significance in increasing lumbar spine BMD (LSBMD). According to SUCRA ranking, zoledronate (SUCRA = 2.5%) might have the highest probability to be the best treatment for increasing LSBMD in CD patients among all agents, followed by sodium-fluoride (27%). For safety assessment, the incidence of adverse events (AEs) demonstrated no statistical difference between agents and placebo. The corresponding SUCRA values indicated that risedronate (SUCRA = 77%) might be the most safe medicine for low BMD in CD patients and alendronate ranked the worst (SUCRA = 16%).
CONCLUSIONS
Zoledronate might have the highest probability to be the best therapeutic strategy for increasing LSBMD. For the safety assessment, risedronate showed the greatest trend to decrease the risk of AEs. In the future, more RCTs with higher qualities are needed to make head-to-head comparison between 2 or more treatments.
Topics: Alendronate; Bayes Theorem; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Crohn Disease; Diphosphonates; Humans; Imidazoles; Network Meta-Analysis; Risedronic Acid; Sodium Fluoride; Zoledronic Acid
PubMed: 28296781
DOI: 10.1097/MD.0000000000006378 -
American Journal of Veterinary Research Jan 2015To evaluate whether a low-dosage regimen of prednisolone induces bone loss and whether administration of alendronate sodium prevents glucocorticoid-induced osteopenia in...
Quantitative computed tomographic assessment of bone mineral density changes associated with administration of prednisolone or prednisolone and alendronate sodium in dogs.
OBJECTIVE
To evaluate whether a low-dosage regimen of prednisolone induces bone loss and whether administration of alendronate sodium prevents glucocorticoid-induced osteopenia in dogs by measuring trabecular bone mineral density (BMD) with quantitative CT.
ANIMALS
8 healthy Beagles.
PROCEDURES
In 4 dogs, prednisolone was administered PO at a dosage of 2 mg/kg once daily for 2 weeks, 1 mg/kg once daily for 4 weeks, and 0.5 mg/kg once daily for 3 weeks. In the other 4 dogs, alendronate sodium (2 mg/kg, PO, q 24 h) was whether administered for 9 weeks in addition to the same dosage of prednisolone used in the prednisolone-treated dogs. Before (day 0 [baseline]) and 21, 42, 63, and 150 days after the start of treatment, BMD of the lumbar vertebrae was measured by quantitative CT.
RESULTS
BMD in the prednisolone treatment group decreased to 84.7% of the baseline value on day 42, increased to 87.9% on day 63, and recovered to 91.6% on day 150. In the prednisolone-alendronate treatment group, BMD decreased to 91% of the baseline value on day 21, increased to 93.8% on day 63, and then recovered to 96.7% on day 150. Bone mineral density in the prednisolone treatment group was generally lower, albeit not significantly, than that of the prednisolone-alendronate treatment group on each examination day.
CONCLUSIONS AND CLINICAL RELEVANCE
BMD temporarily decreased after low-dosage prednisolone administration; however, it gradually improved during tapering of the prednisolone dosage. These results have suggested that a low dosage of prednisolone can be used with little concern for development of osteopenia in dogs.
Topics: Administration, Oral; Alendronate; Animals; Bone Density; Bone Density Conservation Agents; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Drug Administration Schedule; Glucocorticoids; Lumbar Vertebrae; Male; Osteoporosis; Prednisolone; Tomography, X-Ray Computed
PubMed: 25535658
DOI: 10.2460/ajvr.76.1.28 -
The AAPS Journal Dec 2008Liposomes containing bisphosphonates have been shown to deplete circulating monocytes and reduce experimental restenosis. However, acceptable shelf life was not...
Liposomes containing bisphosphonates have been shown to deplete circulating monocytes and reduce experimental restenosis. However, acceptable shelf life was not achieved, and the disruption extent and rate of the vesicles in the circulation has not been examined. Designing an optimal liposomal formulation in general, and for an anti-inflammatory effect in particular, requires careful consideration of the factors that contribute to their in vitro stability and integrity in the blood after injection. An improved liposomal alendronate formulation was prepared by a modified thin lipid film hydration technique followed by extrusion, resulting in relatively smaller size vesicles, narrow size distribution, and low drug to lipid ratio in comparison to the reverse phase evaporation method. In order to rule out premature leakage of the drug, the integrity of the vesicles was examined by means of size-exclusion chromatography in vitro and in vivo, with subsequent analysis of size, drug (fractions of encapsulated and free) and lipid concentrations. Vesicles were found to be stable in serum, with 15 +/- 3% leakage of the drug after 10 min in rabbit's circulation, and intact liposomes were detected in the circulation 24 h following administration. It is concluded that the new formulation results in increased stability (2.5 years) as determined by the insignificant changes in vesicle size, drug leakage, lipid and drug stability, in vitro bioactivity (macrophages inhibition), as well as in vivo in depleting circulating monocytes and inhibition of restenosis in rabbits. Our in vitro stability results regarding dilution in serum paralleled in vivo data. Thus, in vitro assessment may provide a valuable tool in assessing in vivo integrity of liposomal formulations.
Topics: Alendronate; Animals; Anti-Inflammatory Agents; Bone Density Conservation Agents; Cell Division; Cell Line; Drug Stability; Liposomes; Macrophages; Mice; Monocytes; Phosphatidylglycerols
PubMed: 18937071
DOI: 10.1208/s12248-008-9060-5 -
Journal of Bone and Mineral Research :... Aug 2010The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more... (Randomized Controlled Trial)
Randomized Controlled Trial
The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects of each drug on bone microarchitecture and strength. In a phase 2 double-blind pilot study, 247 postmenopausal women were randomized to denosumab (60 mg subcutaneous 6 monthly), alendronate (70 mg oral weekly), or placebo for 12 months. All received daily calcium and vitamin D. Morphologic changes were assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia and QCT at the distal radius. Denosumab decreased serum C-telopeptide more rapidly and markedly than alendronate. In the placebo arm, total, cortical, and trabecular BMD and cortical thickness decreased (-2.1% to -0.8%) at the distal radius after 12 months. Alendronate prevented the decline (-0.6% to 2.4%, p = .051 to <.001 versus placebo), whereas denosumab prevented the decline or improved these variables (0.3% to 3.4%, p < .001 versus placebo). Changes in total and cortical BMD were greater with denosumab than with alendronate (p < or = .024). Similar changes in these parameters were observed at the tibia. The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups (p < .001). Adverse events did not differ by group. These data suggest that structural decay owing to bone remodeling and progression of bone fragility may be prevented more effectively with denosumab.
Topics: Aged; Alendronate; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biomarkers; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Bone and Bones; Demography; Denosumab; Female; Humans; Middle Aged; RANK Ligand; Tomography, X-Ray Computed
PubMed: 20222106
DOI: 10.1002/jbmr.81 -
Medicine Jan 2020Alendronate sodium is used to reduce the risk of bone fracture in aged osteoporosis patients. However, its side effects should be recognized, especially for those aged...
INTRODUCTION
Alendronate sodium is used to reduce the risk of bone fracture in aged osteoporosis patients. However, its side effects should be recognized, especially for those aged patients with one or more basic cardiovascular diseases.
PATIENT CONCERNS
A 90-year-old and a 75-year-old male patient were admitted to our department. These 2 patients were examined by dual energy X-ray absorptiometry (DXA).
DIAGNOSIS
Both patients were diagnosed with osteoporosis, they also had history of atrial fibrillation (AF) and had long term use of warfarin.
INTERVENTIONS
Alendronate sodium was prescribed to the two patients at 70 mg once a week.
OUTCOMES
The 2 patients had experienced dramatic increase of international normalized ratio (INR) to 4.69∼4.86 within 24 hours and gradual decrease in the next 5 days. Both patients experienced spontaneous ecchymoses and petechiae in the skin at the first 72 hours.
CONCLUSION
Alendronate sodium can transiently increase the INR over 50%, induce spontaneous ecchymoses and petechiae in the skin of aged male osteoporosis patients with AF who took warfarin. Clinicians should pay enough attention when using alendronate sodium on these kinds of patients and be aware of the consequent potential bleeding risk.
Topics: Aged; Aged, 80 and over; Alendronate; Anticoagulants; Atrial Fibrillation; Bone Density Conservation Agents; Drug Synergism; Humans; International Normalized Ratio; Male; Osteoporosis; Warfarin
PubMed: 31914073
DOI: 10.1097/MD.0000000000018698