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BMC Musculoskeletal Disorders Jun 2022Osteoarthritis (OA) is a major cause of pain and disability worldwide. Despite the relatively high burden of the disease, the currently available non-surgical treatment...
Effect of alendronate sodium plus vitamin D tablets on knee joint structure and osteoarthritis pain: a multi-center, randomized, double-blind, placebo-controlled study protocol.
BACKGROUND
Osteoarthritis (OA) is a major cause of pain and disability worldwide. Despite the relatively high burden of the disease, the currently available non-surgical treatment options are directed towards symptomatic relief. Therefore, we propose the use of alendronate as a disease modifying agent to help slow and prevent OA. In addition, this study will utilize Whole-Organ Magnetic Resonance Imaging Score (WORMS) to evaluate the structural integrity of cartilage in the study population. High-quality evidence, limited to a few well-conducted randomized trials, highlights contradictory results on the effect of bisphosphonates on knee function and progression of OA. Therefore, a placebo-controlled, randomized trial is needed to evaluate the combined effect of alendronate and vit D on the structure of cartilage utilizing the WORMS score and its ability to treat knee pain in OA patients.
METHODS
This multicenter, randomized, double-blinded, placebo-controlled study will evaluate the efficacy and safety of alendronate in early OA. Patients will undergo a 1:1 double-blinded randomization to receive a one-year course of either alendronate sodium vitamin D or placebo. The primary outcome is to compare WORMS score of knee joint at 6 and 12 months between both groups. Secondary endpoints will include WORMS score at 24 months, knee pain, radiographic progression of OA, severity of OA, quality of life, and serum inflammatory biomarkers at different assessment timepoints. To detect a 2.2% difference in cartilage loss between both groups with power of 80%, a sample size of 60 (30 per group) is proposed.
DISCUSSION
This trial will give helpful and high-quality evidence regarding the potential therapeutic role of alendronate sodium vitamin D3, as compared to placebo, in the management of patients with knee OA regarding its role on cartilage loss, radiographic progression of OA, severity of OA, knee pain, quality of life, and inflammatory biomarkers. If proven effective, this intervention would be a great option for providing beneficial outcomes with a reduced cost in this patient population.
TRIAL REGISTRATION
This trial was registered on clinicaltrials.gov (registration number: NCT04739592 ).
Topics: Alendronate; Cholecalciferol; Double-Blind Method; Humans; Knee Joint; Multicenter Studies as Topic; Osteoarthritis, Knee; Pain; Quality of Life; Randomized Controlled Trials as Topic; Tablets; Treatment Outcome; Vitamin D
PubMed: 35715774
DOI: 10.1186/s12891-022-05521-4 -
BioMed Research International 2022Diabetes is a chronic disease caused by defective insulin secretion in the body, resulting in metabolic abnormalities with persistent blood glucose elevation.... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Diabetes is a chronic disease caused by defective insulin secretion in the body, resulting in metabolic abnormalities with persistent blood glucose elevation. Osteoporosis is the most common diabetes complication. The aim of this study was to perform a meta-analysis of the effects of alendronate combined with atorvastatin compared with alendronate alone in the treatment of osteoporosis in diabetes mellitus.
METHODS
Two researchers independently used PubMed, ScienceDirect, Cochrane Library, Wanfang Data, CNKI, and VIP databases to search for all relevant studies that met the inclusion criteria and used RevMan 5.3 and STATA 16.0 for data analysis.
RESULTS
Fourteen studies that met the inclusion criteria were selected, including 1456 patients. Among the data extracted in this meta-analysis, bone mineral density (BMD) was the primary outcome measurement, while total effective rate, VAS, osteoprotegerin (OPG), bone Gla protein (BGP), bone alkaline phosphatase (BAP), blood P and Ca, and adverse effects were secondary outcome measurements. Our results showed that alendronate combined with atorvastatin is more effective than alendronate alone, with higher BMD, OPG, BGP, and BAP, more significant pain relief, and fewer adverse events.
CONCLUSION
The results of this meta-analysis indicate that alendronate combined with atorvastatin is a better treatment for osteoporosis in diabetes mellitus, showing more effective and higher BMD and fewer adverse events than alendronate alone.
Topics: Alendronate; Alkaline Phosphatase; Atorvastatin; Bone Density; Bone Density Conservation Agents; Diabetes Mellitus; Female; Humans; Osteocalcin; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 35178452
DOI: 10.1155/2022/6747469 -
Journal of Orthopaedic Research :... Oct 2022This study evaluated the effects of AGN1, a triphasic calcium-based material, and alendronate (A) on distal femoral defect bone repair in ovariectomized (OVX) rats. Of...
This study evaluated the effects of AGN1, a triphasic calcium-based material, and alendronate (A) on distal femoral defect bone repair in ovariectomized (OVX) rats. Of 106 rats, 92 were OVX'ed at 12 weeks old and underwent a 12-week induction period. Animals were randomized into five groups: OVX Control, OVX Alendronate Control, Normal Control, OVX Implantation, OVX Alendronate + Implantation. OVX Alendronate Control and OVX Alendronate + Implantation groups received alendronate injection twice weekly (0.015 mg/kg) from 6 weeks until sacrifice. Twelve weeks after OVX, 2.5 mm diameter by 4.0 mm long cylindrical, bilateral distal femoral defects were created in experimental animals. One defect was left empty, and one filled with AGN1. Dual-energy X-ray absorptiometry, microcomputed tomography, and histomorphometry were performed 0-, 6-, 12-, and 18-week postdefect/implantation surgery (N = 6-8/group). Results showed OVX induced significant and progressive bone loss which alendronate prevented. Histomorphometry demonstrated rapid AGN1 resorption: AGN1 resorbed from 95.1 ± 0.7% filling of the implant site (week 0) to 1.3 ± 1.0% (18 weeks) with no significant alendronate effect (1.6 ± 1.1%, 18 weeks). Bone formation in empty defects consisted primarily of cortical wall healing, whereas AGN1 implants demonstrated cortical wall healing with new trabecular bone filling the subcortical space. Alendronate dramatically increased bone formation in empty and AGN1 defects. We conclude AGN1 is resorbed and replaced by new cortical and trabecular bone in this OVX model, and alendronate did not compromise these effects.
Topics: Alendronate; Animals; Bone Density; Bone Density Conservation Agents; Calcium; Diphosphonates; Female; Ovariectomy; Rats; X-Ray Microtomography
PubMed: 34935182
DOI: 10.1002/jor.25255 -
Frontiers in Immunology 2023Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure...
Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include "shock and kill" strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy. Aminobisphosphonates (N-BPs) that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies. Here, we show the use of N-BPs as a novel class of LRA: we found in assays using primary cells from ART-suppressed people living with HIV-1 that N-BPs induce HIV-1 from latency to levels that are comparable to the T cell activator phytohemagglutinin (PHA). RNA sequencing and mechanistic data suggested that reactivation may occur through activation of the activator protein 1 signaling pathway. Stored samples from a prior clinical trial aimed at analyzing the effect of alendronate on bone mineral density, provided further evidence of alendronate-mediated latency reversal and activation of immune effector cells. Decay of the reservoir measured by IPDA was however not detected. Our results demonstrate the novel use of N-BPs to reverse HIV-1 latency while inducing immune effector functions. This preliminary evidence merits further investigation in a controlled clinical setting possibly in combination with therapeutic vaccination.
Topics: Humans; HIV Infections; HIV-1; Virus Activation; Virus Latency; Alendronate; HIV Seropositivity
PubMed: 37744358
DOI: 10.3389/fimmu.2023.1219250 -
Genetics and Molecular Research : GMR Mar 2017Alendronate regulates the activity of osteoclasts and healing of osteoporosis. This study investigated the effect of alendronate on bone healing and changes in the...
Alendronate regulates the activity of osteoclasts and healing of osteoporosis. This study investigated the effect of alendronate on bone healing and changes in the levels of cytokines. Bilateral ovaries of 10 adult female rabbits were removed surgically in aseptic condition to establish the animal model of osteoporosis. Five rabbits in group A were treated with alendronate (1.15 mg·kg·week) once a week by a stomach tube, whereas the remaining 5 in group B were treated with physiological saline. The success of the animal model establishment and the efficacy of alendronate treatment were evaluated by the sports ability score and the Basso, Beattie, and Bresnahan (BBB) score; the healing degree of osteoporosis was determined by X-ray analysis and measurement of biomechanical properties; the changes in the levels of related cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. Treatment improved dyskinesia of the animals in group A than that in group B, with significant improvement occurring in the 4th week of treatment. The BBB score of the group A animals revealed movements similar to normal, but that of the group B animals exhibited significant motor disturbance (P < 0.01). X-ray examination showed that with time, the X-ray ratings increased. Measurement of the biomechanical properties further showed that alendronate had a positive effect on osteoporosis healing. The results of ELISA and immunohistochemistry showed that the levels of ALP, BMP-2, bFGF, and IGF-1 were upregulated in group A. In conclusion, alendronate accelerated osteoporosis healing probably via certain cytokine-related mechanism.
Topics: Alendronate; Animals; Bone Density Conservation Agents; Bone Morphogenetic Protein 2; Cytokines; Disease Models, Animal; Dyskinesias; Female; Fibroblast Growth Factor 2; Humans; Insulin-Like Growth Factor I; Osteoporosis; Ovariectomy; Rabbits; Treatment Outcome; Up-Regulation
PubMed: 28362987
DOI: 10.4238/gmr16019485 -
Biochemical Pharmacology Sep 1997Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a potent bisphosphonate that inhibits osteoclastic bone resorption and has proven effective for the...
Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a potent bisphosphonate that inhibits osteoclastic bone resorption and has proven effective for the treatment of osteoporosis. Its molecular mechanism of action, however, has not been defined precisely. Here we report that alendronate is a potent inhibitor of the protein-tyrosine-phosphatase-meg1 (PTPmeg1). Two substrates were employed in this study: fluorescein diphosphate and the phosphotyrosyl peptide src-pY527. With either substrate, alendronate was a slow binding inhibitor of PTPmeg1. Among the other bisphosphonates studied, alendronate was more potent and selective for PTPmeg1. The hydrolysis of fluorescein diphosphate by PTP epsilon and PTPmeg1 was sensitive to alendronate, with IC50 values of less than 1 microM; PTPsigma, however, under the same conditions, was inhibited by only 50% with 141 microM alendronate. Similarly, with the src-pY527 substrate, alendronate inhibition was also PTP dependent. Alendronate inhibited PTPmeg1 with an IC50 value of 23 microM, PTPsigma with an IC50 value of 2 microM, and did not inhibit PTP epsilon at concentrations up to 1 mM. The alendronate inhibition of these three PTPs and two substrates is consistent with the formation of a ternary complex comprised of enzyme, substrate, and inhibitor. PTP inhibition by hisphosphonates or vanadate was diminished by the metal chelating agent EDTA, or by the reducing agent dithiothreitol, suggesting that a metal ion and the oxidation of a cysteine residue are required for full inhibition. These observations show substrate- and enzyme-specific PTP inhibition by alendronate and support the possibility that a certain PTP(s) may be the molecular target for alendronate action.
Topics: Alendronate; DNA, Complementary; Enzyme Inhibitors; Humans; Protein Tyrosine Phosphatase, Non-Receptor Type 4; Protein Tyrosine Phosphatases; Substrate Specificity; Tumor Cells, Cultured
PubMed: 9310349
DOI: 10.1016/s0006-2952(97)00225-6 -
Journal of Bone and Mineral Research :... Mar 2012Recent studies have reached conflicting conclusions regarding the risk of esophageal cancer with oral bisphosphonates. Prior studies did not record the number of cancer...
Recent studies have reached conflicting conclusions regarding the risk of esophageal cancer with oral bisphosphonates. Prior studies did not record the number of cancer deaths or endoscopy rates, which could be higher in bisphosphonate users and lead to more cancers being diagnosed at a stage when their esophageal or gastric location could be accurately distinguished. We conducted a register-based, open cohort study using national healthcare data for Denmark. Upper endoscopy frequency, cancer incidence and mortality was examined in 30,606 alendronate users (female, age 50+) and 122,424 matched controls. Primary outcomes were esophageal cancer incidence and death because of esophageal cancer. The analysis showed that alendronate users were more likely to have undergone recent upper endoscopy (4.1 versus 1.7%, p < 0.001). Alendronate users had a lower risk of incident gastric cancer [odds ratio (OR) 0.61; 95% confidence interval (CI): 0.39-0.97) and no increased risk of esophageal cancer (OR 0.71; 95% CI: 0.43-1.19). Risk reductions were greater in users with 10+ prescriptions. The risk of dying of esophageal cancer was significantly reduced in alendronate users after 3 years OR 0.45 (95% CI: 0.22-0.92) but not after 9 years (OR 1.01; 95% CI: 0.52-1.95). An additional comparison with etidronate users revealed no statistically significant difference in outcomes. In conclusion, we found no excess in esophageal cancer deaths or incidence. The early decrease in esophageal cancer rates may relate to the greater use of endoscopy before starting alendronate. Longer term observations also indicated no excess risk of esophageal cancer death and a significantly decreased risk of gastric cancer death.
Topics: Adult; Aged; Alendronate; Bone Density Conservation Agents; Denmark; Esophageal Neoplasms; Etidronic Acid; Female; Humans; Incidence; Middle Aged; Stomach Neoplasms
PubMed: 22113985
DOI: 10.1002/jbmr.1481 -
Journal of Biomechanics May 2009Bisphosphonates suppress bone remodeling activity, increase bone volume, and significantly reduce fracture risk in individuals with osteoporosis and other metabolic bone...
Bisphosphonates suppress bone remodeling activity, increase bone volume, and significantly reduce fracture risk in individuals with osteoporosis and other metabolic bone diseases. The objectives of the current study were to develop a mathematical model that simulates control and 1 year experimental results following bisphosphonate treatment (alendronate or risedronate) in the canine fourth lumbar vertebral body, validate the model by comparing simulation predictions to 3 year experimental results, and then use the model to predict potential long term effects of bisphosphonates on remodeling and microdamage accumulation. To investigate the effects of bisphosphonates on bone volume and microdamage, a mechanistic biological model was modified from previous versions to simulate remodeling in a representative volume of vertebral trabecular bone in dogs treated with various doses of alendronate or risedronate, including doses equivalent to those used for treatment of post-menopausal osteoporosis in humans. Bisphosphonates were assumed to affect remodeling by suppressing basic multicellular unit activation and reducing resorption area. Model simulation results for trabecular bone volume fraction, microdamage, and activation frequency following 1 year of bisphosphonate treatment are consistent with experimental measurements. The model predicts that trabecular bone volume initially increases rapidly with 1 year of bisphosphonate treatment, and continues to slowly rise between 1 and 3 years of treatment. The model also predicts that microdamage initially increases rapidly, 0.5-1.5-fold for alendronate or risedronate during the first year of treatment, and reaches its maximum value by 2.5 years before trending downward for all dosages. The model developed in this study suggests that increasing bone volume fraction with long term bisphosphonate treatment may sufficiently reduce strain and damage formation rate so that microdamage does not accumulate above that which is initiated in the first two years of treatment.
Topics: Alendronate; Animals; Computer Simulation; Disease Models, Animal; Dogs; Etidronic Acid; Fractures, Bone; Risedronic Acid; Spine; Substrate Specificity
PubMed: 19285313
DOI: 10.1016/j.jbiomech.2008.07.039 -
Clinical Infectious Diseases : An... Mar 2021No safety concerns were identified in a randomized, crossover study of alendronate/placebo in youth with perinatal HIV infection and low bone mineral density (BMD). BMD... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and Efficacy of 48 and 96 Weeks of Alendronate in Children and Adolescents With Perinatal Human Immunodeficiency Virus Infection and Low Bone Mineral Density for Age.
No safety concerns were identified in a randomized, crossover study of alendronate/placebo in youth with perinatal HIV infection and low bone mineral density (BMD). BMD improved with 48 weeks of alendronate and continued to improve with an additional 48 weeks of therapy. Gains were largely maintained 48 weeks after stopping alendronate.
Topics: Adolescent; Alendronate; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Child; Cross-Over Studies; HIV Infections; Humans
PubMed: 32584996
DOI: 10.1093/cid/ciaa861 -
Head & Face Medicine Apr 2013Bisphosphonates are a common medication for the prevention and therapy of osteoporosis, but are also applied for tumor diseases. They affect bone metabolism, and... (Review)
Review
BACKGROUND
Bisphosphonates are a common medication for the prevention and therapy of osteoporosis, but are also applied for tumor diseases. They affect bone metabolism, and therefore also orthodontic treatments, but how it does has yet not been definitively clarified. Therefore, the aim of this research was to evaluate and demonstrate the reported effects and the current state of scientific research regarding orthodontic treatment and bisphosphonate medication exclusively in humans.
MATERIAL AND METHODS
A systematic research of the literature for selected keywords in the Medline database (Pubmed) as well as a manual search was conducted. The following search terms were used: 'Bisphosphonate' in combination with: orthodontic, orthodontic treatment, tooth movement.
FINDINGS
To date, only nine reported patients (case reports/series) and one original article (retrospective cohort study) regarding orthodontic treatment under bisphosphonate medication in humans have been published. Decelerated tooth movement with increased side effects (especially in high-risk patients) and longer treatment duration was reported in some articles. Patients with initial spacing or extraction cases had a higher risk of incomplete space closure and poor root parallelism.
CONCLUSIONS
Orthodontic tooth movement under bisphosphonate medication is possible, especially in low-risk patients (low dose and short period of intake). But the treatment is still not predictable, especially in high-risk patients. Therefore, the altered bone metabolism and higher extent of side effects should be considered in treatment planning, especially in extraction cases or high-risk patients. Regardless, longer treatment duration, decelerated tooth movement, and more side effects, e.g., incomplete space closure and poor root parallelism, should be expected, especially in extraction cases or space closure.
Topics: Alendronate; Bone Density Conservation Agents; Bone Remodeling; Bone and Bones; Humans; Orthodontic Space Closure; Orthodontics; Osteoporosis; Radiography, Panoramic; Tooth Extraction; Tooth Movement Techniques
PubMed: 23556517
DOI: 10.1186/1746-160X-9-10