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Bone May 2021To compare the efficacy of denosumab and alendronate on raising spine bone mineral density (BMD) in long-term glucocorticoid (GC) users. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To compare the efficacy of denosumab and alendronate on raising spine bone mineral density (BMD) in long-term glucocorticoid (GC) users.
METHODS
Adult patients receiving long-term prednisolone (≥2.5 mg/day for ≥1 year) were recruited and randomized to either subcutaneous denosumab (60 mg/6 months) or oral alendronate (70 mg/week). BMD (lumbar spine, femoral neck, hip) and bone markers (serum P1NP and CTX) were measured at month 0, 6 and 12. The difference in spine BMD (primary outcome) at month 12 was compared between the two groups.
RESULTS
139 subjects were recruited (age 50.0 ± 12.7 years; 96% women): 69 assigned denosumab and 70 assigned alendronate. At entry, 73(53%) patients were osteoporotic and 82(59%) patients were naive to the bisphosphonates. Baseline clinical characteristics and BMD values were similar in the two groups. At month 12, a significant gain in mean BMD at the lumbar spine (+3.5 ± 2.5%; p<0.001), hip (+0.9 ± 2.8%; p=0.01) and femoral neck (+1.04 ± 4.1%; p=0.047); was observed in denosumab-treated patients, whereas the corresponding change was +2.5 ± 2.9% (p<0.001), +1.6 ± 2.7% (p<0.001) and + 1.5 ± 3.9% (p=0.002) in the alendronate group. The spine, but not the hip or femoral neck, BMD at month 12 was significantly higher in the denosumab than alendronate group after adjustment for baseline BMD values, age, sex, osteoporosis risk factors and the cumulative prednisolone doses received in one year. The drop in P1NP and CTX was significantly higher in the denosumab than alendronate group. Frequency of adverse events (AEs), including infections, was similar in the two treatment arms. Seven patients withdrew from the study but not related to AEs.
CONCLUSIONS
In patients receiving long-term GCs, denosumab is superior to alendronate in raising the spine BMD after 12 months. Both drugs are well-tolerated.
Topics: Adult; Alendronate; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Glucocorticoids; Humans; Male; Middle Aged
PubMed: 33631355
DOI: 10.1016/j.bone.2021.115902 -
Journal of Bone and Mineral Metabolism Nov 2023To investigate the differences in the incidence rates of suspected stage 0/1 osteonecrosis of the jaw (ONJ) and incidence risk of relevant clinical findings of suspected... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
To investigate the differences in the incidence rates of suspected stage 0/1 osteonecrosis of the jaw (ONJ) and incidence risk of relevant clinical findings of suspected stage 0 ONJ between patients treated with sequential therapy comprising weekly teriparatide for 72 weeks followed by alendronate for 48 weeks vs. those who received monotherapy with alendronate for 120 weeks.
MATERIALS AND METHODS
Suspected stage 0/1 ONJ was defined by non-specific symptoms. Tooth mobility and periodontal symptoms (gingival bleeding, swelling, and/or pain) were selected as clinical findings of suspected stage 0 ONJ. Poisson regression models were applied to calculate the incidence rate ratios of suspected stage 0/1 between the teriparatide group (TG) and alendronate group (AG). Generalized linear models were used to calculate the risk ratios of clinical findings between groups.
RESULTS
Two hundred and sixty-one participants in the TG and 344 in the AG answered a structured questionnaire on oral health and were included in this study. There were no significant differences between the groups in the incidence rate of suspected stage 0/1 ONJ at both 72 and 120 weeks. The risk ratio of the TG to AG for tooth mobility was 0.34 (95% confidence interval [CI] 0.13-0.88, p = 0.02) at 72 weeks and 0.90 (95% CI 0.40-2.03, p = 0.83) at 120 weeks. The incidence rate of tooth mobility related to periodontal symptoms decreased in the TG and increased in the AG during the study.
CONCLUSION
Tooth mobility accompanied by clinical periodontal symptoms may be a useful early sign of stage 0 ONJ.
Topics: Humans; Alendronate; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Diphosphonates; East Asian People; Osteoporosis; Reproducibility of Results; Teriparatide; Tooth Mobility
PubMed: 37897672
DOI: 10.1007/s00774-023-01466-3 -
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 -
Archives of Osteoporosis Apr 2022This study evaluated the cost-effectiveness of 1 year of romosozumab followed by alendronate versus oral bisphosphonates alone in women with postmenopausal osteoporosis...
UNLABELLED
This study evaluated the cost-effectiveness of 1 year of romosozumab followed by alendronate versus oral bisphosphonates alone in women with postmenopausal osteoporosis at very high risk for fracture in Canada. Results showed that romosozumab sequenced to alendronate is a cost-effective treatment option, dominating both alendronate and risedronate alone.
PURPOSE
To demonstrate the value of romosozumab sequenced to alendronate compared to alendronate or risedronate alone, for the treatment of osteoporosis in postmenopausal women with a history of osteoporotic fracture and who are at very high risk for future fracture in Canada.
METHODS
A Markov model followed a hypothetical cohort of postmenopausal osteoporotic women at very high risk for future fractures, to estimate the cost-effectiveness of romosozumab and alendronate compared to oral bisphosphonates alone. A total treatment period of 5 years was assumed. Quality-adjusted life years and costs were estimated for each comparator across health states defined by different types of fragility fractures.
RESULTS
Romosozumab/alendronate was associated with a lifetime gain of 0.103 and 0.127 QALYs and a cost reduction of $343 and $3805, relative to alendronate and risedronate, respectively. These results were driven by a reduction of the number of fractures (2561 per 1000 patients, versus 2700 for alendronate and 2724 for risedronate over lifetime). Romosozumab/alendronate had the highest probability of being cost-effective, relative to alendronate and risedronate, at any willingness to pay threshold value.
CONCLUSION
Romosozumab/alendronate was associated with reduced costs and greater benefit relative to other comparators. Probabilistic, deterministic, and scenario analyses indicate that romosozumab/alendronate represents the best value for money; the uncertainty analyses are robust, and therefore romosozumab should be considered for reimbursement by public drug plans in Canada .
Topics: Alendronate; Antibodies, Monoclonal; Bone Density Conservation Agents; Cost-Benefit Analysis; Female; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Postmenopause; Quality-Adjusted Life Years; Risedronic Acid
PubMed: 35471711
DOI: 10.1007/s11657-022-01106-9 -
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 -
FASEB Journal : Official Publication of... Jul 2023Nonalcoholic steatohepatitis (NASH) has become a major concern that threatens human health worldwide. The underlying pathogenesis was crucial but remained poorly...
Nonalcoholic steatohepatitis (NASH) has become a major concern that threatens human health worldwide. The underlying pathogenesis was crucial but remained poorly understood. Here, we found that the expression of hepatic farnesyl diphosphate synthase (FDPS) was increased in mice and patients with NASH. Elevated FDPS levels were positively correlated with NASH severity. Overexpression of FDPS in mice provoked increased lipid accumulation, inflammation, and fibrosis, while hepatic FDPS deficiency protected mice from NASH progression. Importantly, pharmacological inhibition of FDPS with clinically used alendronate remarkably attenuated NASH-associated phenotypes in mice. Mechanistically, we demonstrated that FDPS increased its downstream product farnesyl pyrophosphate levels, which could function as an aryl hydrocarbon receptor (AHR) agonist to upregulate the expression of fatty acid translocase CD36, to accelerate the development of NASH. Collectively, these findings suggest that FDPS exacerbates NASH via AHR-CD36 axis and identify FDPS as a promising target for NASH therapy.
Topics: Animals; Humans; Mice; Alendronate; CD36 Antigens; Geranyltranstransferase; Non-alcoholic Fatty Liver Disease; Receptors, Aryl Hydrocarbon
PubMed: 37310396
DOI: 10.1096/fj.202300433RR -
BMC Musculoskeletal Disorders Sep 2023Bisphosphonate medications, including alendronate, ibandronate and risedronate administered orally and zoledronate, administered intravenously, are commonly prescribed...
BACKGROUND
Bisphosphonate medications, including alendronate, ibandronate and risedronate administered orally and zoledronate, administered intravenously, are commonly prescribed for the treatment of osteoporosis based on evidence that, correctly taken, bisphosphonates can improve bone strength and lead to a reduction in the risk of fragility fractures. However, it is currently unclear how decisions to select between bisphosphonate regimens, including intravenous regimen, are made in practice and how clinicians support patients with different treatments.
METHODS
This was an interpretivist qualitative study. 23 semi-structured telephone interviews were conducted with a sample of general practitioners (GPs), secondary care clinicians, specialist experts as well as those providing and leading novel treatments including participants from a community intravenous (IV) zoledronate service. Data analysis was undertaken through a process of iterative categorisation.
RESULTS
The results report clinicians varying experiences of making treatment choices, as well as wider aspects of osteoporosis care. Secondary care and specialist clinicians conveyed some confidence in making treatment choices including on selecting IV treatment. This was aided by access to diagnostic testing and medication expertise. In contrast GPs reported a number of challenges in prescribing bisphosphonate medications for osteoporosis and uncertainty about treatment choice. Results also highlight how administering IV zoledronate was seen as an opportunity to engage in broader care practices.
CONCLUSION
Approaches to making treatment decisions and supporting patients when prescribing bisphosphonates for osteoporosis vary in practice. This study points to the need to co-ordinate osteoporosis treatment and care across different care providers.
Topics: Humans; Female; Zoledronic Acid; Osteoporosis; Diphosphonates; Ibandronic Acid; Alendronate; Bone Density Conservation Agents; Osteoporosis, Postmenopausal
PubMed: 37770860
DOI: 10.1186/s12891-023-06865-1 -
The Cochrane Database of Systematic... Jan 2023Osteoporosis is a disorder of bone mineralisation occurring in about one third of adults with cystic fibrosis. Bisphosphonates can increase bone mineral density and... (Review)
Review
BACKGROUND
Osteoporosis is a disorder of bone mineralisation occurring in about one third of adults with cystic fibrosis. Bisphosphonates can increase bone mineral density and decrease the risk of new fractures in post-menopausal women and people receiving long-term oral corticosteroids. This is an updated version of a previous review.
OBJECTIVES
To assess the effects of bisphosphonates on the frequency of fractures, bone mineral density, quality of life, adverse events, trial withdrawals, and survival in people with cystic fibrosis.
SEARCH METHODS
We searched the Cystic Fibrosis and Genetic Disorders Group's Trials Register of references (identified from electronic database searches and hand searches of journals and abstract books) on 5 May 2022. We performed additional searches of PubMed, clinicaltrials.gov and the WHO ICTRP (International Clinical Trials Registry Platform) on 5 May 2022.
SELECTION CRITERIA
Randomised controlled trials of at least six months duration studying bisphosphonates in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Authors independently selected trials, extracted data and assessed risk of bias in included studies. Trial investigators were contacted to obtain missing data. We judged the certainty of the evidence using GRADE.
MAIN RESULTS
We included nine trials with a total of 385 participants (272 adults and 113 children (aged five to 18 years)). Trial durations ranged from six months to two years. Only two of the studies were considered to have a low risk of bias for all the domains. Bisphosphonates compared to control in people with cystic fibrosis who have not had a lung transplant Seven trials included only adult participants without lung transplants, one trial included both adults and children without lung transplantation (total of 238 adults and 113 children). We analysed adults (n = 238) and children (n = 113) separately. Adults Three trials assessed intravenous bisphosphonates (one assessed pamidronate and two assessed zoledronate) and five trials assessed oral bisphosphonates (one assessed risedronate and four assessed alendronate). Bisphosphonates were compared to either placebo or calcium (with or without additional vitamin D). Data showed no difference between treatment or control groups in new vertebral fractures at 12 months (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.02 to 2.09; 5 trials, 142 participants; very low-certainty evidence) and two trials (44 participants) reported no vertebral fractures at 24 months. There was no difference in non-vertebral fractures at 12 months (OR 2.11, 95% CI 0.18 to 25.35; 4 trials, 95 participants; very low-certainty evidence) and again two trials (44 participants) reported no non-vertebral fractures at 24 months. There was no difference in total fractures between groups at 12 months (OR 0.57, 95% CI 0.13 to 2.50; 5 trials, 142 participants) and no fractures were reported in two trials (44 participants) at 24 months. At 12 months, bisphosphonates may increase bone mineral density at the lumbar spine (mean difference (MD) 6.31, 95% CI 5.39 to 7.22; 6 trials, 171 participants; low-certainty evidence) and at the hip or femur (MD 4.41, 95% 3.44 to 5.37; 5 trials, 155 participants; low-certainty evidence). There was no clear difference in quality of life scores at 12 months (1 trial, 47 participants; low-certainty evidence), but bisphosphonates probably led to more adverse events (bone pain) at 12 months (OR 8.49, 95% CI 3.20 to 22.56; 7 trials, 206 participants; moderate-certainty evidence). Children The single trial in 113 children compared oral alendronate to placebo. We graded all evidence as low certainty. At 12 months we found no difference between treatment and placebo in new vertebral fractures (OR 0.32, 95% CI 0.03 to 3.13; 1 trial, 113 participants) and non-vertebral fractures (OR 0.19, 95% CI 0.01 to 4.04; 1 trial, 113 participants). There was also no difference in total fractures (OR 0.18, 95% CI 0.02 to 1.61; 1 trial, 113 participants). Bisphosphonates may increase bone mineral density at the lumbar spine at 12 months (MD 14.50, 95% CI 12.91 to 16.09). There was no difference in bone or muscle pain (MD 3.00, 95% CI 0.12 to 75.22), fever (MD 3.00, 95% CI 0.12 to 75.22) or gastrointestinal adverse events (OR 0.67, 95% CI 0.20 to 2.26). The trial did not measure bone mineral density at the hip/femur or report on quality of life. Bisphosphonates compared to control in people with cystic fibrosis who have had a lung transplant One trial of 34 adults who had undergone lung transplantation compared intravenous pamidronate to no bisphosphonate treatment. It did not report at 12 months and we report the 24-month data (not assessed by GRADE). There was no difference in the number of fractures, either vertebral or non-vertebral. However, bone mineral density increased with treatment at the lumbar spine (MD 6.20, 95% CI 4.28 to 8.12) and femur (MD 7.90, 95% CI 5.78 to 10.02). No participants in either group reported either bone pain or fever. The trial did not measure quality of life.
AUTHORS' CONCLUSIONS
Oral and intravenous bisphosphonates may increase bone mineral density in people with cystic fibrosis, but there are insufficient data to determine whether treatment reduces fractures. Severe bone pain and flu-like symptoms may occur with intravenous bisphosphonates. Before any firm conclusions can be drawn, trials in larger populations, including children, and of longer duration are needed to determine effects on fracture rate and survival. Additional trials are needed to determine if bone pain is more common or severe (or both) with the more potent zoledronate and if corticosteroids can ameliorate or prevent these adverse events. Future trials should also assess gastrointestinal adverse effects associated with oral bisphosphonates.
Topics: Adult; Child; Female; Humans; Alendronate; Bone Density Conservation Agents; Cystic Fibrosis; Diphosphonates; Fractures, Bone; Musculoskeletal Pain; Osteoporosis; Pamidronate; Quality of Life; Spinal Fractures; Zoledronic Acid; Randomized Controlled Trials as Topic
PubMed: 36625789
DOI: 10.1002/14651858.CD002010.pub5 -
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