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Bone Jan 2020To determine the clinical effectiveness of denosumab (DEN), raloxifene (RLX), romosozumab (ROMO) and teriparatide (TPTD), within their licensed (or anticipated licensed)... (Meta-Analysis)
Meta-Analysis
Clinical effectiveness of denosumab, raloxifene, romosozumab, and teriparatide for the prevention of osteoporotic fragility fractures: A systematic review and network meta-analysis.
OBJECTIVES
To determine the clinical effectiveness of denosumab (DEN), raloxifene (RLX), romosozumab (ROMO) and teriparatide (TPTD), within their licensed (or anticipated licensed) indications, for the treatment of osteoporosis.
METHODS
A systematic review was conducted. Nine electronic databases and trial registries were searched up to the end of July 2018. Studies were eligible for inclusion if they were randomised controlled trials (RCT) in a population at risk of osteoporotic fracture, comparing these four non-bisphosphonates DEN, RLX, ROMO, or TPTD with each other, a non-active treatment, or the bisphosphonates alendronate (ALN), risedronate (RIS), ibandronate (IBN) and zoledronic acid (ZOL). Quality of included studies was assessed using the Cochrane Risk of Bias tool. Network meta-analyses (NMA) were used to determine the relative effectiveness of treatments.
RESULTS
The systematic review identified 7898 citations. Forty-six RCTs of non-bisphosphonates met the inclusion criteria for the review and provided data for analyses. Additionally 49 RCTs of bisphosphonates were used in the NMAs. Forty-six RCTs were included in the NMA of vertebral fracture data, 23 RCTs for hip fractures and 73 RCTs in the NMA of femoral neck bone mineral density (FN BMD). For vertebral fractures, all four non-bisphosphonates showed statistically significant benefit relative to placebo: TPTD HR 0.23 (95% credible internal (CrI) 0.16, 0.32); ROMO followed by ALN 0.25 (95% CrI 0.15, 0.43); DEN HR 0.30 (95% CrI 0.21, 0.43); RLX HR 0.61 (95% CrI 0.44, 0.80). The four non-bisphosphonates interventions studied also showed statistically significant benefit relative to placebo for FN BMD, and for hip fractures TPTD, ROMO followed by ALN, and DEN showed statistically significant benefit relative to placebo.
CONCLUSIONS
The four non-bisphosphonate interventions studied were all statistically significantly clinically effective for reducing vertebral fractures when compared to placebo, and were beneficial for change in FN BMD compared to placebo. All reduced hip fractures, and this was statistically significant for TPTD, ROMO followed by ALN, and DEN.
Topics: Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Denosumab; Diphosphonates; Humans; Network Meta-Analysis; Osteoporotic Fractures; Raloxifene Hydrochloride; Teriparatide; Treatment Outcome
PubMed: 31626995
DOI: 10.1016/j.bone.2019.115081 -
Reumatologia Clinica 2013To determine the efficacy and safety of denosumab in osteoporosis. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To determine the efficacy and safety of denosumab in osteoporosis.
METHODS
A systematic search was performed in MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials (1950 to July 2010), meeting abstracts (2009-2010), trial registries, and reference lists. The selection criteria were as follows: (population) osteoporosis patients of any age; (intervention) treatment with denosumab; (outcome) efficacy and safety; (study design) randomized clinical trials (RCTs); no language restrictions. Two reviewers independently screened titles and abstracts and subsequently extracted data from the selected studies including quality items, and on outcomes of interest. A meta-analysis was performed for safety issues.
RESULTS
A total of 25 studies were included. Denosumab reduces the risk of new radiographic vertebral fracture in a 68% compared with placebo (p<0.001) and increases bone mineral density (BMD) at lumbar spine, total hip, and one-third radius more than alendronate and placebo. A single subcutaneous dose of denosumab resulted in a dose-dependent, rapid, profound, and sustained decrease bone turnover markers (BTMs). Denosumab was in general well tolerated. A meta-analysis has shown an increase in the incidence of urinary infections (p=0.012) and eczema (p<0.001) in the patients treated with denosumab. Meta-analysis of efficacy was complicated due to the study features.
CONCLUSIONS
Denosumab given subcutaneously twice yearly is associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. Denosumab is associated with greater and sustained increases in BMD and reductions in BTMs compared with placebo and/or alendronate and with a risk of urinary infections and eczema.
Topics: Antibodies, Monoclonal, Humanized; Bone Density Conservation Agents; Denosumab; Humans; Injections, Subcutaneous; Models, Statistical; Osteoporosis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 22947600
DOI: 10.1016/j.reuma.2012.06.007 -
Expert Review of Pharmacoeconomics &... Feb 2013Denosumab is a novel biological agent for the treatment of osteoporosis in postmenopausal women with increased risk of fractures. With limited healthcare resources,... (Review)
Review
Denosumab is a novel biological agent for the treatment of osteoporosis in postmenopausal women with increased risk of fractures. With limited healthcare resources, economic evaluations are increasingly being used by decision-makers to optimize healthcare resource allocation. The cost-effectiveness of denosumab has been evaluated in various studies, and a systematic literature study was conducted up to April 2012 to identify all published research articles and research abstracts presented at various congresses. This article provides a systematic review of four articles and eight abstracts reporting on the cost-effectiveness of denosumab in the treatment of osteoporosis. In most economic evaluations, denosumab has been considered as a cost-effective treatment compared with first-line and second-line options (including generic alendronate) in the treatment of women with high risk of fractures.
Topics: Aged; Antibodies, Monoclonal, Humanized; Bone Density Conservation Agents; Cost-Benefit Analysis; Denosumab; Drug Costs; Female; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Quality of Life; Quality-Adjusted Life Years; Risk Assessment; Time Factors; Treatment Outcome
PubMed: 23402442
DOI: 10.1586/erp.12.76 -
The Journal of Bone and Joint Surgery.... Feb 2013In the United States, hip fracture rates have declined by 30% coincident with bisphosphonate use. However, bisphosphonates are associated with sporadic cases of atypical... (Review)
Review
Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts: a systematic review from the Research on Adverse Drug Events And Reports (RADAR) project.
BACKGROUND
In the United States, hip fracture rates have declined by 30% coincident with bisphosphonate use. However, bisphosphonates are associated with sporadic cases of atypical femoral fracture. Atypical femoral fractures are usually atraumatic, may be bilateral, are occasionally preceded by prodromal thigh pain, and may have delayed fracture-healing. This study assessed the occurrence of bisphosphonate-associated nonhealing femoral fractures through a review of data from the U.S. FDA (Food and Drug Administration) Adverse Event Reporting System (FAERS) (1996 to 2011), published case reports, and international safety efforts.
METHODS
We analyzed the FAERS database with use of the proportional reporting ratio (PRR) and empiric Bayesian geometric mean (EBGM) techniques to assess whether a safety signal existed. Additionally, we conducted a systematic literature review (1990 to February 2012).
RESULTS
The analysis of the FAERS database indicated a PRR of 4.51 (95% confidence interval [CI], 3.44 to 5.92) for bisphosphonate use and nonhealing femoral fractures. Most cases (n = 317) were attributed to use of alendronate (PRR = 3.32; 95% CI, 2.71 to 4.17). In 2008, international safety agencies issued warnings and required label changes. In 2010, the FDA issued a safety notification, and the American Society for Bone and Mineral Research (ASBMR) issued recommendations about bisphosphonate-associated atypical femoral fractures.
CONCLUSIONS
Nonhealing femoral fractures are unusual adverse drug reactions associated with bisphosphonate use, as up to 26% of published cases of atypical femoral fractures exhibited delayed healing or nonhealing.
Topics: Adverse Drug Reaction Reporting Systems; Bayes Theorem; Bone Density Conservation Agents; Diphosphonates; Femoral Fractures; Fracture Healing; Humans; Risk Factors; United States; United States Food and Drug Administration
PubMed: 23426763
DOI: 10.2106/JBJS.K.01181 -
The Journal of Clinical Endocrinology... Jun 2012Osteoporosis and osteopenia are associated with increased fracture incidence. (Comparative Study)
Comparative Study Meta-Analysis Review
CONTEXT
Osteoporosis and osteopenia are associated with increased fracture incidence.
OBJECTIVE
The aim of this study was to determine the comparative effectiveness of different pharmacological agents in reducing the risk of fragility fractures.
DATA SOURCES
We searched multiple databases through 12/9/2011.
STUDY SELECTION
Eligible studies were randomized controlled trials enrolling individuals at risk of developing fragility fractures and evaluating the efficacy of bisphosphonates, teriparatide, selective estrogen receptor modulators, denosumab, or calcium and vitamin D.
DATA EXTRACTION
Reviewers working independently and in duplicate determined study eligibility and collected descriptive, methodological quality, and outcome data.
DATA SYNTHESIS
This network meta-analysis included 116 trials (139,647 patients; median age, 64 yr; 86% females and 88% Caucasians; median follow-up, 24 months). Trials were at low to moderate risk of bias. Teriparatide had the highest risk reduction of fractures (odds ratios, 0.42, 0.30, and 0.50 for hip, vertebral, and nonvertebral fractures, respectively) and the highest probability of being ranked first for efficacy (probabilities of 42, 49, and 79% for hip, vertebral, and nonvertebral fractures, respectively). However, differences to denosumab, zoledronate, risedronate, ibandronate, and alendronate were not statistically significant. Raloxifene and bazedoxifene were likely less effective, although these data were limited. Calcium and vitamin D were ineffective given separately but reduced the risk of hip fractures if given in combination (odds ratio, 0.81; 95% confidence interval, 0.68–0.96).
CONCLUSIONS
Teriparatide, bisphosphonates, and denosumab are most effective in reducing the risk of fragility fractures. Differences in efficacy across drugs are small; therefore, patients and clinicians need to consider their associated harms and costs.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bone Density Conservation Agents; Calcium; Denosumab; Fractures, Bone; Humans; Osteoporosis; Selective Estrogen Receptor Modulators; Vitamin D
PubMed: 22466336
DOI: 10.1210/jc.2011-3060 -
Current Molecular Medicine 2022Osteoporosis is the most prevalent metabolic bone disorder worldwide. This review was undertaken to compare the efficacies of bisphosphonates therapies for patient...
OBJECTIVES
Osteoporosis is the most prevalent metabolic bone disorder worldwide. This review was undertaken to compare the efficacies of bisphosphonates therapies for patient persistence and compliance for the treatment of osteoporosis.
METHODS
A systematic review was performed in accordance with the available reporting items. MEDLINE and Cochrane library databases were applied for literature searched up to January 2020. All major studies such as prospective, retrospective and review articles that examined patient persistence or compliance to bisphosphonates for osteoporosis were included.
RESULTS
The literature search found 656 relevant published reports, out of which 87 were included. The 10, 712, 176 osteoporotic patients were studied for patient persistence and 5, 875, 718 patients were studied for patient compliances. Analysis of all studied bisphosphonates showed almost similar patterns for patient persistence rates as it was decreased over the time following initial prescription, but persistence length was found to be significantly higher for alendronate therapy as compared to the other studied bisphosphonates (p<0.001), whereas the length of persistence of all other bisphosphonates (other than alendronate) were almost same (p>0.05). Analysis of patient compliances with etidronate therapy showed the highest percent medication possession ratio (MRP) at 12 months, followed by the MRPs of ibandronate, alendronate, risedronate, and clodronate.
CONCLUSION
This is the first systematic review that shows the comparison of the efficiencies of bisphosphonates for patient persistence and compliance for the treatment of osteoporosis. The data showed that the length of patient persistence was highest for alendronate therapy, whereas patient compliance was highest for etidronate therapy for the treatment of osteoporosis.
Topics: Alendronate; Bone Density Conservation Agents; Diphosphonates; Etidronic Acid; Humans; Osteoporosis; Patient Compliance; Prospective Studies; Retrospective Studies
PubMed: 33855941
DOI: 10.2174/1566524021666210414100227 -
JBMR Plus May 2022Bisphosphonates have been found to be effective in preventing fragility fractures. However, their comparative effectiveness in populations at risk has yet to be defined....
Bisphosphonates have been found to be effective in preventing fragility fractures. However, their comparative effectiveness in populations at risk has yet to be defined. In light of recent clinical trials, we aimed to compare four bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) and to identify which are the most effective for the prevention of fragility fractures. This is an update of a systematic review previously published as part of a NICE HTA report. We conducted a systematic review and network meta-analysis, updating the estimates regarding the comparative effectiveness of the aforementioned bisphosphonates. Studies identified from published and unpublished sources between 2014 and 2021 were added to the studies identified in the previous review. Screening, data extraction and risk of bias assessment were independently undertaken by two reviewers. Outcomes were fractures, femoral neck bone mineral density (BMD), mortality, and adverse events. We identified 25 additional trials, resulting in a total population of 47,007 participants. All treatments had beneficial effects on fractures versus placebo with zoledronate being the most effective treatment in preventing vertebral fractures (hazard ratio [HR] 0.38; 95% credibility interval [CrI], 0.28-0.49). Zoledronate (HR 0.71; 95% CrI, 0.61-0.81) and risedronate (HR 0.70; 95% CrI, 0.53-0.84) were found to be the most effective treatments in preventing nonvertebral fractures. All treatments were associated with increases in femoral neck BMD versus placebo with zoledronate being the most effective treatment mean difference (MD 4.02; 95% CrI, 3.2-4.84). There was a paucity of data regarding hip and wrist fractures. Depending on its cost-effectiveness, zoledronate could be considered a first-line option for people at increased risk of fragility fractures. © 2022 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 35509636
DOI: 10.1002/jbm4.10620 -
Medicine Oct 2018Alendronate has been used to prevent or treat glucocorticoid-induced osteoporosis (GIO), data regarding its efficacy are inconsistent. We conducted the current... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alendronate has been used to prevent or treat glucocorticoid-induced osteoporosis (GIO), data regarding its efficacy are inconsistent. We conducted the current systematic review and meta-analysis to evaluate both efficacy and safety of alendronate in the treatment of GIO.
METHODS
PubMed, Embase, the Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing Databases were searched up through March 1, 2018. Randomized controlled trials (RCTs) involving patients which received alendronate treatment were included. Outcome measures were bone mineral density (BMD) changes, bone fractures, and adverse reactions. Data from the individual studies were pooled using random or fixed effect models based on heterogeneity. Effect size was reported as standardized mean differences (SMD) for continuous outcomes and pooled odds ratios (OR) for dichotomous outcomes, with 95% confidence interval (CI).
RESULTS
Overall, 10 studies involving 1002 patients were included in the present investigation. Alendronate treatment significantly increased BMD of the lumbar spine and femoral neck during 6 to 24 months. These beneficial effects were apparent at 12 months after treatment for the lumbar spine but not the femoral neck BMD. Alendronate treatment did not significantly change fracture risk nor induce significant differences in adverse gastrointestinal effects.
CONCLUSION
Alendronate significantly increases BMD of the lumbar spine and femoral neck in patients with GIO, but does not appear to reduce the risk of fractures. As relatively insufficient data regarding the GIO fracture incidence has been reported, more RCTs need to be carried out to determine the efficacy of alendronate in the prevention of GIO fracture.
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; Female; Glucocorticoids; Humans; Male; Osteoporosis; Osteoporotic Fractures; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30334952
DOI: 10.1097/MD.0000000000012691 -
Clinical Therapeutics Jan 2022The efficacy comparison of osteoporosis treatments can be hindered by the absence of head-to-head trials; instead, network meta-analyses (NMAs) have been used to... (Meta-Analysis)
Meta-Analysis
PURPOSE
The efficacy comparison of osteoporosis treatments can be hindered by the absence of head-to-head trials; instead, network meta-analyses (NMAs) have been used to determine comparative effectiveness. This study was the first to investigate the impact of time point-specific NMAs of osteoporosis treatments on variability in treatments' onset of action caused by their different mechanisms of actions and trial designs.
METHODS
A systematic literature review was conducted to identify randomized controlled trials (RCTs) of treatments for postmenopausal women with osteoporosis, including romosozumab (ROMO), teriparatide (TPTD), abaloparatide (ABL), alendronate (ALN), risedronate (RIS), ibandronate (IB), zoledronic acid/zoledronate (ZOL), denosumab (DEN), and raloxifene (RLX), on at least 1 fracture or bone mineral density (BMD) outcome. Of 100 RCTs identified in 5 databases, 27 RCTs were included for NMAs of new vertebral, nonvertebral, and hip fracture outcomes at 12, 24, and 36 months, and 47 RCTs were included for NMAs of BMD outcomes at lumbar spine, total hip, and femoral neck to compare the relative efficacy of osteoporosis treatments. Quality of included studies was assessed using the Cochrane Risk of Bias tool.
FINDINGS
For vertebral fractures, TPTD (83.63%), ABL (69.11%), and ROMO/ALN (78.70%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO/ALN had the highest probability (54.4%, 64.69%, and 90.29%, respectively) to be the most effective treatment for nonvertebral fractures at 12, 24, and 36 months. For hip fractures, ROMO/ALN (46.31%), ABL (61.1%), and DEN (55.21%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO had the highest probability (76.06%, 44.19%, and 51.78%, respectively) to be the most effective treatment for BMD outcomes at lumbar spine, total hip, and femoral neck.
IMPLICATIONS
The importance of indirectly comparing available osteoporosis treatments using time point-specific NMAs was confirmed because indirect comparison results differed substantially across time points.
Topics: Bone Density; Bone Density Conservation Agents; Female; Humans; Network Meta-Analysis; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Teriparatide; Zoledronic Acid
PubMed: 35058055
DOI: 10.1016/j.clinthera.2021.11.015 -
Medicine Oct 2020The goal of this study was to review relevant randomized controlled trials or case-control studies to determine the clinical efficacy of minodronate in the treatment of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The goal of this study was to review relevant randomized controlled trials or case-control studies to determine the clinical efficacy of minodronate in the treatment of osteoporosis.
METHOD
The relevant studies were identified on PubMed, Cochrane, and Embase databases using appropriate keywords. Pertinent sources in the literature were also reviewed, and all articles published through October 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference, and 95% confidence interval (95% CI) to evaluate and synthesize outcomes.
RESULT
Thirteen studies comprising 3740 patients were included in this study. Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD]: -13.669, 95% confidence interval [CI]: -23.108 to -4.229), bone alkaline phosphatase (BAP) (WMD: -1.26, 95% CI: -2.04 to -0.47) and tartrate-resistant acid phosphatase 5b (WMD: -154.11, 95% CI: -277.85 to -30.37). Minodronate combined with other drugs would significantly decrease BAP (WMD: -3.10, 95% CI: -5.20 to -1.00) than minodronate. Minodronate-naïve would significantly decrease BAP (WMD: -3.00, 95% CI: -5.47 to 0.53) and tartrate-resistant acid phosphatase 5b (WMD: -128.20, 95% CI: -198.11 to -58.29) than minodronate-switch. The incidence of vertebral fracture was significantly decreased in the minodronate group than the other drugs (relative risk: 0.520, 95% CI: 0.363-0.744).
CONCLUSION
Minodronate has better clinical efficacy in the treatment of osteoporosis than other drugs (alendronate, risedronate, raloxifene, or eldecalcitol).
Topics: Aged; Aged, 80 and over; Alendronate; Alkaline Phosphatase; Bone Density Conservation Agents; Case-Control Studies; Collagen Type I; Creatinine; Diphosphonates; Drug Therapy, Combination; Female; Humans; Imidazoles; Male; Middle Aged; Osteoporosis; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Risedronic Acid; Spinal Fractures; Tartrate-Resistant Acid Phosphatase; Treatment Outcome; Vitamin D
PubMed: 33019463
DOI: 10.1097/MD.0000000000022542