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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 -
Health Technology Assessment... Jun 2020Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture.
BACKGROUND
Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture.
OBJECTIVES
The objectives were to evaluate the clinical effectiveness, safety and cost-effectiveness of non-bisphosphonates {denosumab [Prolia; Amgen Inc., Thousand Oaks, CA, USA], raloxifene [Evista; Daiichi Sankyo Company, Ltd, Tokyo, Japan], romosozumab [Evenity; Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and Amgen Inc.] and teriparatide [Forsteo; Eli Lilly and Company, Indianapolis, IN, USA]}, compared with each other, bisphosphonates or no treatment, for the prevention of fragility fracture.
DATA SOURCES
For the clinical effectiveness review, nine electronic databases (including MEDLINE, EMBASE and the World Health Organization International Clinical Trials Registry Platform) were searched up to July 2018.
REVIEW METHODS
A systematic review and network meta-analysis of fracture and femoral neck bone mineral density were conducted. A review of published economic analyses was undertaken and a model previously used to evaluate bisphosphonates was adapted. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years for a simulated cohort of patients with heterogeneous characteristics. This was done for each non-bisphosphonate treatment, a strategy of no treatment, and the five bisphosphonate treatments previously evaluated. The model was populated with effectiveness evidence from the systematic review and network meta-analysis. All other parameters were estimated from published sources. An NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net monetary benefit was estimated using non-parametric regression. A probabilistic sensitivity analysis and scenario analyses were used to assess uncertainty.
RESULTS
Fifty-two randomised controlled trials of non-bisphosphonates were included in the clinical effectiveness systematic review and an additional 51 randomised controlled trials of bisphosphonates were included in the network meta-analysis. All treatments had beneficial effects compared with placebo for vertebral, non-vertebral and hip fractures, with hazard ratios varying from 0.23 to 0.94, depending on treatment and fracture type. The effects on vertebral fractures and the percentage change in bone mineral density were statistically significant for all treatments. The rate of serious adverse events varied across trials (0-33%), with most between-group differences not being statistically significant for comparisons with placebo/no active treatment, non-bisphosphonates or bisphosphonates. The incremental cost-effectiveness ratios were > £20,000 per quality-adjusted life-year for all non-bisphosphonate interventions compared with no treatment across the range of QFracture and FRAX scores expected in the population eligible for fracture risk assessment. The incremental cost-effectiveness ratio for denosumab may fall below £30,000 per quality-adjusted life-year at very high levels of risk or for high-risk patients with specific characteristics. Raloxifene was dominated by no treatment (resulted in fewer quality-adjusted life-years) in most risk categories.
LIMITATIONS
The incremental cost-effectiveness ratios are uncertain for very high-risk patients.
CONCLUSIONS
Non-bisphosphonates are effective in preventing fragility fractures, but the incremental cost-effectiveness ratios are generally greater than the commonly applied threshold of £20,000-30,000 per quality-adjusted life-year.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42018107651.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 29. See the NIHR Journals Library website for further project information.
Topics: Bone Density Conservation Agents; Clinical Trials as Topic; Cost-Benefit Analysis; Denosumab; Diphosphonates; Humans; Osteoporotic Fractures; Quality-Adjusted Life Years; Raloxifene Hydrochloride; Teriparatide; Treatment Outcome
PubMed: 32588816
DOI: 10.3310/hta24290 -
The Journal of Clinical Endocrinology... May 2020Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing.
CONTEXT
Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing.
EVIDENCE ACQUISITION
We performed a systematic review to evaluate effects of teriparatide, raloxifene, and denosumab on healing and occurrence of AFF.
EVIDENCE SYNTHESIS
We retrieved 910 references and reviewed 67 papers, including 31 case reports, 9 retrospective and 3 prospective studies on teriparatide. There were no RCTs. We pooled data on fracture union (n = 98 AFFs on teriparatide) and found that radiological healing occurred within 6 months of teriparatide in 13 of 30 (43%) conservatively managed incomplete AFFs, 9 of 10 (90%) incomplete AFFs with surgical intervention, and 44 of 58 (75%) complete AFFs. In 9 of 30 (30%) nonoperated incomplete AFFs, no union was achieved after 12 months and 4 (13%) fractures became complete on teriparatide. Eight patients had new AFFs during or after teriparatide. AFF on denosumab was reported in 22 patients, including 11 patients treated for bone metastases and 8 without bisphosphonate exposure. Denosumab after AFF was associated with recurrent incomplete AFFs in 1 patient and 2 patients of contralateral complete AFF. Eight patients had used raloxifene before AFF occurred, including 1 bisphosphonate-naïve patient.
CONCLUSIONS
There is no evidence-based indication in patients with AFF for teriparatide apart from reducing the risk of typical fragility fractures, although observational data suggest that teriparatide might result in faster healing of surgically treated AFFs. Awaiting further evidence, we formulate recommendations for treatment after an AFF based on expert opinion.
Topics: Bone Density Conservation Agents; Denosumab; Diphosphonates; Europe; Femoral Fractures; Humans; Osteoporotic Fractures; Practice Patterns, Physicians'; Raloxifene Hydrochloride; Risk Assessment; Risk Factors; Societies, Medical; Teriparatide
PubMed: 31867670
DOI: 10.1210/clinem/dgz295 -
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 -
JAMA Sep 2019Medications to reduce risk of breast cancer are effective for women at increased risk but also cause adverse effects.
IMPORTANCE
Medications to reduce risk of breast cancer are effective for women at increased risk but also cause adverse effects.
OBJECTIVE
To update the 2013 US Preventive Services Task Force systematic review on medications to reduce risk of primary (first diagnosis) invasive breast cancer in women.
DATA SOURCES
Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE, and MEDLINE (January 1, 2013, to February 1, 2019); manual review of reference lists.
STUDY SELECTION
Discriminatory accuracy studies of breast cancer risk assessment methods; randomized clinical trials of tamoxifen, raloxifene, and aromatase inhibitors for primary breast cancer prevention; studies of medication adverse effects.
DATA EXTRACTION AND SYNTHESIS
Investigators abstracted data on methods, participant characteristics, eligibility criteria, outcome ascertainment, and follow-up. Results of individual trials were combined by using a profile likelihood random-effects model.
MAIN OUTCOMES AND MEASURES
Probability of breast cancer in individuals (area under the receiver operating characteristic curve [AUC]); incidence of breast cancer, fractures, thromboembolic events, coronary heart disease events, stroke, endometrial cancer, and cataracts; and mortality.
RESULTS
A total of 46 studies (82 articles [>5 million participants]) were included. Eighteen risk assessment methods in 25 studies reported low accuracy in predicting the probability of breast cancer in individuals (AUC, 0.55-0.65). In placebo-controlled trials, tamoxifen (risk ratio [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials [n = 28 421]), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials [n = 17 806]), and the aromatase inhibitors exemestane and anastrozole (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials [n = 8424]) were associated with a lower incidence of invasive breast cancer. Risk for invasive breast cancer was higher for raloxifene than tamoxifen in 1 trial after long-term follow-up (RR, 1.24 [95% CI, 1.05-1.47]; n = 19 747). Raloxifene was associated with lower risk for vertebral fractures (RR, 0.61 [95% CI, 0.53-0.73]; 2 trials [n = 16 929]) and tamoxifen was associated with lower risk for nonvertebral fractures (RR, 0.66 [95% CI, 0.45-0.98]; 1 trial [n = 13 388]) compared with placebo. Tamoxifen and raloxifene were associated with increased thromboembolic events compared with placebo; tamoxifen was associated with more events than raloxifene. Tamoxifen was associated with higher risk of endometrial cancer and cataracts compared with placebo. Symptomatic effects (eg, vasomotor, musculoskeletal) varied by medication.
CONCLUSIONS AND RELEVANCE
Tamoxifen, raloxifene, and aromatase inhibitors were associated with lower risk of primary invasive breast cancer in women but also were associated with adverse effects that differed between medications. Risk stratification methods to identify patients with increased breast cancer risk demonstrated low accuracy.
Topics: Adult; Area Under Curve; Aromatase Inhibitors; Breast Neoplasms; Female; Genes, BRCA1; Genes, BRCA2; Humans; Mutation; Practice Guidelines as Topic; Raloxifene Hydrochloride; Risk Assessment; Risk Factors; Selective Estrogen Receptor Modulators; Tamoxifen
PubMed: 31479143
DOI: 10.1001/jama.2019.5780