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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 Studies identified from published and unpublished sources between 2014 and 2021 were added to the studies identified in the previous review.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 -
Frontiers in Endocrinology 2022To assess the benefit and harm of Chinese medicine Xianling Gubao (XLGB) capsule compared to conventional medication or placebo to inform clinical practice. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the benefit and harm of Chinese medicine Xianling Gubao (XLGB) capsule compared to conventional medication or placebo to inform clinical practice.
METHODS
We included randomized controlled trials (RCTs) with Jadad score ≥3 of XLGB capsule compared to pharmaceutical medication, placebo, or no treatment for primary osteoporosis. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database (Sino-Med) from their inception till November 13, 2021. Study selection and data extraction were done by two authors independently. The methodological quality of the RCTs was assessed using Cochrane's risk of bias tool. The effect size was presented as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI).
RESULTS
Our searches identified 2292 records and after exclusions, eight trials involving 846 participants were included. There was no statistically significant difference between conventional medications with or without XLGB on new fracture (RR: 0.50, 95% CI: [0.13, 1.87]). Quality of life by SF-36 questionnaire of XLGB plus calcium carbonate, vitamin D, and calcitriol was improved than that of without XLGB (MD: 6.72 scores, 95% CI: [2.82, 10.62]). XLGB increased bone mineral density similarly as calcium carbonate plus vitamin D (MD: 0.21, 95% CI: [-0.16, 0.58]) or as alendronate sodium, calcium carbonate plus vitamin D (MD: 0.00, 95% CI: [-0.10, 0.10]), but it had no additional effect as an add-on treatment to conventional medications (MD: 0.13, 95% CI: [-0.12, 0.37]). XLGB relieved pain visual analog scale more effectively when combined with medications (MD: -1.55 score, 95% CI: [-2.47, -0.63]). XLGB as monotherapy did not increase adverse events (RR: 0.63, 95% CI: [0.28, 1.41]), or as an add-on treatment (RR: 0.25, 95% CI: [0.03, 2.16]).
CONCLUSION
This systematic review shows that XLGB capsule appears to be safe and has a beneficial effect on the quality of life and pain relief when used alone or in combination with conventional medications in osteoporosis patients. Further large, rigorous trials are warranted to test its long-term benefit.
Topics: Calcium Carbonate; Humans; Osteoporosis; Pain; Randomized Controlled Trials as Topic; Vitamin D
PubMed: 35464071
DOI: 10.3389/fendo.2022.870277 -
Yakugaku Zasshi : Journal of the... 2022Medical big data are accumulated daily by medical staff in clinical settings. We developed a formulary in 2016 using medical big data from eight hospitals affiliated...
Medical big data are accumulated daily by medical staff in clinical settings. We developed a formulary in 2016 using medical big data from eight hospitals affiliated with Showa University, Japan (3200 beds). In 2019, we revised the procedure from the perspective of authenticity, reproducibility, and clarity to develop a medicine formulary with unbiased data. Briefly, we organized two teams of expert physicians. Team 1 was a systematic review team that conducted a literature search using systematic review. Team 2 was a medical big data team that conducted the analysis using medical big data. Both teams developed a bisphosphonate formulary. First and second team recommendations were alendronic acid and minodronic acid, and alendronic acid and risedronic acid, respectively. Discussion between the two teams yielded alendronic acid only in the bisphosphonate formulary. We developed reports for the bisphosphonate formulary that included conflicts of interest, the role of each staff member in developing the formulary, and the process for determining the formulary. To use our formulary in a community context, we updated the formulary on our website. We tried to substantiate our bisphosphonate formulary and make a recommendation to change the bisphosphonates according to our formulary. The formulary is focused on controlling the economic burden of medical expenses. We believe that the formulary needs to represent authenticity, reproducibility, and clarity in the procedure and conflicts of interest, with unbiased data to preclude context (hospital)-convenient decisions.
Topics: Big Data; Humans; Japan; Reproducibility of Results
PubMed: 35370186
DOI: 10.1248/yakushi.21-00178-2 -
Frontiers in Endocrinology 2022Although some studies have found that nitrates were beneficial for bone health, the findings are inconsistent. To assess the efficacy of nitrates for bone health, we... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although some studies have found that nitrates were beneficial for bone health, the findings are inconsistent. To assess the efficacy of nitrates for bone health, we conducted a meta-analysis.
METHODS
PubMed, EMBASE databases, Cochrane Library for relevant articles published before December 2021 were searched. All observational and randomized controlled studies that reporting bone mineral density (BMD), fractures with nitrates use were included. A meta-analysis was performed to calculate risk ratios (RRs) for fractures, change differences for bone mineral density.
RESULTS
Four cohort studies and two case-control studies examining the association between nitrates use and fractures were identified. The nitrates use was not associated with any fracture risk (RR = 0.97; 95% CI, 0.94-1.01; = 31.5%) and hip fracture (RR = 0.88; 95% CI, 0.76-1.02; = 74.5%). Subgroup analyses revealed no differences in fracture risk, whereas two cohort studies revealed a reduced risk of hip fracture (RR = 0.71, 95% CI, 0.58-0.86, = 0.0%). There were no statistically significant differences in BMD percent changes at lumbar spine (WMD = -0.07, 95% CI,-0.78-0.65; = 0.0%), total hip (WMD = -0.42, 95% CI,-0.88-0.04; = 0.0%), femoral neck (WMD = -0.38, 95% CI,-1.02-0.25; = 0.0%), or total body (WMD = -0.17, 95% CI,-0.51-0.17; = 0.0%) in two randomized controlled trials (RCTs) compared with a placebo. Another two RCTs compared nitrates with alendronate. Nitrates were comparable to alendronate in increasing bone mineral density at lumbar spine (WMD = 0.00, 95% CI,-0.01-0.02; = 0.0%). Besides, the most common adverse effect was headache, contributing to low adherence to therapy.
CONCLUSION
Our meta-analysis showed no association between nitrates use and fractures in observational studies. The results of RCTs on the usage of nitrates and their effects on BMD were inconsistent. High-quality, long-term studies are needed to clarify the efficacy of nitrates for bone health.
Topics: Bone Density; Bone and Bones; Female; Fractures, Bone; Humans; Isosorbide Dinitrate; Male; Nitrates; Nitric Oxide Donors; Nitroglycerin; Risk Factors
PubMed: 35222289
DOI: 10.3389/fendo.2022.833932 -
Frontiers in Pharmacology 2022Chronic kidney disease (CKD) is associated with bone and mineral metabolism. In this study we evaluated the comparative efficacies and safety of osteoporosis... (Review)
Review
Chronic kidney disease (CKD) is associated with bone and mineral metabolism. In this study we evaluated the comparative efficacies and safety of osteoporosis medications in patients with CKD or a history of kidney transplantation, and make recommendations for the best choice of osteoporosis treatment among patients with CKD or a history of kidney transplantation. We systemically searched for randomized controlled trials published in PubMed, Embase, and Cochrane databases up to June 2020. Network-meta analysis was used to compare the relative effectiveness of different treatments. A random-effects model was used when heterogeneity was expected. The safety of different treatments was also evaluated in terms of reported major adverse events. A total of 17 studies with data from 10,214 patients who had stage 2-5 CKD, were receiving dialysis, or had a history of kidney transplantation were included in the network meta-analysis. Treatment with teriparatide, denosumab, alendronate, and raloxifene were all associated with a significantly reduced risk of fractures compared to treatment with placebos [teriparatide: odds ratio (OR) = 0.19, 95% confidence interval (CI): 0.10-0.35; denosumab: OR = 0.40, 95% CI: 0.27-0.58; alendronate: OR = 0.61, 95% CI: 0.40-0.92; raloxifene: OR = 0.52, 95% CI: 0.41-0.67]. The rank probability and the surface under the cumulative ranking (SUCRA) values suggested that teriparatide ranked the highest for improvement in vertebral bone mineral density (BMD) (SUCRA = 97.8%), whereas denosumab ranked the highest for improvement in femoral neck BMD (SUCRA = 88.3%). Teriparatide and denosumab seem to be the most effective treatments for preventing bone loss and reducing the risk of fracture in our network comparison. However, because of the limitations and potential biases in the reviewed studies, there is still some uncertainty about the best treatment options for osteoporosis in patients with CKD or a history of kidney transplantation. : [PROSPERO], identifier [CRD42020209830].
PubMed: 35222037
DOI: 10.3389/fphar.2022.822178 -
Otology & Neurotology : Official... Jun 2022To systematically review the evidence for the use of bisphosphonate therapy in otosclerosis through clinically relevant outcomes.
OBJECTIVE
To systematically review the evidence for the use of bisphosphonate therapy in otosclerosis through clinically relevant outcomes.
DATABASES REVIEWED
MEDLINE, EMBASE, PubMed, and CINAHL databases were searched up to July 12, 2021.
METHODS
RCTs and cohort studies investigating the effect of bisphosphate therapy on adults or children diagnosed with otosclerosis were included. The risk of bias within trials was examined using the ROB2 tool for RCTs, and the ROBINS-I for non-RCTs.
RESULTS
Three studies reported over five publications were included in the systematic review. Data from one RCT at 6 months did not demonstrate any improvement nor deterioration in audiological outcomes in participants treated with Sodium Alendronate. Data from MRI in this group demonstrated improvements in the SI of the otosclerotic foci at the RAOW compared to participants taking placebo. In another RCT, improvements in audiological outcomes were seen at 12 and 24 months in individuals treated with Etidronate Sodium. Long-term data from a retrospective cohort study demonstrated stabilisation of hearing in individuals with otosclerosis and progressive SNHL.
CONCLUSION
There is insufficient evidence to recommend the routine use of bisphosphonates in otosclerosis patients at present. Long-term retrospective data has suggested a role for bisphosphonates in the subset of patients with deteriorating sensorineural hearing loss with the aim of hearing stabilisation. Adequately powered RCTs with long term follow up will be required to evaluate this further.
Topics: Adult; Child; Diphosphonates; Etidronic Acid; Hearing Loss, Sensorineural; Humans; Otosclerosis; Retrospective Studies; Sodium
PubMed: 35213475
DOI: 10.1097/MAO.0000000000003510 -
Osteoporosis International : a Journal... Jun 2022Bisphosphonates are effective in preventing fragility fractures; however, high rates of adherence are needed to preserve clinical benefits. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bisphosphonates are effective in preventing fragility fractures; however, high rates of adherence are needed to preserve clinical benefits.
OBJECTIVE
To investigate persistence and compliance to oral and intravenous bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate).
METHODS
Searches of 12 databases, unpublished sources, and trial registries were conducted, covering the period from 2000 to April 2021. Screening, data extraction, and risk of bias assessment (Cochrane Collaboration risk-of-bias tool 1.0 & ROBINS-I) were independently undertaken by two study authors. Randomised controlled trials (RCTs) and observational studies that used prescription claim databases or hospital medical records to examine patients' adherence were included. Network meta-analyses (NMA) embedded within a Bayesian framework were conducted, investigating users' likelihood in discontinuing bisphosphonate treatment. Where meta-analysis was not possible, data were synthesised using the vote-counting synthesis method.
RESULTS
Fifty-nine RCTs and 43 observational studies were identified, resulting in a total population of 2,656,659 participants. Data from 59 RCTs and 24 observational studies were used to populate NMAs. Zoledronate users were the least likely to discontinue their treatment HR = 0.73 (95%CrI: 0.61, 0.88). Higher rates of compliance were observed in those receiving intravenous treatments. The paucity of data and the heterogeneity in the reported medication possession ratio thresholds precluded a NMA of compliance data.
CONCLUSIONS
Users of intravenously administered bisphosphonates were found to be the most adherent to treatment among bisphosphonates' users. Patterns of adherence will permit the more precise estimation of clinical and cost-effectiveness of bisphosphonates.
TRIAL REGISTRATION
PROSPERO 2020 CRD42020177166.
Topics: Bone Density Conservation Agents; Diphosphonates; Fractures, Bone; Humans; Medication Adherence; Network Meta-Analysis; Zoledronic Acid
PubMed: 35188591
DOI: 10.1007/s00198-022-06350-w -
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 -
Osteoporosis International : a Journal... May 2022This paper systematically reviewed and assessed all retrievable pharmacoeconomic studies on denosumab for the treatment of osteoporosis. Denosumab was more... (Review)
Review
UNLABELLED
This paper systematically reviewed and assessed all retrievable pharmacoeconomic studies on denosumab for the treatment of osteoporosis. Denosumab was more cost-effective in patients with older age, prior fracture experience, lower BMD T-scores, and more risk factors. ESCEO-IOF guidelines were more applicable to improve the quality of pharmacoeconomic studies in osteoporosis.
INTRODUCTION
There are many pharmacoeconomic studies on denosumab for osteoporosis. However, the corresponding reviews are outdated or incomplete and need to be updated and refined. This article aims to systematically review and evaluate all retrievable pharmacoeconomic studies of denosumab for osteoporosis.
METHODS
A systematic literature search was performed utilizing PubMed, EMBASE(Ovid), Proquest(EconLit), Chongqing VIP, WanFang Database, and Chinese National Knowledge Infrastructure to identify full-text articles published before September 2021. The quality of full-text articles was evaluated by the Consolidated Health Economic Evaluation Reporting Standards(CHEERS) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases International Osteoporosis Foundation guideline(ESCEO-IOF).
RESULTS
In total, 21 full-text articles were eligible for inclusion. Denosumab for postmenopausal osteoporosis was not dominant compared to zoledronate and teriparatide. However, denosumab was dominant compared with strontium ranelate, raloxifene, and ibandronate in patients over 65 years. The probabilities of denosumab being cost-effective or dominant were more than 85% compared with no treatment and risedronate in patients aged over 70 years. Compared to alendronate, the highest rate of denosumab dominance occurred in patients aged 65 to 75 years, at about 65%. Most of the articles had higher CHEERS scores than ESCEO-IOF scores (converted into percentages).
CONCLUSIONS
The cost-effectiveness of denosumab for the treatment of osteoporosis was influenced by multiple factors. Generally, denosumab was more cost-effective in patients with older age, prior fracture experience, lower BMD T-scores, and more risk factors. ESCEO-IOF guidelines were more applicable to improve the transparency, generalization, and quality of pharmacoeconomic studies in osteoporosis.
Topics: Bone Density Conservation Agents; Cost-Benefit Analysis; Denosumab; Female; Fractures, Bone; Humans; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 35059777
DOI: 10.1007/s00198-021-06268-9 -
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