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The Cochrane Database of Systematic... Mar 2016Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis represents an important cause of morbidity in people with beta-thalassaemia and its pathogenesis is multifactorial. Factors include bone marrow expansion due to ineffective erythropoiesis, resulting in reduced trabecular bone tissue with cortical thinning; endocrine dysfunction secondary to excessive iron loading, leading to increased bone turnover; and lastly, a predisposition to physical inactivity due to disease complications with a subsequent reduction in optimal bone mineralization.A number of therapeutic strategies have been applied to treat osteoporosis in people with beta-thalassaemia, which include bisphosphonates, with or without, hormone replacement therapy. There are various forms of bisphosphonates, such as clodronate, pamidronate, alendronate and zoledronic acid. Other treatments include calcitonin, calcium, zinc supplementation, hydroxyurea and hormone replacement therapy for preventing hypogonadism.
OBJECTIVES
To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 04 February 2016.
SELECTION CRITERIA
Randomised, placebo-controlled trials in people with thalassaemia with a bone mineral density z score of less than -2 standard deviations for: children less than 15 years old; adult males (15 to 50 years old); and all pre-menopausal females above 15 years and a bone mineral density t score of less than -2.5 standard deviations for post-menopausal females and males above 50 years old.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the eligibility and risk of bias of the included trials, extracted and analysed data and completed the review. We summarised results using risk ratios or rate ratios for dichotomous data and mean differences for continuous data. We combined trial results where appropriate.
MAIN RESULTS
Four trials (with 211 participants) were included; three trials investigated the effect of bisphosphonate therapies and one trial investigated the effect of zinc supplementation. Only one trial was judged to be of good quality (low risk of bias); the remaining trials had a high or unclear risk of bias in at least one key domain.One trial (data not available for analysis) assessing the effect of neridronate (118 participants) reported significant increases in favour of the bisphosphonate group for bone mineral density at the lumbar spine and hip at both six and 12 months. For the femoral neck, a significant difference was noted at 12 months only. A further trial (25 participants) assessed the effect of alendronate and clodronate and found that after two years, bone mineral density increased significantly in the alendronate and clodronate groups as compared to placebo at the lumbar spine, mean difference 0.14 g/cm(2) (95% confidence interval 0.05 to 0.22) and at the femoral neck, mean difference 0.40 g/cm(2) (95% confidence interval 0.22 to 0.57). One 12-month trial (26 participants) assessed the effects of different doses of pamidronate (30 mg versus 60 mg) and found a significant difference in bone mineral density in favour of the 60 mg dose at the lumbar spine and forearm, mean difference 0.43 g/cm(2) (95% CI 0.10 to 0.76), mean difference 0.87 g/cm(2) (95% CI 0.23 to 1.51), respectively, but not at the femoral neck.In a zinc sulphate supplementation trial (42 participants), bone mineral density increased significantly compared to placebo at the lumbar spine after 12 months (37 participants), mean difference 0.15 g/cm(2) (95% confidence interval 0.10 to 0.20) and after 18 months (32 participants), mean difference 0.34 g/cm(2) (95% confidence interval 0.28 to 0.40). The same was true for bone mineral density at the hip after 12 months, mean difference 0.15 g/cm(2) (95% confidence interval 0.11 to 0.19) and after 18 months, mean difference 0.26 g/cm(2) (95% confidence interval 0.21 to 0.31).Fractures were not observed in one trial and not reported in three trials. There were no major adverse effects reported in two of the bisphosphonate trials; in the neridronate trial there was a reduction noted in the use of analgesic drugs and in the reported back pain score in favour of bisphosphonate treatment. Adverse effects were not reported in the trial of different doses of pamidronate or the zinc supplementation trial.
AUTHORS' CONCLUSIONS
There is evidence to indicate an increase in bone mineral density at the femoral neck, lumbar spine and forearm after administration of bisphosphonates and at the lumbar spine and hip after zinc sulphate supplementation. The authors recommend that further long-term randomised control trials on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia and osteoporosis are undertaken.
Topics: Adolescent; Adult; Alendronate; Bone Density; Bone Density Conservation Agents; Child; Clodronic Acid; Diphosphonates; Female; Femur Neck; Humans; Male; Middle Aged; Osteoporosis; Randomized Controlled Trials as Topic; Zinc Sulfate; beta-Thalassemia
PubMed: 26964506
DOI: 10.1002/14651858.CD010429.pub2 -
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 -
The Korean Journal of Internal Medicine Sep 2011The aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
The aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO).
METHODS
A systematic review and meta-analysis were performed to determine treatment efficacy and safety outcomes between monthly oral 150 mg ibandronate and weekly 70 mg alendronate, daily 2.5 mg ibandronate, and a placebo.
RESULTS
Eight randomized controlled trials were included in this systematic review and meta-analysis. Once-monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, showing increased bone mineral density (BMD) in both the lumbar spine and total hip. Pooled data from two cross-over trials showed that significantly more women with PMO preferred once-monthly ibandronate therapy to once-weekly alendronate therapy (relative risk [RR], 2.422; 95% confidence interval [CI], 2.111 to 2.825; p < 1 × 10(-8)) and found the monthly ibandronate regimen more convenient than the weekly alendronate regimen (RR, 3.096; 95% CI, 2.622 to 3.622; p < 1 × 10(-8)). Monthly 150 mg ibandronate therapy resulted in a significantly higher change in BMD of the lumbar spine than with the placebo. A once monthly 150 mg regimen produced greater increases in lumbar spine, total hip, femoral neck, and trochanter BMD than daily treatment, with a similar incidence of adverse events between the groups.
CONCLUSIONS
Once monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, and patients strongly preferred the convenience of monthly ibandronate over weekly alendronate. Monthly 150 mg ibandronate was superior to, and as well tolerated as, the daily treatment.
Topics: Administration, Oral; Alendronate; Bone Density; Bone Density Conservation Agents; Bone and Bones; Diphosphonates; Drug Administration Schedule; Evidence-Based Medicine; Female; Humans; Ibandronic Acid; Osteoporosis, Postmenopausal; Patient Preference; Radiography; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 22016595
DOI: 10.3904/kjim.2011.26.3.340 -
The Cochrane Database of Systematic... Jan 2008Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Alendronate belongs to the bisphosphonate class of drugs,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Alendronate belongs to the bisphosphonate class of drugs, which act to inhibit bone resorption by interfering with the activity of osteoclasts.
OBJECTIVES
To assess the efficacy of alendronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women.
SEARCH STRATEGY
We searched CENTRAL, MEDLINE and EMBASE for relevant randomized controlled trials published between 1966 to 2007.
SELECTION CRITERIA
Women receiving at least one year of alendronate, for postmenopausal osteoporosis, were compared to those receiving placebo and/or concurrent calcium/vitamin D. The outcome was fracture incidence.
DATA COLLECTION AND ANALYSIS
We undertook study selection and data abstraction in duplicate. We performed meta-analysis of fracture outcomes using relative risks and a > 15% relative change was considered clinically important. We assessed study quality through reporting of allocation concealment, blinding and withdrawals.
MAIN RESULTS
Eleven trials representing 12,068 women were included in the review. Relative (RRR) and absolute (ARR) risk reductions for the 10 mg dose were as follows. For vertebral fractures, a significant 45% RRR was found (RR 0.55, 95% CI 0.45 to 0.67). This was significant for both primary prevention, with 45% RRR (RR 0.55, 95% CI 0.38 to 0.80) and 2% ARR, and secondary prevention with 45% RRR (RR 0.55, 95% CI 0.43 to 0.69) and 6% ARR. For non-vertebral fractures, a significant 16% RRR was found (RR 0.84, 95% CI 0.74 to 0.94). This was significant for secondary prevention, with 23% RRR (RR 0.77, 95% CI 0.64 to 0.92) and 2% ARR, but not for primary prevention (RR 0.89, 95% CI 0.76 to 1.04). There was a significant 40% RRR in hip fractures (RR 0.60, 95% CI 0.40 to 0.92), but only secondary prevention was significant with 53% RRR (RR 0.47, 95% CI 0.26 to 0.85) and 1% ARR. The only significance found for wrist was in secondary prevention, with a 50% RRR (RR 0.50 95% CI 0.34 to 0.73) and 2% ARR. For adverse events, we found no statistically significant differences in any included study. However, observational data raise concerns regarding potential risk for upper gastrointestinal injury and, less commonly, osteonecrosis of the jaw.
AUTHORS' CONCLUSIONS
At 10 mg per day, both clinically important and statistically significant reductions in vertebral, non-vertebral, hip and wrist fractures were observed for secondary prevention ('gold' level evidence, www.cochranemsk.org). We found no statistically significant results for primary prevention, with the exception of vertebral fractures, for which the reduction was clinically important ('gold' level evidence).
Topics: Alendronate; Bone Density Conservation Agents; Female; Fractures, Bone; Fractures, Spontaneous; Hip Fractures; Humans; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Spinal Fractures
PubMed: 18253985
DOI: 10.1002/14651858.CD001155.pub2 -
Journal of Clinical Rheumatology :... Mar 2023This study aims to evaluate ibandronate clinical effectiveness in the prevention of osteoporosis-related vertebral fractures (VFs) and nonvertebral fractures (NVFs) in...
BACKGROUND/OBJECTIVE
This study aims to evaluate ibandronate clinical effectiveness in the prevention of osteoporosis-related vertebral fractures (VFs) and nonvertebral fractures (NVFs) in the treatment of postmenopausal osteoporosis.
METHODS
This systematic review was conducted in accordance with the Centre for Reviews and Dissemination's guidance and reporting in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement 2020. A literature search was performed in PubMed and EMBASE since their inception until February 7, 2022. Randomized controlled trials (RCTs), meta-analysis, experimental, and observational studies evaluating adult patients treated with ibandronate and assessed to osteoporotic fractures prevention were included. The risk of bias was assessed according to study design. Data were analyzed using descriptive statistics.
RESULTS
Eight references from 4 RCTs, 7 meta-analyses, and 6 observational studies were included. In RCTs, oral ibandronate was superior to placebo in the prevention of VF. However, the doses were lower than those approved. The meta-analyses confirmed these results and showed that adequate doses of oral ibandronate reduce the risk of NVF compared with insufficient doses. In observational studies, oral ibandronate (in approved doses) reduced the risk of VF compared with no treatment or risedronate or alendronate and the risk of NVF versus risedronate or alendronate; the risk of hip fractures was similar between ibandronate and other oral bisphosphonates.
CONCLUSIONS
There is strong evidence that ibandronate reduces the risk of VF in postmenopausal osteoporosis. The available evidence further suggests that ibandronate may reduce the risk of NVF versus insufficient doses of ibandronate, as well as risedronate or alendronate.
Topics: Female; Humans; Alendronate; Bone Density Conservation Agents; Diphosphonates; Ibandronic Acid; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Risedronic Acid; Observational Studies as Topic
PubMed: 36731043
DOI: 10.1097/RHU.0000000000001902 -
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 -
Journal of Orthopaedic Surgery and... Aug 2021Osteoporosis affects mostly postmenopausal women, leading to deterioration of the microarchitectural bone structure and low bone mass, with an increased fracture risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoporosis affects mostly postmenopausal women, leading to deterioration of the microarchitectural bone structure and low bone mass, with an increased fracture risk with associated disability, morbidity and mortality. This Bayesian network meta-analysis compared the effects of current anti-osteoporosis drugs on bone mineral density.
METHODS
The present systematic review and network meta-analysis follows the PRISMA extension statement to report systematic reviews incorporating network meta-analyses of health care interventions. The literature search was performed in June 2021. All randomised clinical trials that have investigated the effects of two or more drug treatments on BMD for postmenopausal osteoporosis were accessed. The network comparisons were performed through the STATA Software/MP routine for Bayesian hierarchical random-effects model analysis. The inverse variance method with standardised mean difference (SMD) was used for analysis.
RESULTS
Data from 64 RCTs involving 82,732 patients were retrieved. The mean follow-up was 29.7 ± 19.6 months. Denosumab resulted in a higher spine BMD (SMD -0.220; SE 3.379), followed by pamidronate (SMD -5.662; SE 2.635) and zoledronate (SMD -10.701; SE 2.871). Denosumab resulted in a higher hip BMD (SMD -0.256; SE 3.184), followed by alendronate (SMD -17.032; SE 3.191) and ibandronate (SMD -17.250; SE 2.264). Denosumab resulted in a higher femur BMD (SMD 0.097; SE 2.091), followed by alendronate (SMD -16.030; SE 1.702) and ibandronate (SMD -17.000; SE 1.679).
CONCLUSION
Denosumab results in higher spine BMD in selected women with postmenopausal osteoporosis. Denosumab had the highest influence on hip and femur BMD.
LEVEL OF EVIDENCE
Level I, Bayesian network meta-analysis of RCTs.
Topics: Alendronate; Bayes Theorem; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Ibandronic Acid; Network Meta-Analysis; Osteoporosis; Osteoporosis, Postmenopausal; Pharmaceutical Preparations
PubMed: 34452621
DOI: 10.1186/s13018-021-02678-x -
Maturitas Jul 2017Bisphosphonates and denosumab are used extensively in the treatment of postmenopausal osteoporosis. Despite their proven efficacy in the reduction of vertebral and... (Review)
Review
BACKGROUND
Bisphosphonates and denosumab are used extensively in the treatment of postmenopausal osteoporosis. Despite their proven efficacy in the reduction of vertebral and non-vertebral fractures, their optimal duration of use has not been determined. The occurrence of adverse effects, such as osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF), has raised the issue of bisphosphonate or denosumab discontinuation ("drug holiday") after a certain treatment period.
AIM
To assess the effect of bisphosphonate and denosumab discontinuation on fracture risk, as well as its possible benefits in reducing the risk of adverse effects.
METHODS
Systematic review and consensus of expert opinion.
RESULTS AND CONCLUSIONS
Discontinuation of bisphosphonates should be considered in all patients who have beentreated for more than five years with alendronate, risedronate or zoledronic acid. In view of the limited evidence, no robust recommendations can be made for ibandronate and denosumab. If the patient has not experienced fractures before or during therapy and the fracture risk is low, a "drug holiday" canbe recommended. Although there is no solid evidence, 1-2 years for risedronate, 3-5 years for alendronate and 3-6 years for zoledronic acid are suggested. After this time, the patient should be reassessed. If a new fracture is experienced, or fracture risk has increased or BMD remains low (femoral neck T-score ≤-2.5), anti-osteoporotic treatment should be resumed. In the case of denosumab discontinuation, close monitoring is suggested, due to the possibility of rebound fractures.
Topics: Bone Density Conservation Agents; Denosumab; Diphosphonates; Female; Humans; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic
PubMed: 28539165
DOI: 10.1016/j.maturitas.2017.04.008 -
Clinical Rheumatology Nov 2020Osteoporosis is a chronic skeletal disease with an increasing prevalence. Romosozumab, as a monoclonal anti-sclerostin antibody with a dual function, has been produced.... (Meta-Analysis)
Meta-Analysis Review
Osteoporosis is a chronic skeletal disease with an increasing prevalence. Romosozumab, as a monoclonal anti-sclerostin antibody with a dual function, has been produced. In this meta-analysis, we aimed to examine the efficacy of Romosozumab in patients with low bone mineral density. A systematic search was conducted in the most important electronic search engines like Cochrane Library, PubMed, Web of Science, Scopus, Google Scholar, and ClinicalTrials.gov at the end of July 2019 to retrieve randomized controlled trials (RCTs), which evaluated the effect of Romosozumab in patients with osteoporosis and/or low bone mineral density. After evaluating the quality of articles with the Cochrane checklist, data related to the outcomes of bone mineral density (BMD) of lumbar spine, femoral neck, and total hip, risk of clinical, vertebral and non-vertebral fractures, and risk of adverse events were extracted. Quality of evidence was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Heterogeneity between studies was evaluated by I2 and Q statistics. The meta-analysis was performed using CMA v.2.0 software. Of all the 671 initially retrieved articles, seven articles were entered into the meta-analysis after removing duplicates and reviewing papers with inclusion and exclusion criteria. The results of the meta-analysis showed that Romosozumab 210, 140, and 70 mg compared with Alendronate, Teriparatide, and placebo can increase the bone mineral density in the lumbar spine, femoral neck, and total hip. The risk of adverse events like adjudicated cardiovascular serious adverse events and adjudicated cardiovascular death was more in Romosozumab 210 mg in comparison with placebo. However, this difference was not statistically significant. Treatment with anti-sclerostin antibodies can be a proper therapeutic option in patients with osteoporosis and low bone mineral density. Based on the results of this meta-analysis, it seems that Romosozumab, with its dual function, has a positive role in the treatment of osteoporosis and low bone mineral density.
Topics: Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Humans; Teriparatide
PubMed: 32385757
DOI: 10.1007/s10067-020-04948-1 -
Health Technology Assessment... Oct 2016Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture.
OBJECTIVES
To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax and Fosamax Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel and Actonel Once a Week, Warner Chilcott UK Ltd), ibandronic acid (Bonviva, Roche Products Ltd) and zoledronic acid (Aclasta, Novartis Pharmaceuticals UK Ltd)] for the prevention of fragility fracture and to assess their cost-effectiveness at varying levels of fracture risk.
DATA SOURCES
For the clinical effectiveness review, six electronic databases and two trial registries were searched: MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science and BIOSIS Previews, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform. Searches were limited by date from 2008 until September 2014.
REVIEW METHODS
A systematic review and network meta-analysis (NMA) of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for each bisphosphonate treatment strategy and a strategy of no treatment for a simulated cohort of patients with heterogeneous characteristics. The model was populated with effectiveness evidence from the systematic review and NMA. All other parameters were estimated from published sources. A 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 benefit (INB) was estimated using non-parametric regression. Probabilistic sensitivity analysis (PSA) and scenario analyses were used to assess uncertainty.
RESULTS
Forty-six randomised controlled trials (RCTs) were included in the clinical effectiveness systematic review, with 27 RCTs providing data for the fracture NMA and 35 RCTs providing data for the femoral neck bone mineral density (BMD) NMA. All treatments had beneficial effects on fractures versus placebo, with hazard ratios varying from 0.41 to 0.92 depending on treatment and fracture type. The effects on vertebral fractures and percentage change in BMD were statistically significant for all treatments. There was no evidence of a difference in effect on fractures between bisphosphonates. A statistically significant difference in the incidence of influenza-like symptoms was identified from the RCTs for zoledronic acid compared with placebo. Reviews of observational studies suggest that upper gastrointestinal symptoms are frequently reported in the first month of oral bisphosphonate treatment, but pooled analyses of placebo-controlled trials found no statistically significant difference. A strategy of no treatment was estimated to have the maximum INB for patients with a 10-year QFracture risk under 1.5%, whereas oral bisphosphonates provided maximum INB at higher levels of risk. However, the PSA suggested that there is considerable uncertainty regarding whether or not no treatment is the optimal strategy until the QFracture score is around 5.5%. In the model using FRAX, the mean INBs were positive for all oral bisphosphonate treatments across all risk categories. Intravenous bisphosphonates were estimated to have lower INBs than oral bisphosphonates across all levels of fracture risk when estimated using either QFracture or FRAX.
LIMITATIONS
We assumed that all treatment strategies are viable alternatives across the whole population.
CONCLUSIONS
Bisphosphonates are effective in preventing fragility fractures. However, the benefit-to-risk ratio in the lowest-risk patients may be debatable given the low absolute QALY gains and the potential for adverse events. We plan to extend the analysis to include non-bisphosphonate therapies.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013006883.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Alendronate; Bone Density Conservation Agents; Cost of Illness; Cost-Benefit Analysis; Diphosphonates; Humans; Ibandronic Acid; Imidazoles; Models, Econometric; Osteoporotic Fractures; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risedronic Acid; Risk Factors; Social Work; State Medicine; United Kingdom; Zoledronic Acid
PubMed: 27801641
DOI: 10.3310/hta20780