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Osteoporosis International : a Journal... Feb 2015We performed a systematic review and meta-analysis of randomized clinical trials. Early administration of bisphosphonates (BPs) after surgery did not appear to delay... (Meta-Analysis)
Meta-Analysis Review
SUMMARY
We performed a systematic review and meta-analysis of randomized clinical trials. Early administration of bisphosphonates (BPs) after surgery did not appear to delay fracture healing time either radiologically or clinically. Furthermore, the anti-resorptive efficacy of BPs given immediately after surgical repair should positively affect the rate of subsequent fractures.
INTRODUCTION
Bisphosphonates (BPs) are widely used in the prophylaxis and treatment of osteoporosis. However, early administration of BPs after surgical repair of a fracture may limit the reserve capacity of bone to heal. The aim of this review and meta-analysis was to analyze the benefits and adverse effects of early administration of BPs and give recommendations regarding when BPs should be utilized.
METHODS
We identified randomized controlled trials comparing the early administration of BPs to placebo, delayed BP treatment, or no therapy in adult patients after surgery. The search was performed in PubMed, the Cochrane Library, and Embase.
RESULTS
Ten studies with 2888 patients were included. Four trials used alendronate, three trials used zoledronic, two trials used risedronate, and one trial used etidronate. Early administration of BPs was considered less than 3 months after surgery. Patients treated with BP therapy had no significant differences in radiological fracture healing times compared with patients in the control group (mean difference [MD] 0.47, 95% confidence interval [CI] -2.75 to 3.69). There were also no significant differences in the rate of delay or nonunion of fracture healing (odds ratio [OR] 0.98, 95% CI 0.64 to 1.50). However, the bone mineral density (BMD) of total hips did significantly improve after 12 months of treatment with BPs. And most bone turnover markers of patients in the study group were significantly decreased.
CONCLUSIONS
Early administration of BPs after surgery did not appear to delay fracture healing time either radiologically or clinically. Furthermore, according to the changes in BMD and bone turnover markers, the anti-resorptive efficacy of BPs given immediately after surgical repair should positively affect the rate of subsequent fractures.
Topics: Aged; Aged, 80 and over; Alendronate; Bone Density Conservation Agents; Bone Remodeling; Diphosphonates; Etidronic Acid; Female; Fracture Healing; Humans; Imidazoles; Male; Middle Aged; Randomized Controlled Trials as Topic; Risedronic Acid; Treatment Outcome; Zoledronic Acid
PubMed: 25266485
DOI: 10.1007/s00198-014-2903-2 -
Bone Aug 2016To assess the relative efficacy of bisphosphonates (alendronate, risedronate, ibandronate and zoledronic acid) for the treatment of osteoporosis using network... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the relative efficacy of bisphosphonates (alendronate, risedronate, ibandronate and zoledronic acid) for the treatment of osteoporosis using network meta-analysis (NMA).
METHODS
A systematic review of the literature was conducted using PRISMA guidelines. A network meta-analysis was used to determine the relative efficacy of treatments on four fracture outcomes (vertebral, non-vertebral, hip and wrist) and percentage change in femoral neck bone mineral density (BMD). Treatment effects were modelled using an exchangeable treatment effects model. Heterogeneity in treatment effects was explored by considering potential treatment effect modifiers using meta-regression. Where appropriate, inconsistency between direct and indirect evidence was assessed using node-splitting.
RESULTS
46 randomised controlled trials (RCTs) were identified. Twenty seven RCTs provided fracture data and 35 RCTs provided BMD data for analysis. Zoledronic acid was associated with the greatest treatment effect on vertebral fractures (HR 0.41, 95% CrI: 0.28, 0.56) and percentage change in BMD (3.21, 95%: CrI 2.52, 3.86) compared to placebo. The greatest treatment effect on non-vertebral and wrist fractures was given by risedronate (HR 0.72, 95%: CrI 0.53, 0.89 and HR 0.77, 95%: CrI 0.44, 1.24, respectively). For hip fractures the greatest treatment effect was given by alendronate (HR 0.78, 95% CrI: 0.44, 1.30).
CONCLUSIONS
All treatments examined were associated with beneficial effects on fractures and femoral neck BMD relative to placebo. For vertebral fractures and percentage change in femoral neck BMD the treatment effects were statistically significant for all treatments. Pairwise comparisons between treatments indicated that no active treatment was statistically significantly more effective than any other active treatment for fracture outcomes. There was some heterogeneity in treatment effects between studies suggesting differential treatment effects according to study characteristics; however, there was no evidence of differential treatment effects with respect to gender and age.
Topics: Bone Density Conservation Agents; Diphosphonates; Female; Humans; Male; Network Meta-Analysis; Osteoporotic Fractures
PubMed: 27262775
DOI: 10.1016/j.bone.2016.05.013 -
Journal of Bone Metabolism Aug 2020The present study performed a systematic review and meta-analysis of clinical trials using bisphosphonates for bone demineralization in human immunodeficiency virus...
Use of Bisphosphonates, Calcium and Vitamin D for Bone Demineralization in Patients with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome: A Systematic Review and Meta-Analysis of Clinical Trials.
BACKGROUND
The present study performed a systematic review and meta-analysis of clinical trials using bisphosphonates for bone demineralization in human immunodeficiency virus (HIV) patients.
METHODS
A comprehensive literature search was performed from January 2004 to January 2020 considering the bone mineral density (BMD) of the lumbar spine (LS) as the main outcome. Out of 214 titles that met criteria, 9 studies fulfilled the selection criteria.
RESULTS
A total of 394 patients were identified, and they were allocated into 2 groups: the intervention group (200 patients), to whom a combination of alendronate or zoledronate with calcium and vitamin D was administered; and control group (194 patients), to whom only calcium and vitamin D was administered. Clinical profile and indicators of bone metabolism of the participants were evaluated regarding effect size, homogeneity, and consistency. No substantial heterogeneity between the groups was found for the baseline variables, and there was high consistency to the main outcome. The meta-analysis shows a significant difference in post-treatment BMD, favoring the intervention over the control treatment. The intervention improved LS density up to 0.227 g/cm², raising the average to the levels of general population. Adverse effects related to intervention were fever immediately after zoledronate administration and gastrointestinal complaints during alendronate usage. Other adverse effects were barely reported and poorly connected to intervention by studies' authors, despite all of them have been successfully resolved.
CONCLUSIONS
This study provides evidence that BMD post-treatment is better in HIV patients who used bisphosphonates combined with calcium and vitamin D.
PubMed: 32911582
DOI: 10.11005/jbm.2020.27.3.175 -
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 -
The Cochrane Database of Systematic... Mar 2015Pain is one of the most common symptoms in children and young people (CYP) with life-limiting conditions (LLCs) which include a wide range of diagnoses including cancer.... (Review)
Review
BACKGROUND
Pain is one of the most common symptoms in children and young people (CYP) with life-limiting conditions (LLCs) which include a wide range of diagnoses including cancer. The current literature indicates that pain is not well managed, however the evidence base to guide clinicians is limited. There is a clear need for evidence from a systematic review to inform prescribing.
OBJECTIVES
To evaluate the evidence on the effectiveness of different pharmacological interventions used for pain in CYP with LLCs.
SEARCH METHODS
The following electronic databases were searched up to December 2014: CENTRAL (in the Cochrane Library), MEDLINE, EMBASE, PsycINFO and CINAHL. In addition, we searched conference proceedings and reference lists of included studies. For completeness, we also contacted experts in the field. No language restrictions were applied.
SELECTION CRITERIA
Randomised controlled trials (RCTs), quasi-randomised studies and other studies that included a clearly defined comparator group were included. The studies investigated pharmacological treatments for pain associated with LLCs in CYP. The treatment included those specifically developed to treat pain and those that acted as an adjuvant, where the treatment was not primarily developed to treat pain but has pain relieving properties. The LLC was identified by its inclusion in the Richard Hain Directory of LLCs.
DATA COLLECTION AND ANALYSIS
Citations were screened by five review authors. Data were extracted by one review author and checked by a second. Two review authors assessed the risk of bias of included studies. A sufficient number of studies using homogeneous outcomes was not identified so a meta-analysis was not possible.
MAIN RESULTS
We identified 24,704 citations from our database search. Nine trials with 379 participants fulfilled our inclusion criteria. Participants had cerebral palsy (CP) in five of the studies and osteogenesis imperfecta (OI) in the other four. Participants across the trials ranged in age from 2 to 19 years. All studies, apart from one cross-over trial, were parallel designed RCTs. Three of the trials on CP evaluated intrathecal baclofen (ITB) and two botulinum toxin A (BoNT-A). All of the OI trials evaluated the use of bisphosphonates (two alendronate and one pamidronate). No trials were identified that evaluated a commonly used analgesic in this patient group. Pain was a secondary outcome in five of the eight identified studies. Overall the quality of the trials was mixed. Only one study involved over 100 participants.For the two ITB studies for pain in CP, in the same study population but assessed at different time points in their disease, both found an effect on pain favouring the intervention compared to the control group (standard care or placebo) (mean difference (MD) 4.20, 95% confidence interval (CI) 2.15 to 6.25; MD 26.60, 95% CI 2.61 to 50.59, respectively). In these studies most of the adverse events related to the procedure or device for administration rather than the drug, such as swelling at the pump site. In one trial there were also eight serious adverse effects; these included difficulty swallowing and an epileptic seizure. The trial did not state if these occurred in the intervention group. At follow-up in both BoNT-A trials there was no evidence of a difference in pain between the trial arms among CP participants. The adverse events in the BoNT-A trials mostly involved those who received the intervention drug and involved seizures. Gastrointestinal problems were the most frequent adverse event in those who received alendronate. The trial investigating pamidronate found no evidence of a difference in pain compared to the control group. No adverse events were reported in this trial.
AUTHORS' CONCLUSIONS
Published, controlled evidence on the pharmacological interventions for pain in CYP with LLCs is limited. The evidence that is currently available evaluated pain largely as a secondary outcome and the drugs used were all adjuvants and not always commonly used in general paediatric palliative care for pain. Based on current data this systematic review is unable to determine the effects of pharmacological interventions for pain for CYP with LLCs. Future trials with larger populations should examine the effects of the drugs commonly used as analgesics; with the rising prevalence of many LLCs this becomes more necessary.
Topics: Adolescent; Alendronate; Baclofen; Botulinum Toxins, Type A; Cerebral Palsy; Child; Child, Preschool; Diphosphonates; Gastrointestinal Diseases; Humans; Injections, Spinal; Neuromuscular Agents; Osteogenesis Imperfecta; Pain; Pamidronate; Seizures; Young Adult
PubMed: 25768935
DOI: 10.1002/14651858.CD010750.pub2 -
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 -
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 -
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 -
AIDS Reviews 2014An increased prevalence of osteopenia and osteoporosis has been observed in HIV-infected cohorts. We investigated the effect of bisphosphonates on bone mineral density... (Meta-Analysis)
Meta-Analysis Review
An increased prevalence of osteopenia and osteoporosis has been observed in HIV-infected cohorts. We investigated the effect of bisphosphonates on bone mineral density in adults with HIV infection. Outcomes of interest were bone mineral density changes measured by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck, and total hip, and adverse events. Data were pooled using the fixed-effects model. We identified eight randomized controlled trials meeting our inclusion criteria, involving 328 participants. Five trials compared alendronate with placebo or no intervention; in three trials the intervention arm received zoledronate. A significant increase in bone mineral density at the lumbar spine was observed in the bisphosphonate group at 48 weeks (MD: 2.84%; 95% CI: 2.11-3.57) and 96 weeks (MD: 6.76%; 95% CI: 4.98-8.54); analogously, bisphosphonates were associated with an increase in total hip bone mineral density at 48 weeks (MD: 2.12%; 95% CI: 1.43-2.81) and 96 weeks (MD: 3.2%; 95% CI: 1.52-4.88). Bisphosphonates were generally well tolerated; no drug-related withdrawals were reported in the five randomized controlled trials assessing alendronate, whereas two patients out of 104 receiving zoledronate experienced acute-phase reactions. In conclusion, administration of oral and intravenous bisphosphonates was associated with increased bone mineral density at the lumbar spine and total hip over two years in HIV-positive patients. However, none of the included trials were long enough to detect the impact of bisphosphonates on a clinically important outcome such as fracture risk. Larger studies with extended follow-up are warranted.
Topics: Absorptiometry, Photon; Alendronate; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Diphosphonates; Evidence-Based Medicine; Femur Neck; Fractures, Bone; HIV Infections; Hip; Humans; Imidazoles; Lumbar Vertebrae; Osteoporosis; Randomized Controlled Trials as Topic; Zoledronic Acid
PubMed: 25300622
DOI: No ID Found -
Journal of Orthopaedic Science :... Feb 2024Periprosthetic bone loss following total hip arthroplasty (THA) threatens prosthesis stability. This systematic review and network meta-analysis aimed to compare the...
BACKGROUND
Periprosthetic bone loss following total hip arthroplasty (THA) threatens prosthesis stability. This systematic review and network meta-analysis aimed to compare the efficacy of anti-osteoporotic drugs for measures of hip function according to functional outcomes, periprosthetic femoral bone mineral density loss in each Gruen zone, and revision surgery after THA.
METHODS
The systematic search of six literature databases was conducted in December 2021 in accordance with PRISMA guidelines. Adult participants who underwent primary THA were included. A random-effects network meta-analysis was performed within a frequentist framework, and the confidence in the evidence for each outcome was evaluated using the CINeMA tool, which assessed the credibility of results from the network meta-analysis. We included 22 randomized controlled trials (1243 participants) comparing the efficacy and safety of bisphosphonates (including etidronate, clodronate, alendronate, risedronate, pamidronate, and zoledronate), denosumab, selective estrogen receptor modulator, teriparatide, calcium + vitamin D, calcium, and vitamin D. We defined the period for revision surgery as the final follow-up period.
RESULTS
Raloxifene, bisphosphonate, calcium + vitamin D, and denosumab for prosthetic hip function might have minimal differences when compared with placebos. The magnitude of the anti-osteoporotic drug effect on periprosthetic femoral bone loss varied across different Gruen zones. Bisphosphonate, denosumab, teriparatide might be more effective than placebo in Gruen zone 1 at 12 months after THA. Additionally, bisphosphonate might be more effective than placebo in Gruen zones 2, 5, 6, and 7 at 12 months after THA. Denosumab was efficacious in preventing bone loss in Gruen zones 6 and 7 at 12 months after THA. Teriparatide was likely to be efficacious in preventing bone loss in Gruen zone 7 at 12 months after THA. Raloxifene was slightly efficacious in preventing bone loss in Gruen zones 2 and 3 at 12 months after THA. Calcium was slightly efficacious in preventing bone loss in Gruen zone 5 at 12 months after THA. None of the studies reported revision surgery.
CONCLUSIONS
Bisphosphonate and denosumab may be effective anti-osteoporotic drugs for preventing periprosthetic proximal femoral bone loss due to stress shielding after THA, particularly in cementless proximal fixation stems, which are the most commonly used prostheses worldwide.
PubMed: 38342711
DOI: 10.1016/j.jos.2024.01.011