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The Cochrane Database of Systematic... Dec 2017Bisphosphonates are specific inhibitors of osteoclastic activity and are used in the treatment of patients with multiple myeloma (MM). While bisphosphonates are shown to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bisphosphonates are specific inhibitors of osteoclastic activity and are used in the treatment of patients with multiple myeloma (MM). While bisphosphonates are shown to be effective in reducing vertebral fractures and pain, their role in improving overall survival (OS) remains unclear. This is an update of a Cochrane review first published in 2002 and previously updated in 2010 and 2012.
OBJECTIVES
To assess the evidence related to benefits and harms associated with use of various types of bisphosphonates (aminobisphosphonates versus non-aminobisphosphonates) in the management of patients with MM. Our primary objective was to determine whether adding bisphosphonates to standard therapy in MM improves OS and progression-free survival (PFS), and decreases skeletal-related morbidity. Our secondary objectives were to determine the effects of bisphosphonates on pain, quality of life, incidence of hypercalcemia, incidence of bisphosphonate-related gastrointestinal toxicities, osteonecrosis of jaw (ONJ) and hypocalcemia.
SEARCH METHODS
We searched MEDLINE, Embase (September 2011 to July 2017) and the CENTRAL (2017, Issue 7) to identify all randomized controlled trial (RCT) in MM up to July 2017 using a combination of text and MeSH terms.
SELECTION CRITERIA
Any randomized controlled trial (RCT) comparing bisphosphonates versus placebo/no treatment/bisphosphonates and observational studies or case reports examining bisphosphonate-related ONJ in patients with MM were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors extracted the data. Data were pooled and reported as hazard ratio (HR) or risk ratio (RR) using a random-effects model. We used meta-regression to explore statistical heterogeneity. Network meta-analysis using Bayesian approach was conducted.
MAIN RESULTS
In this update, we included four new studies (601 participants), resulting in a total of 24 included studies.Twenty RCTs compared bisphosphonates with either placebo or no treatment and four RCTs involved another bisphosphonate as a comparator. The 24 included RCTs enrolled 7293 participants. Pooled results showed that there was moderate-quality evidence of a reduction in mortality with on OS from 41% to 31%, but the confidence interval is consistent with a larger reduction and small increase in mortality compared with placebo or no treatment (HR 0.90, 95% CI 0.76 to 1.07; 14 studies; 2706 participants). There was substantial heterogeneity among the included RCTs (I = 65%) for OS. To explain this heterogeneity we performed a meta-regression assessing the relationship between bisphosphonate potency and improvement in OS, which found an OS benefit with zoledronate but limited evidence of an effect on PFS. This provided a further rationale for performing a network meta-analyses of the various types of bisphosphonates that were not compared head-to-head in RCTs. Results from network meta-analyses showed evidence of a benefit for OS with zoledronate compared with etidronate (HR 0.56, 95% CI 0.29 to 0.87) and placebo (HR 0.67, 95% CI 0.46 to 0.91). However, there was no evidence for a difference between zoledronate and other bisphosphonates.The effect of bisphosphonates on disease progression (PFS) is uncertain. Based on the HR of 0.75 (95% CI 0.57 to 1.00; seven studies; 908 participants), 47% participants would experience disease progression without treatment compared with between 30% and 47% with bisphosphonates (low-quality evidence). There is probably a similar risk of non-vertebral fractures between treatment groups (RR 1.03, 95% CI 0.68 to 1.56; six studies; 1389 participants; moderate-quality evidence). Pooled analysis demonstrated evidence for a difference favoring bisphosphonates compared with placebo or no treatment on prevention of pathological vertebral fractures (RR 0.74, 95% CI 0.62 to 0.89; seven studies; 1116 participants; moderate-quality evidence) and skeletal-related events (SREs) (RR 0.74, 95% CI 0.63 to 0.88; 10 studies; 2141 participants; moderate-quality evidence). The evidence for less pain with bisphosphonates was of very low quality (RR 0.75, 95% CI 0.60 to 0.95; eight studies; 1281 participants).Bisphosphonates may increase ONJ compared with placebo but the confidence interval is very wide (RR 4.61, 95% CI 0.99 to 21.35; P = 0.05; six studies; 1284 participants; low-quality evidence). The results from the network meta-analysis did not show any evidence for a difference in the incidence of ONJ (eight RCTs, 3746 participants) between bisphosphonates. Data from nine observational studies (1400 participants) reported an incidence of 5% to 51% with combination of pamidronate and zoledronate, 3% to 11% with zoledronate alone, and 0% to 18% with pamidronate alone.The pooled results showed no evidence for a difference in increase in frequency of gastrointestinal symptoms with the use of bisphosphonates compared with placebo or no treatment (RR 1.23, 95% CI 0.95 to 1.59; seven studies; 1829 participants; low-quality evidence).The pooled results showed no evidence for a difference in increase in frequency of hypocalcemia with the use of bisphosphonates compared with placebo or no treatment (RR 2.19, 95% CI 0.49 to 9.74; three studies; 1090 participants; low-quality evidence). The results from network meta-analysis did not show any evidence for differences in the incidence of hypocalcemia, renal dysfunction and gastrointestinal toxicity between the bisphosphonates used.
AUTHORS' CONCLUSIONS
Use of bisphosphonates in participants with MM reduces pathological vertebral fractures, SREs and pain. Bisphosphonates were associated with an increased risk of developing ONJ. For every 1000 participants treated with bisphosphonates, about one patient will suffer from the ONJ. We found no evidence of superiority of any specific aminobisphosphonate (zoledronate, pamidronate or ibandronate) or non-aminobisphosphonate (etidronate or clodronate) for any outcome. However, zoledronate was found to be better than placebo and first-generation bisposphonate (etidronate) in pooled direct and indirect analyses for improving OS and other outcomes such as vertebral fractures. Direct head-to-head trials of the second-generation bisphosphonates are needed to settle the issue if zoledronate is truly the most efficacious bisphosphonate currently used in practice.
Topics: Antineoplastic Agents; Bone Density Conservation Agents; Bone Diseases; Clodronic Acid; Diphosphonates; Disease-Free Survival; Etidronic Acid; Fractures, Bone; Humans; Imidazoles; Multiple Myeloma; Pamidronate; Randomized Controlled Trials as Topic; Spinal Fractures; Zoledronic Acid
PubMed: 29253322
DOI: 10.1002/14651858.CD003188.pub4 -
The Journal of Craniofacial Surgery Oct 2021To critically examine reported data to compare patient outcomes between load-sharing and load-bearing plate fixation for edentulous mandibular fractures. (Meta-Analysis)
Meta-Analysis
PURPOSE
To critically examine reported data to compare patient outcomes between load-sharing and load-bearing plate fixation for edentulous mandibular fractures.
MATERIALS AND METHODS
A systematic review and meta-analysis were designed to test the null hypothesis of no difference in postoperative outcomes between load-sharing and load-bearing plate fixation in atrophic, edentulous mandibular fractures. The PubMed, EMBASE, Cochrane Library, Elsevier text mining tool database, and clinicaltrials.gov trial registries were queried up until July 2016. The quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation method.
RESULTS
A total of 1212 studies were screened for inclusion of which we included 1 high-quality Cochrane review, 6 narrative reviews, and 21 publications of case reports and case series. Overall, the quality of evidence was low. No difference was found between load-bearing and load-sharing fixation in functional recovery, nonunion, or infection. An uncontrolled case series portrayed complete functional and morphological restoration in 96.9% of patients (83.2-99.5; 95% confidence interval) in load-bearing osteosynthesis while another demonstrated the same outcome in only 40.0% of patients (17.5-65.0; 95% confidence interval).
CONCLUSIONS
The authors did not find a statistically significant difference between load-bearing and load-sharing plate fixation in edentulous atrophic mandibular fracture patients; although this finding may be influenced by type 2 statistical error. Surgeons should continue to use their best clinical judgment in deciding on treatment approach for these challenging fractures. Future studies with higher level evidence are necessary to guide optimal fracture management.
Topics: Bone Plates; Fracture Fixation, Internal; Humans; Mandibular Fractures; Mouth, Edentulous; Weight-Bearing
PubMed: 34705386
DOI: 10.1097/SCS.0000000000007927 -
Journal of Oral and Maxillofacial... Apr 2024This study investigates whether the intraoral approach to mandibular open reduction and internal fixation, through exposure to the oral cavity's microbiome, results in... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This study investigates whether the intraoral approach to mandibular open reduction and internal fixation, through exposure to the oral cavity's microbiome, results in higher infection rates compared to the extraoral approach, thus addressing a critical public health concern, potentially offering an opportunity to reduce health-care costs, and aiming to guide effective clinical practice.
METHODS
In this systematic review with meta-analyses, a review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search was conducted using Embase and PubMed for articles published between 1989 and 2023. Inclusion criteria targeted studies on open reduction and internal fixation mandibular fractures comparing intraoral and extraoral approaches and reporting infection rates. Exclusion criteria eliminated non-English articles, case reports, and studies with insufficient approach-specific data. The primary outcome was the postoperative infection rate, with surgical approach as the predictor. Covariates such as age, sex, diabetes, and smoking status were included when reported. Data were analyzed using R software, employing random-effects models due to anticipated heterogeneity (I statistics).
RESULTS
From 61 studies, 11 provided direct comparisons involving 1,317 patients-937 intraoral and 380 extraoral. Infection rates were 5.9% for intraoral and 10% for extraoral approaches. Pooled relative risk was 0.94 [95% confidence interval, 0.63, 1.39], suggesting no significant risk difference. Prevalence of infections was estimated at 9% for intraoral and 6.1% for extraoral procedures, with significant heterogeneity (I = 84% for intraoral and 56% for extraoral).
CONCLUSION
Our meta-analysis found no significant difference in infection rates between the two approaches. There is opportunity to expand on reporting complication rates comparing the various approaches to mandibular fixation. Until these data are presented, surgeon preference may dictate the operative approach to expose the mandible for reduction and fixation.
Topics: Humans; Mandibular Fractures; Mandible; Fracture Fixation, Internal; Open Fracture Reduction; Postoperative Complications
PubMed: 38336352
DOI: 10.1016/j.joms.2024.01.011 -
International Journal of Oral and... Oct 2017Since the introduction of rigid internal fixation devices, more and more surgeons favour an open approach to treating condylar fractures of the mandible in adult... (Review)
Review
Since the introduction of rigid internal fixation devices, more and more surgeons favour an open approach to treating condylar fractures of the mandible in adult patients. Different indications for open treatment have been published. Open treatment is associated with surgical complications because of the technique employed. The aim of this systematic review was to provide an overview of the studies published exclusively on open treatment, and to summarize the existing open treatment modalities and their clinical outcomes. A total of seventy studies were selected for detailed analysis. Most studies reported good results with regard to the outcome measures of open treatment. Surgical complications including hematoma, wound infection, weakness of the facial nerve, sialocele, salivary fistula, sensory disturbance of the great auricular nerve, unsatisfactory scarring, and fixation failure were reported in the studies. This review suggests that because of the high level of methodological variance in the relevant studies published to date, among other factors, there are currently no evidence-based conclusions or guidelines that can be formulated with regard to the most appropriate open treatment. Establishment of such standards could potentially improve treatment outcomes.
Topics: Adult; Fracture Fixation, Internal; Humans; Jaw Fixation Techniques; Mandibular Condyle; Mandibular Fractures; Mandibular Reconstruction
PubMed: 28732561
DOI: 10.1016/j.ijom.2017.06.018 -
Orphanet Journal of Rare Diseases Jan 2021Langerhans cell histiocytosis (LCH) is a rare disease that originates from the uncontrolled proliferation and accumulation of bone marrow-derived immature myeloid... (Review)
Review
BACKGROUND
Langerhans cell histiocytosis (LCH) is a rare disease that originates from the uncontrolled proliferation and accumulation of bone marrow-derived immature myeloid dendritic cells. Dendritic cells are a type of histiocyte that play an important role in the human immune system and are found in the bone, skin, stomach, eyes, intestines, and lungs.
OBJECTIVE
This systematic review aimed to collect and report published case reports of rare bone disease caused by LCH to avoid misdiagnoses or delays in diagnosis.
METHODS
We systematically searched Scopus, PubMed, Embase, and Web of Sciences from August 1, 2000 to December 31, 2019. Studies reporting cases of LCH with rare bone involvement were included.
RESULTS
We identified 60 articles including 64 cases. Of the identified cases, 31 (48.4%) involved children, and 33 (51.6%) involved adults. Additionally, 46.9% (30 individuals) were from Asian countries. The mean age of the children was 7.6 ± 4.3 years and that of the adults was 36 ± 12 years. The findings indicated that unifocal bone involvements were the most prevalent form of the disease (68.7%), and, overall, the skull and chest wall were the most commonly affected bones in both adults and children. The spine and long bones were the second most commonly affected bones in children, and the spine and jaw were the second most commonly affected bones in adults. Pain and swelling were the most frequent presenting signs among the investigated cases, and loss of consciousness, myelopathy, nerve palsy, visual loss, torticollis and clicking sounds were rare signs. Osteolytic lesions were the most frequent radiologic feature (62.5%), and intracranial hemorrhage, fluid-fluid level, dura and intracranial extension and pathologic fractures were rare radiological features. Total excision, curettage and observation in the unifocal group of patients and systemic chemotherapy in the other groups (i.e., multifocal and multisystem) were the most frequent management approaches. The recovery rates of the unifocal and multifocal groups were 77.3% and 81.8%, respectively, while that of the multisystem group was 55.5%. The rates of recurrence and mortality in the multisystem group were 11% and were higher than those in the other groups.
CONCLUSIONS
LCH is a rare disease that can affect any organ in the human body. However, bone is the most commonly involved organ, and rare bone involvements may be the first or only symptom of the disease due to the rarity of such lesions; a lack of familiarity with them may result in misdiagnosis or delayed diagnosis.
Topics: Adult; Asia; Bone Diseases; Child; Child, Preschool; Histiocytosis, Langerhans-Cell; Humans; Retrospective Studies; Skull
PubMed: 33388073
DOI: 10.1186/s13023-020-01625-z -
The Cochrane Database of Systematic... Dec 2017Bisphosphonates are considered to be the treatment of choice for people with Paget's disease of bone. However, the effects of bisphosphonates on patient-centred outcomes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bisphosphonates are considered to be the treatment of choice for people with Paget's disease of bone. However, the effects of bisphosphonates on patient-centred outcomes have not been extensively studied. There are insufficient data to determine whether reducing and maintaining biochemical markers of bone turnover to within the normal range improves quality of life and reduces the risk of complications.
OBJECTIVES
To assess the benefits and harms of bisphosphonates for adult patients with Paget's disease of bone.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ISI Web of Knowledge and trials registers up to March 2017. We searched regulatory agency published information for rare adverse events.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of bisphosphonates as treatment for Paget's disease in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results, extracted data and assessed studies for risk of bias. We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included 20 trials (25 reports, 3168 participants). Of these, 10 trials (801 participants) compared bisphosphonates (etidronate, tiludronate, ibandronate, pamidronate, olpadronate, alendronate, risedronate, zoledronate) versus placebo, seven compared two bisphosphonates (992 participants), one trial compared a bisphosphonates with a bisphosphonate plus calcitonin (44 participants), and two studies, the largest trial (1331 participants) and its interventional extension study (502 participants), compared symptomatic treatment and intensive treatment where the goal was to normalise alkaline phosphatase.Most studies were assessed at low or unclear risk of bias. Six of 10 studies comparing bisphosphonates versus placebo were assessed at high risk of bias, mainly around incomplete outcome data and selective outcome reporting.Participant populations were reasonably homogeneous in terms of age (mean age 66 to 74 years) and sex (51% to 74% male). Most studies included participants who had elevated alkaline phosphatase levels whether or not bone pain was present. Mean follow-up was six months.Bisphosphonates versus placeboBisphosphonates tripled the proportion (31% versus 9%) of participants whose bone pain disappeared (RR 3.42, 95% confidence interval (CI) 1.31 to 8.90; 2 studies, 205 participants; NNT 5, 95% CI 1 to 31; moderate-quality evidence). This result is clinically important. Data were consistent when pain change was measured as any reduction (RR 1.97, 95% CI 1.29 to 3.01; 7 studies, 481 participants).There was uncertainty about differences in incident fractures: 1.4% fractures occurred in the bisphosphonates group and none in the placebo group (RR 0.89, 95% CI 0.18 to 4.31; 4 studies, 356 participants; very low-quality evidence).None of the studies reported data on orthopaedic surgery, quality of life or hearing thresholds.Results regarding adverse effects and treatment discontinuation were uncertain. There was a 64% risk of mild gastrointestinal adverse events in intervention group participants and 48% in the control group (RR 1.32, 95% CI 0.91 to 1.92; 6 studies, 376 participants; low-quality evidence). The likelihood of study participants discontinuing due to adverse effects was slightly higher in intervention group participants (4.4%) than the control group (4.1%) (RR 1.01, 95% CI 0.41 to 2.52; 6 studies, 517 participants; low-quality evidence). Zoledronate was associated with an increased risk of transient fever or fatigue (RR 2.57, 95% CI 1.21 to 5.44; 1 study, 176 participants; moderate-quality evidence).Bisphosphonates versus active comparatorMore participants reported pain relief with zoledronate than pamidronate (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 89 participants; NNT 5, 95% CI 3 to 11) or risedronate (RR 1.36, 95% CI 1.06 to 1.74; 1 study, 347 participants; NNT 7, 95% CI 4 to 24; very low quality evidence). This result is clinically important.There was insufficient evidence to confirm or exclude differences in adverse effects of bisphosphonates (RR 1.05, 95% CI 0.95 to 1.76; 2 studies, 437 participants; low-quality evidence) and treatment discontinuation (2 studies, 437 participants) (RR 2.04, 95% CI 0.43 to 9.59; 2 studies, 437 participants; very low-quality evidence).Intensive versus symptomatic treatmentThere was no consistent evidence of difference to response in bone pain, bodily pain or quality of life in participants who received intensive versus symptomatic treatment.Inconclusive results were observed regarding fractures and orthopaedic procedures for intensive versus symptomatic treatment (intensive treatment for fracture: RR 1.84, 95% CI 0.76 to 4.44; absolute risk 8.1% versus 5.2%; orthopaedic procedures: RR 1.58, 95% CI 0.80 to 3.11; absolute risk 5.6% versus 3.0%; 1 study, 502 participants; low-quality evidence).There was insufficient evidence to confirm or exclude an important difference in adverse effects between intensive and symptomatic treatment (RR 1.05, 95% CI 0.79 to 1.41; low-quality evidence).There was insufficient evidence to confirm or exclude an important difference of risk of rare adverse events (including osteonecrosis of the jaw) from the regulatory agencies databases.
AUTHORS' CONCLUSIONS
We found moderate-quality evidence that bisphosphonates improved pain in people with Paget's disease of bone when compared with placebo. We are uncertain about the results of head-to-head studies investigating bisphosphonates. We found insufficient evidence of benefit in terms of pain or quality of life from intensive treatment. Information about adverse effects was limited, but serious side effects were rare, and rate of withdrawals due to side effects was low.
Topics: Aged; Alkaline Phosphatase; Bone Density Conservation Agents; Calcitonin; Diphosphonates; Female; Humans; Male; Musculoskeletal Pain; Osteitis Deformans; Patient Dropouts; Randomized Controlled Trials as Topic
PubMed: 29192423
DOI: 10.1002/14651858.CD004956.pub3 -
The Journal of Craniofacial SurgeryMandible fractures can be treated with different plate systems, that is, miniplates or three-dimensional (3D) plates. This systematic review describes the effectiveness...
OBJECTIVES
Mandible fractures can be treated with different plate systems, that is, miniplates or three-dimensional (3D) plates. This systematic review describes the effectiveness and clinical outcomes of 3D plates used in fractures of the mandible and aims to critically evaluate its risks and benefits.
MATERIALS AND METHODS
A comprehensive electronic search was conducted without date but with restriction to articles written in English. Studies in humans, including randomized or quasi-randomized controlled trials and retrospective studies, were included. The outcome parameters measured were number of patients, fracture classification, results, follow-up period, postoperative complications, and mean age of patients. Major complications were defined as those needing additional surgical intervention, for example, malocclusion, infection or plate fracture. Accordingly, complications not needing additional surgical intervention were defined as minor (ie, dehiscence, trismus).
RESULTS
Guided by the PRISMA statement and the Cochrane Handbook for Systematic Reviews of Interventions, the authors identified 44 publications with a total of 1790 patients. Among the articles selected for the final review, there were 32 reported prospective studies, 12 reported retrospective studies. Regarding the evaluation of quality, 8 studies showed a low value of the risk of bias, 17 a moderate risk, and 19 a high risk. There were statistically significant advantages for 3D plates in mandibular fractures in terms of postoperative complications, for example, wound dehiscences or plate fracture.
CONCLUSIONS
The 3D plate is an effective treatment modality for mandibular fractures, with low incidence of major complications, decreased length of operation time, and increased stability of osteosynthesis.
Topics: Bone Plates; Fracture Fixation, Internal; Humans; Mandibular Fractures; Prospective Studies; Retrospective Studies; Treatment Outcome
PubMed: 34172684
DOI: 10.1097/SCS.0000000000007709 -
The British Journal of Oral &... Apr 2021The treatment of mandibular fractures by gunshot ranges from late conservative repair to more aggressive early repair in a single stage. Treatments that preserve bony... (Meta-Analysis)
Meta-Analysis Review
The treatment of mandibular fractures by gunshot ranges from late conservative repair to more aggressive early repair in a single stage. Treatments that preserve bony architecture as much as possible should be used, minimising patient morbidity and the complexity of future surgeries. The purpose of this study was to use a systematic review to determine which method of treatment was most effective for mandibular fractures by gunshot. Searches were conducted on Medline via PubMed, Scopus, Central Cochrane, and Sigle via Open Grey up to August 2019. Four studies were eligible to this systematic review, considering the previously establish inclusion and exclusion criteria. A total of 211 patients were evaluated. The mandibular body was the region more fractured followed by the symphyseal/parasymphyseal region. The closed treatment with intermaxillary fixation (IMF) was the most used followed by open surgery with internal rigid fixation (IRF) and external fixator. Considering the total adverse effects, the meta-analysis showed no statistically significant difference between the IMF and IRF groups (p=0.840), but IMF showed five times less infection and IRF six times less malunion. The algorithm was delineated from the types of injuries by gunshot, proposing forms of treatment from initial stabilisation to functional rehabilitation with implant-supported prostheses. The treatment of mandibular fractures by gunshot remains a challenge for surgeons. There was a statistically significant prevalence of success in the IRF group, however this group was also associated with a higher index of infection than the IMF group. New studies with high methodological quality and larger numbers of participants are needed to offer more safety for surgeons who treat patients with mandibular fractures by gunshot.
Topics: Algorithms; Fracture Fixation, Internal; Humans; Jaw Fixation Techniques; Mandibular Fractures; Treatment Outcome
PubMed: 33678448
DOI: 10.1016/j.bjoms.2020.08.019 -
Oral and Maxillofacial Surgery Mar 2020This study aims to investigate rehabilitation strategies to reduce trismus, pain, and edema in patients with maxillofacial trauma. (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aims to investigate rehabilitation strategies to reduce trismus, pain, and edema in patients with maxillofacial trauma.
METHODS
An electronic search in main databases was performed, including studies published until November 2017. Clinical trials aiming to investigate therapeutic techniques to improve mandibular range of motion and to reduce pain and edema compared to other treatments were included.
RESULTS
Nine studies were included in the review with different therapy modalities: photobiomodulation, kinesiologic tape, hilotherapy, jaw exercises, and TENS. Only five studies had available data to be included in a meta-analysis. There were no differences between any of the proposed strategies and its controls to prevent trismus. Individuals treated with hilotherapy presented less pain compared to controls. Kinesiologic tape or hilotherapy reduced edema when compared to controls daily until postoperative day 3.
CONCLUSIONS
There is diversity among the proposed rehabilitation techniques, and types of fractures and there are few numbers of included participants in each study. The results obtained in this review do not promote evidence to guide the use of non-drug rehabilitation techniques in patients with maxillofacial trauma after surgical intervention.
Topics: Edema; Fractures, Bone; Humans; Maxillofacial Injuries; Pain Measurement; Trismus
PubMed: 31802332
DOI: 10.1007/s10006-019-00808-8 -
The Cochrane Database of Systematic... Oct 2017Bone is the most common site of metastatic disease associated with breast cancer (BC). Bisphosphonates inhibit osteoclast-mediated bone resorption, and novel targeted... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bone is the most common site of metastatic disease associated with breast cancer (BC). Bisphosphonates inhibit osteoclast-mediated bone resorption, and novel targeted therapies such as denosumab inhibit other key bone metabolism pathways. We have studied these agents in both early breast cancer and advanced breast cancer settings. This is an update of the review originally published in 2002 and subsequently updated in 2005 and 2012.
OBJECTIVES
To assess the effects of bisphosphonates and other bone agents in addition to anti-cancer treatment: (i) in women with early breast cancer (EBC); (ii) in women with advanced breast cancer without bone metastases (ABC); and (iii) in women with metastatic breast cancer and bone metastases (BCBM).
SEARCH METHODS
In this review update, we searched Cochrane Breast Cancer's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 19 September 2016.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing: (a) one treatment with a bisphosphonate/bone-acting agent with the same treatment without a bisphosphonate/bone-acting agent; (b) treatment with one bisphosphonate versus treatment with a different bisphosphonate; (c) treatment with a bisphosphonate versus another bone-acting agent of a different mechanism of action (e.g. denosumab); and (d) immediate treatment with a bisphosphonate/bone-acting agent versus delayed treatment of the same bisphosphonate/bone-acting agent.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, and assessed risk of bias and quality of the evidence. The primary outcome measure was bone metastases for EBC and ABC, and a skeletal-related event (SRE) for BCBM. We derived risk ratios (RRs) for dichotomous outcomes and the meta-analyses used random-effects models. Secondary outcomes included overall survival and disease-free survival for EBC; we derived hazard ratios (HRs) for these time-to-event outcomes where possible. We collected toxicity and quality-of-life information. GRADE was used to assess the quality of evidence for the most important outcomes in each treatment setting.
MAIN RESULTS
We included 44 RCTs involving 37,302 women.In women with EBC, bisphosphonates were associated with a reduced risk of bone metastases compared to placebo/no bisphosphonate (RR 0.86, 95% confidence interval (CI) 0.75 to 0.99; P = 0.03, 11 studies; 15,005 women; moderate-quality evidence with no significant heterogeneity). Bisphosphonates provided an overall survival benefit with time-to-event data (HR 0.91, 95% CI 0.83 to 0.99; P = 0.04; 9 studies; 13,949 women; high-quality evidence with evidence of heterogeneity). Subgroup analysis by menopausal status showed a survival benefit from bisphosphonates in postmenopausal women (HR 0.77, 95% CI 0.66 to 0.90; P = 0.001; 4 studies; 6048 women; high-quality evidence with no evidence of heterogeneity) but no survival benefit for premenopausal women (HR 1.03, 95% CI 0.86 to 1.22; P = 0.78; 2 studies; 3501 women; high-quality evidence with no heterogeneity). There was evidence of no effect of bisphosphonates on disease-free survival (HR 0.94, 95% 0.87 to 1.02; P = 0.13; 7 studies; 12,578 women; high-quality evidence with significant heterogeneity present) however subgroup analyses showed a disease-free survival benefit from bisphosphonates in postmenopausal women only (HR 0.82, 95% CI 0.74 to 0.91; P < 0.001; 7 studies; 8314 women; high-quality evidence with no heterogeneity). Bisphosphonates did not significantly reduce the incidence of fractures when compared to placebo/no bisphosphonates (RR 0.77, 95% CI 0.54 to 1.08, P = 0.13, 6 studies, 7602 women; moderate-quality evidence due to wide confidence intervals). We await mature overall survival and disease-free survival results for denosumab trials.In women with ABC without clinically evident bone metastases, there was no evidence of an effect of bisphosphonates on bone metastases (RR 0.96, 95% CI 0.65 to 1.43; P = 0.86; 3 studies; 330 women; moderate-quality evidence with no heterogeneity) or overall survival (RR 0.89, 95% CI 0.73 to 1.09; P = 0.28; 3 studies; 330 women; high-quality evidence with no heterogeneity) compared to placebo/no bisphosphonates however the confidence intervals were wide. One study reported a trend towards an extended period of time without a SRE with bisphosphonate compared to placebo (low-quality evidence). One study reported quality of life and there was no apparent difference in scores between bisphosphonate and placebo (moderate-quality evidence).In women with BCBM, bisphosphonates reduced the SRE risk by 14% (RR 0.86, 95% CI 0.78 to 0.95; P = 0.003; 9 studies; 2810 women; high-quality evidence with evidence of heterogeneity) compared with placebo/no bisphosphonates. This benefit persisted when administering either intravenous or oral bisphosphonates versus placebo. Bisphosphonates delayed the median time to a SRE with a median ratio of 1.43 (95% CI 1.29 to 1.58; P < 0.00001; 9 studies; 2891 women; high-quality evidence with no heterogeneity) and reduced bone pain (in 6 out of 11 studies; moderate-quality evidence) compared to placebo/no bisphosphonate. Treatment with bisphosphonates did not appear to affect overall survival (RR 1.01, 95% CI 0.91 to 1.11; P = 0.85; 7 studies; 1935 women; moderate-quality evidence with significant heterogeneity). Quality-of-life scores were slightly better with bisphosphonates than placebo at comparable time points (in three out of five studies; moderate-quality evidence) however scores decreased during the course of the studies. Denosumab reduced the risk of developing a SRE compared with bisphosphonates by 22% (RR 0.78, 0.72 to 0.85; P < 0.001; 3 studies, 2345 women). One study reported data on overall survival and observed no difference in survival between denosumab and bisphosphonate.Reported toxicities across all settings were generally mild. Osteonecrosis of the jaw was rare, occurring less than 0.5% in the adjuvant setting (high-quality evidence).
AUTHORS' CONCLUSIONS
For women with EBC, bisphosphonates reduce the risk of bone metastases and provide an overall survival benefit compared to placebo or no bisphosphonates. There is preliminary evidence suggestive that bisphosphonates provide an overall survival and disease-free survival benefit in postmenopausal women only when compared to placebo or no bisphosphonate. This was not a planned subgroup for these early trials, and we await the completion of new large clinical trials assessing benefit for postmenopausal women. For women with BCBM, bisphosphonates reduce the risk of developing SREs, delay the median time to an SRE, and appear to reduce bone pain compared to placebo or no bisphosphonate.
Topics: Administration, Oral; Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Clodronic Acid; Denosumab; Diphosphonates; Female; Humans; Imidazoles; Injections, Intravenous; Randomized Controlled Trials as Topic; Zoledronic Acid
PubMed: 29082518
DOI: 10.1002/14651858.CD003474.pub4