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PloS One 2018In advanced prostate cancer, osteoclast inhibitors prevent and palliate skeletal related events associated with bone metastases. However, it is uncertain whether they... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In advanced prostate cancer, osteoclast inhibitors prevent and palliate skeletal related events associated with bone metastases. However, it is uncertain whether they play a disease-modifying role earlier in the course of the disease.
METHODS
Medline, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews and ASCO conference proceedings were searched for randomized controlled trials that compared osteoclast inhibitors with placebo and/or standard of care (SOC) in patients with high-risk, non-metastatic prostate cancer. The primary outcome measure was incidence of new bone metastases; secondary outcomes included overall survival (OS), prostate cancer specific survival, mortality unrelated to prostate cancer, toxicity and health related quality of life outcomes. Results are presented as relative risk (RR) with 95% confidence intervals (CI).
RESULTS
Six randomized controlled trials (5947 participants) were included, five evaluating bisphosphonates and one denosumab. Overall, there was no difference in incidence of bone metastases between participants treated with osteoclast inhibitors versus placebo/SOC (RR 1.09, 95%CI 0.84-1.41, p = 0.51) however significant heterogeneity was observed between studies. The denosumab trial was the largest and only positive trial amongst the included studies (RR 0.83, 95%CI 0.73-0.95, p = 0.007). No significant difference was observed in OS (RR 0.99 95% CI 0.89-1.10, p = 0.84) nor prostate cancer specific survival (RR 1.12 95%CI 0.93-1.36, p = 0.24). Most studies reported increased rates of osteonecrosis of the jaw (5% or less) and hypocalcemia (2% or less) with osteoclast inhibitors.
CONCLUSIONS
While there is limited evidence that bisphosphonates alter the natural history of high-risk, non-metastatic prostate cancer, denosumab delays onset of bone metastases in this patient population. Neither class of osteoclast inhibitor demonstrated an impact on survival outcomes. Future trials with better defined patient selection and a robust definition for high risk disease is critical.
Topics: Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Diphosphonates; Humans; Male; Osteoclasts; Outcome Assessment, Health Care; Prostatic Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 29370211
DOI: 10.1371/journal.pone.0191455 -
The Cochrane Database of Systematic... Dec 2017The prevalence and incidence of pain and skeletal complications of metastatic bone disease such as pathologic fractures, spinal cord compression and hypercalcemia is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence and incidence of pain and skeletal complications of metastatic bone disease such as pathologic fractures, spinal cord compression and hypercalcemia is high and an important contributor to morbidity, poor performance status and decreased quality of life. Moreover, pathologic fractures are associated with increased risk of death in people with disseminated malignancies. Therefore, prevention of pain and fractures are important goals in men with prostate cancer at risk for skeletal complications.
OBJECTIVES
To assess the effects of bisphosphonates in men with bone metastases from prostate cancer.
SEARCH METHODS
We identified studies by electronic search of bibliographic databases including the Cochrane Controlled Trials Register and MEDLINE on 13 July 2017 and trial registries. We handsearched the Proceedings of American Society of Clinical Oncology (to July 2017) and reference lists of all eligible trials identified. This is an update of a review last published in 2006.
SELECTION CRITERIA
We included randomized controlled studies comparing the effectiveness of bisphosphonates in men with bone metastases from prostate cancer.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the quality of trials. We defined the proportion of participants with pain response as the primary end point; secondary outcomes were skeletal-related events, mortality, quality of life, adverse events, analgesic consumption and disease progression. We assessed the quality of the evidence for the main outcomes using the GRADE approach.
MAIN RESULTS
We included 18 trials reporting on 4843 participants comparing the effect of bisphosphonate administration to control regimens.
PRIMARY OUTCOME
there was no clear difference in the proportion of participants with pain response (RR 1.15, 95% CI 0.93 to 1.43; P = 0.20; I = 0%; 3 trials; 876 participants; low quality evidence). In absolute terms, bisphosphonates resulted in a pain response in 40 more participants per 1000 (19 fewer to 114 more).
SECONDARY OUTCOMES
bisphosphonates probably reduced the incidence of skeletal-related events in participants with prostate cancer metastatic to bone (RR 0.87, 95% CI 0.81 to 0.94; P = 0.27; I = 19%; 9 trials; 3153 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 58 fewer SREs per 1000 (85 fewer to 27 fewer).We found no clinically relevant differences in mortality (RR 0.97, 95% CI 0.91 to 1.04; P = 0.43; I = 1%; 9 trials; 2450 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 16 fewer deaths per 1000 (47 fewer to 21 more).Outcome definition of quality of life and the measurement tools varied greatly across trials and we were unable to extract any quantitative data for meta-analysis.Bisphosphonates probably increased the number of participants affected by nausea (RR 1.19, 95% CI 1.00 to 1.41; P = 0.05; I = 0%; 9 trials; 3008 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in seven more cases of nausea per 1000 (0 fewer to 14 more). Bisphosphonates probably increased the number of renal adverse events (RR 1.65, 95% CI 1.11 to 2.46; P = 0.01; I = 0%; 7 trials; 1794 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 22 more renal adverse events per 1000 (4 more to 50 more). We found no clear difference in the number of participants with osteonecrosis of the jaw between groups (RR 1.92, 95% CI 0.75 to 4.90; P = 0.17; I = 0%; 5 trials; 1626 participants; very low quality evidence). In absolute terms, bisphosphonates resulted in seven more cases with osteonecrosis of the jaw per 1000 (2 fewer to 29 more). We observed no clinically relevant difference in the proportion of participants with decreased analgesic consumption (RR 1.19, 95% CI 0.87 to 1.63; P = 0.28; I = 37%; 4 trials; 416 participants). Statistical analysis revealed that bisphosphonates probably reduced the number of participants with disease progression (RR 0.94, 95% CI 0.90 to 0.98; P = 0.006; I = 0%; 7 trials; 2115 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 36 fewer cases of disease progression per 1000 (71 fewer to 7 fewer).Findings of our predefined subgroup and sensitivity analyses were no different from those of the primary analyses.
AUTHORS' CONCLUSIONS
Based on low quality evidence, there may be no clinically relevant difference in the proportion of men with pain response between bisphosphonates and control regimens in men with bone metastases from prostate cancer. Bisphosphonates probably decrease the number of skeletal-related events and disease progression. These benefits need to be weighed against the increased risk of renal impairment and nausea in men receiving bisphosphonates. Future studies should explicitly evaluate patient important outcomes such as quality of life and pain by using standardized and comparable assessment tools.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Bone Neoplasms; Diphosphonates; Humans; Kidney; Male; Nausea; Pain; Prostatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 29278410
DOI: 10.1002/14651858.CD006250.pub2 -
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 -
The Cochrane Database of Systematic... Oct 2017Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction experienced by some individuals to certain medicines commonly used in the treatment of... (Review)
Review
BACKGROUND
Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction experienced by some individuals to certain medicines commonly used in the treatment of cancer and osteoporosis (e.g. bisphosphonates, denosumab and antiangiogenic agents) and involves the progressive destruction of bone in the mandible or maxilla. Depending on the drug, its dosage, and the duration of exposure, the occurrence of this adverse drug reaction may be rare (e.g. following the oral administration of bisphosphonate or denosumab treatments for osteoporosis, or antiangiogenic agent-targeted cancer treatment) or common (e.g. following intravenous bisphosphonate for cancer treatment). MRONJ is associated with significant morbidity, adversely affects quality of life (QoL), and is challenging to treat.
OBJECTIVES
To assess the effects of interventions versus no treatment, placebo, or an active control for the prophylaxis of MRONJ in people exposed to antiresorptive or antiangiogenic drugs.To assess the effects of non-surgical or surgical interventions (either singly or in combination) versus no treatment, placebo, or an active control for the treatment of people with manifest MRONJ.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 23 November 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 10), MEDLINE Ovid (1946 to 23 November 2016), and Embase Ovid (23 May 2016 to 23 November 2016). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on language or publication status when searching the electronic databases; however, the search of Embase was restricted to the last six months due to the Cochrane Embase Project to identify all clinical trials and add them to CENTRAL.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing one modality of intervention with another for the prevention or treatment of MRONJ. For 'prophylaxis of MRONJ', the primary outcome of interest was the incidence of MRONJ; secondary outcomes were QoL, time-to-event, and rate of complications and side effects of the intervention. For 'treatment of established MRONJ', the primary outcome of interest was healing of MRONJ; secondary outcomes were QoL, recurrence, and rate of complications and side effects of the intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results, extracted the data, and assessed the risk of bias in the included studies. For dichotomous outcomes, we reported the risk ratio (RR) (or rate ratio) and 95% confidence intervals (CI).
MAIN RESULTS
We included five RCTs (1218 participants) in the review. Three trials focused on the prophylaxis of MRONJ. Two trials investigated options for the treatment of established MRONJ. The RCTs included only participants treated with bisphosphonates and, thus, did not cover the entire spectrum of medications associated with MRONJ. Prophylaxis of MRONJOne trial compared standard care with regular dental examinations in three-month intervals and preventive treatments (including antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone) in men with metastatic prostate cancer treated with zoledronic acid. The intervention seemed to lower the risk of MRONJ: RR 0.10; 95% CI 0.02 to 0.39 (253 participants; low-quality evidence). Secondary outcomes were not evaluated.As dentoalveolar surgery is considered a common predisposing event for developing MRONJ, one trial investigated the effect of plasma rich in growth factors (PRGF) for preventing MRONJ in people with cancer undergoing dental extractions. There was insufficient evidence to support or refute a benefit of PRGF on MRONJ incidence when compared with standard treatment (RR 0.08, 95% CI 0.00 to 1.51; 176 participants; very low-quality evidence). Secondary outcomes were not reported. In another trial comparing wound closure by primary intention with wound closure by secondary intention after dental extractions in people treated with oral bisphosphonates (700 participants), no cases of intraoperative complications or postoperative MRONJ were observed. QoL was not investigated. Treatment of MRONJOne trial analysed hyperbaric oxygen (HBO) treatment used in addition to standard care (antiseptic rinses, antibiotics, and surgery) compared with standard care alone. HBO in addition to standard care did not significantly improve healing from MRONJ compared with standard care alone (at last follow-up: RR 1.56; 95% CI 0.77 to 3.18; 46 participants included in the analysis; very low-quality evidence). QoL data were presented qualitatively as intragroup comparisons; hence, an effect estimate of treatment on QoL was not possible. Other secondary outcomes were not reported.The other RCT found no significant difference between autofluorescence- and tetracycline fluorescence-guided sequestrectomy for the surgical treatment of MRONJ at any timepoint (at one-year follow-up: RR 1.05; 95% CI 0.86 to 1.30; 34 participants included in the analysis; very low-quality evidence). Secondary outcomes were not reported.
AUTHORS' CONCLUSIONS
Prophylaxis of MRONJOne open-label RCT provided some evidence that dental examinations in three-month intervals and preventive treatments may be more effective than standard care for reducing the incidence of MRONJ in individuals taking intravenous bisphosphonates for advanced cancer. We assessed the certainty of the evidence to be low.There is insufficient evidence to either claim or refute a benefit of either of the interventions tested for prophylaxis of MRONJ (i.e. PRGF inserted into the postextraction alveolus during dental extractions, and wound closure by primary or secondary intention after dental extractions). Treatment of MRONJAvailable evidence is insufficient to either claim or refute a benefit for hyperbaric oxygen therapy as an adjunct to conventional therapy. There is also insufficient evidence to draw conclusions about autofluorescence-guided versus tetracycline fluorescence-guided bone surgery.
Topics: Angiogenesis Inhibitors; Anti-Bacterial Agents; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Denosumab; Dental Care; Diphosphonates; Female; Humans; Hyperbaric Oxygenation; Imidazoles; Intercellular Signaling Peptides and Proteins; Jaw Diseases; Male; Oral Health; Osteonecrosis; Postoperative Complications; Prostatic Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Time Factors; Tooth Extraction; Zoledronic Acid
PubMed: 28983908
DOI: 10.1002/14651858.CD012432.pub2 -
Brazilian Dental Journal 2017Here is described a case of ameloblastic fibrosarcoma (AFS) affecting the posterior mandible of a woman who was treated surgically and recovered without signs of... (Review)
Review
Here is described a case of ameloblastic fibrosarcoma (AFS) affecting the posterior mandible of a woman who was treated surgically and recovered without signs of recurrence or metastasis after 12 years of follow-up. Tumor sections were immunostained for cell cycle, epithelial and mesenchymal markers. Immunohistochemical analysis evidenced high Ki-67 positivity in stromal cells (mean of 20.9 cells/High power field). Epithelial cells displayed strong positivity for p53, p63 and cytokeratin 19. In addition to the case report, a systematic review of current knowledge is presented on the AFS's clinical-demographic features and prognostic factors. Based on the review, 88/99 cases were diagnosed as AFS, 9/99 as ameloblastic fibro-odontosarcoma and 2/99 as ameloblastic fibrodentinosarcoma. All these lesions displayed very similar clinical-demographic and prognostic features. Moreover, the review provided evidence that first treatment, regional metastasis, distant metastasis and local recurrence were significant prognostic values for malignant odontogenic mesenchymal lesions. Based on the findings, segregation among ameloblastic fibrosarcoma, ameloblastic fibrodentinosarcoma and ameloblastic fibro-odontosarcoma seems illogical, considering all these lesions have similar predilections and outcomes.
Topics: Adult; Female; Fibrosarcoma; Humans; Immunohistochemistry; Mandibular Neoplasms; Odontogenic Tumors
PubMed: 28492759
DOI: 10.1590/0103-6440201701050 -
BMJ Open Jun 2015Randomised controlled trials (RCTs) have given contradictory results about the efficacy and safety of ibandronate in treating metastatic bone disease (MBD) or multiple... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Randomised controlled trials (RCTs) have given contradictory results about the efficacy and safety of ibandronate in treating metastatic bone disease (MBD) or multiple myeloma. This review meta-analysed the literature to gain a more comprehensive picture.
DESIGN
Systematic review and meta-analysis of ibandronate compared with placebo or zoledronate.
DATA SOURCES
PubMed, EMBASE and the Cochrane Library databases were systematically searched to identify RCTs published up to March 2015 evaluating ibandronate to treat MBD or multiple myeloma.
REVIEW METHOD
10 RCTs involving 3474 patients were included. Six RCTs were placebo-controlled and four compared ibandronate with zoledronate. The studies included in this review were mainly from European countries.
RESULTS
Intravenous ibandronate (6 mg) or oral drug (50 mg) decreased the risk of skeletal-related events compared to placebo (risk ratio (RR) 0.80, 95% CI 0.71 to 0.90, p=0.002). It also reduced the bone pain score below baseline significantly more than did placebo at 96 weeks (weighted mean difference -0.41, 95% CI -0.56 to -0.27, p<0.001). The incidence of diarrhoea, nausea and adverse renal events was similar between the ibandronate and placebo groups, but ibandronate was associated with greater risk of abdominal pain. Ibandronate was associated with similar risk of skeletal-related events as another bisphosphonate drug, zoledronate (RR 1.02, 95% CI 0.82 to 1.26, p=0.87). The incidence of nausea, jaw osteonecrosis and fatigue was similar for the two drugs, but the incidence of adverse renal events was significantly lower in the ibandronate group.
CONCLUSIONS
Ibandronate significantly reduces the incidence of skeletal-related events and bone pain in patients with MBD or multiple myeloma relative to placebo. It is associated with a similar incidence of skeletal-related events as zoledronate.
Topics: Bone Density Conservation Agents; Bone Neoplasms; Bone Resorption; Diphosphonates; Europe; Humans; Ibandronic Acid; Multiple Myeloma; Musculoskeletal Pain; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26038356
DOI: 10.1136/bmjopen-2014-007258 -
PloS One 2015Ameloblastoma is the second most common odontogenic tumor, known to be slow-growing, persistent, and locally aggressive. Recent data suggests that ameloblastoma is best... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ameloblastoma is the second most common odontogenic tumor, known to be slow-growing, persistent, and locally aggressive. Recent data suggests that ameloblastoma is best treated with wide resection and adequate margins. Following primary excision, bony reconstruction is often necessary for a functional and aesthetically satisfactory outcome, making early diagnosis paramount. Despite earlier diagnosis potentially limiting the extent of resection and reconstruction, an understanding of the growth rate and natural history of ameloblastoma has been notably lacking from the literature.
METHOD
A systematic review of the literature was conducted by reviewing relevant articles from PubMed and Web of Science databases. Each article's level of evidence was formally appraised according to the Centre of Evidence Based Medicine (CEBM), with data from each utilized in a meta-analysis of growth rates for ameloblastoma.
RESULTS
Literature regarding the natural history of ameloblastoma is limited since the tumor is immediately acted upon at its initial detection, unless the patient voluntarily refuses a surgical intervention. From the limited data, it is derived that the highest estimated growth rate is associated with solid, multicystic type and the lowest rate with peripheral ameloblastomas. After meta-analysis, the calculated mean specific grow rate is 87.84% per year.
CONCLUSION
The growth rate of ameloblastoma has been demonstrated, offering prognostic and management information, particularly in cases where a delay in management is envisaged.
Topics: Adult; Aged; Ameloblastoma; Female; Humans; Jaw Neoplasms; Male; Middle Aged; Young Adult
PubMed: 25706407
DOI: 10.1371/journal.pone.0117241 -
Annals of Internal Medicine Nov 2014Osteoporosis is a major contributor to the propensity to fracture among older adults, and various pharmaceuticals are available to treat it. (Review)
Review
BACKGROUND
Osteoporosis is a major contributor to the propensity to fracture among older adults, and various pharmaceuticals are available to treat it.
PURPOSE
To update a review about the benefits and harms of pharmacologic treatments used to prevent fractures in adults at risk.
DATA SOURCES
Multiple computerized databases were searched between 2 January 2005 and 4 March 2014 for English-language studies.
STUDY SELECTION
Trials, observational studies, and systematic reviews.
DATA EXTRACTION
Duplicate extraction and assessment of data about study characteristics, outcomes, and quality.
DATA SYNTHESIS
From more than 52 000 titles screened, 315 articles were included in this update. There is high-strength evidence that bisphosphonates, denosumab, and teriparatide reduce fractures compared with placebo, with relative risk reductions from 0.40 to 0.60 for vertebral fractures and 0.60 to 0.80 for nonvertebral fractures. Raloxifene has been shown in placebo-controlled trials to reduce only vertebral fractures. Since 2007, there is a newly recognized adverse event of bisphosphonate use: atypical subtrochanteric femur fracture. Gastrointestinal side effects, hot flashes, thromboembolic events, and infections vary among drugs.
LIMITATIONS
Few studies have directly compared drugs used to treat osteoporosis. Data in men are very sparse. Costs were not assessed.
CONCLUSION
Good-quality evidence supports that several medications for bone density in osteoporotic range and/or preexisting hip or vertebral fracture reduce fracture risk. Side effects vary among drugs, and the comparative effectiveness of the drugs is unclear.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality and RAND Corporation.
Topics: Absorptiometry, Photon; Adult; Antibodies, Monoclonal, Humanized; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density; Bone Density Conservation Agents; Comparative Effectiveness Research; Denosumab; Female; Fractures, Bone; Humans; Male; Neoplasms; Osteoporosis; Osteoporotic Fractures; Teriparatide
PubMed: 25199883
DOI: 10.7326/M14-0317