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Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer.

ABSTRACT: OBJECTIVE:To review the evidence for the use of bisphosphonates to reduce skeletal morbidity in cancer patients with bone metastases. DATA SOURCES:Electronic databases, scanning reference lists, and consultation with experts and pharmaceutical companies. Foreign language papers were included. STUDY SELECTION:Included trials were randomised controlled trials of patients with malignant disease and bone metastases who were treated with oral or intravenous bisphosphonate compared with another bisphosphonate, placebo, or standard care. All trials measured at least one outcome of skeletal morbidity. RESULTS:95 articles were identified; 30 studies fulfilled inclusion criteria. In studies that lasted > or = 6 months, compared with placebo bisphosphonates significantly reduced the odds ratio for fractures (vertebral 0.69, 95% confidence interval 0.57 to 0.84, P < 0.0001; non-vertebral 0.65, 0.54 to 0.79, P < 0.0001; combined 0.65, 0.55 to 0.78, P < 0.0001), radiotherapy (0.67, 0.57 to 0.79, P < 0.0001), and hypercalcaemia (0.54, 0.36 to 0.81, P = 0.003) but not for orthopaedic surgery (0.70, 0.46 to 1.05, P = 0.086) or spinal cord compression (0.71, 0.47 to 1.08, P = 0.113). The reduction in orthopaedic surgery was significant in studies that lasted over a year (0.59, 0.39 to 0.88, P = 0.009). Use of bisphosphonates significantly increased time to first skeletal related event but did not increase survival. Subanalyses showed that most evidence supports use of intravenous aminobisphosphonates. CONCLUSIONS:In people with metastatic bone disease bisphosphonates significantly decrease skeletal morbidity, except for spinal cord compression and increased time to first skeletal related event. Treatment should start when bone metastases are diagnosed and continue until it is no longer clinically relevant.

SUBMITTER: Ross JR

PROVIDER: S-EPMC188427 | biostudies-literature | 2003 Aug

REPOSITORIES: biostudies-literature

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Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer.

Ross J R JR Saunders Y Y Edmonds P M PM Patel S S Broadley K E KE Johnston S R D SR

BMJ (Clinical research ed.) 20030801 7413

<h4>Objective</h4>To review the evidence for the use of bisphosphonates to reduce skeletal morbidity in cancer patients with bone metastases.<h4>Data sources</h4>Electronic databases, scanning reference lists, and consultation with experts and pharmaceutical companies. Foreign language papers were included.<h4>Study selection</h4>Included trials were randomised controlled trials of patients with malignant disease and bone metastases who were treated with oral or intravenous bisphosphonate compar ...[more]

PMID: 12946966

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Project description:BackgroundSarcopenia might function as an indicator for frailty, and as such as a risk factor for the development of postoperative complications. The aim of this study was to meta-analyse the relation between preoperative sarcopenia and the development of severe postoperative complications in patients undergoing oncological surgery.MethodsPubMed and Embase databases were systematically searched from inception until May 2018. Included were studies reporting on the incidence of severe postoperative complications and radiologically determined preoperative sarcopenia. Studies reporting the skeletal muscle as a continuous variable only were excluded. Data were extracted independently by two reviewers. Random effect meta-analyses were applied to estimate the pooled odds ratio (OR) with 95% confidence intervals (95% CI) for severe postoperative complications, defined as Clavien-Dindo grade ≥3, including 30-day mortality. Heterogeneity was evaluated with I2 testing. Analyses were performed overall and stratified by measurement method, tumour location and publication date.ResultsA total of 1924 citations were identified, and 53 studies (14 295 patients) were included in the meta-analysis. When measuring the total skeletal muscle area, 43% of the patients were sarcopenic, versus 33% when measuring the psoas area. Severe postoperative complications were present in 20%, and 30-day mortality was 3%. Preoperative sarcopenia was associated with an increased risk of severe postoperative complications (ORpooled : 1.44, 95% CI: 1.24-16.8, P<0.001, I2 =55%) and 30-day mortality (ORpooled : 2.15, 95% CI: 1.46-3.17, P<0.001, I2 =14%). A low psoas mass was a stronger predictor for severe postoperative complications compared with a low total skeletal muscle mass (ORpooled : 2.06, 95% CI: 1.37-3.09, ORpooled : 1.32, 95% CI: 1.14-1.53, respectively) and 30-day mortality [ORpooled : 6.17 (95% CI: 2.71-14.08, ORpooled : 1.80 (95% CI: 1.24-2.62), respectively]. The effect was independent of tumour location and publication date.ConclusionsThe presence of low psoas mass prior to surgery, as an indicator for sarcopenia, is a common phenomenon and is a strong predictor for the development of postoperative complications. The presence of low total skeletal muscle mass, which is even more frequent, is a less informative predictor for postoperative complications and 30-day mortality. The low heterogeneity indicates that the finding is consistent over studies. Nevertheless, the value of sarcopenia relative to other assessments such as frailty screening is not clear. Research is needed in order to determine the place of sarcopenia in future preoperative risk stratification.

Project description:BackgroundBisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients, attempts at comprehensive quantification of potential adverse effects have been limited. We undertook a meta-analysis with novel methodology to identify and quantify these adverse effects.MethodsWe systematically reviewed randomised controlled trials in breast cancer where at least one of the treatments was a bisphosphonate (zoledronic acid, ibandronate, pamidronate, alendronate or clodronate). Neoadjuvant, adjuvant and metastatic settings were examined. Primary outcomes were adverse events of any type or severity (excluding death). We carried out pairwise and network meta-analyses to estimate the size of any adverse effects potentially related to bisphosphonates. In order to ascertain whether adverse effects differed by individual factors such as age, or interacted with other common adjuvant breast cancer treatments, we examined individual-level patient data for one large trial, AZURE.FindingsWe identified 56 trials that reported adverse data, which included a total of 29,248 patients (18,301 receiving bisphosphonate drugs versus 10,947 not). 24 out of the 103 different adverse outcomes analysed showed a statistically and practically significant increase in patients receiving a bisphosphonate drug compared with those not (2 additional outcomes that appeared statistically significant came only from small studies with low event counts and no clinical suspicion so are likely artifacts). Most of these 24 are already clinically recognised: 'flu-like symptoms, fever, headache and chills; increased bone pain, arthralgia, myalgia, back pain; cardiac events, thromboembolic events; hypocalcaemia and osteonecrosis of the jaw; as well as possibly stiffness and nausea. Oral clodronate appeared to increase the risk of vomiting and diarrhoea (which may also be increased by other bisphosphonates), and there may be some hepatotoxicity. Four additional potential adverse effects emerged for bisphosphonate drugs in this analysis which have not classically be recognised: fatigue, neurosensory problems, hypertonia/muscle spasms and possibly dysgeusia. Several symptoms previously reported as potential side effects in the literature were not significantly increased in this analysis: constipation, insomnia, respiratory problems, oedema or thirst/dry mouth. Individual patient-level data and subgroup analysis revealed little variation in side effects between women of different ages or menopausal status, those with metastatic versus non-metastatic cancer, or between women receiving different concurrent breast cancer therapies.ConclusionsThis meta-analysis has produced estimates for the absolute frequencies of a range of side effects significantly associated with bisphosphonate drugs when used by breast cancer patients. These results show good agreement with previous literature on the subject but are the first systematic quantification of side effects and their severities. However, the analysis is limited by the availability and quality of data on adverse events, and the potential for bias introduced by a lack of standards for reporting of such events. We therefore present a table of adverse effects for bisphosphonates, identified and quantified to the best of our ability from a large number of trials, which we hope can be used to improve the communication of the potential harms of these drugs to patients and their healthcare providers.

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Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer.

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Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer.

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