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Dental Press Journal of Orthodontics Oct 2015Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated... (Review)
Review
INTRODUCTION
Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed.
OBJECTIVES
The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage.
METHODS
The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed.
RESULTS
Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs).
CONCLUSIONS
Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements.
Topics: Acetylcysteine; Animals; Anti-Inflammatory Agents; Antioxidants; Bone Remodeling; Celecoxib; Clodronic Acid; Diclofenac; Diphosphonates; Humans; Imidazoles; Interferon-gamma; Isoxazoles; Lactones; Mice; Orthodontic Anchorage Procedures; Osteoclasts; Osteoprotegerin; Pamidronate; Rats; Resveratrol; Stilbenes; Sulfones; Tooth Mobility; Tooth Movement Techniques; Zoledronic Acid
PubMed: 26560822
DOI: 10.1590/2177-6709.20.5.058-065.oar -
Annals of Oncology : Official Journal... Nov 2015De-escalation of bone-targeted agents, such as bisphosphonates and denosumab, from 4- to 12-weekly dosing is an increasingly used strategy in patients with bone... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
De-escalation of bone-targeted agents, such as bisphosphonates and denosumab, from 4- to 12-weekly dosing is an increasingly used strategy in patients with bone metastases from breast cancer. It is unclear whether there is sufficient evidence to support de-escalation as a standard of care.
METHODS
A systematic review of randomized trials comparing standard 4-weekly administration of bone-targeted agents with de-escalated (Q12-weekly) dosing in breast cancer patients was carried out. Medline, PubMed and the Cochrane Register of Controlled Trials were searched from inception until November 2014 for relevant studies. Outcomes of interest included skeletal-related event (SRE) rates, bone pain, adverse events (AEs) and bone turnover biomarkers. Random-effects meta-analyses were carried out.
RESULTS
A total of nine citations representing seven unique studies were eligible. One study is ongoing with no reported data. Six studies reported data for at least one outcome of interest. Data were available comparing standard versus de-escalated therapy for pamidronate (1 study, 38 patients), zoledronate (3 studies, 1117 patients) and denosumab (2 studies, 284 patients). Meta-analysis of five trials reporting data for on-study SRE rates between standard (61/443 patients) and de-escalated (49/392 patients) arms produced a summary risk ratio of 0.90 (95% confidence interval 0.63-1.29). Meta-analyses of data for AEs and bone turnover biomarkers also showed no statistically significant differences between standard and de-escalated arms, though only limited numbers of patients and events were present for most analyses.
CONCLUSION
In this systematic review of studies of bisphosphonates and denosumab, there appears to be no difference in SREs or pain with de-escalated therapy. While a large, hopefully definitive study is ongoing, the data presented so far are consistent with de-escalation of bone-targeting agents becoming a standard of care for patients with bone metastases from breast cancer.
Topics: Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Clinical Trials as Topic; Drug Administration Schedule; Female; Humans; Standard of Care
PubMed: 26122727
DOI: 10.1093/annonc/mdv284 -
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 -
The Oncologist Apr 2015Complications from skeletal-related events (SREs) constitute a challenge in the care of cancer patients with bone metastasis (BM). (Comparative Study)
Comparative Study Meta-Analysis
Systematic literature review and network meta-analysis comparing bone-targeted agents for the prevention of skeletal-related events in cancer patients with bone metastasis.
BACKGROUND
Complications from skeletal-related events (SREs) constitute a challenge in the care of cancer patients with bone metastasis (BM).
OBJECTIVES
This study evaluated the comparative effectiveness of pamidronate, ibandronate, zoledronate, and denosumab in reducing the morbidity of SREs in cancer patients with BM.
METHODS
Medline (1948 to January 2014), Embase (1980 to January 2014), the Cochrane Library (2014 issue 1), and Web of Science with Conference Proceedings (1970 to January 2014) were searched. Only randomized controlled trials assessing denosumab, bisphosphonates, or placebo in cancer patients with BM were included. The primary outcomes were SREs and SREs by type. The network meta-analysis (NMA) was performed with a random-effects Bayesian model.
RESULTS
The NMA included 14 trials with 10,192 patients. Denosumab was superior to placebo in reducing the risk of SREs (odds ratio [OR]: 0.49; 95% confidence interval [CI]: 0.31-0.75), followed by zoledronate (OR: 0.57; 95% CI: 0.41-0.77) and pamidronate (OR: 0.55; 95% CI: 0.41-0.72). Ibandronate compared with placebo could not reduce the risk of SREs. Denosumab was superior to placebo in reducing the risk of pathologic fractures (OR: 0.50; 95% CI: 0.32-0.79), followed by zoledronate (OR: 0.61; 95% CI: 0.43-0.86). Denosumab was superior to placebo in reducing the risk of radiation (OR: 0.51; 95% CI: 0.35-0.75), followed by pamidronate (OR: 0.67; 95% CI: 0.52-0.86) and zoledronate (OR: 0.70; 95% CI: 0.52-0.96).
CONCLUSION
This NMA showed that denosumab, zoledronate, and pamidronate were generally effective in preventing SREs in cancer patients with BM. Denosumab and zoledronate were also associated with reductions in the risk of pathologic fractures and radiation compared with placebo. Denosumab was shown to be the most effective of the bone-targeted agents.
Topics: Bone Density Conservation Agents; Bone Diseases; Bone Neoplasms; Denosumab; Diphosphonates; Humans; Ibandronic Acid; Imidazoles; Neoplasms; Pamidronate; Spinal Cord Compression; Treatment Outcome; Zoledronic Acid
PubMed: 25732263
DOI: 10.1634/theoncologist.2014-0328