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Rheumatology (Oxford, England) Feb 2023Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease. The distinct CNO subtype that affects the anterior chest wall is descriptively named... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease. The distinct CNO subtype that affects the anterior chest wall is descriptively named sternocostoclavicular hyperostosis (SCCH) and mainly occurs in adults. Literature on CNO/SCCH is scattered and lacks diagnostic and therapeutic consensus.
METHODS
Systematic review and meta-analysis aiming to characterize clinical presentation and therapeutic modalities applied in adult CNO/SCCH patients. Untransformed numerical data and double-arcsine transformed proportional data were pooled in a random effects model in R-4.0.5; proportions were reported with 95% CI.
RESULTS
Forty studies were included, containing data on 2030 and 642 patients for aim 1 and 2, respectively. A female predisposition (67%, 95% CI 60, 73) and major diagnostic delay (5 years 95% CI 3, 7) were noted. Clinical presentation included chest pain (89%, 95% CI 79, 96) and swelling (79%, 95% CI 62, 91). Patients suffered from pustulosis palmoplantaris (53%, 95% CI 37, 68), arthritis (24%, 95% CI 11, 39) and acne (8%, 95% CI 4, 13). Inflammatory markers were inconsistently elevated. Autoantibody and HLA-B27 prevalence was normal, and histopathology unspecific. Increased isotope uptake (99%, 95% CI 96, 100) was a consistent imaging finding. Among manifold treatments, pamidronate and biologicals yielded good response in 83%, 95% CI 60, 98 and 56%, 95% CI 26, 85, respectively.
CONCLUSION
CNO/SCCH literature proves heterogeneous regarding diagnostics and treatment. Timely diagnosis is challenging and mainly follows from increased isotope uptake on nuclear examination. Biopsies, autoantibodies and HLA status are non-contributory, and biochemical inflammation only variably detected. Based on reported data, bisphosphonates and biologicals seem reasonably effective, but due to limitations in design and heterogeneity between studies the precise magnitude of their effect is uncertain. Fundamentally, international consensus seems imperative to advance clinical care for CNO/SCCH.
Topics: Adult; Humans; Female; Acquired Hyperostosis Syndrome; Delayed Diagnosis; Osteomyelitis; Psoriasis
PubMed: 35961032
DOI: 10.1093/rheumatology/keac443 -
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 -
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 -
PloS One 2021Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bisphosphonate 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.
METHODS
We 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.
FINDINGS
We 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.
CONCLUSIONS
This 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.
Topics: Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents; Breast Neoplasms; Diphosphonates; Female; Humans; Middle Aged; Network Meta-Analysis; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33544765
DOI: 10.1371/journal.pone.0246441 -
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 -
Osteoporosis International : a Journal... Jan 2020Skeletal fragility is a common complication of childhood acute lymphoblastic leukaemia (ALL) but the impact of bisphosphonate therapy on bone mass and fracture is...
UNLABELLED
Skeletal fragility is a common complication of childhood acute lymphoblastic leukaemia (ALL) but the impact of bisphosphonate therapy on bone mass and fracture is unclear. We aim to conduct a systematic review to evaluate the effects of bisphosphonates on bone mineral density (BMD) and fracture incidence in children with ALL.
METHODS
EMBASE, Medline and the Cochrane Library were thoroughly searched by two researchers. Inclusion criteria was any child under the age of 18 years with a diagnosis of ALL, who had received any bisphosphonate treatment and had serial measurements of bone density performed thereafter. All primary research studies of any study design, excluding case reports, were included.
RESULTS
Ten full text papers were identified with two exclusively meeting the inclusion criteria. Both studies administered bisphosphonates to children receiving maintenance chemotherapy for varying durations. Bone density was assessed at regular intervals by dual x-ray absorptiometry (DXA). The majority of participants had an improvement in bone density at the end of each study. However, no size adjustment of DXA data was performed. Limited information on fracture occurrence was provided by one study but did not include routine screening for vertebral fractures.
CONCLUSIONS
This systematic review identified that there is insufficient evidence to support routine use of prophylactic bisphosphonate therapy in childhood ALL for prevention of fracture and improvement of bone mass. Future well-designed clinical trials in those at highest risk of fractures in ALL are now needed.
Topics: Adolescent; Bone Density; Child; Diphosphonates; Female; Fractures, Bone; Humans; Incidence; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Retrospective Studies
PubMed: 31377915
DOI: 10.1007/s00198-019-05082-8 -
Cancer Management and Research 2018Compared with application of bone-modifying agents (BMAs) every 4 weeks, it is unclear whether 12-weekly de-escalated therapy can be used as a substitute strategy.
BACKGROUND
Compared with application of bone-modifying agents (BMAs) every 4 weeks, it is unclear whether 12-weekly de-escalated therapy can be used as a substitute strategy.
METHODS
A systematic search of PubMed, EMBASE, and the Cochrane Register of Controlled Trials until November 22, 2017, was performed. Randomized controlled trials (RCTs) were included to assess skeletal-related event (SRE) rates, adverse events, and bone turnover biomarkers, comparing 12-weekly de-escalated treatments with standard 4-weekly dosage regimens. Risk ratios (RRs) with 95% CIs were pooled in fixed-effect meta-analyses.
RESULTS
A total of eight citations were eligible comprising 2,878 patients: zoledronate (three studies, 2,650 patients), pamidronate (two studies, 68 patients), and denosumab (three studies, 160 patients). Summary RR (0.98; 95% CI 0.87-1.12; =0.82) for SRE rates between de-escalated and standard arms was produced when seven low risk of bias trials (695 patients) were pooled, and results without statistical significance also appeared in the analysis of adverse events and bone turnover biomarkers. Due to the limited sample size and methodological differences, the data for skeletal morbidity rates (SMRs), time to first SRE, serum C-telopeptide (sCTx) levels, and hypocalcemia were not combined, but systematic review still obtained similar indistinguishableness.
CONCLUSION
In this meta-analysis of randomized clinical trials, the results "appeared" to show non-inferiority of the 12-weekly treatment. Due to the difference in available data, the results for bisphosphonates are more solid than for the receptor activator of nuclear factor-κB ligand (RANKL) antibodies.
PubMed: 30288112
DOI: 10.2147/CMAR.S176811 -
Critical Reviews in Oncology/hematology May 2019Bone-modifying agents like bisphosphonates and receptor activator of nuclear factor kappaβ ligand (RANK-L) inhibitors are used as supportive treatments in breast cancer... (Meta-Analysis)
Meta-Analysis
Bone-modifying agents like bisphosphonates and receptor activator of nuclear factor kappaβ ligand (RANK-L) inhibitors are used as supportive treatments in breast cancer patients with bone metastases to prevent skeletal-related events (SREs). Due to missing head-to-head comparisons, a network meta-analysis was performed to provide a hierarchy of these therapeutic options. Through a systematic literature search, 21 randomized controlled trials (RCTs) that fulfilled the inclusion criteria were identified. To prevent SREs, the ranking through P-scores showed denosumab (RR: 0.62; 95%CI: 0.50-0.76), zoledronic acid (RR: 0.72; 95%CI: 0.61-0.84) and pamidronate (RR: 0.76; 95%CI: 0.67-0.85) to be significantly superior to placebo. Due to insufficient or heterogeneous data, overall survival, quality of life, pain response and adverse events were not able to be analyzed within the network. Although data were sparse on adverse events, the risk of significant adverse events appeared low. The results of this review can therefore be used to formulate clinical studies more precisely in order to standardise and focus on patient-relevant outcomes.
Topics: Adjuvants, Immunologic; Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Female; Humans; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Receptor Activator of Nuclear Factor-kappa B
PubMed: 31014505
DOI: 10.1016/j.critrevonc.2019.02.004 -
The Angle Orthodontist Jul 2020To investigate and synthesize systematically the evidence from animal studies pertaining to the effect of pharmacological agents on tooth movement relapse following...
OBJECTIVES
To investigate and synthesize systematically the evidence from animal studies pertaining to the effect of pharmacological agents on tooth movement relapse following cessation of orthodontic force application.
MATERIALS AND METHODS
An electronic search was conducted in seven online databases (including gray sources) without restrictions until the third week of April 2019, followed by a hand search in the reference lists of eligible articles. Controlled animal studies investigating the effect of pharmacological agents on tooth movement relapse following orthodontic treatment were selected. Relevant data were extracted from eligible studies and the risk of bias assessment was done using SYRCLE's risk of bias tool. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation tool.
RESULTS
The search identified 2354 records, of which 7 studies were deemed eligible for inclusion in the qualitative synthesis, with the majority presenting an unclear risk of bias. Orthodontic relapse was shown to decrease with the administration of pamidronate disodium, atorvastatin, aspirin, and chemically modified tetracycline-3. Inconsistent effects on relapse were observed after the use of simvastatin. The overall quality of retrieved evidence was assessed as low at best.
CONCLUSIONS
The available evidence shows that the investigated pharmacological agents may demonstrate variable effects on tooth movement relapse following cessation of orthodontic force. Additional evidence of higher quality is required to draw definitive conclusions on their effects and to make potential recommendations for clinical application.
Topics: Animals; Dental Care; Health Behavior; Humans; Recurrence; Tooth Movement Techniques
PubMed: 33378496
DOI: 10.2319/092619-613.1 -
JBMR Plus Oct 2019Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder that results in bone fragility and deformity. Management is multi-disciplinary. Although...
Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder that results in bone fragility and deformity. Management is multi-disciplinary. Although pharmacologic intervention with bisphosphonates (BP) is a standard of care for individuals with severe OI, no consensus or reviews were found that focus on the effects of bisphosphonates on function and mobility. PubMed, CINAHL, Cochrane Library, Web of Science, and PEDro databases were searched for eligible articles for this review. Methodological quality was assessed using the Cochrane Collaboration's tool for risk of bias. Twenty-six studies (801 children) were reviewed and five showed a low risk of bias. Included studies showed significant variability among clinical protocols for administering BP. Randomized controlled trials did not demonstrate a significant improvement in function and mobility with oral BP administration, while non-randomized open-label uncontrolled studies demonstrated that oral and intravenous BP administration objectively improved function and mobility. The most common outcome measure used by the studies included in this review was the Bleck score. Effect sizes (d = 0.28 - 4.5) varied among studies. This systematic review also summarized the apparent confounding variables affecting results of previous studies and provided suggestions to improve the quality of future studies.
PubMed: 31687649
DOI: 10.1002/jbm4.10216