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Current Oncology (Toronto, Ont.) Mar 2021The role of denosumab in patients with resectable giant cell tumour of bone remains unclear. We asked the following research question: for patients (aged ≥ 12 years)...
The role of denosumab in patients with resectable giant cell tumour of bone remains unclear. We asked the following research question: for patients (aged ≥ 12 years) with resectable giant cell tumour of bone, what are the benefits and harms of denosumab compared with no denosumab in terms of (1) facilitation of surgery (operative time, blood loss), (2) disease recurrence, (3) pain control, (4) disease stability, and (5) adverse effects (e.g., malignant transformation, osteonecrosis of jaw, atypical femur fracture)? One previous systematic review addressed only one outcome-disease recurrence. Therefore, we undertook this new systematic review to address the above five outcomes. MEDLINE, EMBASE, PubMed, and Cochrane Database of Systematic Reviews databases were searched on June 30, 2020. This systematic review included one previous systematic review and five comparative studies. Due to poor quality, non-randomized studies fraught with selection bias, it is difficult to determine if a significant difference exists in the outcomes for surgical giant cell tumour of bone with perioperative denosumab. There were no reported cases of adverse effects from denosumab. To date, there is insufficient evidence to understand the value of denosumab in the perioperative setting in patients with giant cell tumour of bone.
Topics: Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Giant Cell Tumor of Bone; Humans; Neoplasm Recurrence, Local; Systematic Reviews as Topic; Treatment Outcome
PubMed: 33809979
DOI: 10.3390/curroncol28020124 -
Journal of Research in Medical Sciences... 2021Medication related osteonecrosis of the jaw (MRONJ) is a severe condition affecting the jaws of patients exposed to specific drugs, and is primarily described in... (Review)
Review
Medication related osteonecrosis of the jaw (MRONJ) is a severe condition affecting the jaws of patients exposed to specific drugs, and is primarily described in patients receiving bisphosphonate (BP) therapy. However, more recently it has been observed in patients taking other medications, such as the RANK ligand inhibitor (denosumab) and antiangiogenic drugs. It has been proposed that the existence of other concomitant medical conditions may increase the incidence of MRONJ. The primary aim of this research was to analyze all available evidence and evaluate the reported outcomes of osteonecrosis of the jaws (ONJ) due to antiresorptive drugs in immunosuppressed patients. A multi-database (PubMed, MEDLINE, EMBASE and CINAHL) systematic search was performed. The search generated twenty-seven studies eligible for the analysis. The total number of patients included in the analysis was two hundred and six. All patients were deemed to have some form of immunosuppression, with some patients having more than one disorder contributing to their immunosuppression. Within this cohort the commonest trigger for MRONJ was a dental extraction (n=197). MRONJ complications and recurrence after treatment was sparsely reported in the literature, however a total of fourteen cases were observed. The data reviewed have confirmed that an invasive procedure is the commonest trigger of MRONJ with relatively high frequency of post-operative complications or recurrence following management. However, due to low-quality research available in the literature it is difficult to draw a definitive conclusion on the outcomes analysed in this systematic review.
PubMed: 34221052
DOI: 10.4103/jrms.JRMS_794_20 -
PloS One 2020Giving patients anti-osteoporotic agents peri-operatively is a well-accepted strategy to increase fusion rate and prevent complications. The purpose of this study was to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Giving patients anti-osteoporotic agents peri-operatively is a well-accepted strategy to increase fusion rate and prevent complications. The purpose of this study was to investigate effectiveness of teriparatide and bisphosphonate on fusion surgery of thoracic and lumbar spine.
METHODS
We searched EMBASE and PubMed for randomized clinical trials (RCTs) and prospective comparative studies using teriparatide or bisphosphonate in peri-operative spinal fusion surgery. Our synthesized data of fusion rate, Oswestry disability index (ODI), and adverse event in contrast-based network meta-analysis. Pooled results were presented in risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI).
RESULTS
Our search hit eight RCTs and three prospective studies with 676 patients receiving spinal surgery. Pooled result showed that teriparatide+Denosumab leads to significantly higher fusion rate than placebo (RR, 2.84; 95% CI: 1.22 to 6.60) and bisphosphonate (RR, 2.59; 95% CI: 1.13 to 5.96). We did not observe significant finding among placebo, teriparatide, and bisphosphonate in the two network models.
CONCLUSION
This is the first network meta-analysis providing an overview of the use of teriparatide and bisphosphonate for spinal fusion surgery. Teriparatide treatments are worth to be consider for spinal fusion surgery.
Topics: Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Diphosphonates; Humans; Lumbar Vertebrae; Spinal Diseases; Spinal Fusion; Teriparatide; Thoracic Vertebrae; Treatment Outcome
PubMed: 32870946
DOI: 10.1371/journal.pone.0237566 -
Annals of Geriatric Medicine and... Dec 2023
PubMed: 38185872
DOI: 10.4235/agmr.22.0139.r1 -
Endokrynologia Polska 2023The antifracture efficacy of vitamin D is still controversial. The aim of this systematic review was to examine if the vitamin D trials were designed adequately to...
INTRODUCTION
The antifracture efficacy of vitamin D is still controversial. The aim of this systematic review was to examine if the vitamin D trials were designed adequately to reliably assess its antifracture activity.
MATERIAL AND METHODS
The electronic databases PubMed, Medline, Embase, Web of Science, and Cochrane Library were searched to identify clinical trials evaluating the antifracture efficacy of vitamin D in adults. We compared the protocols of the trials against the opinions of the American Society for Bone and Mineral Research (ASBMR), International Society for Clinical Densitometry (ISCD), National Osteoporosis Foundation (NOF), European Medicines Agency (EMEA) experts, and the consensus statement from the 2nd International Conference on Controversies in Vitamin D, and against the protocols of the trials of the medications with proven antifracture efficacy (bisphosphonates, teriparatide, abaloparatide, raloxifene, denosumab, romosozumab). We assessed the prospective character, study design, group description, number of patients, study duration, and vitamin D (serum examination and dosage) supplementation. A description of the desired characteristics of the study protocol was presented.
RESULTS
Thirteen eligible trials were identified. All but 2 were conducted in the elderly population only. Nine trials were included in the final analysis. Serum 25-hydroxy vitamin D (25OHD) was not measured in a representative number of subjects before (except in 2 studies), during, or after treatment in any study.
CONCLUSIONS
The analysed studies did not conclusively assess the vitamin D antifracture efficacy in patients with prestudy low serum vitamin levels, due to the lack of assessment of whether sufficient doses of vitamin D were used. They informed about the relevant doses and preparations of vitamin D in particular groups (specific fracture risk, age, place of residence) only.
Topics: Humans; Adult; Aged; Prospective Studies; Vitamin D; Osteoporosis; Vitamins; Fractures, Bone; Bone Density Conservation Agents
PubMed: 37779375
DOI: 10.5603/ep.95639 -
Heliyon Apr 2020A temporary discontinuation (drug holiday) of high-dose antiresorptive (AR) agents has been proposed to reduce the risk of medication-related osteonecrosis of the jaw... (Review)
Review
A temporary discontinuation (drug holiday) of high-dose antiresorptive (AR) agents has been proposed to reduce the risk of medication-related osteonecrosis of the jaw (MRONJ). The aim of this systematic review was to answer the question: Is high-dose AR drug holiday, at the time of tooth extraction or dentoalveolar surgery, necessary to prevent the development of MRONJ in patients with cancer? This protocol was registered in the PROSPERO database. Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant studies up to and including April 2019. Randomized controlled trials (RCTs), cohort and cross-sectional studies, surveys, and case reports with more than five patients were included. Records were imported into www.covidence.org. Electronic searches were supplemented by manual searches and reference linkage. The Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) were followed. Although only one study fitted the population, intervention, comparison, outcome (PICO) framework, valuable information on AR drug holiday could be extracted from 14 of 371 reviewed articles. Among these, 3 were prospective and 11 were retrospective studies. These studies described or evaluated high-dose AR drug holidays. In 2 studies, patients were being treated with denosumab, but neither showed that a drug holiday was effective. The remaining 12 studies evaluated bisphosphonate treatment and 2 of these studies found no reason to use AR drug holiday before surgery. Three studies recommended drug holidays, whereas most of the studies recommended assessing each patient separately. The only paper that fitted the PICO approach was a non-randomized, prospective study with a control group. This study concluded that drug holiday was not necessary. Thus, there are no evidence for using drug holiday, but it is also clear that caused by a limited numbers of eligible patients, and a great variation in between these patient, high-level evidence for using AR drug holiday is almost impossible to obtain.
PubMed: 32373730
DOI: 10.1016/j.heliyon.2020.e03795 -
Clinical Therapeutics Aug 2020Bone metastases from solid tumors and multiple myeloma (MM) represent an important source of morbidity. The present meta-analysis was performed with the purpose of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Bone metastases from solid tumors and multiple myeloma (MM) represent an important source of morbidity. The present meta-analysis was performed with the purpose of comparing the efficacy and tolerability of denosumab versus zoledronic acid (ZA) in the prevention of skeletal-related events (SREs) in patients with bone metastases secondary to solid tumors or bone lesions in multiple myeloma.
METHODS
We searched PubMed, PubMed Central, EMBASE, the Cochrane Library, and ClinicalTrials.gov for relevant studies published until April 23, 2020. We included randomized, controlled trials that investigated the efficacy and tolerability of denosumab 120 mg SC versus ZA 4 mg IV, given every 4 weeks, in patients with bone lesions in multiple myeloma or bone metastases secondary to advanced solid tumors. Two reviewers independently identified studies, assessed the risk for bias, and extracted the data. Times to event outcomes were analyzed using hazard ratios (HRs) and 95% CIs. We analyzed tolerability outcomes using risk ratios (RRs) and 95% CIs, with a fixed-effects model.
FINDINGS
Four randomized, controlled trials (7379 patients) were identified as suitable for analysis. The pooled data indicated that denosumab was more favorable than ZA in delaying the time to first on-study SRE (HR = 0.86; 95% CI, 0.80-0.93; P = 0.0001) as well as the time to first and subsequent on-study SREs (HR = 0.83; 95% CI, 0.76-0.90; P < 0.0001); however, the results on overall survival and disease progression were similar between the 2 drugs. Additionally, denosumab was associated with lower risks for bone pain (risk ratio [RR] = 0.88; 95% CI, 0.80-0.97; P = 0.01), osteonecrosis of the jaw (RR = 0.75; 95% CI, 0.61-0.93; P = 0.007), and acute-phase reactions (RR = 0.47; 95% CI, 0.40-0.56; P < 0.00001).
IMPLICATIONS
Compared with ZA, denosumab demonstrated efficacy in significantly delaying on-study SREs. Furthermore, it showed a better tolerability profile, despite being associated with potential yet manageable adverse events. This study was registered with PROSPERO (identifier: CRD42019126390).
Topics: Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Humans; Multiple Myeloma; Randomized Controlled Trials as Topic; Zoledronic Acid
PubMed: 32718784
DOI: 10.1016/j.clinthera.2020.05.019 -
BMC Cancer Oct 2019While denosumab has been shown to prevent skeletal-related events in patients with bone metastasis, there is a concern that it may cause atypical femoral fracture (AFF)....
BACKGROUND
While denosumab has been shown to prevent skeletal-related events in patients with bone metastasis, there is a concern that it may cause atypical femoral fracture (AFF). While AFF has been reported in patients with osteoporosis receiving denosumab, data are scarce in the context of AFF occurring in patients with bone metastasis receiving monthly denosumab therapy.
METHODS
To analyze the incidence of AFF in patients with bone metastasis, we reviewed the medical records of patients who had received monthly denosumab (120 mg) treatment from May 2012 to June 2017 at any of the three participant institutions.
RESULTS
The study population consisted of 277 patients who had received a median of 10 doses (range, 1-79) of denosumab. Five patients were diagnosed as having AFF or symptomatic atypical femoral stress reaction (AFSR) needing surgical intervention, representing an incidence rate of 1.8% (95% confidence interval, 0.77-4.2). These patients had received 15, 45, 45, 46 or 47 doses of denosumab, respectively. Four of the patients had received prior zoledronic acid treatment. The results of our analysis suggested that long-term use of denosumab, especially for more than 3.5 years, and prior use of zoledronic acid were risk factors for the development of AFF.
CONCLUSIONS
We found the AFF events in 5 patients (1.8%) among 277 cancer patients who had received monthly denosumab (120 mg) treatment. Long-term denosumab treatment and prior zoledronic acid treatment were identified as risk factors for the development of AFF.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Femoral Fractures; Incidence; Osteoporosis; Retrospective Studies; Risk Factors; Zoledronic Acid
PubMed: 31640606
DOI: 10.1186/s12885-019-6236-6 -
Osteoporosis International : a Journal... Jul 2024To determine and appraise the certainty of fracture liaison service (FLS) in reducing the risk of secondary fragility fractures in older adults aged ≥ 50 years... (Meta-Analysis)
Meta-Analysis Review
To determine and appraise the certainty of fracture liaison service (FLS) in reducing the risk of secondary fragility fractures in older adults aged ≥ 50 years and to examine the nature of the FLS and the roles of various disciplines involved in the delivery of the FLS. Medline, EMBASE, PubMed, CINAHL, SCOPUS, and The Cochrane Library were searched from January 1st, 2010, to May 31st, 2022. Two reviewers independently extracted data. The risk of bias was evaluated using the Newcastle-Ottawa Scale for cohort studies and the PEDro scale for randomized trials, while the GRADE approach established the certainty of the evidence. Thirty-seven studies were identified of which 34 (91.9%) were rated as having a low risk of bias and 22 (59.5%) were meta-analyzed. Clinically important low certainty evidence at 1 year (RR 0.26, CI 0.13 to 0.52, 6 pooled studies) and moderate certainty evidence at ≥ 2 years (RR 0.68, CI 0.55 to 0.83, 13 pooled studies) indicate that the risk of secondary fragility fracture was lower in the FLS intervention compared to the non-FLS intervention. Sensitivity analyses with no observed heterogeneity confirmed these findings. This review found clinically important moderate certainty evidence showing that the risk of secondary fragility fracture was lower in the FLS intervention at ≥ 2 years. More high-quality studies in this field could improve the certainty of the evidence. Review registration: PROSPERO-CRD42021266408.
Topics: Humans; Osteoporotic Fractures; Aged; Secondary Prevention; Middle Aged; Osteoporosis
PubMed: 38536447
DOI: 10.1007/s00198-024-07052-1 -
Journal of Bone Oncology Jun 2020
Reply to: Denosumab for bone health in prostate and breast cancer patients receiving endocrine therapy? A systematic review and a meta-analysis of randomized trials (Galvano et al., J Bone Oncol 2019; 18:100252).
PubMed: 32742917
DOI: 10.1016/j.jbo.2020.100295