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Supportive Care in Cancer : Official... Jun 2021Bisphosphonates and denosumab are both antiresorptive medications, each with their own mechanism of action; yet both may result in the same adverse effect:...
OBJECTIVE
Bisphosphonates and denosumab are both antiresorptive medications, each with their own mechanism of action; yet both may result in the same adverse effect: medication-related osteonecrosis of the jaw (ONJ). The present systematic review aims to answer the following question: "Are bisphosphonate-related ONJ and denosumab-related ONJ any different, regarding clinical and imaging aspects?"
METHODS
This review followed the Joanna Briggs Review's Manual, and the searches were performed on PubMed, Cochrane, Scopus, Web of Science, and Lilacs databases and on the grey literature (ProQuest, Open Grey, and Google Scholar).
RESULTS
The searches resulted in 7535 articles that were critically assessed. Based on the selection criteria, seven studies were included in the review: five cross-sectional studies and two randomized clinical trials. A total of 7755 patients composed the final population. An increase in bone sequestra, cortical bone lysis, and bone density was observed in bisphosphonate-related ONJ, while larger bone sequestra, more frequent periosteal reactions, and mandibular canal enhancement were noted in denosumab-related ONJ.
CONCLUSION
This systematic review demonstrated that the imaging characteristics of bisphosphonate-related and denosumab-related ONJ are not similar. Although clinically similar conditions, they were found to be radiographically distinct. More studies are necessary to further elucidate these differences.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Cross-Sectional Studies; Denosumab; Diphosphonates; Humans
PubMed: 33140246
DOI: 10.1007/s00520-020-05855-6 -
Journal of Musculoskeletal & Neuronal... Dec 2022Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM)... (Meta-Analysis)
Meta-Analysis Review
Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM) patients. The NCBI PubMed, Web of Science, Scopus and ClinicalTrials.gov databases, were systematically searched for interventional studies, assessing the use of BP and DENOS in MM patients. Overall survival, disease progression, skeletal-related events, bone pain, osteonecrosis of the jaw (ONJ) and renal toxicity were the outcomes of interest. A total of 993 studies were retrieved and 43 were used for qualitative synthesis. Clodronate (CLOD) and zoledronic acid (ZOL) were effective in reducing skeletal complications compared to placebo. Results are mixed regarding the efficacy of pamidronate in reducing skeletal related events. ONJ rates were higher for ZOL, but under 5%, with CLOD having the safest profile. DENOS demonstrated non-inferiority to ZOL, in improving overall survival [pooled Hazard Ratio(HR) 1.02(95% CI 0.72,1.44)], progression free survival [pooled HR 0.92(95% CI 0.76,1.11)] and in reducing skeletal related events [pooled HR 1.03(95% CI 0.92,1.16)], with similar rates of ONJ and better safety profile regarding renal toxicity. Denosumab has comparable efficacy and safety with ZOL and may even replace BPs in the future, in the management of myeloma bone disease.
Topics: Humans; Diphosphonates; Multiple Myeloma; Denosumab; Zoledronic Acid; Clodronic Acid
PubMed: 36458395
DOI: No ID Found -
Reviews in Endocrine & Metabolic... Dec 2023Fibrous dysplasia (FD) is a rare skeletal disorder in which normal bone is replaced by a fibro-osseous tissue, resulting in possible deformities and fractures. The aim... (Meta-Analysis)
Meta-Analysis Review
Fibrous dysplasia (FD) is a rare skeletal disorder in which normal bone is replaced by a fibro-osseous tissue, resulting in possible deformities and fractures. The aim of this systematic review and meta-analysis was to synthesize the available evidence on the use of antiresorptive drugs in FD in terms of changes in bone turnover markers (BTMs), bone mineral density (BMD), and reducing pain. Three databases were searched in October 2022, with an update in July 2023. Of the 1037 studies identified, 21 were retained after eligibility assessment. A random-effects model was used to calculate global effect size and the corresponding standard error. Pamidronate and Denosumab were the most reported drugs in a total of 374 patients assessed. The initiation of treatments was accompanied by an average reduction of 40.5% [CI -51.6, -29.3] in the bone resorption parameters, and 22.0% [CI -31.9, -12.1] in the parameters of bone formation after 6-12 months. BMD was increased in both FD lesions and in the unaffected skeleton. Pain was reduced by 32.7% [CI -52.7, -12.6] after 6-12 months of treatment, and by 44.5% [CI -65.3, -23.6] after a mean 41.2 months of follow-up. The variation in pain was highly correlated to variation in bone resorption (R = 0.08, p < 0.0001) and formation parameters (R = 0.17, p < 0.0001). This study supports the overall efficacy of antiresorptive therapies in terms of reducing bone remodeling, improving bone density, and pain in FD.
Topics: Humans; Bone Density Conservation Agents; Fibrous Dysplasia, Polyostotic; Diphosphonates; Fibrous Dysplasia of Bone; Bone Resorption; Pain
PubMed: 37632645
DOI: 10.1007/s11154-023-09832-2 -
Journal of the American Board of Family... Feb 2023There are multiple classes of pharmacologic agents approved for treatment of osteoporosis, but their costs vary widely, and systematic data on their efficacy compared... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are multiple classes of pharmacologic agents approved for treatment of osteoporosis, but their costs vary widely, and systematic data on their efficacy compared with the traditional standard, bisphosphonates, for reducing fractures in postmenopausal women are lacking. The objective was to perform a systematic review and meta-analysis assessing the efficacy of denosumab compared with bisphosphonates.
METHODS
Researchers selected randomized controlled trials (RCTs) comparing denosumab to bisphosphonates that included information on clinical and/or osteoporotic fracture events over the follow-up period. Each clinical outcome was meta-analyzed using a fixed-effects analysis, with clinical and osteoporotic fractures as the outcomes of interest. A meta-regression was performed using change in bone mineral density (BMD) as the moderator variable.
RESULTS
Seven RCTs were included. Denosumab was not associated with a reduction in clinical or osteoporotic fractures compared with bisphosphonates. There was no association between the change in BMD with denosumab and bisphosphonates and denosumab's effect on both osteoporotic and clinical fractures.
DISCUSSION
Existing data do not support the use of the more expensive denosumab as a first-line agent over bisphosphonates for reduction of fractures in postmenopausal women with osteoporosis. One limitation in this study was each RCT was not individually powered for fracture incidences.
Topics: Female; Humans; Diphosphonates; Osteoporotic Fractures; Bone Density Conservation Agents; Postmenopause; Osteoporosis, Postmenopausal; Osteoporosis; Bone Density
PubMed: 36653115
DOI: 10.3122/jabfm.2022.220099R1 -
Osteoporosis International : a Journal... May 2022This paper systematically reviewed and assessed all retrievable pharmacoeconomic studies on denosumab for the treatment of osteoporosis. Denosumab was more... (Review)
Review
UNLABELLED
This paper systematically reviewed and assessed all retrievable pharmacoeconomic studies on denosumab for the treatment of osteoporosis. Denosumab was more cost-effective in patients with older age, prior fracture experience, lower BMD T-scores, and more risk factors. ESCEO-IOF guidelines were more applicable to improve the quality of pharmacoeconomic studies in osteoporosis.
INTRODUCTION
There are many pharmacoeconomic studies on denosumab for osteoporosis. However, the corresponding reviews are outdated or incomplete and need to be updated and refined. This article aims to systematically review and evaluate all retrievable pharmacoeconomic studies of denosumab for osteoporosis.
METHODS
A systematic literature search was performed utilizing PubMed, EMBASE(Ovid), Proquest(EconLit), Chongqing VIP, WanFang Database, and Chinese National Knowledge Infrastructure to identify full-text articles published before September 2021. The quality of full-text articles was evaluated by the Consolidated Health Economic Evaluation Reporting Standards(CHEERS) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases International Osteoporosis Foundation guideline(ESCEO-IOF).
RESULTS
In total, 21 full-text articles were eligible for inclusion. Denosumab for postmenopausal osteoporosis was not dominant compared to zoledronate and teriparatide. However, denosumab was dominant compared with strontium ranelate, raloxifene, and ibandronate in patients over 65 years. The probabilities of denosumab being cost-effective or dominant were more than 85% compared with no treatment and risedronate in patients aged over 70 years. Compared to alendronate, the highest rate of denosumab dominance occurred in patients aged 65 to 75 years, at about 65%. Most of the articles had higher CHEERS scores than ESCEO-IOF scores (converted into percentages).
CONCLUSIONS
The cost-effectiveness of denosumab for the treatment of osteoporosis was influenced by multiple factors. Generally, denosumab was more cost-effective in patients with older age, prior fracture experience, lower BMD T-scores, and more risk factors. ESCEO-IOF guidelines were more applicable to improve the transparency, generalization, and quality of pharmacoeconomic studies in osteoporosis.
Topics: Bone Density Conservation Agents; Cost-Benefit Analysis; Denosumab; Female; Fractures, Bone; Humans; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 35059777
DOI: 10.1007/s00198-021-06268-9 -
Rheumatology Advances in Practice 2021Denosumab is used for osteoporosis because it inhibits osteoclast maturation and suppresses bone resorption. Although denosumab is expected to inhibit the bone erosion...
OBJECTIVES
Denosumab is used for osteoporosis because it inhibits osteoclast maturation and suppresses bone resorption. Although denosumab is expected to inhibit the bone erosion in RA, its therapeutic efficacy is not well established. The aim of this study was to estimate the effects of denosumab on RA through a meta-analysis.
METHODS
A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Web of Science and Scopus were searched for original studies providing information on BMD, joint destruction and disease activity in denosumab-treated RA. A random-effects model was used in the meta-analysis.
RESULTS
Of the 367 studies identified, 18 met the selection criteria. The BMDs of the lumbar spine, total hip and femoral neck at 12 months after denosumab treatment increased by 5.27% (95% CI: 4.37, 6.18), 2.82% (2.46, 3.18) and 3.07% (2.66, 3.48), respectively. In the sensitivity analysis, age and sex tended to influence the effect of denosumab therapy on the rate of variation of BMD, but not glucocorticoid use. The changes in the modified total sharp, erosion and joint space narrowing scores at 12 months after denosumab treatment were significantly smaller with denosumab than with placebo, although the DAS did not change after denosumab treatment.
CONCLUSION
Although denosumab has an inhibitory effect on the bone resorption in RA, its effects might be influenced by the age and sex of RA patients, but not by glucocorticoid use.
PubMed: 34988358
DOI: 10.1093/rap/rkab099 -
Oral Diseases Sep 2023The current literature on multiple idiopathic cervical root resorption (MICRR), a rare and aggressive form of external root resorption, is limited to case reports and... (Review)
Review
The current literature on multiple idiopathic cervical root resorption (MICRR), a rare and aggressive form of external root resorption, is limited to case reports and series. Therefore, we performed a systematic review of this condition. A comprehensive search of PubMed, Embase, Web of science, Cochrane Library, CNKI, and WANFANG was conducted using key terms relevant to MICRR, supplemented by a grey literature search. Risk of bias was assessed using Cochrane's and Joanna Briggs Institute's tools. A total of 36 studies with 47 cases were included. MICRR is more common among younger females and may be related to hormonal changes and denosumab use. Initially, the premolars are usually affected but all permanent teeth may eventually be involved. Cone-beam computed tomography is recommended for diagnosis and assessment of resorptive lesions. The management is focused on complete removal and restoration of the resorptive tissue to maintain the tooth's structural integrity. However, MICRR usually has a poor prognosis. Due to its invasive and aggressive behavior, MICRR requires greater attention.
Topics: Female; Humans; Root Resorption; Cone-Beam Computed Tomography
PubMed: 36251582
DOI: 10.1111/odi.14406 -
Osteoporosis International : a Journal... Mar 2021The immunomodulatory effects of denosumab have raised concerns for risk of malignancy. This meta-analysis of 25 randomized controlled trials (21,523 patients) shows... (Meta-Analysis)
Meta-Analysis Review
The immunomodulatory effects of denosumab have raised concerns for risk of malignancy. This meta-analysis of 25 randomized controlled trials (21,523 patients) shows similar risk of malignancy between denosumab (60 mg every 6 months, up to 48 months) and any comparator. Post-marketing surveillance may detect rare or late-occurring drug effects. Possible increased risk of malignancy in patients treated with denosumab has been concerned due to inhibition of the immune modulator receptor activator of nuclear factor κ-Β ligand (RANKL). We aimed to assess the risk of malignancy associated with denosumab treatment. PubMed and Cochrane Central Register of Controlled Trials were searched up to May 27, 2019 to include all randomized controlled trials of denosumab (60 mg every 6 months) versus any comparator. Trials using higher drug doses for prevention of skeletal-related events were excluded. Data were independently extracted by two reviewers and analyzed using a fixed-effect model to pool risk ratios (RRs) with 95% confidence intervals (CI). Twenty-five trials (21,523 patients) were included. The risk of malignancy was similar between denosumab and other comparators (absolute risk difference 0%, RR 1.08 [95% CI, 0.93-1.24], I = 0%). Sensitivity analysis based on adequate allocation concealment showed similar results. The risk of malignancy did not differ between groups in any of the subgroup analyses, including stratification by race, individual comparators, indications for treatment, and longer drug exposure (≥ 24 months, 9 studies). The risk ratio of malignancy-related death was similar between groups. Early concerns about a potential increased risk of malignancy resulting from an immunomodulatory effect of denosumab are not supported by evidence from this meta-analysis of 25 RCTs with drug exposure of up to 48 months. Since RCTs with longer observation for safety outcomes are not expected, post-marketing surveillance will be the main means for detection of rare or late-occurring events.
Topics: Bone Density Conservation Agents; Denosumab; Humans; Neoplasms; Randomized Controlled Trials as Topic
PubMed: 33145606
DOI: 10.1007/s00198-020-05704-6 -
Frontiers in Pharmacology 2024Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian...
Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of denosumab, teriparatide and bisphosphonates for patients with GIO. Relevant randomized controlled trials published in PubMed, Embase, Cochrane Library and ClinicalTrials.gov up to August 2023 were searched. The following efficiency and safety outcomes were extracted for comparison: bone mineral density (BMD) percentage changes in lumbar spine, femur neck and total hip, and incidences of adverse events (AEs), serious adverse events (SAEs), vertebrae and non-vertebrae fracture. Bayesian random effects models were used for multiple treatment comparisons. 11 eligible RCTs involving 2,877 patients were identified. All the six medications including alendronate, risedronate, etidronate, zoledronate, teriparatide, and denosumab and were effective in increasing BMD. Teriparatide and denosumab were more effective in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. Alendronate and denosumab were more effective in improving total hip BMD. Alendronate and teriparatide had the lowest incidences of AEs and SAEs. Teriparatide denosumab and the bisphosphonates are all effective in improving BMD for GIO patients. Based on this network meta-analysis, teriparatide and denosumab have higher efficiency in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. 10.17605/OSF.IO/2G8YA, identifier CRD42023456305.
PubMed: 38313307
DOI: 10.3389/fphar.2024.1336075 -
Journal of Dentistry Nov 2023There is limited scientific evidence regarding the medication-related osteonecrosis of the jaw (MRONJ) induced by regenerative therapy (RT) associated with dental... (Review)
Review
OBJECTIVES
There is limited scientific evidence regarding the medication-related osteonecrosis of the jaw (MRONJ) induced by regenerative therapy (RT) associated with dental implant treatment. Thus, the current scoping review systematically maps the MRONJ research induced by RTs in implant dentistry and recognizes the existing gaps in knowledge.
DATA
Original studies and reviews investigating the impact of RT on the development of MRONJ were included.
SOURCES
Two reviewers independently searched the MEDLINE-PubMed and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) extension for Scoping Review and included articles published in English up to March 31, 2023.
STUDY SELECTION
Eighteen articles that fulfilled the inclusion and exclusion criteria were included in this study. Ten mapping parameters for investigating the association of RTs with MRONJ development were examined and evaluated within the selected articles.
RESULTS
There was severely limited information regarding the procedures of RTs including; the grafting materials, surgical protocols, and success and failure rates. The RT associated with MRONJ cases was sinus floor augmentation in patients taking bisphosphonate and denosumab. Moreover, there were limited data on the implant treatment associated with RTs such as time of insertion, implant length and diameter, and loading protocol.
CONCLUSION
The current scoping review revealed that some specific RTs associated with other factors hold a potential risk of MRONJ occurrence. However, the scientific evidence is limited with many gaps. Further investigations are needed to establish an evidence-based clinical guideline for treating high-risk patients.
CLINICAL SIGNIFICANCE
Clinicians should cautiously assess the risk of MRONJ development during implant treatment planning for patients undertaking antiresorptive medications. The adverse outcome of RT procedures should not be underestimated and a complete explanation of the possible risks should be given to the patients.
Topics: Humans; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Diphosphonates; Sinus Floor Augmentation
PubMed: 37708930
DOI: 10.1016/j.jdent.2023.104682