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Frontiers in Immunology 2021The purpose of this study was to evaluate the efficacy of denosumab treatment in patients with rheumatoid arthritis (RA). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this study was to evaluate the efficacy of denosumab treatment in patients with rheumatoid arthritis (RA).
METHODS
The Medline, Embase and Cochrane Library databases were searched for relevant clinical studies. Studies that assessed the efficacy of denosumab in patients with RA were identified. The primary endpoints were the percent changes in bone mineral density (BMD), and the changes in modified total Sharp score (mTSS), modified Sharp erosion score and joint space narrowing (JSN) score. Pooled analyses were calculated using random-effect models.
RESULTS
After searching the literature and performing further detailed assessments, 10 studies with a total of 1758 patients were included in the quantitative analysis. Pooled analyses showed that denosumab treatment significantly increased the percent changes in lumbar spine BMD [mean difference (MD): 5.12, confidence intervals (CI): 4.15 to 6.09], total hip BMD (MD: 2.72, 95% CI: 1.80 to 3.64) and femoral neck BMD (MD: 2.20, 95% CI: 0.94 to 3.46) compared with controls. Moreover, denosumab treatment significantly decreased the changes in mTSS (MD: -0.63, 95% CI: -0.86 to -0.41) and modified Sharp erosion score (MD: -0.62, 95% CI: -0.88 to -0.35). Subgroup analysis indicated that denosumab was superior to bisphosphonates for the improvement of BMD and the mitigation of joint destruction.
CONCLUSION
Denosumab treatment was associated with increased BMD and alleviated progression of joint destruction in RA patients, even when compared with bisphosphonates.
Topics: Arthritis, Rheumatoid; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Joints; Lumbar Vertebrae; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35069583
DOI: 10.3389/fimmu.2021.799575 -
Bone Reports Jun 2020As a result of the negative impact of bone metastases on patient quality of life, it is important to identify patients at increased risk of skeletal-related events... (Review)
Review
What is the relationship between bone turnover markers and skeletal-related events in patients with bone metastases from solid tumors and in patients with multiple myeloma? A systematic review and meta-regression analysis.
INTRODUCTION
As a result of the negative impact of bone metastases on patient quality of life, it is important to identify patients at increased risk of skeletal-related events (SREs). Biochemical markers produced by osteoblasts and osteoclasts may provide an early indicator of treatment response to antiresorptive therapy. We aimed to explore the relationship between change in the urinary bone turnover marker cross-linked N-terminal telopeptide of type 1 collagen (uNTX) at the earliest time of steady state and risk of SREs.
METHODS
A comprehensive search of eight bibliographic databases and two trial registries was conducted (June 2017). We included randomized controlled trials of adults (≥18 years old) with bone metastases from solid tumors (including breast, lung, prostate) or bone lesions from multiple myeloma that compared denosumab or bisphosphonate(s) with each other or a placebo. Meta-analyses were used to evaluate the relationship between uNTX and SREs. The primary outcomes were based on uNTX at week 13 and SREs in those studies.
RESULTS
Seventeen studies (12,130 patients) were included. The analysis results indicated a positive association between uNTX reduction, measured by the between-group difference of the natural logarithm of the ratio between uNTX at week 13 and baseline, and SRE risk reduction, measured by the natural logarithm of the hazard ratio (HR) for time to first SRE between the two groups (uNTX effect on SRE risk, defined as SRE HR increase corresponding to one unit smaller in the magnitude of uNTX reduction: 0.3560, 95% confidence interval 0.0249-0.6871; = .0390, R = 0.7360). Results were similar for studies that reported change in uNTX from baseline to week 13 and to later than week 13. The limitation of this review is that it depends on how comprehensive study data were that could be included in the meta-regression.
CONCLUSIONS
Our findings support a positive relationship between reduction of bone turnover markers at the earliest time of steady state and reduction in longer-term risk of SREs.
PubMed: 32420416
DOI: 10.1016/j.bonr.2020.100272 -
Journal of Clinical Medicine Apr 2024This systematic review aimed to evaluate the impact of antiresorptive drug therapy on osseointegrated dental implants and the association with medication-related... (Review)
Review
This systematic review aimed to evaluate the impact of antiresorptive drug therapy on osseointegrated dental implants and the association with medication-related osteonecrosis of the jaw (MRONJ). A systematic search, including a computer search of several databases with specific keywords, a reference search, and a manual search of four key maxillofacial journals were performed. Relevant articles were then evaluated and those that fulfilled the five predetermined criteria were chosen to enter the final review. A total of 445 implants in 135 subjects were included in the eight studies analyzed in the final review. The failure rate of dental implants after antiresorptive medication in the included studies was 23%, with 83% of failures attributed to MRONJ. The average time from antiresorptive drug initiation to MRONJ development was approximately 34 months, ranging from 3 months to 16 years. The majority of MRONJ cases were classified as stage 2, and all sites showed either complete healing or substantial mucosal coverage after treatment. This review highlights the significant impact of antiresorptive drugs on osseo- integrated implants, with MRONJ identified as a leading cause of implant failure. The potential role of peri-implantitis as a trigger for MRONJ is emphasized. Regular monitoring and maintaining good periodontal health, especially within the first three years of antiresorptive drug therapy initiation, are crucial for implant success. Physicians and dentists should provide comprehensive information to patients prescribed with antiresorptive drugs, emphasizing the need for an awareness of the risks of MRONJ in the context of osseointegrated implants. A longer term of follow-up is recommended to identify and manage MRONJ around dental implants in an early manner.
PubMed: 38610856
DOI: 10.3390/jcm13072091 -
Cancer Control : Journal of the Moffitt... 2020Denosumab is a human monoclonal antibody that has been used successfully in the treatment of giant cell tumors of bone. These tumors are rare and, in principle, benign,... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Denosumab is a human monoclonal antibody that has been used successfully in the treatment of giant cell tumors of bone. These tumors are rare and, in principle, benign, but they are highly aggressive, locally advanced, osteolytic bone tumors that can metastasize to the lungs. Denosumab is an effective treatment when these tumors cannot be surgically removed or when surgical resection is likely to lead to severe morbidity (eg, loss of limbs or joints). The aim of this systematic review and meta-analysis was to investigate patients with giant cell tumors of bone who experienced tumor progression during treatment with denosumab and to compare them with patients who experienced reduction of their giant cell tumors of bone during treatment with denosumab.
METHODS
Embase, Cochrane Library, and MEDLINE/PubMed databases were searched for trials submitted by January 7, 2020, that reported the efficacy and safety of denosumab in patients with giant cell tumors of bone.
RESULTS
Sixty studies were reviewed, involving a total of 1074 patients who had giant cell tumors of bone and were treated with denosumab. Of the 60 studies, 58% of the patients were from case series studies, 39% from open-label phase II studies, and 3% from case reports. The response rate for denosumab as a treatment for giant cell tumors of bone was 97.5%, with statistical significance ( < .0001). Pain in the limbs was statistically the most common adverse event for denosumab treatment in case series studies ( < .0001). No treatment-related deaths occurred in the reviewed studies.
CONCLUSION
Cumulative evidence supports the addition of surgery to optimal medical therapy with denosumab to reduce tumor size, clinical symptoms, and mortality among patients with giant cell tumors of bone.
Topics: Biopsy; Bone Neoplasms; Bone and Bones; Chemotherapy, Adjuvant; Curettage; Denosumab; Disease-Free Survival; Giant Cell Tumors; Humans; Lung Neoplasms; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Osteotomy; Tumor Burden
PubMed: 32869648
DOI: 10.1177/1073274820934822 -
Journal of Immunotherapy and Precision... Nov 2021Medication-related osteonecrosis of the jaws (MRONJ) is a known adverse event related to the use of antiresorptive (AR) drugs. More recently, an association between... (Review)
Review
INTRODUCTION
Medication-related osteonecrosis of the jaws (MRONJ) is a known adverse event related to the use of antiresorptive (AR) drugs. More recently, an association between antiangiogenic (AA) drugs and MRONJ has been suggested. This review aimed to investigate the overall prevalence and relative risk of MRONJ in patients treated concurrently with AA and AR agents in comparison with a single AA or AR drug.
METHODS
A review protocol was registered with PROSPERO (ID: CRD42020214244). A systematic literature search, study selection, quality assessment, and data extraction were carried out following PRISMA guidelines. Random-effects meta-analysis models were used to summarize relative estimates for the outcomes, namely prevalence and relative risk of MRONJ. Exposure variable included type of drug, specifically AA and AR agents administered either concurrently or individually.
RESULTS
Eleven studies were included in the final qualitative and quantitative syntheses. The overall pooled weighted prevalence of MRONJ with concurrent AA-AR drugs was 6% (95% CI: 3-8%), compared with 0% (95% CI: 0-0%) for AA only and 5% (95% CI: 0-10%) for AR only. However, high heterogeneity was noted among included studies. Retrospective cohort studies showed a higher pooled prevalence of 13% (95% CI: 10-17%) for concurrent AA-AR therapy. The pooled risk ratio for MRONJ revealed a risk with concurrent AA-AR drugs 2.57 times as high as with AR only (95% CI: 0.84-7.87); however, this difference was not statistically significant. Concurrent AA-AR drugs had a risk for MRONJ 23.74 times as high as with AA only (95% CI: 3.71-151.92).
CONCLUSIONS
High-quality, representative studies are needed for accurate estimation of relative risk of MRONJ with concurrent AA and AR therapy.
PubMed: 35665023
DOI: 10.36401/JIPO-21-14 -
BMC Musculoskeletal Disorders Apr 2020In 2013, denosumab was introduced as peri-operative adjuvant treatment for giant cell tumor (GCT) of bone as it inhibits osteoclast activity. It is suggested that... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In 2013, denosumab was introduced as peri-operative adjuvant treatment for giant cell tumor (GCT) of bone as it inhibits osteoclast activity. It is suggested that denosumab relives pain, facilitate curettage in lesions requiring resection initially. However, controversy remains whether denosumab increases the risk of local recurrence after surgery.
METHODS
Medline, Embase and the Cochrane Library were comprehensively searched in June 2019 to identify studies investigating the clinical outcome of GCT of bone with and without peri-operative denosumab after surgery. Data were gathered and a meta-analysis was conducted.
RESULT
Ten studies with 1082 cases (169 in denosumab group, 913 in control group) were included. Overall, denosumab was associated with significantly higher risk of recurrence(P < 0.02) and inferior 5 year recurrence free survival(P = 0.000). Denosumab and curettage has a relatively higher risk of recurrence comparing to curettage alone(P = 0.07). The risk of recurrence is not significantly increased if denosumab was administered both preoperatively and postoperatively(P = 0.24).
CONCLUSION
Administration of denosumab is associated with increased risk of recurrence due to a variety of reasons, though it is proven effective in relieving pain, enabling curettage and improved functional outcome. Post-operative denosumab is recommended as it continuously suppress/eliminate residue tumor cells.
Topics: Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Follow-Up Studies; Giant Cell Tumor of Bone; Humans; Incidence; Neoplasm Recurrence, Local; Preoperative Care; Retrospective Studies; Risk; Treatment Outcome
PubMed: 32312263
DOI: 10.1186/s12891-020-03294-2 -
Medicina (Kaunas, Lithuania) May 2023: Although it is very uncommon, medication-induced osteonecrosis of the jaw (also known as MRONJ) can have serious consequences. Traditionally, this adverse event has... (Meta-Analysis)
Meta-Analysis Review
The Use of Human Amniotic Membrane (hAM) as a Treatment Strategy of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Systematic Review and Meta-Analysis of the Literature.
: Although it is very uncommon, medication-induced osteonecrosis of the jaw (also known as MRONJ) can have serious consequences. Traditionally, this adverse event has been recognised in patients who were treated with bisphosphonate (BP) drugs. Nevertheless, in recent years, it has been established that individuals having treatment with various types of medications, such as a receptor activator of nuclear factor kappa-Β ligand inhibitor (denosumab) and antiangiogenic agents, have had the same issue. The purpose of this research is to determine if the application of human amniotic membrane (hAM) may be used as a therapy for MRONJ. : A multi-source database (MEDLINE, EMBASE, AMED, and CENTRAL) systematic search was performed. The major objective of this study is to obtain an understanding of the efficacy of hAM when it is employed as a treatment modality for MRONJ. The protocol of this review was registered in the INPLASY register under the number NPLASY202330010. : The authors were able to include a total of five studies for the quality analysis, whereas for the quantity evaluation, only four studies were eligible. A total of 91 patients were considered for the investigation. After treatment with human amniotic membrane (hAM), a recurrence of osteonecrosis was observed in n = 6 cases (8.8%). The combined efficacy of surgical therapy and the use of hAM resulted in an overall success rate of 91.2%. Intraoperative complications were only documented in one article, and they were mostly caused by the positioning of the hAM, which led to wound breakdown at the surgical site. Based on the small amount of data and low-quality research included in this study, using human amniotic membranes to treat MRONJ might represent a feasible option. Nevertheless, further studies with a wider patient population are required to understand the long-term impacts.
Topics: Humans; Bisphosphonate-Associated Osteonecrosis of the Jaw; Amnion; Denosumab; Diphosphonates; Bone Density Conservation Agents
PubMed: 37241200
DOI: 10.3390/medicina59050968 -
Drugs in R&D Dec 2020Subacute cutaneous lupus erythematosus (SCLE) lacks consensus diagnostic criteria and the pathogenesis is poorly understood. There are increasing reports of SCLE induced...
BACKGROUND
Subacute cutaneous lupus erythematosus (SCLE) lacks consensus diagnostic criteria and the pathogenesis is poorly understood. There are increasing reports of SCLE induced by monoclonal antibodies (mAbs), but there are limited data on the aetiology, clinical characteristics and natural course of this disease.
METHODS
We devised a set of diagnostic criteria for SCLE in collaboration with a multinational, multispecialty panel. This systematic review employed a two-layered search strategy of five databases for cases of mAb-induced SCLE (PROSPERO registered protocol CRD42019116521). To explore the relationship between relative mAb use and the number of SCLE cases reported, the estimated number of mAb users was modelled from 2013 to 2018 global commercial data and estimated annual therapy costs.
RESULTS
From 40 papers, we identified 52 cases of mAb-induced SCLE, occurring in a cohort that was 73% female and with a median age of 61 years. Fifty percent of cases were induced by anti-tumour necrosis factor (TNF)-ɑ agents. A median of three drug doses preceded SCLE onset and the lesions lasted a median of 7 weeks after drug cessation. Oral and topical corticosteroids were most frequently used. Of the licensed mAbs, adalimumab, denosumab, rituximab, etanercept and infliximab were calculated to have the highest relative number of yearly users based on global sales data. Comparing the number of mAb-induced SCLE cases with estimated yearly users, the checkpoint inhibitors pembrolizumab and nivolumab showed strikingly high rates of SCLE relative to their global use, but ipilimumab did not.
CONCLUSION
We present the first systematic review characterising mAb-induced SCLE with respect to triggers, clinical signs, laboratory findings, prognosis and treatment approaches. We identify elevated rates associated with the use of checkpoint inhibitors and anti-TNFɑ agents.
Topics: Antibodies, Monoclonal; Humans; Immunologic Factors; International Cooperation; Lupus Erythematosus, Cutaneous; Prognosis; Treatment Outcome
PubMed: 32960413
DOI: 10.1007/s40268-020-00320-5 -
HNO Jul 2022Antiresorptive agents are some of the most frequently used drugs worldwide, with indications in osteology and oncology. They are generally well tolerated and display... (Review)
Review
BACKGROUND
Antiresorptive agents are some of the most frequently used drugs worldwide, with indications in osteology and oncology. They are generally well tolerated and display a favorable safety profile. A potentially severe unwanted side effect is medication-related osteonecrosis of the jaw (MRONJ).
PURPOSE OF THIS REVIEW
This review summarizes the latest developments in etiology, diagnosis, and treatment of MRONJ, and compares new insights with established algorithms.
METHODS
A systematic review of relevant studies exploring diagnostic methods, prospective management trials, and innovative studies on the pathogenesis of MRONJ published between 2016 and 2021 was performed. The study quality was assessed using the MINORS (methodological index for non-randomized studies) rating score.
RESULTS AND DISCUSSION
The prevalence of MRONJ in patients undergoing treatment with antiresorptive drugs for oncological reasons is remarkable (2-12%). MRONJ prevalence in patients receiving antiresorptive drugs for the treatment of osteoporosis is much lower (0.1-1%). MRONJ treatment should be initiated early and involve a surgical approach. MRONJ treatment is safe and predictable, with long-term success rates of more than 85%.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Diphosphonates; Humans; Osteoporosis; Prospective Studies
PubMed: 35050392
DOI: 10.1007/s00106-021-01130-0 -
Clinical Therapeutics Jan 2022The efficacy comparison of osteoporosis treatments can be hindered by the absence of head-to-head trials; instead, network meta-analyses (NMAs) have been used to... (Meta-Analysis)
Meta-Analysis
PURPOSE
The efficacy comparison of osteoporosis treatments can be hindered by the absence of head-to-head trials; instead, network meta-analyses (NMAs) have been used to determine comparative effectiveness. This study was the first to investigate the impact of time point-specific NMAs of osteoporosis treatments on variability in treatments' onset of action caused by their different mechanisms of actions and trial designs.
METHODS
A systematic literature review was conducted to identify randomized controlled trials (RCTs) of treatments for postmenopausal women with osteoporosis, including romosozumab (ROMO), teriparatide (TPTD), abaloparatide (ABL), alendronate (ALN), risedronate (RIS), ibandronate (IB), zoledronic acid/zoledronate (ZOL), denosumab (DEN), and raloxifene (RLX), on at least 1 fracture or bone mineral density (BMD) outcome. Of 100 RCTs identified in 5 databases, 27 RCTs were included for NMAs of new vertebral, nonvertebral, and hip fracture outcomes at 12, 24, and 36 months, and 47 RCTs were included for NMAs of BMD outcomes at lumbar spine, total hip, and femoral neck to compare the relative efficacy of osteoporosis treatments. Quality of included studies was assessed using the Cochrane Risk of Bias tool.
FINDINGS
For vertebral fractures, TPTD (83.63%), ABL (69.11%), and ROMO/ALN (78.70%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO/ALN had the highest probability (54.4%, 64.69%, and 90.29%, respectively) to be the most effective treatment for nonvertebral fractures at 12, 24, and 36 months. For hip fractures, ROMO/ALN (46.31%), ABL (61.1%), and DEN (55.21%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO had the highest probability (76.06%, 44.19%, and 51.78%, respectively) to be the most effective treatment for BMD outcomes at lumbar spine, total hip, and femoral neck.
IMPLICATIONS
The importance of indirectly comparing available osteoporosis treatments using time point-specific NMAs was confirmed because indirect comparison results differed substantially across time points.
Topics: Bone Density; Bone Density Conservation Agents; Female; Humans; Network Meta-Analysis; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Teriparatide; Zoledronic Acid
PubMed: 35058055
DOI: 10.1016/j.clinthera.2021.11.015