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Journal of Bone and Mineral Research :... Jan 2021The cardiovascular safety of denosumab has not yet been evaluated in a systematic review. This systematic review and meta-analysis sought to quantify the number of... (Meta-Analysis)
Meta-Analysis
The cardiovascular safety of denosumab has not yet been evaluated in a systematic review. This systematic review and meta-analysis sought to quantify the number of randomized controlled trials (RCTs) of denosumab (against comparators) reporting cardiovascular adverse events (CAEs) and examine the balance of CAEs between treatment arms. MEDLINE, Embase, and clinicaltrials.gov were searched from inception to October 26, 2019, for RCTs of denosumab versus comparators for any indication. Included trials were randomized, enrolled ≥100 participants, and reported bone-related outcomes. Primary outcome for analysis was all CAEs, a composite endpoint representing summation of all CAEs as reported by included trials. Secondary outcomes included major adverse cardiovascular events (MACE). Data were pooled using a fixed effects model to determine relative risk (RR) and 95% confidence interval (95% CI). Risk of bias was assessed using the Cochrane risk-of-bias tool. Of 554 records screened, 49 were included, while 36 reported CAEs. Twenty-seven included trials (12 eligible for meta-analysis) were conducted in 13,202 postmenopausal women. Compared with bisphosphonates, there was a 46% (95% CI 1.05 to 2.02) increase in CAEs (85/2136 events in denosumab-treated versus 58/2131 events in bisphosphonate-treated; seven trials). There was a similar imbalance in a five-point (stroke, myocardial infarction, cardiovascular death, heart failure, atrial fibrillation) MACE endpoint (28/2053 versus 12/2050; RR = 2.33 [1.19 to 4.56]). Compared with placebo-treated women, there was no imbalance in total CAEs (439/4725 events in denosumab versus 399/4467 in placebo; RR = 0.79 [0.41 to 1.52]; seven trials). No imbalance in total AEs (versus bisphosphonates: 0.98 [0.92 to 1.04]; versus placebo: 0.99 [0.98 to 1.01]) occurred. Other indications showed no statistically significant results. The excess CAEs in postmenopausal women treated with denosumab compared with bisphosphonates, but not placebo, indirectly supports claims that bisphosphonates may suppress CAEs. Future trials should use standardized CAE reporting to better describe cardiovascular effects of bone active medications. (PROSPERO: CRD42019135414.) © 2020 American Society for Bone and Mineral Research (ASBMR).
Topics: Bone Density Conservation Agents; Denosumab; Diphosphonates; Female; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic
PubMed: 32780899
DOI: 10.1002/jbmr.4157 -
Clinical and Experimental Dental... Feb 2023Antiresorptive medication has been reported to be associated with medication-related osteonecrosis of the jaw (MRONJ). This systematic review aims at investigating the... (Review)
Review
OBJECTIVES
Antiresorptive medication has been reported to be associated with medication-related osteonecrosis of the jaw (MRONJ). This systematic review aims at investigating the incidence of and risk factors for MRONJ after tooth extractions in cancer patients treated with high-dose bisphosphonate and denosumab (BP and DS). MATERIAL AND METHODS: The protocol followed the PRISMA statement list and was registered in PROSPERO. Searches were performed for literature published up to April 2021 in the electronic databases PubMed, Embase, Web of Science, and CINAHL and then supplemented by manual research.
RESULTS
The search process resulted in 771 identified articles, of which seven studies fitted the population, intervention, comparison, and outcome framework. All were observational studies and four had control groups. A total of 550 patients treated with BP and DS were identified of whom 271 had received tooth extractions after medication onset. Due to significant heterogenicity in the collected data, only a qualitative analysis was performed. The MRONJ incidence after tooth extractions varied between 11% and 50% at the patient level. MRONJ occurred up to 3 years after the tooth extraction. Teeth affected by inflammation before the extraction and additional osteotomy during the surgical procedure were identified as risk factors.
CONCLUSIONS
Reliable methods of diagnosing MRONJ and adequate follow-up periods are important factors in obtaining the actual incidence of MRONJ after tooth extractions in patients treated with high-dose BP and DS.
Topics: Humans; Bisphosphonate-Associated Osteonecrosis of the Jaw; Incidence; Diphosphonates; Tooth Extraction; Risk Factors; Neoplasms
PubMed: 36464958
DOI: 10.1002/cre2.698 -
Frontiers in Pharmacology 2022Chronic kidney disease (CKD) is associated with bone and mineral metabolism. In this study we evaluated the comparative efficacies and safety of osteoporosis... (Review)
Review
Chronic kidney disease (CKD) is associated with bone and mineral metabolism. In this study we evaluated the comparative efficacies and safety of osteoporosis medications in patients with CKD or a history of kidney transplantation, and make recommendations for the best choice of osteoporosis treatment among patients with CKD or a history of kidney transplantation. We systemically searched for randomized controlled trials published in PubMed, Embase, and Cochrane databases up to June 2020. Network-meta analysis was used to compare the relative effectiveness of different treatments. A random-effects model was used when heterogeneity was expected. The safety of different treatments was also evaluated in terms of reported major adverse events. A total of 17 studies with data from 10,214 patients who had stage 2-5 CKD, were receiving dialysis, or had a history of kidney transplantation were included in the network meta-analysis. Treatment with teriparatide, denosumab, alendronate, and raloxifene were all associated with a significantly reduced risk of fractures compared to treatment with placebos [teriparatide: odds ratio (OR) = 0.19, 95% confidence interval (CI): 0.10-0.35; denosumab: OR = 0.40, 95% CI: 0.27-0.58; alendronate: OR = 0.61, 95% CI: 0.40-0.92; raloxifene: OR = 0.52, 95% CI: 0.41-0.67]. The rank probability and the surface under the cumulative ranking (SUCRA) values suggested that teriparatide ranked the highest for improvement in vertebral bone mineral density (BMD) (SUCRA = 97.8%), whereas denosumab ranked the highest for improvement in femoral neck BMD (SUCRA = 88.3%). Teriparatide and denosumab seem to be the most effective treatments for preventing bone loss and reducing the risk of fracture in our network comparison. However, because of the limitations and potential biases in the reviewed studies, there is still some uncertainty about the best treatment options for osteoporosis in patients with CKD or a history of kidney transplantation. : [PROSPERO], identifier [CRD42020209830].
PubMed: 35222037
DOI: 10.3389/fphar.2022.822178 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Post-transplant bone disease (PTBD) is a common complication in kidney transplant recipients. This systematic review and meta-analysis evaluates the efficiency and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Post-transplant bone disease (PTBD) is a common complication in kidney transplant recipients. This systematic review and meta-analysis evaluates the efficiency and safety of denosumab for the treatment of PTBD in kidney transplant recipients.
METHODS
Comprehensive search of PubMed Central, SCOPUS, EMBASE, MEDLINE, Cochrane trial registry, Google Scholar, and Clinicaltrials.gov databases was done for studies, published until April 2023. Primary outcomes included changes in bone mineral density (BMD) and T-scores. Secondary outcomes included incidence of fractures, alterations in bone turnover markers, and the incidence of adverse events.
RESULTS
Eleven studies with a total of 511 participants that underwent kidney transplant were included. Denosumab treatment resulted in a significant improvement in lumbar spine BMD (SMD: -0.31, 95% CI: -0.56 to -0.06) and T-score (SMD: -1.07, 95% CI: -1.51 to -0.64), while no differences were detected in hip/femoral neck BMD and the T-score. There was no marked change in the fracture incidence (OR: 0.42, 95% CI: 0.06 to 3.07). However, patients who received denosumab treatment had an increased incidence rate of hypocalcemia (OR: 9.98, 95% CI: 1.72 to 57.88).
CONCLUSIONS
Denosumab treatment may improve lumbar spine BMD and T-scores in patients with PTBD. However, it does not significantly affect fracture incidence and may increase the risk of hypocalcemia. These findings underline the necessity for well-powered, randomized controlled trials to further clarify the role of denosumab in managing PTBD.
Topics: Humans; Bone Density; Denosumab; Bone Density Conservation Agents; Hypocalcemia; Kidney Transplantation
PubMed: 37659288
DOI: 10.1016/j.trre.2023.100793 -
Special Care in Dentistry : Official... 2024This study aimed to assess the overall incidence of osteonecrosis of the jaw (ONJ) caused by bisphosphonates and denosumab when used for controlling bone cancer... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study aimed to assess the overall incidence of osteonecrosis of the jaw (ONJ) caused by bisphosphonates and denosumab when used for controlling bone cancer metastasis or as adjuvant therapy.
SUBJECTS AND METHODS
A systematic search of the PubMed, Embase, and Cochrane Library databases and major meetings' proceedings as of July 30, 2022, identified randomized controlled trials (RCTs) and observational trials that evaluated ONJ caused by denosumab or bisphosphonates. The total incidence and risk ratio (RR) for ONJ were calculated using a random-effects model.
RESULTS
A total of 42 003 patients with various solid tumors reported in 23 RCTs were included. The overall ONJ incidence in cancer patients receiving denosumab or bisphosphonates was 2.08% (95% CI 1.37-2.91; p < .01; I = 94.99%). Patients receiving denosumab had a higher ONJ incidence than those receiving bisphosphonates (RR 1.64, 95% CI 1.10-2.44; p < .05; I = 65.4%). Subgroup analyses showed that prostate cancer patients receiving denosumab and receiving zoledronic acid had the highest ONJ incidences, 5.0% and 3.0%, respectively. The incidence of ONJ induced by different doses was also different.
CONCLUSIONS
The incidence of ONJ caused by denosumab and bisphosphonates is low, the dose of the drug and the type of cancer have certain influence on ONJ. Therefore, clinicians should use the drug reasonably to improve the quality of life of patients.
Topics: Male; Humans; Diphosphonates; Denosumab; Incidence; Bone Density Conservation Agents; Osteonecrosis; Neoplasms; Bisphosphonate-Associated Osteonecrosis of the Jaw
PubMed: 37219080
DOI: 10.1111/scd.12877 -
BMC Musculoskeletal Disorders Nov 2022Both denosumab and bisphosphonates have been demonstrated effective for glucocorticoid-induced osteoporosis. However, evidence-based medicine is still lacking to prove... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Both denosumab and bisphosphonates have been demonstrated effective for glucocorticoid-induced osteoporosis. However, evidence-based medicine is still lacking to prove the clinical results between denosumab and bisphosphonates. This meta-analysis aims to compare the efficacy and safety between denosumab and oral bisphosphonates for the treatment of glucocorticoid-induced osteoporosis through evidence-based medicine.
METHODS
MEDLINE, EMBASE, and the Cochrane library databases were searched up to June 2022 for randomized controlled trials that compared denosumab and oral bisphosphonates in the treatment of glucocorticoid-induced osteoporosis. The following outcomes were extracted for comparison: percentage change in bone mineral density from baseline at the lumbar spine, total hip, femoral neck, and ultra-distal radius; percentage change from baseline in serum concentration of bone turnover markers; and incidence of treatment-emergent adverse events.
RESULTS
Four randomized controlled trials involving 714 patients were included. The pooled results showed that denosumab was superior to bisphosphonates in improving bone mineral density in lumbar spine (mean difference (MD) 1.70; 95% confidence interval (CI) 1.11-2.30; P < 0.001) and ultra-distal radius (MD 0.87; 95% CI 0.29-1.45; P = 0.003), and in suppressing C-terminal telopeptide of type 1 collagen (MD -34.83; 95% CI -67.37--2.28; P = 0.04) and procollagen type 1 N-terminal propeptide (MD -14.29; 95% CI -23.65- -4.94; P = 0.003) at 12 months. No significant differences were found in percentage change in total hip or femoral neck bone mineral density at 12 months, or in the incidence of treatment-emergent adverse events or osteoporosis-related fracture.
CONCLUSIONS
Compared with bisphosphonates, denosumab is superior in improving bone mineral density in lumbar spine and ultra-distal radius for glucocorticoid-induced osteoporosis. Further studies are needed to prove the efficacy of denosumab.
Topics: Humans; Bone Density; Denosumab; Diphosphonates; Glucocorticoids; Osteoporosis; Osteoporotic Fractures; Randomized Controlled Trials as Topic
PubMed: 36447169
DOI: 10.1186/s12891-022-05997-0 -
Journal of Drug Assessment 2021Receptor activator of NF-κβ ligand (RANKL) is crucial for the development of hepatic insulin resistance and poor glucose uptake; therefore, inhibiting RANKL with...
OBJECTIVE
Receptor activator of NF-κβ ligand (RANKL) is crucial for the development of hepatic insulin resistance and poor glucose uptake; therefore, inhibiting RANKL with Denosumab could improve fasting plasma glucose (FPG) and insulin (FPI).
METHODS
A systematic review was conducted to evaluate the effects of Denosumab on glycemic parameters. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of Denosumab on FPG, glycated hemoglobin (HbA1c), FPI, and Homeostatic Model Assessment for Insulin Resistance (HOMA1-IR). The pooled standard difference in means (SDM) and 95% confidence intervals (95%CI) were calculated. The results were stratified into (1) Normal Glucose Tolerance (NGT) and (2) Impaired Glucose Tolerance (IGT).
RESULTS
Six publications (1203 participants) were included. There was a significant association between Denosumab and FPG (SDM = -0.388, 95%CI: -0.705 to -0.070, = .017) and with HOMA1-IR (SDM = -0.223, 95%CI: -0.388 to -0.058, = .008), but not for HbA1c and FPI. When stratified by glucose tolerance, the association between Denosumab and FPG, HbA1c, and HOMA1-IR was present for the IGT group. Lastly, Denosumab had a time-dependent effect on HbA1c (slope = -0.037, 95%CI: -0.059 to -0.015, < .005).
CONCLUSIONS
Denosumab significantly improved glycemic parameters. This outcome was more prominent for subjects with compromised glucose tolerance, positing that Denosumab can be used as a treatment to improve glucose metabolism for persons with pre-diabetes and diabetes.
PubMed: 34676131
DOI: 10.1080/21556660.2021.1989194 -
Journal of Bone Oncology Oct 2019Hormonal therapies for receptor positive-breast and prostate cancer patients have shown clinical efficacy but also several side effects including osteoporosis, loss of... (Review)
Review
Hormonal therapies for receptor positive-breast and prostate cancer patients have shown clinical efficacy but also several side effects including osteoporosis, loss of bone mass and increased fracture risk. Denosumab represents an anti RANKL (receptor activator of nuclear factor-kB ligand) monoclonal anti-body acting as inhibitor of osteoclasts formation, function, and survival, then increasing bone mass. Herein, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the role of Denosumab in saving bone health in prostate and breast cancer patients receiving respectively androgen deprivation therapy and adjuvant endocrine therapy. Moreover, selected patients have to be treated with Denosumab at the dose of 60 mg every six month or placebo. Outcomes studied included the bone mass density (BMD) increase at 24 and 36 months, BMD loss, reduction of fractures risk (in particular vertebral) at 24 and 36 months and safety (overall, serious adverse events - SAEs and discontinuation rate). Our results showed a reduction of the BMD loss up to 36 months both at the lumbar and femoral level and a BMD increase both at 24 and 36 months. It was also found a reduction in the number of new vertebral and femoral fractures at 24 and 36 months. Finally, our pooled analysis showed that Denosumab did not affect both the SAEs and therapy discontinuation risk. In conclusion, Denosumab administration can be considered effective and safe in the prevention and management of the above mentioned adverse events related to hormonal therapies designed for breast and prostate tumors.
PubMed: 31440444
DOI: 10.1016/j.jbo.2019.100252 -
Frontiers in Pharmacology 2022Evidence on the efficacy of combination treatment of teriparatide and denosumab for osteoporosis remains controversial. We aim to compare the efficacy between the...
Evidence on the efficacy of combination treatment of teriparatide and denosumab for osteoporosis remains controversial. We aim to compare the efficacy between the combination treatment and monotherapy among patients with postmenopausal osteoporosis. We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science up to 26 January 2022, for relevant studies. This meta-analysis reviewed all randomized controlled trials (RCTs) that reported on the combination treatment of teriparatide and denosumab in patients with postmenopausal osteoporosis. The articles were examined individually by two reviewers, and the relevant data was extracted. We combined weighted mean difference (WMD) for bone mineral density (BMD) using random- or fixed- effect models and conducted subgroup analyses. Sensitivity analyses were performed, and possible publication bias was also assessed. Overall, combination treatment enhanced the mean percent change of bone mineral density in lumbar spine than monotherapy (WMD = 2.91, 95%CI: 1.983.83; = 0.00). And, combination treatment has been beneficial for enhancing the mean percent change of BMD in hip (WMD = 3.19, 95%CI: 2.25∼4.13; = 0.00). There was no significant difference between combination treatment and monotherapy in terms of the adverse events (RR = 0.81, 95%CI: 0.45∼1.45; = 0.472). The meta-analysis indicates that combination treatment led to greater BMD at the lumbar spine and hip in comparison to monotherapy, without an increased incidence of adverse events. (https://inplasy.com/), identifier (Inplasy Protocol 2734).
PubMed: 35685637
DOI: 10.3389/fphar.2022.888208 -
Archives of Osteoporosis Mar 2021The Brazilian guidelines for prevention and treatment of glucocorticoid-induced osteoporosis were updated and important topics were included such as assessment of risk... (Review)
Review
UNLABELLED
The Brazilian guidelines for prevention and treatment of glucocorticoid-induced osteoporosis were updated and important topics were included such as assessment of risk fracture using FRAX Brazil, use of denosumab, and also recommendations for the use of glucocorticoid pulse therapy and inhaled glucocortiocoid.
INTRODUCTION
Glucocorticoids (GCs) are used in almost all medical specialties and the incidences of vertebral/nonvertebral fractures range from 30 to 50% in individuals treated with GCs for over 3 months. Thus, osteoporosis and frailty fractures should be prevented and treated in patients initiating treatment or already being treated with GCs. The Committee for Osteoporosis and Bone Metabolic Disorders of the Brazilian Society of Rheumatology (BSR) established in 2012 the Brazilian Guidelines for glucocorticoid-induced osteoporosis (GIO). Herein, we provide a comprehensive update of the original guidelines based on improved available scientific evidence and/or expert experience.
METHODS
From March to June 2020, the Osteoporosis Committee of the BRS had meetings to update the questions presented in the first consensus (2012). Thus, twenty-six questions considered essential for the preparation of the recommendations were selected. A systematic literature review based on real-life scenarios was undertaken to answer the proposed questions. The MEDLINE, EMBASE, and SCOPUS databases were searched using specific search keywords.
RESULTS
Based on the review and expert opinion, the recommendations were updated for each of the 26 questions. We included 48 new bibliographic references that became available after the date of the publication of the first version of the consensus.
CONCLUSION
We updated the Brazilian guidelines for the prevention/treatment of GIO. New topics were added in this update, such as the assessment of risk fracture using FRAX Brazil, the use of denosumab, and approaches for the treatment of children and adolescents. Furthermore, we included recommendations for the use of inhaled GCs and GC pulse therapy in clinical settings.
Topics: Adolescent; Bone Density Conservation Agents; Brazil; Child; Fractures, Bone; Glucocorticoids; Humans; Osteoporosis; Rheumatology
PubMed: 33646403
DOI: 10.1007/s11657-021-00902-z