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Frontiers in Endocrinology 2023To assess the alterations in bone mineral density and bone turnover marker concentrations following the administration of denosumab and romosozumab therapies in patients... (Meta-Analysis)
Meta-Analysis
PURPOSE
To assess the alterations in bone mineral density and bone turnover marker concentrations following the administration of denosumab and romosozumab therapies in patients with osteoporosis.
METHODS
PubMed was searched for studies published until January 28, 2023, that investigated the clinical efficacy and bone turnover marker changes of denosumab and romosozumab in the treatment of osteoporosis, with a minimum follow-up of 3 months in each study. Studies were screened, and data on changes in bone mineral density (BMD), P1NP, and TRACP-5b levels after treatment were extracted and included in the analysis.
RESULTS
Six studies were analyzed. At 3 months after treatment, the romosozumab group showed greater changes in lumbar BMD and bone turnover markers. BMD of total hip and femoral neck was relatively delayed. Beginning at 6 to 12 months, romosozumab showed greater changes in bone mineral density and markers of bone turnover.
CONCLUSION
Both romosozumab and denosumab have antiosteoporotic effects, with greater effects on BMD and bone turnover markers observed within 12 months of romosozumab treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42023395034.
Topics: Humans; Bone Density; Denosumab; Bone Density Conservation Agents; Osteoporosis
PubMed: 37529613
DOI: 10.3389/fendo.2023.1188969 -
Clinical Medicine (London, England) Sep 2023Hypercalcaemia of malignancy (HCM) is a common metabolic complication of advanced malignancies with a prevalence varying from 2-30%, depending on cancer type and disease... (Meta-Analysis)
Meta-Analysis
Hypercalcaemia of malignancy (HCM) is a common metabolic complication of advanced malignancies with a prevalence varying from 2-30%, depending on cancer type and disease stage. HCM is associated with impaired quality of life, increased risk of hospitalisation and limited survival. Evidence-based guidelines for management of HCM have been lacking to date, despite its prevalence and detrimental impact. This concise guidance highlights key recommendations from the recent Endocrine Society Clinical Practice Guidelines on Treatment of Hypercalcaemia of Malignancy in Adults, published in December 2022. A systematic review and meta-analysis was commissioned to support the guideline development process. Key suggestions include the use of denosumab in preference to intravenous bisphosphonates as first-line treatment for HCM and the use of denosumab in cases of recurrent or refractory HCM in patients previously treated with intravenous bisphosphonates. The guideline also identifies priority areas for future research.
Topics: Humans; Adult; Hypercalcemia; Denosumab; Diphosphonates; Quality of Life; Neoplasms; Bone Density Conservation Agents
PubMed: 37775175
DOI: 10.7861/clinmed.2023-0227 -
Revista Medica de Chile Jul 2020Medication-related osteonecrosis of the jaw is a disease where there is necrotic bone exposed or that can be explored by means of a fistula in the maxillofacial region.... (Review)
Review
Medication-related osteonecrosis of the jaw is a disease where there is necrotic bone exposed or that can be explored by means of a fistula in the maxillofacial region. It has been associated with the use Biphosphonates and denosumab for osteoporosis. Although its etiology is unclear, it may be related to a decrease in bone turnover produced by these drugs, rendering the bone more prone to generate cell necrosis during invasive dental procedures, especially in the posterior region of the jaw. There is no consensus about the prevention and treatment of this condition. The aim of this paper is to present a review of the literature with the main characteristics of osteonecrosis of the jaws associated with drugs, together with a proposal for prevention and treatment for these patients.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Denosumab; Diphosphonates; Humans; Jaw Diseases; Osteonecrosis; Osteoporosis
PubMed: 33399683
DOI: 10.4067/S0034-98872020000700983 -
Scientific Reports Jul 2023Atypical femur fracture (AFF) is a rare but catastrophic adverse event first reported in the long-term use of alendronate, one of the most commonly used drugs for...
Atypical femur fracture (AFF) is a rare but catastrophic adverse event first reported in the long-term use of alendronate, one of the most commonly used drugs for osteoporosis currently. However, further evidence is needed to learn more regarding other common anti-osteoporosis drugs and the risk for AFF. In this study, reports of AFF were identified from Food and Drug Administration Adverse Event Reporting System database. Disproportionality analyses were performed to examine the reporting odds ratio (ROR), information component (IC) and adjusted ROR (adj. ROR) signals for AFF for common anti-osteoporosis drugs. A total of 1692 unique AFF reports were identified. The disproportionality signals (the lower bound of 95% confidence interval > 1 for ROR and adjusted ROR, and > 0 for IC) were detected for alendronate, denosumab, pamidronate, risedronate, zoledronate, ibandronate, and teriparatide while no signal was detected for raloxifene, abaloparatide, and romosozumab. When restricted in patients with osteoporosis, the disproportionality signals were still detected for alendronate, pamidronate, risedronate, denosumab, and ibandronate. Our results suggest that alendronate has the largest risk signal, while the risks varied among different bisphosphonates. In addition, denosumab was found statistically associated with AFF in both the entire database and patients with osteoporosis.
Topics: Humans; Alendronate; Bone Density Conservation Agents; Risedronic Acid; Denosumab; Ibandronic Acid; Pharmaceutical Preparations; Pamidronate; Osteoporosis; Diphosphonates; Femur
PubMed: 37407650
DOI: 10.1038/s41598-023-37944-x -
Current Osteoporosis Reports Dec 2022Inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) with denosumab is an effective treatment in a number of conditions including osteoporosis where... (Review)
Review
PURPOSE OF REVIEW
Inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) with denosumab is an effective treatment in a number of conditions including osteoporosis where suppression of bone resorption is desired. However, denosumab discontinuation is associated with rebound increase in bone resorption and subsequent loss in bone mass and a rapid return to baseline fracture risk. We review recent data on the rebound increase in bone resorption following denosumab discontinuation and the potential mechanisms behind this phenomenon.
RECENT FINDINGS
Osteoclasts have been considered to be highly specialised cells that undergo apoptosis after fulfilling their function of bone resorption. However, recent studies suggest that osteoclasts are longer lived cells which migrate through vasculature and are capable of undergoing fission into a novel cell type (the osteomorph) and re-fusion in a process termed osteoclast recycling. The life cycle of the osteoclast is more complex than previously appreciated. Osteoclast recycling provides a novel mechanistic framework to examine changes in osteoclast biology in response to treatment of bone diseases and provides an exciting new avenue towards personalised medicine.
Topics: Humans; Osteoclasts; Denosumab; RANK Ligand; Bone Resorption; Osteoporosis
PubMed: 36201122
DOI: 10.1007/s11914-022-00756-5 -
BioDrugs : Clinical Immunotherapeutics,... Mar 2023Denosumab has been approved for the treatment of bone metastases from solid tumors. QL1206 is the first denosumab biosimilar and needs to be compared with denosumab in a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Denosumab has been approved for the treatment of bone metastases from solid tumors. QL1206 is the first denosumab biosimilar and needs to be compared with denosumab in a phase III trial.
OBJECTIVE
This phase III trial aims to compare the efficacy, safety, and pharmacokinetics between QL1206 and denosumab in patients with bone metastases from solid tumors.
METHODS
This randomized, double-blind, phase III trial was conducted in 51 centers in China. Patients aged 18-80 years, with solid tumors and bone metastases, and an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. This study was divided into a 13-week double-blind period, a 40-week open-label period, and a 20-week safety follow-up period. In the double-blind period, patients were randomly assigned (1:1) to receive three doses of QL1206 or denosumab (120 mg subcutaneously every 4 weeks, each). Randomization was stratified by tumor types, previous skeletal-related events, and current systemic anti-tumor therapy. In the open-label period, up to ten doses of QL1206 could be given in both groups. The primary endpoint was percentage change in urinary N-telopeptide/creatinine ratio (uNTX/uCr) from baseline to Week 13. Equivalence margins were ± 0.135. Secondary endpoints included percentage change in uNTX/uCr at Week 25 and 53, percentage change in serum bone-specific alkaline phosphatase at Week 13, 25, and 53, and time to on-study skeletal-related events. The safety profile was evaluated based on adverse events and immunogenicity.
RESULTS
From September 2019 to January 2021, in the full analysis set, 717 patients were randomly assigned to receive QL1206 (n = 357) or denosumab (n = 360). Median percentage changes in uNTX/uCr at Week 13 in two groups were - 75.2% and - 75.8%, respectively. Least-squares mean difference in the natural log-transformed ratio of uNTX/uCr at Week 13 to baseline between the two groups was 0.012 (90% confidence interval - 0.078 to 0.103), within the equivalence margins. There were no differences in the secondary endpoints between the two groups (all p > 0.05). Adverse events, immunogenicity, and pharmacokinetics were similar in the two groups.
CONCLUSIONS
Denosumab biosimilar QL1206 had promising efficacy, tolerable safety, and pharmacokinetics equivalent to denosumab and could benefit patients with bone metastases from solid tumors.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04550949, retrospectively registered on 16 September, 2020.
Topics: Humans; Denosumab; Biosimilar Pharmaceuticals; Bone Neoplasms; Double-Blind Method
PubMed: 36802320
DOI: 10.1007/s40259-023-00579-5 -
La Clinica Terapeutica 2023Denosumab, an antiresorptive agent, has shown results in improving bone mineral density and reducing fractures in postmenopausal women. While bisphosphonates are... (Review)
Review
OBJECTIVE
Denosumab, an antiresorptive agent, has shown results in improving bone mineral density and reducing fractures in postmenopausal women. While bisphosphonates are commonly used as initial therapy for osteoporosis, some studies suggest that denosumab could be an alternative initial treatment for high-risk patients, particularly the elderly population. This narrative literature review aimed to assess the use of denosumab in elderly individuals with osteoporosis, excluding its oncology applications.
METHOD
Multiple online databases including Scopus, PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and PEDro were searched for relevant English-language trials.
RESULTS
Between about hundred identified, the review selected 21 articles full-meeting the inclusion criteria. These papers all reporting that Denosumab demonstrated significant efficacy in reducing vertebral and nonvertebral fractures in postmenopausal and senile osteoporosis.
CONCLUSION
Even if limited evidence exists regarding its long-term effectiveness in elderly patients, nevertheless denosumab may be considered a first-line treatment for high-risk elderly patients with senile osteoporosis, particularly for those unable to take bisphosphonates. It has shown superior outcomes in improving bone density and reducing fracture risk, even in frail elderly individuals. Long-term use of denosumab has been reported as safe and effective, enhancing treatment compliance and outcomes.
Topics: Humans; Aged; Female; Denosumab; Osteoporosis; Bone Density; Diphosphonates; Frail Elderly
PubMed: 38048119
DOI: 10.7417/CT.2023.5023 -
Osteoporosis International : a Journal... Dec 2022In this post hoc analysis, we assessed romosozumab efficacy and safety in European patients enrolled in FRAME. Romosozumab treatment through 12 months, followed by... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
In this post hoc analysis, we assessed romosozumab efficacy and safety in European patients enrolled in FRAME. Romosozumab treatment through 12 months, followed by denosumab for a further 24 months, resulted in early and sustained risk reduction for major fracture categories, associated with large gains in bone mineral density.
INTRODUCTION
In the multinational FRAME phase 3 trial of romosozumab in postmenopausal women with osteoporosis, marked differences between clinical and non-vertebral fracture outcomes were observed among patients from Central and Southern America versus rest of world. This post hoc analysis assessed romosozumab efficacy and safety in European patients enrolled in the FRAME trial and extension study.
METHODS
In FRAME (NCT01575834), patients were randomised 1:1 to romosozumab 210 mg or placebo monthly (QM) for 12 months, followed by open-label denosumab 60 mg Q6M to month 36, including a 12-month extension study. We report incidence of major fracture outcomes, bone mineral density (BMD) change from baseline and safety for European patients enrolled in FRAME.
RESULTS
In FRAME, 3013/7180 (41.96%) patients were European; 1494 received romosozumab and 1519 received placebo. Through 12 months, romosozumab reduced fracture risk versus placebo for non-vertebral fracture (1.4% versus 3.0%; p = 0.004), clinical fracture (1.4% versus 3.6%; p < 0.001), new vertebral fracture (0.4% versus 2.1%; p < 0.001) and major osteoporotic fracture (0.9% versus 2.8%; p < 0.001), with results sustained through 36 months following transition to denosumab. Hip fractures were numerically reduced with romosozumab at month 12 (0.2% versus 0.6%; p = 0.092). Romosozumab increased BMD versus placebo at month 12; all patients in the romosozumab and placebo groups experienced further increases by month 36 after transition to denosumab. Adverse events were balanced between groups.
CONCLUSIONS
Among European patients in FRAME, romosozumab resulted in early and sustained risk reduction for all major fracture categories, associated with large BMD gains that continued after transition to denosumab.
Topics: Humans; Female; Denosumab; Double-Blind Method; Bone Density; Bone Density Conservation Agents; Osteoporotic Fractures; Osteoporosis, Postmenopausal
PubMed: 36173415
DOI: 10.1007/s00198-022-06544-2 -
Joint Bone Spine Jan 2022Aneurysmal bone cyst (ABC) is a benign, locally aggressive tumour that arises predominantly in long bones and spine. Following the encouraging results of denosumab use... (Review)
Review
BACKGROUND
Aneurysmal bone cyst (ABC) is a benign, locally aggressive tumour that arises predominantly in long bones and spine. Following the encouraging results of denosumab use in Giant Cell Tumors (GCT) and the histological similarities between ABC and GCT, the interest on the role of denosumab in the therapeutic arsenal of the most advanced ABC is growing. The purpose of this literature review is to investigate the current state of knowledge about the use of denosumab in ABCs.
METHODS
A literature research was conducted through PUBMED, COCHRANE and GOOGLE SCHOLAR using the keywords "aneurysmal bone cyst" AND "denosumab". Seventeen articles were included.
RESULTS
A total of 43 cases were reported in the literature. There were 23 males, 20 females. The mean age was 15,9±8,1 year. Pain relief and neurological improvement were rapid and sustained. Radiological assessment showed ossification and/or volume reduction in 36/39 patients. Eight patients (18,6%) presented a recurrence after or during denosumab therapy of whom 7 were adults. Adverse events occurred in 11 patients, 5 of them were admitted to the intensive care unit due to hypercalcemia.
CONCLUSION
Denosumab use in non-surgical ABCs has shown a positive impact in pain and neurological symptoms. The oncological outcome remains unclear with a recurrence rate of 18,6% during/after denosumab therapy, mostly in adults. However, regarding the potential clinical benefits, its use might be discussed in the most advanced cases. Further research and clinical trials are mandatory to precise its belonging in the therapeutic arsenal.
Topics: Adult; Bone Cysts, Aneurysmal; Bone Density Conservation Agents; Bone Neoplasms; Bone and Bones; Denosumab; Female; Humans; Hypercalcemia; Infant, Newborn; Male
PubMed: 34481945
DOI: 10.1016/j.jbspin.2021.105260 -
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