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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 -
Journal of Bone and Mineral Research :... Apr 2024Denosumab is a monoclonal antibody used to reduce risk of fractures in osteoporosis. ROSALIA was a multicenter, double-blind, randomized, integrated phase I/phase III... (Comparative Study)
Comparative Study Randomized Controlled Trial
Denosumab is a monoclonal antibody used to reduce risk of fractures in osteoporosis. ROSALIA was a multicenter, double-blind, randomized, integrated phase I/phase III study comparing the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and safety of proposed biosimilar denosumab GP2411 with reference denosumab (REF-DMAb) (Prolia®; Amgen). Postmenopausal women with osteoporosis were randomized 1:1 to 2 60-mg doses of GP2411 or REF-DMAb, one at study start and one at week 26. At week 52, the REF-DMAb group was re-randomized 1:1 to a third dose of REF-DMAb or switch to GP2411. The primary efficacy endpoint was percentage change from baseline (%CfB) in LS-BMD at week 52. Secondary efficacy endpoints were %CfB in LS-BMD, FN-BMD, and TH-BMD at weeks 26 and 78 (and week 52 for FN-BMD and TH-BMD). Primary PK and PD endpoints were the area under the serum concentration-time curve extrapolated to infinity and maximum drug serum concentration at week 26, and the area under the effect-time curve of the %CfB in serum CTX at week 26. Secondary PK and PD endpoints included drug serum concentrations and %CfB in serum CTX and P1NP during the study period. Similar efficacy was demonstrated at week 52, with 95% CIs of the difference in %CfB in LS-BMD between treatment groups fully contained within prespecified equivalence margins. Similarity in PK and PD was demonstrated at week 26. Immunogenicity was similar between groups and was not impacted by treatment switch. The rate of new vertebral fractures was comparable. Treatment-emergent adverse events were comparable between groups (63.6% [GP2411/GP2411]; 76.0% [REF-DMAb/REF-DMAb]; 76.6% [REF-DMAb/GP2411]). In conclusion, ROSALIA showed similar efficacy, PK and PD, and comparable safety and immunogenicity of GP2411 to REF-DMAb in postmenopausal osteoporosis.
Topics: Female; Humans; Biosimilar Pharmaceuticals; Bone Density; Bone Density Conservation Agents; Denosumab; Osteoporosis; Osteoporosis, Postmenopausal; Double-Blind Method
PubMed: 38477751
DOI: 10.1093/jbmr/zjae016 -
Cureus Sep 2023An aberrant growth of plasma cells in the bone marrow characterizes the hematological neoplasm known as multiple myeloma, which is typically accompanied by increased... (Review)
Review
An aberrant growth of plasma cells in the bone marrow characterizes the hematological neoplasm known as multiple myeloma, which is typically accompanied by increased bone pain and skeletal-related events such as pathological fractures and/or spinal cord compression. Changes in the bone marrow microenvironment brought on by increased osteoclastic activity and/or decreased osteoblastic activity as a result of myeloma bone disease have a detrimental effect on quality of life. Bone-modifying medications such as bisphosphonates or denosumab are used to treat myeloma bone disease. These substances can lessen bone pain and the chance of pathological fracture, but they do not stimulate the growth of new bone or heal already damaged bone. In order to conduct this study, we searched the PubMed, Google Scholar, and Cochrane databases for complete free papers published in English and studied people over the previous five years, starting in 2018. The search covered randomized clinical trials (RCT), observational studies, meta-analyses, systemic reviews, and conventional reviews. Twenty-five publications are picked after using quality evaluation techniques to determine the type of study. These papers' full-text articles are investigated, examined, and tallied. We spoke about the various treatments for bone damage in multiple myeloma. It was discovered that bisphosphonates lessen the frequency and severity of bone problems. However, we are unsure of their contribution to survival. Although these medicines enhance life quality, it is unknown if they also increase overall survival. The focus of this study is on several kinds of bone-modifying drugs, their processes of action, the point at which therapy is started, how long it lasts, and any possible mortality advantages.
PubMed: 37846237
DOI: 10.7759/cureus.45270 -
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 -
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 -
Frontiers in Endocrinology 2023
Topics: Humans; Hypercalcemia; Cinacalcet; Calcium; Neoplasms
PubMed: 37780626
DOI: 10.3389/fendo.2023.1281731 -
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 -
Science Advances Nov 2023Treatment for type 1 diabetes (T1D) requires stimulation of functional β cell regeneration and survival under stress. Previously, we showed that inhibition of the...
Treatment for type 1 diabetes (T1D) requires stimulation of functional β cell regeneration and survival under stress. Previously, we showed that inhibition of the RANKL/RANK [receptor activator of nuclear factor kappa Β (NF-κB) ligand] pathway, by osteoprotegerin and the anti-osteoporotic drug denosumab, induces rodent and human β cell proliferation. We demonstrate that the RANK pathway mediates cytokine-induced rodent and human β cell death through RANK-TRAF6 interaction and induction of NF-κB activation. Osteoprotegerin and denosumab protected β cells against this cytotoxicity. In human immune cells, osteoprotegerin and denosumab reduce proinflammatory cytokines in activated T-cells by inhibiting RANKL-induced activation of monocytes. In vivo, osteoprotegerin reversed recent-onset T1D in nonobese diabetic/Ltj mice, reduced insulitis, improved glucose homeostasis, and increased plasma insulin, β cell proliferation, and mass in these mice. Serum from T1D subjects induced human β cell death and dysfunction, but not α cell death. Osteoprotegerin and denosumab reduced T1D serum-induced β cell cytotoxicity and dysfunction. Inhibiting RANKL/RANK could have therapeutic potential.
Topics: Humans; Mice; Animals; Osteoprotegerin; Cytokines; Diabetes Mellitus, Type 1; Receptor Activator of Nuclear Factor-kappa B; Denosumab; NF-kappa B; Rodentia; RANK Ligand; Cell Death
PubMed: 37910614
DOI: 10.1126/sciadv.adf5238 -
Nature Reviews. Rheumatology Apr 2024Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent,... (Review)
Review
Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.
Topics: Male; Female; Humans; Osteoporosis; Fractures, Bone; Musculoskeletal Diseases; Osteoarthritis; Bone Density
PubMed: 38485753
DOI: 10.1038/s41584-024-01094-9 -
Therapeutic Advances in Musculoskeletal... 2023Bone fragility is the determinant of the increased risk of minimal trauma fracture and must be treated with a multimodal approach that includes pharmacological therapy,... (Review)
Review
Bone fragility is the determinant of the increased risk of minimal trauma fracture and must be treated with a multimodal approach that includes pharmacological therapy, physical exercise, and adequate nutrition. Pharmacological therapy, to date based on the administration of antiresorptive drugs, such as bisphosphonates and denosumab, or osteoanabolic drugs, such as teriparatide and abaloparatide, has shown to be effective in reducing the risk of fracture in osteoporotic patients. In the context of the cellular and molecular mechanisms that regulate bone metabolism, the discovery of the Wnt signaling pathway and its role in bone tissue homeostasis has allowed the identification of sclerostin as an inhibitor of osteoblastic activity and simultaneously as a stimulator of osteoclastic activity. Therefore, the use of a monoclonal antibody, romosozumab, against this protein has been tested as a potential drug with a dual action, stimulating bone neo-apposition and inhibiting bone resorption. The efficacy of romosozumab has been demonstrated in numerous clinical trials against both placebo and other drugs commonly used in the treatment of patients affected by osteoporosis. The advantages of this drug lie above all in its rapid action which makes it particularly suitable in clinical situations where it is necessary to improve bone strength very quickly due to the imminent risk of fragility fracture. Clinical studies and guidelines suggest romosozumab as an initial drug in an ideal sequential approach from osteoanabolic to antiresorptive drugs. Some aspects of cardiovascular safety remain to be fully investigated, therefore its use in osteoporotic patients at high cardiovascular risk should be avoided until further data become available.
PubMed: 37694185
DOI: 10.1177/1759720X231197094