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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 -
Journal of Bone and Mineral Research :... Nov 2022Type 2 diabetes (T2D) is associated with increased risk of fractures. However, it is unclear whether current osteoporosis treatments reduce fractures in individuals with... (Clinical Trial)
Clinical Trial
Type 2 diabetes (T2D) is associated with increased risk of fractures. However, it is unclear whether current osteoporosis treatments reduce fractures in individuals with diabetes. The aim of the study was to determine whether presence of T2D influences the efficacy of antiresorptive treatment for osteoporosis using the Foundation for the National Institutes of Health (FNIH)-American Society for Bone and Mineral Research (ASBMR)-Study to Advance Bone Mineral Density (BMD) as a Regulatory Endpoint (SABRE) cohort, which includes individual patient data from randomized trials of osteoporosis therapies. In this study we included 96,385 subjects, 6.8% of whom had T2D, from nine bisphosphonate trials, two selective estrogen receptor modulator (SERM) trials, two trials of menopausal hormone therapy, one denosumab trial, and one odanacatib trial. We used Cox regression to obtain the treatment hazard ratio (HR) for incident nonvertebral, hip, and all fractures and logistic regression to obtain the treatment odds ratio (OR) for incident morphometric vertebral fractures, separately for T2D and non-DM. We used linear regression to estimate the effect of treatment on 2-year change in BMD (n = 49,099) and 3-month to 12-month change in bone turnover markers (n = 12,701) by diabetes status. In all analyses, we assessed the interaction between treatment and diabetes status. In pooled analyses of all 15 trials, we found that diabetes did not impact treatment efficacy, with similar reductions in vertebral, nonvertebral, all, and hip fractures, increases in total hip and femoral neck BMD, and reductions in serum C-terminal cross-linking telopeptide (CTX), urinary N-telopeptide of type I collagen/creatinine (NTX/Cr) and procollagen type 1 N propeptide (P1NP) (all interactions p > 0.05). We found similar results for the pooled analysis of bisphosphonate trials. However, when we considered trials individually, we found a few interactions within individual studies between diabetes status and the effects of denosumab and odanacatib on fracture risk, change in BMD or bone turnover markers (BTMs). In sum, these results provide strong evidence that bisphosphonates and most licensed antiresorptive drugs are effective at reducing fracture risk and increasing BMD irrespective of diabetes status. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Bone Density; Bone Density Conservation Agents; Denosumab; Diabetes Mellitus, Type 2; Diphosphonates; Hip Fractures; Osteoporosis
PubMed: 36065588
DOI: 10.1002/jbmr.4697 -
Medicine Nov 2015The purpose of this study was to perform a meta-analysis to examine the efficacy and safety of denosumab in postmenopausal women with osteoporosis.Medline, Cochrane... (Meta-Analysis)
Meta-Analysis Review
The purpose of this study was to perform a meta-analysis to examine the efficacy and safety of denosumab in postmenopausal women with osteoporosis.Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until October 30, 2014 using combinations of the following search terms: osteoporosis, postmenopause, postmenopausal, women, denosumab. The primary outcome was bone mineral density (BMD) change, and secondary outcomes were change in the bone turnover markers β-isomerized carboxy-terminal cross-linking telopeptide of type I collagen (CTX) and serum procollagen type I amino-terminal propeptide (P1NP), and adverse events.Patients treated with denosumab had significantly increased BMD of the lumbar spine (7.58%), total hip (4.86%), and distal third of the radius (2.92%) than those treated with placebo (all, P < 0.001). Patients treated with denosumab had a significant decrease of CTX (-66.16%) and P1NP (-64.65%) as compared with those treated with placebo (both, P < 0.001). Adverse events were similar between the 2 groups (pooled odds ratio = 1.04, P = 0.625).Denosumab increases BMD and decreases markers of bone turnover in postmenopausal women with osteoporosis, and is not associated with significant side-effects.
Topics: Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Osteoporosis, Postmenopausal
PubMed: 26554766
DOI: 10.1097/MD.0000000000001674 -
Best Practice & Research. Clinical... Mar 2022Over the last two decades there have been significant developments in the pharmacotherapy of osteoporosis. The therapeutic arsenal has expanded with monoclonal... (Review)
Review
Over the last two decades there have been significant developments in the pharmacotherapy of osteoporosis. The therapeutic arsenal has expanded with monoclonal antibodies which have been developed based on discoveries of the molecular mechanisms underlying bone resorption and bone formation. Denosumab, the antibody binding RANKL, inhibits bone resorption, and romosozumab, the antibody binding sclerostin, inhibits bone resorption and stimulates bone formation as well. Both antibodies have shown potent anti-fracture efficacy in randomized clinical trials and this review will discuss the preclinical and clinical studies focusing on the effects on bone mass. After discontinuation of these antibodies, bone mineral density quickly returns to baseline and in the case of denosumab, discontinuation can not only induce rebound bone loss, but also the occurrence of vertebral fractures. Therefore, sequential antiresorptive therapy to maintain bone mass gains and anti-fracture efficacy is of utmost importance and will also be discussed in this review.
Topics: Bone Density; Bone Density Conservation Agents; Bone Resorption; Denosumab; Fractures, Bone; Humans; Osteoporosis
PubMed: 35219602
DOI: 10.1016/j.beem.2022.101623 -
Archives of Endocrinology and Metabolism Nov 2022Denosumab (DMAb) is a human monoclonal antibody used as an antiresorptive drug in the treatment of osteoporosis. Approval at a dosage of 60 mg every 6 months was based... (Review)
Review
Denosumab (DMAb) is a human monoclonal antibody used as an antiresorptive drug in the treatment of osteoporosis. Approval at a dosage of 60 mg every 6 months was based on the results of the randomized, placebo-controlled trial (FREEDOM). The design of this 3-year study included an extension for up to 10 years. Those who were randomized to DMAb continued on drug, while those who were randomized to placebo transitioned to DMAb. The 10-year experience with DMAb provides data on efficacy of drug in terms of reduced fractures and continued increases in bone mineral density (BMD). The 10-year experience with denosumab also provides information about rare complications associated with the use of DMAb, such as osteonecrosis of the jaw (ONJ), and atypical femoral fractures (AFF). This experience provided new insights into the reversibility of effects upon discontinuation without follow-on therapy with another agent. This review focuses upon prolonged treatment with DMAb, with regard to beneficial effects on fracture reduction and safety. Additionally, its use in patients with impaired renal function, compare its results with those of bisphosphonates (BPs), the occurrence/frequency of complications, in addition to the use of different tools, from imaging techniques to histological findings, to evaluate its effects on bone tissue.
Topics: Humans; Female; Denosumab; Osteoporosis; Bone Density Conservation Agents; Diphosphonates; Bone Density; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic
PubMed: 36382761
DOI: 10.20945/2359-3997000000560 -
Current Rheumatology Reports May 2024The purpose of this literature review was to determine if medications used to treat osteoporosis are also effective for treating osteoarthritis (OA). (Review)
Review
PURPOSE OF REVIEW
The purpose of this literature review was to determine if medications used to treat osteoporosis are also effective for treating osteoarthritis (OA).
RECENT FINDINGS
A total of 40 relevant articles were identified. Studies were categorized into those (1) discussing estrogen and selective estrogen receptor modulators (SERMs), (2) bisphosphonates, (3) parathyroid hormone (PTH) analogs, and (4) denosumab, and (5) prior review articles. A large amount of evidence suggests that estrogen and SERMs are effective at reducing OA symptoms and disease progression. Evidence suggests that bisphosphonates, the most common medications used to treat osteoporosis, can reduce OA symptoms and disease progression. In vivo studies suggest that PTH analogs may improve the cartilage destruction associated with OA; however, few human trials have examined its use for OA. Denosumab is approved to treat osteoporosis, bone metastases, and certain types of breast cancer, but little study has been done with respect to its effect on OA. The current evidence indicates that medications used to treat osteoporosis are also effective for treating OA. Estrogen, SERMs, and bisphosphonates have the most potential as OA therapies. Less is known regarding the effectiveness of PTH analogs and denosumab in OA, and more research is needed.
Topics: Humans; Disease Progression; Osteoarthritis; Bone Density Conservation Agents; Female; Diphosphonates; Denosumab; Selective Estrogen Receptor Modulators; Osteoporosis, Postmenopausal; Parathyroid Hormone; Estrogens; Antibodies, Monoclonal, Humanized; Treatment Outcome
PubMed: 38372871
DOI: 10.1007/s11926-024-01139-8 -
Current Opinion in Pediatrics Feb 2023Aneurysmal bone cysts are rare, locally aggressive bone tumors. Optimal treatment of ABCs is still matter of debate as therapies including sclerotherapy, selective... (Review)
Review
PURPOSE OF REVIEW
Aneurysmal bone cysts are rare, locally aggressive bone tumors. Optimal treatment of ABCs is still matter of debate as therapies including sclerotherapy, selective arterial embolization and systemic treatment with denosumab are increasingly utilized, in addition to or instead of traditional curettage. The purpose of this review is to discuss current concepts and difficulties in diagnosing and treating primary ABCs, based on latest available literature.
RECENT FINDINGS
In diagnostics, multiple new fusion partners of USP-6 have been described on next-generation sequencing specifically for primary ABCs. In a recent systematic review, failure rates of percutaneous injections and surgery were comparable. In a literature review, the use of denosumab seemed effective but resulted in multiple cases of severe hypercalcemia in children.
SUMMARY
Accurately diagnosing primary ABC is crucial for treatment decisions. Curettage remains a valid treatment option, especially with adjuvant burring, autogenous bone grafting and phenolization. Percutaneous sclerotherapy represents a solid alternative to surgery, with polidocanol showing good results in larger studies. Systematic therapy with denosumab exhibits favorable results but should be reserved in the pediatric population for unresectable lesions, as it may result in severe hypercalcemia in children. When selecting a treatment option, localization, stability and safety should be considered.
Topics: Humans; Child; Denosumab; Bone Cysts, Aneurysmal; Hypercalcemia; Neoplasm Recurrence, Local; Polidocanol; Treatment Outcome
PubMed: 36409159
DOI: 10.1097/MOP.0000000000001205 -
JCI Insight Sep 2023Denosumab is an anti-RANKL Ab that potently suppresses bone resorption, increases bone mass, and reduces fracture risk. Discontinuation of denosumab causes rapid rebound...
Denosumab is an anti-RANKL Ab that potently suppresses bone resorption, increases bone mass, and reduces fracture risk. Discontinuation of denosumab causes rapid rebound bone resorption and bone loss, but the molecular mechanisms are unclear. We generated humanized RANKL mice and treated them with denosumab to examine the cellular and molecular conditions associated with rebound resorption. Denosumab potently suppressed both osteoclast and osteoblast numbers in cancellous bone in humanized RANKL mice. The decrease in osteoclast number was not associated with changes in osteoclast progenitors in bone marrow. Long-term, but not short-term, denosumab administration reduced osteoprotegerin (OPG) mRNA in bone. Localization of OPG expression revealed that OPG mRNA is produced by a subpopulation of osteocytes. Long-term denosumab administration reduced osteocyte OPG mRNA, suggesting that OPG expression declines as osteocytes age. Consistent with this, osteocyte expression of OPG was more prevalent near the surface of cortical bone in humans and mice. These results suggest that new osteocytes are an important source of OPG in remodeling bone and that suppression of remodeling reduces OPG abundance by reducing new osteocyte formation. The lack of new osteocytes and the OPG they produce may contribute to rebound resorption after denosumab discontinuation.
Topics: Humans; Mice; Animals; Osteocytes; Denosumab; Osteoprotegerin; Osteoclasts; Bone Resorption
PubMed: 37581932
DOI: 10.1172/jci.insight.167790 -
Journal of Bone and Mineral Research :... Dec 2023Denosumab (Dmab) is increasingly prescribed worldwide. Unlike bisphosphonates (BPs), its effect on mortality has yet to be well explored. This study examined the...
Denosumab (Dmab) is increasingly prescribed worldwide. Unlike bisphosphonates (BPs), its effect on mortality has yet to be well explored. This study examined the association between Dmab and all-cause mortality compared with no treatment in subjects with a fracture and BPs in subjects without a fracture. The study population was from the Sax Institute's 45 and Up Study (n = 267,357), a prospective population-based cohort with questionnaire data linked to hospital admissions (Admitted Patients Data Collection [APDC] data were linked by the Centre for Health Record Linkage), medication records (Pharmaceutical Benefits Scheme [PBS] provided by Services Australia), and stored securely (secure data access was provided through the Sax Institute's Secure Unified Research Environment [SURE]). The new-user cohort design with propensity-score (PS) matching was implemented. In the fracture cohort, Dmab and oral BP users were matched 1:2 to no treatment (Dmab: 617 women, 154 men; oral BPs: 615 women, 266 men). In the no-fracture cohort, Dmab users were matched 1:1 with oral BPs and zoledronic acid (Zol) users (Dmab:oral BPs: 479 men, 1534 women; Dmab:Zol: 280 men, 625 women). Mortality risk was measured using sex-specific pairwise multivariable Cox models. In the fracture cohort, compared with no treatment, Dmab was associated with 48% lower mortality in women (hazard ratio [HR] = 0.52, 95% confidence interval [CI] 0.36-0.72) but not in men. Oral BPs were associated with 44% lower mortality in both sexes (women HR = 0.56, 95% CI 0.42-0.77; men HR = 0.56, 95% CI 0.40-0.78). In the no-fracture cohort, compared with BPs, Dmab was associated with 1.5- to 2.5-fold higher mortality than oral BPs (women HR = 1.49, 95% CI 1.13-1.98; men HR = 2.74; 95% CI 1.82-4.11) but similar mortality to Zol. Dmab in women and oral BPs were associated with lower post-fracture mortality than no treatment. However, Dmab users had generally higher mortality than oral BP users in those without fractures. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Male; Humans; Female; Bone Density Conservation Agents; Denosumab; Prospective Studies; Diphosphonates; Zoledronic Acid; Fractures, Bone
PubMed: 37915252
DOI: 10.1002/jbmr.4930