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The World Journal of Men's Health Oct 2023The introduction of novel therapeutic agents for advanced prostate cancer has led to a wide range of treatment options for patients with metastatic castration-resistant... (Review)
Review
The introduction of novel therapeutic agents for advanced prostate cancer has led to a wide range of treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC). In the past decade, new treatment options for mCRPC, including abiraterone, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, radium-223, Lu-PSMA-617, and Olaparib, have demonstrated a survival benefit in phase 3 trials. Bone-modifying agents have become part of the overall treatment strategy for mCRPC, in which denosumab and zoledronic acid reduce skeletal-related events. Recently, androgen receptor-signaling inhibitors (ARSIs) and docetaxel have been used upfront against metastatic castration-sensitive prostate cancer. Further, triplet therapy with ARSI, docetaxel, and androgen deprivation therapy is emerging. However, cross-resistance may occur between these treatments, and the optimal treatment sequence must be considered. The sequential administration of ARSIs, such as abiraterone and enzalutamide, is associated with limited efficacy; however, cabazitaxel is effective for patients with mCRPC who were previously treated with docetaxel and had disease progression during treatment with ARSI. Radioligand therapy with Lu-PSMA-617 is a new effective class of therapy for patients with advanced PSMA-positive mCRPC. Tumors with gene alterations that affect homologous recombination repair, such as and alterations, are sensitive to poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in mCRPC. This review sought to highlight recent advances in systemic therapy for mCRPC and strategies to support patient selection and treatment sequencing.
PubMed: 36792090
DOI: 10.5534/wjmh.220200 -
Journal of Bone and Mineral Research :... Aug 2023In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics,...
In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 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: Male; Female; Humans; Middle Aged; Aged; Incidence; Hip Fractures; Osteoporosis; Osteoporotic Fractures; Diphosphonates
PubMed: 37118993
DOI: 10.1002/jbmr.4821 -
European Review For Medical and... Sep 2023This study aims to compare the efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of women with postmenopausal... (Meta-Analysis)
Meta-Analysis
Drug efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of postmenopausal osteoporosis: a network meta-analysis of randomized controlled trials.
OBJECTIVE
This study aims to compare the efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of women with postmenopausal osteoporosis.
MATERIALS AND METHODS
Randomized controlled trials (RCTs) were searched in Medline, Embase, and Cochrane up to April 2022. Statistical analysis was performed using R 4.1.3 software, and quality evaluation was conducted using Review Manager 5.3.
RESULTS
51 RCTs containing 39,095 patients met our selection criteria. The efficacy results indicated that teriparatide was more effective than ibandronic acid in reducing vertebral fractures [relative risk (RR) = 0.536; 95% confidence interval (CI) (0.266, 0.998)]. Denosumab [mean difference (MD) = -4.19; 95% CI (-8.03, -0.355)] and teriparatide [MD = 4.64; 95% CI (1.60, 7.72)] showed better efficacy than ibandronic acid in improving spine bone mineral density (BMD). Denosumab showed better efficacy than teriparatide in improving radius BMD [MD = -4.14; 95% CI (-6.72, -1.54)], hip bone mineral density (BMD) [MD = -2.01; 95% CI (-3.80, -0.162)], and one-third radius BMD [MD = -3.63; 95% CI (-7.04, -0.151)]. Denosumab was associated with the greatest benefit in increasing radius BMD [the surface under the cumulative ranking curve area (SUCRA) = 0.999], hip BMD [surface under the cumulative ranking curve area (SUCRA) = 0.979], femoral neck BMD (SUCRA = 0.971), one-third radius BMD (SUCRA = 0.994) and preventing vertebral fractures (SUCRA = 0.806). Teriparatide was associated with the greatest benefit in preventing non-vertebral fractures (SUCRA = 0.927) and improving spine BMD (SUCRA = 0.899). The safety results indicated that teriparatide was safer than zoledronic acid regarding the risk of adverse events [RR = 0.958; 95% CI (0.919, 0.988)]. Teriparatide was associated with the greatest benefit in preventing adverse events (SUCRA = 0.908) and serious adverse events (SUCRA = 0.813).
CONCLUSIONS
Our current results suggested that when considering both safety and efficacy, denosumab or teriparatide might be a better choice for women with postmenopausal osteoporosis.
Topics: Female; Humans; Denosumab; Ibandronic Acid; Network Meta-Analysis; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Spinal Fractures; Teriparatide; Zoledronic Acid
PubMed: 37750653
DOI: 10.26355/eurrev_202309_33586 -
Osteoporosis International : a Journal... Sep 2023Trabecular bone score (TBS) is a grey-level textural measurement acquired from dual-energy X-ray absorptiometry lumbar spine images and is a validated index of bone...
Update on the clinical use of trabecular bone score (TBS) in the management of osteoporosis: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), and the International...
PURPOSE
Trabecular bone score (TBS) is a grey-level textural measurement acquired from dual-energy X-ray absorptiometry lumbar spine images and is a validated index of bone microarchitecture. In 2015, a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) published a review of the TBS literature, concluding that TBS predicts hip and major osteoporotic fracture, at least partly independent of bone mineral density (BMD) and clinical risk factors. It was also concluded that TBS is potentially amenable to change as a result of pharmacological therapy. Further evidence on the utility of TBS has since accumulated in both primary and secondary osteoporosis, and the introduction of FRAX and BMD T-score adjustment for TBS has accelerated adoption. This position paper therefore presents a review of the updated scientific literature and provides expert consensus statements and corresponding operational guidelines for the use of TBS.
METHODS
An Expert Working Group was convened by the ESCEO and a systematic review of the evidence undertaken, with defined search strategies for four key topics with respect to the potential use of TBS: (1) fracture prediction in men and women; (2) initiating and monitoring treatment in postmenopausal osteoporosis; (3) fracture prediction in secondary osteoporosis; and (4) treatment monitoring in secondary osteoporosis. Statements to guide the clinical use of TBS were derived from the review and graded by consensus using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.
RESULTS
A total of 96 articles were reviewed and included data on the use of TBS for fracture prediction in men and women, from over 20 countries. The updated evidence shows that TBS enhances fracture risk prediction in both primary and secondary osteoporosis, and can, when taken with BMD and clinical risk factors, inform treatment initiation and the choice of antiosteoporosis treatment. Evidence also indicates that TBS provides useful adjunctive information in monitoring treatment with long-term denosumab and anabolic agents. All expert consensus statements were voted as strongly recommended.
CONCLUSION
The addition of TBS assessment to FRAX and/or BMD enhances fracture risk prediction in primary and secondary osteoporosis, adding useful information for treatment decision-making and monitoring. The expert consensus statements provided in this paper can be used to guide the integration of TBS in clinical practice for the assessment and management of osteoporosis. An example of an operational approach is provided in the appendix. This position paper presents an up-to-date review of the evidence base, synthesised through expert consensus statements, which informs the implementation of Trabecular Bone Score in clinical practice.
Topics: Male; Female; Humans; Cancellous Bone; Osteoporosis; Osteoporotic Fractures; Bone Density; Absorptiometry, Photon; Lumbar Vertebrae; Osteoarthritis; Aging; Consensus; World Health Organization; Risk Assessment
PubMed: 37393412
DOI: 10.1007/s00198-023-06817-4 -
Ugeskrift For Laeger Jan 2024Bone turnover markers (BTM) are highly responsive to initiation and changes in anti-osteoporotic therapy. In contrast to the slow treatment-induced changes in bone... (Review)
Review
Bone turnover markers (BTM) are highly responsive to initiation and changes in anti-osteoporotic therapy. In contrast to the slow treatment-induced changes in bone mineral density, the fast changes in BTM enable the clinician to adjust treatment management within a short timeframe. This review describes how BTM can be used for treatment monitoring, including monitoring during discontinuation of alendronate and denosumab therapy. In addition, sources of errors and pitfalls when using BTM monitoring will be described.
Topics: Humans; Bone Density Conservation Agents; Biomarkers; Osteoporosis; Bone Density; Bone Remodeling; Denosumab
PubMed: 38327195
DOI: 10.61409/V07230432 -
Risk Management and Healthcare Policy 2023Chronic kidney disease (CKD) and hemodialysis (HD) patients have a high incidence of bone disease and increased fracture risk, making effective management of their bone... (Review)
Review
Chronic kidney disease (CKD) and hemodialysis (HD) patients have a high incidence of bone disease and increased fracture risk, making effective management of their bone health a clinical challenge. Denosumab, a human monoclonal antibody, has been investigated as a therapeutic option in this patient population. In this review, we summarize the current evidence on the efficacy and safety of denosumab in CKD and HD patients. A comprehensive search of the relevant literature was conducted, including randomized controlled trials, observational studies, and meta-analyses. The findings suggest that denosumab reduces the risk of fractures and improves bone mineral density in all stages of CKD. The results of this review support the use of denosumab as a promising option for managing bone disease in CKD and HD patients.
PubMed: 37719685
DOI: 10.2147/RMHP.S426869 -
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 -
Annals of Joint 2023Osteoporosis is a skeletal disorder classified by the loss of bone density in older adults leading to compromised bone strength and an increased risk of fracture. It can... (Review)
Review
BACKGROUND AND OBJECTIVE
Osteoporosis is a skeletal disorder classified by the loss of bone density in older adults leading to compromised bone strength and an increased risk of fracture. It can be divided into categories based on its etiology: senile, post-menopausal, and secondary osteoporosis. Specific prevention measures and treatments exist for targeting bone loss. Here we review and summarize the literature regarding the presentation of osteoporosis and discuss pharmaceutical therapies.
METHODS
PubMed and Google Scholar were searched for articles published in English between 1980 and 2021. Search terms combined "senile osteoporosis", "osteoporosis treatment", "osteoporosis", "bisphosphonates", "denosumab", types of hormone therapy, and other relevant keywords used in various combinations.
KEY CONTENT AND FINDINGS
Osteoporosis affects millions but often goes undiagnosed until a pathologic fracture. Dual-energy X-ray absorptiometry (DEXA) scans evaluate bone mineral density (BMD) and are a diagnostic tool for osteoporosis. Adults over the age of 65, post-menopausal women, and those with risk factors such as previous fractures are recommended to receive DEXA scans every one to two years. Bisphosphonates, denosumab, and hormonal therapies are among the most common pharmacologic treatments for osteoporosis.
CONCLUSIONS
Daily, orally administered bisphosphonates are the first-line therapy for osteoporosis given their efficacy in decreasing fracture risk and favorable safety profile. Denosumab is an alternative that is administered subcutaneously every six months and may be given as initial therapy to select patients. Hormonal therapies are used if patients cannot tolerate bisphosphonates or denosumab or are refractory to these medications. Preventative measures for osteoporosis include tailored exercise and sufficient intake of calcium and vitamin D via diet or supplementation.
PubMed: 38529240
DOI: 10.21037/aoj-23-2