Denosumab (Prolia®; Pralia®) is a human monoclonal antibody targeting the key bone resorption mediator RANKL. The drug is administered via subcutaneous injection once every 6 months and is approved for various indications, including the treatment of postmenopausal (PM) women with osteoporosis at increased/high risk of fracture or failure/intolerance of other osteoporosis therapies (indications featured in this review). Denosumab showed benefit in several phase 3 or 4 studies in PM women with osteoporosis or low bone mineral density (BMD), including the pivotal 3-year double-blind FREEDOM trial and its 7-year open-label extension. Denosumab reduced the risk of vertebral, nonvertebral and hip fractures and increased BMD across skeletal sites versus placebo in FREEDOM, with these benefits maintained over up to 10 years’ therapy in the extension. The drug was also more effective in improving BMD than bisphosphonates, including in women switched from a bisphosphonate regimen, in 1-year trials; however, whether these differences translate into differences in anti-fracture efficacy is unclear. Denosumab was generally well tolerated over up to 10 years’ treatment, although an increased risk of multiple vertebral fractures was observed after discontinuation of the drug. Thus, denosumab is a key treatment option for PM women with osteoporosis who have an increased/high risk of fracture or failure/intolerance of other osteoporosis therapies, although the potential for multiple vertebral fractures to occur after discontinuation of the drug requires consideration of subsequent management options.

Denosumab: A Review in Postmenopausal Osteoporosis.

Study Type – Therapy (population cohort)

Level of Evidence 2a

What's known on the subject? and What does the study add?

Clomiphene citrate (CC) has previously been documented to be efficacious in the treatment of hypogonadism. However little is known about the long term efficacy and safety of CC. Our study demonstrates that CC is efficacious after 3 years of therapy. Testosterone levels and bone mineral density measurement improved significantly and were sustained over this prolonged period. Subjective improvements were also demonstrated. No adverse events were reported.

OBJECTIVE
• To assess the efficacy and safety of long-term clomiphene citrate (CC) therapy in symptomatic patients with hypogonadism (HG).


PATIENTS AND METHODS
• Serum T, oestradiol and luteinizing hormone (LH) were measured in patients who were treated with CC for over 12 months.
• Additionally, bone densitometry (BD) results were collected for all patients. Demographic, comorbidity, treatment and Androgen Deficiency in Aging Men (ADAM) score data were also recorded.
• Comparison was made between baseline and post-treatment variables, and multivariable analysis was conducted to define predictors of successful response to CC.
• The main outcome measures were predictors of response and long-term results with long-term CC therapy in hypogonadal patients.


RESULTS
• The 46 patients (mean age 44 years) had baseline serum testosterone (T) levels of 228 ng/dL.
• Follow-up T levels were 612 ng/dL at 1 year, 562 ng/dL at 2 years, and 582 ng/dL at 3 years (P < 0.001).
• Mean femoral neck and lumbar spine BD scores improved significantly.
• ADAM scores (and responses) fell from a baseline of 7 to a nadir of 3 after 1 year.
• No adverse events were reported by any patients.


CONCLUSIONS
• Clomiphene citrate is an effective long-term therapy for HG in appropriate patients.
• The drug raises T levels substantially in addition to improving other manifestations of HG such as osteopenia/osteoporosis and ADAM symptoms.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1464-410X.2012.10968.x

Clomiphene citrate is safe and effective for long-term management of hypogonadism.

Background
Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture

Objectives
The objectives were to evaluate the clinical effectiveness, safety and cost-effectiveness of non-bisphosphonates {denosumab [Prolia®; Amgen Inc, Thousand Oaks, CA, USA], raloxifene [Evista®; Daiichi Sankyo Company, Ltd, Tokyo, Japan], romosozumab [Evenity®; Union Chimique Belge (UCB) SA (Brussels, Belgium) and Amgen Inc] and teriparatide [Forsteo®; Eli Lilly and Company, Indianapolis, IN, USA]}, compared with each other, bisphosphonates or no treatment, for the prevention of fragility fracture

Data sources
For the clinical effectiveness review, nine electronic databases (including MEDLINE, EMBASE and the World Health Organization International Clinical Trials Registry Platform) were searched up to July 2018

Review methods
A systematic review and network meta-analysis of fracture and femoral neck bone mineral density were conducted A review of published economic analyses was undertaken and a model previously used to evaluate bisphosphonates was adapted Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years for a simulated cohort of patients with heterogeneous characteristics This was done for each non-bisphosphonate treatment, a strategy of no treatment, and the five bisphosphonate treatments previously evaluated The model was populated with effectiveness evidence from the systematic review and network meta-analysis All other parameters were estimated from published sources An NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 35% per annum Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 39, University of Sheffield, Sheffield, UK) tools The relationship between fracture risk and incremental net monetary benefit was estimated using non-parametric regression A probabilistic sensitivity analysis and scenario analyses were used to assess uncertainty

Results
Fifty-two randomised controlled trials of non-bisphosphonates were included in the clinical effectiveness systematic review and an additional 51 randomised controlled trials of bisphosphonates were included in the network meta-analysis All treatments had beneficial effects compared with placebo for vertebral, non-vertebral and hip fractures, with hazard ratios varying from 023 to 094, depending on treatment and fracture type The effects on vertebral fractures and the percentage change in bone mineral density were statistically significant for all treatments The rate of serious adverse events varied across trials (0–33%), with most between-group differences not being statistically significant for comparisons with placebo/no active treatment, non-bisphosphonates or bisphosphonates The incremental cost-effectiveness ratios were > £20,000 per quality-adjusted life-year for all non-bisphosphonate interventions compared with no treatment across the range of QFracture and FRAX scores expected in the population eligible for fracture risk assessment The incremental cost-effectiveness ratio for denosumab may fall below £30,000 per quality-adjusted life-year at very high levels of risk or for high-risk patients with specific characteristics Raloxifene was dominated by no treatment (resulted in fewer quality-adjusted life-years) in most risk categories

Limitations
The incremental cost-effectiveness ratios are uncertain for very high-risk patients

Conclusions
Non-bisphosphonates are effective in preventing fragility fractures, but the incremental cost-effectiveness ratios are generally greater than the commonly applied threshold of £20,000–30,000 per quality-adjusted life-year

Study registration
This study is registered as PROSPERO CRD42018107651

Funding
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol 24, No 29 See the NIHR Journals Library website for further project information

pdf/denosumab-raloxifene-romosozumab-and-teriparatide-to-prevent-4jawuz9dx8.pdf

Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation

The 2010 clinical practice guideline for the diagnosis and management of osteoporosis in Canada[1][1] focused on the care of adults living in the community. However, the fracture rate for adults living in long-term care (residents) is two to four times that of adults of similar age living in the

/pdf/recommendations-for-preventing-fracture-in-long-term-care-148b6zttjy.pdf

Recommendations for preventing fracture in long-term care

Summary
Hip fractures are associated with reduced health-related quality of life (HrQoL). We found pre-existing need of care or limited function, cognitive impairment, and depression to be independent factors associated with lower HrQoL during the postsurgical period. In contrast, joint replacement was associated with better HrQoL compared to internal fixation. Patients’ treatment should be focused on functional recovery and treatment of depression.

What determines health-related quality of life in hip fracture patients at the end of acute care?--a prospective observational study.

Summary
In the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) study, women with incident clinical fractures reported significant declines in health-related quality of life (HRQoL). The largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain.

Impact of clinical fractures on health-related quality of life is dependent on time of assessment since fracture: results from the FREEDOM trial

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

S Ragi-Eis

Author Tools

Chat about Author

Papers

Impact of clinical fractures on health-related quality of life is dependent on time of assessment since fracture: results from the FREEDOM trial