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Risk of Fracture During Androgen Deprivation Therapy Among Patients With Prostate Cancer: A Systematic Review and Meta-Analysis of Cohort Studies
- Source :
- Frontiers in Pharmacology, Vol 12 (2021), Frontiers in Pharmacology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- Background: Androgen deprivation therapy (ADT) suppresses the production of androgen, and ADT is broadly used for intermediate or higher risk disease including advanced and metastatic cancer. ADT is associated with numerous adverse effects derived from the pharmacological properties. Previous meta-analysis on fracture risk among ADT users possessed limited data without further subgroup analysis. Risk estimation of updated real-world evidence on ADT-related fracture remains unknown.Objectives: To assess the risk of fracture and fracture requiring hospitalization associated with ADT among prostate cancer population on different disease conditions, treatment regimen, dosage level, fracture sites.Methods: The Cochrane Library, PubMed, and Embase databases were systematically screened for eligible cohort studies published from inception to March 2020. Two authors independently reviewed all the included studies. The risks of any fracture and of fracture requiring hospitalization were assessed using a random-effects model, following by leave-one-out, stratified, and sensitivity analyses. The Grading of Recommendations Assessments, Development and Evaluations (GRADE) system was used to grade the certainty of evidence.Results: Sixteen eligible studies were included, and total population was 519,168 men. ADT use is associated with increasing fracture risk (OR, 1.39; 95% CI, 1.26–1.52) and fracture requiring hospitalization (OR, 1.55; 95% CI, 1.29–1.88). Stratified analysis revealed that high-dose ADT results in an elevated risk of fracture with little statistical heterogeneity, whereas sensitivity analysis restricted to adjust for additional factors indicated increased fracture risks for patients with unknown stage prostate cancer or with no restriction on age with minimal heterogeneity. The GRADE level of evidence was moderate for any fracture and low for fracture requiring hospitalization.Conclusion: Cumulative evidence supports the association of elevated fracture risk with ADT among patients with prostate cancer, including those with different disease conditions, treatment regimens, dose levels, and fracture sites. Further prospective trials with intact information on potential risk factors on fracture under ADT use are warranted to identify the risky population.
- Subjects :
- medicine.medical_specialty
Population
Subgroup analysis
androgen deprivation therapy
RM1-950
Cochrane Library
Androgen deprivation therapy
Prostate cancer
Internal medicine
Medicine
Pharmacology (medical)
education
Adverse effect
Pharmacology
education.field_of_study
luteinizing hormone-releasing hormone agonist
business.industry
prostate cancer
medicine.disease
fracture
Meta-analysis
antiandrogen
Systematic Review
Therapeutics. Pharmacology
business
Cohort study
Subjects
Details
- ISSN :
- 16639812
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pharmacology
- Accession number :
- edsair.doi.dedup.....9f36042655984d2f5e918bd95c5a3767
- Full Text :
- https://doi.org/10.3389/fphar.2021.652979