Risk of Clinical Fractures After Gonadotropin-Releasing Hormone Agonist Therapy for Prostate Cancer

ArticleinThe Journal of Urology 175(1):136-9; discussion 139 · February 2006with9 Reads
DOI: 10.1016/S0022-5347(05)00033-9 · Source: PubMed
We assessed the relationship between GnRH agonists and the risk of clinical fractures in men with prostate cancer. Using a database of medical claims from 16 large American companies we identified a study group of 3,779 men with prostate cancer who received treatment with a GnRH agonist and a control group of 8,341 with prostate cancer who were not treated with a GnRH agonist. Men with 1 or more medical claims for bone metastases were excluded. The rates of any clinical fracture, hip fracture and vertebral fracture were compared between the groups. The rate of any fracture was 7.91/100 vs 6.55/100 person-years at risk in men who received vs did not receive a GnRH agonist (relative risk 1.21, 95% CI 1.09 to 1.34). The rates of hip fracture (relative risk 1.76, 95% CI 1.33 to 2.33) and vertebral fracture (relative risk 1.18, 95% CI 0.94 to 1.48) were also higher in men who received a GnRH agonist. GnRH agonist treatment was independently associated with fracture risk on multivariate analyses. GnRH agonists increase the risk of clinical fracture in men with prostate cancer.
    • "patients with rising PSA and/or clinical progression, serum testosterone must be evaluated in all cases to confirm a castrate-resistant state. During long-term therapy, ADT reduces bone mineral density (BMD) and increases the risk of fractures [65]. In the absence of associated risk factors, it is recommended that BMD and serum vitamin D and calcium levels should be measured every 2 yr [66] . "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: To present a summary of the 2016 version of the European Association of Urology (EAU) – European Society for Radiotherapy & Oncology (ESTRO) – International Society of Geriatric Oncology (SIOG) Guidelines on the treatment of relapsing, meta-static, and castration-resistant prostate cancer (CRPC). Evidence acquisition: The working panel performed a literature review of the new data (2013–2015). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature. Evidence synthesis: Relapse after local therapy is defined by a rising prostate-specific antigen (PSA) level >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir after radiation therapy (RT). 11 C-choline positron emission tomography/ computed tomography is of limited importance if PSA is <1.0 ng/ml; bone scans and computed tomography can be omitted unless PSA is >10 ng/ml. Multiparametric magnetic resonance imaging and biopsy are important to assess biochemical failure following RT. Therapy for PSA relapse after RP includes salvage RT at PSA levels <0.5 ng/ ml and salvage RP, high-intensity focused ultrasound, cryosurgical ablation or salvage brachytherapy of the prostate in radiation failures. Androgen deprivation therapy (ADT) remains the basis for treatment of men with metastatic prostate cancer (PCa). However, docetaxel combined with ADT should be considered the standard of care for men with metastases at first presentation, provided they are fit enough to receive the drug. Follow-up of ADT should include analysis of PSA, testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Level 1 evidence for the treatment of metastatic CRPC (mCRPC) includes, abiraterone acetate plus prednisone (AA/P), enzalutamide, radium 223 (Ra 223), docetaxel at 75 mg/m 2 every 3 wk and sipuleu-cel-T. Cabazitaxel, AA/P, enzalutamide, and radium are approved for second-line * Corresponding author. Royal Liverpool and Broadgreen Hospitals NHS Trust,
    Full-text · Article · Sep 2016
    • "Use of ADT, both GnRH agonists and orchiectomy, results in hypogonadism, which is associated with multiple adverse effects including loss of libido, hot flushes, erectile dysfunction, insulin resistance, dyslipidemia, anaemia , fatigue and accelerated bone loss [2,6789. ADT has been associated with an increased risk of bone fracture , as reported in retrospective cohort studies101112. However, few studies have examined the effect of different types of ADT or whether anti-androgens have a different effect on fracture rates. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Androgen deprivation therapy (ADT) administered as a prostate cancer treatment is known to exert multiple side effects including bone deterioration leading to bone fracture. The current analysis is to evaluate the burden of fracture risk in the New Zealand prostate cancer (PCa) population treated with ADT, and to understand the subsequent risk of mortality after a fracture. Methods Using datasets created through linking records from the New Zealand Cancer Registry, National Minimal Dataset, Pharmaceutical Collection and Mortality Collection, we studied 25,544 men (aged ≥40 years) diagnosed with PCa between 2004 and 2012. ADT was categorised into the following groups: gonadotropin-releasing hormone (GnRH) agonists, anti-androgens, combined androgen blockade (GnRH agonists plus anti-androgens), bilateral orchiectomy, and bilateral orchiectomy plus pharmacologic ADT (anti-androgens and/or GnRH agonists). Results Among patients receiving ADT, 10.8 % had a fracture compared to 3.2 % of those not receiving ADT (p < 0.0001). After controlling for age and ethnicity, the use of ADT was associated with a significantly increased risk of any fracture (OR = 2.83; 95 % CI 2.52–3.17) and of hip fracture requiring hospitalisation (OR = 1.82; 95 % CI 1.44–2.30). Those who received combined androgen blockade (OR = 3.48; 95 % CI 3.07–3.96) and bilateral orchiectomy with pharmacologic ADT (OR = 4.32; 95 % CI 3.34–5.58) had the greatest risk of fracture. The fracture risk following different types of ADT was confounded by pathologic fractures and spinal cord compression (SCC). ADT recipients with fractures had a 1.83-fold (95 % CI 1.68–1.99) higher mortality risk than those without a fracture. However, after the exclusion of pathologic fractures and SCC, there was no increased risk of mortality. Conclusions ADT was significantly associated with an increased risk of any fracture and hip fracture requiring hospitalisation. The excess risk was partly driven by pathologic fractures and SCC which are associated with decreased survival in ADT users. Identification of those at higher risk of fracture and close monitoring of bone health while on ADT is an important factor to consider. This may require monitoring of bone density and bone marker profiles.
    Full-text · Article · Dec 2015
    • "Adverse changes in body composition, specifically a reduction in skeletal muscle and increase in body fat (Smith et al. 2002, Haseen et al. 2010), occur as early as 3–6 months after initiation of ADT (Boxer et al. 2005, Smith et al. 2006a). In an uncontrolled study of 79 men with non-metastatic cancer, treatment with ADT for 12 months led to an 11% increase in fat mass and a 4% decrease in lean mass (Smith 2004). "
    [Show abstract] [Hide abstract] ABSTRACT: Androgen deprivation therapy is increasingly used to treat advanced prostate cancer and is also utilised as adjuvant or neo-adjuvant treatment for high risk disease. The resulting suppression of endogenous testosterone production has deleterious effects on quality of life including hot flushes, reduced mood and cognition, and diminished sexual function. Cross-sectional and longitudinal studies show that androgen deprivation therapy has adverse bone and cardio-metabolic effects. The rate of bone loss is accelerated increasing the risk of osteoporosis and subsequent fracture. Fat mass is increased and lean mass reduced, and adverse effects with deleterious effects on lipid levels and insulin resistance are observed, the latter increasing the risk of developing type 2 diabetes. Androgen deprivation therapy also appears to increase the risk of incident cardiovascular events, although whether it increases cardiovascular mortality is not certain from the observational evidence published to date. Until high-quality evidence is available to guide management, it is reasonable to consider men using androgen deprivation to be at higher risk of psychosexual dysfunction, osteoporotic fracture, diabetes and cardiovascular disease especially when men are treated with these modalities for extended periods of time and are therefore subjected to profound and prolonged hypoandrogenism. Health professionals caring for men undergoing treatment for prostate cancer treatment should be aware of the potential risks of androgen deprivation therapy and ensure appropriate monitoring and clinical management.
    Full-text · Article · May 2014
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