Gonadotropin-Releasing Hormone Agonists and Fracture Risk: A Claims-Based Cohort Study of Men With Nonmetastatic Prostate Cancer

Smith, Matthew R.; Lee, Won Chan; Brandman, J.; Wang, Qin; Botteman, Marc; Pashos, Chris L.

doi:10.1200/jco.2004.00.6908

Cited by 335 publications

(236 citation statements)

References 26 publications

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“…Estradiol plays a role in bone formation and bone resorption in men (5). Therefore, ADT decreases bone mineral density (BMD) and increases the incidence of clinical fractures (6,7). The risk of fracture increases with an increasing duration of ADT (6,7).…”

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confidence: 99%

“…Therefore, ADT decreases bone mineral density (BMD) and increases the incidence of clinical fractures (6,7). The risk of fracture increases with an increasing duration of ADT (6,7). Patients with prostate carcinoma bone metastases are faced with the risk of skeletal complications, including pathologic fractures, which are collectively termed skeletal-related events (SREs) (8).…”

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confidence: 99%

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Evaluation of Bone Turnover / Quality Markers and Bone Mineral Density in Prostate Cancer Patients Receiving Androgen Deprivation Therapy with or without Denosumab

Miyazawa

Sekine

Syuto

et al. 2017

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Abstract. Background/Aim: Androgen deprivation therapy (ADT) is a mainstay therapy for prostate cancer (PCa). ADT induces bone loss and increases the risk of osteoporosis and fractures. Recently, loss of bone quality has received attention as a factor that causes loss of bone strength independent of bone mineral density (BMDProstate cancer (PCa) is the most common cancer in males in Western countries and its incidence has increased in Japan (1). Androgen deprivation therapy (ADT) with gonadotropinreleasing hormone (GnRH) agonists, GnRH antagonists or bilateral orchiectomy is a well-established treatment for advanced PCa (2). ADT is also used to manage cases of localized PCa when radical treatment cannot be administered (3). The administration of ADT improves disease-free survival and overall survival in men with locally advanced PCa treated with radiation therapy (4). ADT functions by decreasing testosterone to castrate levels. ADT also markedly decreases serum estradiol levels because estradiol is derived from the peripheral conversion of testosterone by aromatase, also called estrogen synthase. Therefore, side-effects associated with estrogen deficiency are also observed. Estradiol plays a role in bone formation and bone resorption in men (5). Therefore, ADT decreases bone mineral density (BMD) and increases the incidence of clinical fractures (6, 7). The risk of fracture increases with an increasing duration of ADT (6, 7). Patients with prostate carcinoma bone metastases are faced with the risk of skeletal complications, including pathologic fractures, which are collectively termed skeletal-related events (SREs) (8). SREs are associated with mortality, increased pain, decreased quality of life and increased treatment costs (9).Although several drugs, including bisphosphonates and selective estrogen-receptor modulators, can prevent a decreased BMD, clinical trials of those drugs have revealed that the effects on fracture prevention are insufficient (10, 11). In contrast, denosumab was found to increase BMD at all sites and decrease the incidence of new vertebral fractures among men receiving ADT for non-metastatic PCa (12). Furthermore, denosumab decreased the risk of skeletal complications compared to zoledronic acid in castrationresistant prostate cancer (CRPC) patients with bone metastases (13). The administration of denosumab decreased the serum levels of bone turnover markers (BTMs), including type-1 C-teropeptide (sCTX) and tartrate-resistant alkaline phosphatase 5b (TRAP-5b) compared to placebo (14). Therefore, BTMs are often used to predict the effects of denosumab during CRPC patient care.

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confidence: 99%

mentioning

confidence: 99%

Evaluation of Bone Turnover / Quality Markers and Bone Mineral Density in Prostate Cancer Patients Receiving Androgen Deprivation Therapy with or without Denosumab

Miyazawa

Sekine

Syuto

et al. 2017

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“…In a study of medical claims data from a 5% national random sample of Medicare beneficiaries, men receiving GnRH agonist treatment for prostate cancer were more likely to develop fractures than a control group of men with prostate cancer who had not received a GnRH agonist (hazard ratio 1.4; 95% CI 1.16-1.70; P <0.001) [14]. After controlling for age, race, geographic location, and comorbidity, GnRH agonist treatment independently predicted fracture risk.…”

Section: Androgen Deprivation Therapy and Fracture Riskmentioning

confidence: 99%

“…Three large claims-based studies provide the best evidence that GnRH agonists increase the risk of clinical fractures [14][15][16].…”

Section: Androgen Deprivation Therapy and Fracture Riskmentioning

confidence: 99%

Androgen deprivation therapy for prostate cancer: new concepts and concerns

Smith

2007

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

148

129

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Purpose of review-The aim of this review is to summarize new concepts and concerns regarding treatment-related osteoporosis, diabetes, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer.Recent findings-Gonadotropin-releasing hormone agonists increase bone turnover, decrease bone mineral density, and increase fracture risk. Bisphosphonates, selective and estrogen receptor modulators significantly increase bone mineral density during androgen deprivation therapy. Ongoing randomized controlled trials will assess efficacy of denosumab, toremifene, and zoledronic acid to prevent fractures in this setting. Gonadotropin-releasing hormone agonists also increase fat mass, decrease insulin sensitivity, and increase serum lipoproteins. In contrast to the classical metabolic syndrome, however, the phenotype of men during androgen deprivation therapy is characterized by increased high-density lipoprotein cholesterol and preferential accumulation of subcutaneous fat. Gonadotropin-releasing hormone agonists are associated with greater risk of incident diabetes and cardiovascular disease in men with prostate cancer.Summary-Androgen therapy increases risk of fractures, diabetes mellitus, and cardiovascular disease in men with prostate cancer. Current and planned studies will evaluate strategies to prevent these treatment-related adverse effects.

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“…10 The use of ADT is associated with a number of side effects that offset its palliative benefits. 11,12 In addition, ADT has recently been linked to an increased risk of bone fracture [13][14][15] and metabolic syndrome, both of which are associated with high mortality rates. [16][17][18] When patients are suffering from symptomatic prostate cancer, virtually all practitioners would agree that the benefits of ADT in improving symptoms outweigh the side effects, and men should be placed on ADT; however, what is not clear is whether to start ADT before the patient develops symptoms of progressive prostate cancer postradiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Hormone use after radiotherapy failure: a survey of Canadian uro-oncology specialists

Loblaw

Pickles

Cheung

et al. 2013

CUAJ

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Introduction: A survey of Canadian uro-oncology specialists was performed to assess practice patterns of patients with recurrent prostate cancer postradiotherapy and to assess the feasibility of conducting a trial in this setting.Methods: There were 14 survey questions and 1 demographic question. Responses were reported by frequency.Results: There were 96 respondents. Most respondents use both prostate-specific antigen doubling time (PSAdt) and PSA level when deciding to start androgen deprivation therapy (ADT) in asymptomatic patients. About half of respondents start ADT when PSA is greater than 10 ng/mL or when the PSAdt is less than 6 months. Eighty-six percent felt that the timing of ADT was an important research question. Over 1500 patients per year were estimated as being available for such a trial. Conclusion:After radiotherapy failure, respondents initiated ADT about half of the time when PSA is less than 10 ng/mL and/or PSAdt is less than 6 months. A clinical trial examining the timing of ADT has strong support and appears to be feasible. Résultats : Quatre-vingt-seize médecins ont participé au sondage. Can UrolLa majorité des répondants se basent sur le temps de doublement de l'APS et les taux d'APS pour décider du moment optimal pour amorcer un traitement antiandrogène chez les patients asymptomatiques. Environ la moitié des répondants entreprennent un traitement antiandrogène lorsque le taux d'APS dépasse 10 ng/mL ou lorsque le temps de doublement de l'APS est inférieur à 6 mois. Quatre-vingt-six pour cent des répondants ont indiqué que le moment optimal pour l'amorce du traitement antiandrogène représentait une importante question de recherche. On estime que plus de 1500 patients par année seraient admissibles à une telle étude. Conclusion :Après l'échec d'une radiothérapie, les répondants entreprennent un traitement antiandrogène dans environ la moitié des cas lorsque l'APS est inférieur à 10 ng/mL et/ou lorsque le temps de doublement de l'APS est inférieur à 6 mois. Un essai clinique portant sur la détermination du moment optimal pour l'amorce du traitement antiandrogène est fortement souhaité et semble faisable.

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Gonadotropin-Releasing Hormone Agonists and Fracture Risk: A Claims-Based Cohort Study of Men With Nonmetastatic Prostate Cancer

Abstract: GnRH agonists significantly increase risk for any clinical fracture, hip fractures, and vertebral fractures in men with prostate cancer.

Cited by 335 publications

References 26 publications

Evaluation of Bone Turnover / Quality Markers and Bone Mineral Density in Prostate Cancer Patients Receiving Androgen Deprivation Therapy with or without Denosumab

Evaluation of Bone Turnover / Quality Markers and Bone Mineral Density in Prostate Cancer Patients Receiving Androgen Deprivation Therapy with or without Denosumab

Androgen deprivation therapy for prostate cancer: new concepts and concerns

Hormone use after radiotherapy failure: a survey of Canadian uro-oncology specialists

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