Bone management in Japanese patients with prostate cancer: hormonal therapy leads to an increase in the FRAX score

BMC Urology, Jun 2016

Background Osteoporosis is a common consequence of androgen deprivation therapy (ADT) for prostate cancer. Up to 20 % of men on ADT have suffered from fractures within 5 years. The WHO Fracture Risk Assessment Tool (FRAX) has been utilized to predict the 10-year probability of major osteoporotic and hip fracture. However, to date, no large studies assessing the utility of the FRAX score in prostate cancer patients with or without ADT have been performed. We herein evaluated the impact of ADT on the FRAX score in prostate cancer patients. Methods The assessment of the FRAX score was performed in a total of 1220 prostate cancer patients, including patients who underwent brachytherapy (n = 547), radical prostatectomy (n = 200), external beam radiation therapy (n = 264) and hormonal therapy alone (n = 187) at Yokohama City University Hospital (Yokohama, Japan). We evaluated the effect of ADT on the FRAX score. Results Using the FRAX model, the median and mean 10-year probability of a major osteoporotic fracture according to the clinical risk factors alone was 7.9 % (8.8 ± 4.3 %), while the 10-year probability of hip fracture risk was 2.7 % (3.5 ± 3.1 %). In the ADT group, the duration of ADT was correlated with both major osteoporotic risk and hip fracture risk (R 2  = 0.141, p < 0.001 and R 2  = 0.166, p < 0.001, respectively). A comparison between the ADT (n = 187) and non-ADT (n = 399) groups demonstrated that the major fracture risk was > 20 % higher and the hip fracture risk was > 3 % higher in the ADT group than in the non-ADT group (ADT: 10 (5.3 %) and 118 (63.1 %), non-ADT 13 (3.3 %) and 189 (47.4 %), p < 0.001 and p < 0.001, respectively). Conclusions These results suggested that the longer duration of ADT led to an increased FRAX score, and the FRAX score may be a predictor of bone management treatment, particularly in prostate cancer patients.

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Bone management in Japanese patients with prostate cancer: hormonal therapy leads to an increase in the FRAX score

Kawahara et al. BMC Urology Bone management in Japanese patients with prostate cancer: hormonal therapy leads to an increase in the FRAX score Takashi Kawahara 0 1 2 Shusei Fusayasu 0 2 Koji Izumi 2 Yumiko Yokomizo 2 Hiroki Ito 2 Yusuke Ito 2 Kayo Kurita 2 Kazuhiro Furuya 2 Hisashi Hasumi 2 Narihiko Hayashi 2 Yasuhide Myoshi 1 Hiroshi Miyamoto 3 Masahiro Yao 2 Hiroji Uemura 1 2 0 Equal contributors 1 Department of Urology and Renal Transplantation, Yokohama City University Medical Center , 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 , Japan 2 Department of Urology, Yokohama City University, Graduate School of Medicine , Yokohama , Japan 3 Departments of Pathology and Urology, Johns Hopkins University School of Medicine , Baltimore , USA Background: Osteoporosis is a common consequence of androgen deprivation therapy (ADT) for prostate cancer. Up to 20 % of men on ADT have suffered from fractures within 5 years. The WHO Fracture Risk Assessment Tool (FRAX) has been utilized to predict the 10-year probability of major osteoporotic and hip fracture. However, to date, no large studies assessing the utility of the FRAX score in prostate cancer patients with or without ADT have been performed. We herein evaluated the impact of ADT on the FRAX score in prostate cancer patients. Methods: The assessment of the FRAX score was performed in a total of 1220 prostate cancer patients, including patients who underwent brachytherapy (n = 547), radical prostatectomy (n = 200), external beam radiation therapy (n = 264) and hormonal therapy alone (n = 187) at Yokohama City University Hospital (Yokohama, Japan). We evaluated the effect of ADT on the FRAX score. Results: Using the FRAX model, the median and mean 10-year probability of a major osteoporotic fracture according to the clinical risk factors alone was 7.9 % (8.8 ± 4.3 %), while the 10-year probability of hip fracture risk was 2.7 % (3.5 ± 3.1 %). In the ADT group, the duration of ADT was correlated with both major osteoporotic risk and hip fracture risk (R2 = 0.141, p < 0.001 and R2 = 0.166, p < 0.001, respectively). A comparison between the ADT (n = 187) and non-ADT (n = 399) groups demonstrated that the major fracture risk was > 20 % higher and the hip fracture risk was > 3 % higher in the ADT group than in the non-ADT group (ADT: 10 (5.3 %) and 118 (63.1 %), non-ADT 13 (3.3 %) and 189 (47.4 %), p < 0.001 and p < 0.001, respectively). Conclusions: These results suggested that the longer duration of ADT led to an increased FRAX score, and the FRAX score may be a predictor of bone management treatment, particularly in prostate cancer patients. Androgen deprivation therapy; FRAX; Prostate cancer; Bone fracture Background Following the widespread implementation of PSA screening, the incidence of prostate cancer has been increasing in Japan [ 1, 2 ]. By the end of 2015, 98,400 men will have been newly diagnosed and 12,200 men will have died of prostate cancer. Many patients diagnosed with prostate cancer are elderly and must be treated with hormonal therapy [3]. Men with prostate cancer are often at risk for other age-related adverse events, such as hip fractures. The risk of hip fractures can increase in men with prostate cancer because the bone density often decreases due to androgen deprivation therapy (ADT), occult bone metastases, or a combination thereof [ 4–8 ]. The mechanism is believed to be due to a decrease in sexual hormone levels, which induces receptor activator of nuclear factor-kappa-B ligand (RANKL) expression from osteoblasts. Consequently, osteoclasts are involved in bone resorption [ 9 ]. The skeleton is the third most common site of metastatic cancers, and one-third to one-half of all cancers metastasize to the bone. In prostate cancer, bone metastasis is the most common site for tumor development [ 10 ]. Osteoporosis or low bone mineral density (BMD) is a highly prevalent health problem in the elderly as well as in prostate cancer patients treated with ADT. The FRAX score is a fracture risk assessment tool developed by the World Health Organization (WHO) to predict the fracture risk of patients according to clinical risk factors alone or in combination with BMD at the femoral neck [ 11 ]. It is a computer-based algorithm which provides the 10-year probability of hip and major osteoporotic fractures (e.g., clinical spine, forearm, hip, or shoulder fracture) according to age, sex, body mass index, and clinical risk factors [ 12, 13 ]. There have been no proven methods for predicting pathologic fractures in patients with skeletal metastasis thus far [14]. The fracture risk varies depending on the geographic location and ethnicity, and the FRAX algorithm has been calibrated to account for this [ 11 ]. Algorithms are available for diverse ethnic groups, including Asians, based largely on data from Japan and China [ 13 ]. Despite its importance, there have been few studies which investigated the fracture risk among Asian (...truncated)


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Takashi Kawahara, Shusei Fusayasu, Koji Izumi, Yumiko Yokomizo, Hiroki Ito, Yusuke Ito, Kayo Kurita, Kazuhiro Furuya, Hisashi Hasumi, Narihiko Hayashi, Yasuhide Myoshi, Hiroshi Miyamoto, Masahiro Yao, Hiroji Uemura. Bone management in Japanese patients with prostate cancer: hormonal therapy leads to an increase in the FRAX score, BMC Urology, 2016, pp. 32, 16, DOI: 10.1186/s12894-016-0151-9