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)