Title
Author
DOI
Article Type
Special Issue
Volume
Issue
The relationship between serum testosterone and bone mineral density in Japanese men and the effects zoledronic acid in prostate cancer patients with low serum testosterone
1Department of Urology, Juntendo University Urayasu Hospital, 279-0021 Chiba, Japan
2D-Clinic TOKYO, 100-6210 Tokyo, Japan
DOI: 10.22514/jomh.2024.006 Vol.20,Issue 1,January 2024 pp.35-41
Submitted: 16 October 2023 Accepted: 03 November 2023
Published: 30 January 2024
*Corresponding Author(s): Akira Tsujimura E-mail: atsujimu@juntendo.ac.jp
Although hormone therapy is definitely beneficial for patients with prostate cancer, a decrease in bone mineral density and an increased risk of fracture have been noted as adverse events. Improving bone metabolism in these patients is especially important in an aging society. We herein report the results of two studies: the first examined the effect of low serum testosterone levels on bone mineral density in a large number of Japanese men; the second study investigated the effect of a 12-month formulation of zoledronic acid injection for multiple years in prostate cancer patients with castration levels of serum testosterone due to androgen deprivation therapy. The first study included 1112 patients with late-onset hypogonadism. A multiple regression analysis that included factors that were significant in the simple regression analysis showed that only age (p < 0.001) and testosterone (p = 0.013) were significantly associated with bone mineral density. A significant relationship between serum testosterone and bone mineral density was also found in an age-adjusted regression analysis (p = 0.008) and a trend analysis (Ptrend = 0.001). The second study included 12 prostate cancer patients with castration levels of serum testosterone due to androgen deprivation therapy, and who had received a 12-month formulation of zoledronic acid injection for multiple years. A trend analysis clearly showed that bone mineral density tended to increase year by year during the 4-year observation period (Ptrend < 0.001). In addition, we found no treatment-related adverse events in patients who received long-acting zoledronic acid. Thus, we conclude that men with lower serum testosterone levels are likely to have reduced bone mineral density and wish to emphasize that bone mineral density can be increased in prostate cancer patients by the continuous administration of long-acting zoledronic acid at 12-month intervals, even when their serum testosterone levels are below castration level.
Testosterone; Bone mineral density; Late-onset hypogonadism; Prostate cancer; Castration level; Long-acting zoledoronic acid; Four years
Akimasa Kure,Keisuke Ishikawa,Masataka Sano,Yuta Anno,Ayumu Taniguchi,Yuka Uesaka,Taiji Nozaki,Masato Shirai,Kazuhiro Kobayashi,Akira Tsujimura. The relationship between serum testosterone and bone mineral density in Japanese men and the effects zoledronic acid in prostate cancer patients with low serum testosterone. Journal of Men's Health. 2024. 20(1);35-41.
[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68: 394–424.
[2] Rawla P. Epidemiology of prostate cancer. World Journal of Oncology. 2019; 10: 63–89.
[3] Hinotsu S, Akaza H, Usami M, Ogawa O, Kagawa S, Kitamura T, et al. Current status of endocrine therapy for prostate cancer in Japan analysis of primary androgen deprivation therapy on the basis of data collected by J-CaP. Japanese Journal of Clinical Oncololy. 2007; 37: 775–781.
[4] Akaza H. Future prospects for luteinizing hormone-releasing hormone analogues in prostate cancer treatment. Pharmacology. 2010; 85: 110–120.
[5] Cooperberg MR, Hinotsu S, Namiki M, Carroll PR, Akaza H. Trans-pacific variation in outcomes for men treated with primary androgen-deprivation therapy (ADT) for prostate cancer. BJU International. 2016; 117: 102–109.
[6] Kakehi Y, Sugimoto M, Taoka R. Evidenced‐based clinical practice guideline for prostate cancer (summary: Japanese Urological Association, 2016 edition). International Journal of Urology. 2017; 24: 648–666.
[7] Fukumoto S, Soen S, Taguchi T, Ishikawa T, Matsushima H, Terauchi M, et al. Management manual for cancer treatment-induced bone loss (CTIBL): position statement of the JSBMR. Journal of Bone and Mineral Metabolism. 2020; 38: 141–144.
[8] Shapiro CL, Van Poznak C, Lacchetti C, Kirshner J, Eastell R, Gagel R, et al. Management of osteoporosis in survivors of adult cancers with nonmetastatic disease: ASCO clinical practice guideline. Journal of Clinical Oncology. 2019; 37: 2916–2946.
[9] Coleman R, Hadji P, Body J-, Santini D, Chow E, Terpos E, et al. Bone health in cancer: ESMO clinical practice guidelines. Annals of Oncology. 2020; 31: 1650–1663.
[10] Solomon DH. Compliance with osteoporosis medications. Archives of Internal Medicine. 2005; 165: 2414.
[11] Parker C, Castro E, Fizazi K, Heidenreich A, Ost P, Procopio G, et al. Prostate cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2020; 31: 1119–1134.
[12] Mellström D, Johnell O, Ljunggren O, Eriksson A, Lorentzon M, Mallmin H, et al. Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden. Journal of Bone and Mineral Research. 2006; 21: 529–535.
[13] Ye J, Zhai X, Yang J, Zhu Z. Association between serum testosterone levels and body composition among men 20–59 years of age. International Journal of Endocrinology. 2021; 2021: 1–8.
[14] Shahinian VB, Kuo Y, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. New England Journal of Medicine. 2005; 352: 154–164.
[15] Leslie WD, Martineau P, Bryanton M, Lix LM. Which is the preferred site for bone mineral density monitoring as an indicator of treatment-related anti-fracture effect in routine clinical practice? A registry-based cohort study. Osteoporosis International. 2019; 30: 1445–1453.
[16] Satoh T, Kimura M, Matsumoto K, Tabata K, Okusa H, Bessho H, et al. Single infusion of zoledronic acid to prevent androgen deprivation therapy-induced bone loss in men with hormone-naive prostate carcinoma. Cancer. 2009; 115: 3468–3474.
[17] Takahashi S, Iwase T, Kohno N, Ishikawa T, Taguchi T, Takahashi M, et al. Efficacy of zoledronic acid in postmenopausal Japanese women with early breast cancer receiving adjuvant letrozole: 12-month results. Breast Cancer Research and Treatment. 2012; 133: 685–693.
[18] Nakatsukasa K, Koyama H, Ouchi Y, Ono H, Sakaguchi K, Matsuda T, et al. Effect of denosumab on low bone mineral density in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: 24-month results. Breast Cancer. 2019; 26: 106–112.
[19] Nguyen PL, Alibhai SMH, Basaria S, D’Amico AV, Kantoff PW, Keating NL, et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. European Urology. 2015; 67: 825–836.
[20] Smith MR, McGovern FJ, Zietman AL, Fallon MA, Hayden DL, Schoenfeld DA, et al. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. New England Journal of Medicine. 2001; 345: 948–955.
[21] Kishimoto H, Maehara M. Compliance and persistence with daily, weekly, and monthly bisphosphonates for osteoporosis in Japan: analysis of data from the CISA. Archives of Osteoporosis. 2015; 10: 27.
[22] Wang B, Zhan Y, Yan L, Hao D. How zoledronic acid improves osteoporosis by acting on osteoclasts. Frontiers in Pharmacology. 2022; 13: 961941.
[23] Kojima I, Naito Y, Yamamoto A, Terashima Y, Sho N, Nagayama J, et al. Efficacy of zoledronic acid in older prostate cancer patients undergoing androgen deprivation therapy. Osteoporosis and Sarcopenia. 2019; 5: 128–131.
[24] Watanabe D, Kimura T, Watanabe K, Takano H, Uehara Y, Minowa T, et al. Effects of once-yearly zoledronic acid on bone density and incident vertebral fractures in nonmetastatic castration-sensitive prostate cancer patients with osteoporosis. BMC Cancer. 2021; 21: 422.
Top