Skip to main content
Top
Published in: Osteoporosis International 3/2008

01-03-2008 | Original Article

The effect of combined androgen blockade on bone turnover and bone mineral density in men with prostate cancer

Authors: Y. Yamada, S. Takahashi, T. Fujimura, H. Nishimatsu, A. Ishikawa, H. Kume, K. Tomita, T. Takeuchi, T. Kitamura

Published in: Osteoporosis International | Issue 3/2008

Login to get access

Abstract

Summary

Our study and previous reports suggest that castration results in increased bone turnover and lowered BMD and that these changes might be attenuated by anti-androgens, such as BL and EMP.

Introduction

Recent studies have shown that castration for PC decreases bone mineral density (BMD), while estrogen therapy or bicalutamide (BL) monotherapy maintains BMD. However, the effect of combined androgen blockade (CAB) on bone turnover is not well studied.

Methods

A total of 204 men were evaluated in the study (control group: n = 56, castration group: n = 102, ‘CAB with BL’ group: n = 22, ‘CAB with estramustine phosphate (EMP)’ group: n = 24). We measured steroid hormone levels, BMD (measured at one-third distal radius), bone turnover markers (levels of urinary N-telopeptide cross links of type 1 collagen (u-NTx) and deoxypyridinoline (u-DPD), serum concentrations of osteocalcin (OC)) in order to assess differences between groups.

Results

The BMD % Z score of the castration group was significantly lower than that of the control group or the ‘CAB with EMP’ group (90.6% vs. 95.5%, 98.6%; p < 0.042, p < 0.044, respectively). Levels of u-NTx, u-DPD, OC of the castration group were the highest followed by the control group, then the ‘CAB with BL’ group and the ‘CAB with EMP’ group.

Conclusions

Our study and previous reports suggests that castration results in increased bone turnover and lowered BMD and that these changes might be attenuated by anti-androgens, such as BL and EMP.
Literature
1.
go back to reference Shahinian VB, Kuo Y-F, Freeman JL, Goodwin JS (2005) Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 352:154–164PubMedCrossRef Shahinian VB, Kuo Y-F, Freeman JL, Goodwin JS (2005) Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 352:154–164PubMedCrossRef
2.
go back to reference Ross RW, Small EJ (2001) Osteoporosis in men treated with androgen deprivation therapy for prostate cancer. J Urol 67:1952–1956 Ross RW, Small EJ (2001) Osteoporosis in men treated with androgen deprivation therapy for prostate cancer. J Urol 67:1952–1956
3.
go back to reference Townsend MF, Sanders WH, Northway RO, Graham Jr SD (1997) Bone fractures associated with luteinizing hormone-releasing hormone agonists used in the treatment of prostate carcinoma. Cancer 79:545–550CrossRef Townsend MF, Sanders WH, Northway RO, Graham Jr SD (1997) Bone fractures associated with luteinizing hormone-releasing hormone agonists used in the treatment of prostate carcinoma. Cancer 79:545–550CrossRef
4.
go back to reference Stoch SA, Parker RA, Chen L, Bubley G, Ko YJ, Vincelette, Greenspan SL (2001) Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists. J Clin Endocrinol Metab 86:2787–2791PubMedCrossRef Stoch SA, Parker RA, Chen L, Bubley G, Ko YJ, Vincelette, Greenspan SL (2001) Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists. J Clin Endocrinol Metab 86:2787–2791PubMedCrossRef
5.
go back to reference Smith MR, Goode M, Zieman AL, McGovern FJ, Lee H, Finkestein JS (2004) Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition. J Clin Oncol 22:2546–2552PubMedCrossRef Smith MR, Goode M, Zieman AL, McGovern FJ, Lee H, Finkestein JS (2004) Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition. J Clin Oncol 22:2546–2552PubMedCrossRef
6.
go back to reference Taxel P, Fall PM, Albertsen PC, Dowsett RD, Trahiotis M, Zimmerman J, et al (2002) The effect of micronized estradiol on bone turnover and calciotropic hormones in older men receiving hormonal suppression therapy for prostate cancer. J Clin Endocrinol Metab 87:4907–4913PubMedCrossRef Taxel P, Fall PM, Albertsen PC, Dowsett RD, Trahiotis M, Zimmerman J, et al (2002) The effect of micronized estradiol on bone turnover and calciotropic hormones in older men receiving hormonal suppression therapy for prostate cancer. J Clin Endocrinol Metab 87:4907–4913PubMedCrossRef
7.
go back to reference Ockrim JL, Lalani EN, Laniado ME, Carter SStC, Abel PD (2003) Transdermal estradiol therapy for advanced prostate cancer-forward to the past? J Urol 169:1735–1737PubMedCrossRef Ockrim JL, Lalani EN, Laniado ME, Carter SStC, Abel PD (2003) Transdermal estradiol therapy for advanced prostate cancer-forward to the past? J Urol 169:1735–1737PubMedCrossRef
8.
go back to reference Eriksson S, Eriksson A, Stege R, Carlstrom K (1995) Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogen. Calcif Tissue Int 57:97–99PubMedCrossRef Eriksson S, Eriksson A, Stege R, Carlstrom K (1995) Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogen. Calcif Tissue Int 57:97–99PubMedCrossRef
9.
go back to reference Suzuki Y, Aikawa K, Oishi Y, Yamazaki H, Onishi T, Suzuki M, et al (1998) A clinical study of decreased bone mineral density in the patients treated with long-term luteinizing hormone releasing hormone analogue (LHRH-a)-the risk of iatrogenic osteoporosis due to treatment of carcinoma of prostate. Nippon Hinyoukika Gakkai Zasshi 89:961–966 Suzuki Y, Aikawa K, Oishi Y, Yamazaki H, Onishi T, Suzuki M, et al (1998) A clinical study of decreased bone mineral density in the patients treated with long-term luteinizing hormone releasing hormone analogue (LHRH-a)-the risk of iatrogenic osteoporosis due to treatment of carcinoma of prostate. Nippon Hinyoukika Gakkai Zasshi 89:961–966
10.
go back to reference Sieber PR, Keiller DL, Kahnoski RJ, Gallo J, Mcfadden S (2004) Bicalutamide 150 mg maintains bone mineral density during monotherapy for localized or locally advanced prostate cancer. J Urol 171:2272–2276PubMedCrossRef Sieber PR, Keiller DL, Kahnoski RJ, Gallo J, Mcfadden S (2004) Bicalutamide 150 mg maintains bone mineral density during monotherapy for localized or locally advanced prostate cancer. J Urol 171:2272–2276PubMedCrossRef
11.
go back to reference Scherr D, Pitts Jr WR, Vaughan Jr ED (2002) Diethylstilbestrol revisited: androgen deprivation, osteoporosis and prostate cancer. J Urol 167:535–538PubMedCrossRef Scherr D, Pitts Jr WR, Vaughan Jr ED (2002) Diethylstilbestrol revisited: androgen deprivation, osteoporosis and prostate cancer. J Urol 167:535–538PubMedCrossRef
12.
go back to reference Noguchi M, Yahara J, Noda S (2003) Serum levels of bone turnover markers parallel the results of bone scintigraphy in monitoring bone activity of prostate cancer. Urology 61:993–998PubMedCrossRef Noguchi M, Yahara J, Noda S (2003) Serum levels of bone turnover markers parallel the results of bone scintigraphy in monitoring bone activity of prostate cancer. Urology 61:993–998PubMedCrossRef
13.
go back to reference Diamond T, Campbell J, Bryant C, et al (1998) The effect of combined androgen blockade on bone turnover and bone mineral densities in men treated for prostate carcinoma: longitudinal evaluation and response to intermittent cyclic etidronate therapy Cancer 83:1561–1566PubMedCrossRef Diamond T, Campbell J, Bryant C, et al (1998) The effect of combined androgen blockade on bone turnover and bone mineral densities in men treated for prostate carcinoma: longitudinal evaluation and response to intermittent cyclic etidronate therapy Cancer 83:1561–1566PubMedCrossRef
14.
go back to reference Falahati-Nini A, Riggs BL, Atkinson EJ, 0’Fallon WM, Eastell R, Khosla S (2000) Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 106:1553–1560PubMedCrossRef Falahati-Nini A, Riggs BL, Atkinson EJ, 0’Fallon WM, Eastell R, Khosla S (2000) Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 106:1553–1560PubMedCrossRef
15.
go back to reference Colvard DS, Eriksen EF, Keeting PE, Wilson EM, Lubahn DB, French FS, et al (1989) Identification of androgen receptors in normal human osteoblast-like cells. Proc Natl Acad Sci USA 86:854–857PubMedCrossRef Colvard DS, Eriksen EF, Keeting PE, Wilson EM, Lubahn DB, French FS, et al (1989) Identification of androgen receptors in normal human osteoblast-like cells. Proc Natl Acad Sci USA 86:854–857PubMedCrossRef
16.
go back to reference Oursler MJ, Pederson L, Fitzpatrick L, Riggs BL Spelsberg T (1994) Human giant cell tumors of the bone (osteoclastomas) are estrogen target cells. Proc Natl Acad Sci USA 91:5227–5231PubMedCrossRef Oursler MJ, Pederson L, Fitzpatrick L, Riggs BL Spelsberg T (1994) Human giant cell tumors of the bone (osteoclastomas) are estrogen target cells. Proc Natl Acad Sci USA 91:5227–5231PubMedCrossRef
17.
go back to reference Lorentzon M, Lorentzon R, Bäckström T, Nordström P (1999) Estrogen receptor gene polymorphism, but not estradiol levels, is related to bone density in healthy adolescent boys: a cross sectional and longitudinal study. J Clin Endocrinol Metab 84:4597–4601PubMedCrossRef Lorentzon M, Lorentzon R, Bäckström T, Nordström P (1999) Estrogen receptor gene polymorphism, but not estradiol levels, is related to bone density in healthy adolescent boys: a cross sectional and longitudinal study. J Clin Endocrinol Metab 84:4597–4601PubMedCrossRef
18.
go back to reference Draper MW (2003) The role of selective estrogen receptor modulators (SERMs) in post menopausal health. Ann N Y Acad Sci 997:373–377PubMedCrossRef Draper MW (2003) The role of selective estrogen receptor modulators (SERMs) in post menopausal health. Ann N Y Acad Sci 997:373–377PubMedCrossRef
19.
go back to reference Lefort M, Curiel MD, Carrascal MT, Mendez-Davila C, de la Piedra C (2005) Comparative effects of bicalutamide (Casodex) versus orchidectomy on bone mineral density, bone remodeling, and bone biomechanics in healthy rats. Urol Int 74:301–307PubMedCrossRef Lefort M, Curiel MD, Carrascal MT, Mendez-Davila C, de la Piedra C (2005) Comparative effects of bicalutamide (Casodex) versus orchidectomy on bone mineral density, bone remodeling, and bone biomechanics in healthy rats. Urol Int 74:301–307PubMedCrossRef
20.
go back to reference Hfbauer LC, Ten RM, Kholsa S (1999) The anti-androgen hydroxyflutamide and androgens inhibit interleukin-6 production by an androgen-responsive human osteoblastic cell line. J Bone Miner Res 14:1330–1337CrossRef Hfbauer LC, Ten RM, Kholsa S (1999) The anti-androgen hydroxyflutamide and androgens inhibit interleukin-6 production by an androgen-responsive human osteoblastic cell line. J Bone Miner Res 14:1330–1337CrossRef
21.
go back to reference Nottestad S, Baumel J, Kimmel D, Recker RR, Heaney RP (1987) The proportion of trabecular bone in human vertebrae. J Bone Miner Res 2:221–229PubMedCrossRef Nottestad S, Baumel J, Kimmel D, Recker RR, Heaney RP (1987) The proportion of trabecular bone in human vertebrae. J Bone Miner Res 2:221–229PubMedCrossRef
22.
go back to reference Drinka PJ, DeSmet AA, Bauwens SF, Rogot A (1992) The effect of overlying calcification is on lumbar bone densitometry. Calcif Tissue Int 50:507–510PubMedCrossRef Drinka PJ, DeSmet AA, Bauwens SF, Rogot A (1992) The effect of overlying calcification is on lumbar bone densitometry. Calcif Tissue Int 50:507–510PubMedCrossRef
Metadata
Title
The effect of combined androgen blockade on bone turnover and bone mineral density in men with prostate cancer
Authors
Y. Yamada
S. Takahashi
T. Fujimura
H. Nishimatsu
A. Ishikawa
H. Kume
K. Tomita
T. Takeuchi
T. Kitamura
Publication date
01-03-2008
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 3/2008
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-007-0472-3

Other articles of this Issue 3/2008

Osteoporosis International 3/2008 Go to the issue