Skip to main content
Top
Published in: Breast Cancer Research and Treatment 3/2010

01-10-2010 | Invited Commentary

Estrogen deficiency and bone loss in women with breast cancer

Author: Charles L. Shapiro

Published in: Breast Cancer Research and Treatment | Issue 3/2010

Login to get access

Excerpt

All women will lose bone as a consequence of normal aging and menopause-mediated bone loss due to the estrogen deficiency. However, not all women will develop osteoporosis. The development of osteoporosis can be thought of as an equation [1]: on one side of the equation peak bone mass usually attained by about age 30; on the other side is ongoing bone loss due to normal aging, menopausal-related bone loss, and genetic determinants such as family history, race, and low body mass index, as well as exposures or conditions that are potentially modifiable (i.e., current cigarette smoking, alcohol intake greater than two drinks per day, and chronic glucocorticoid therapy) [2, 3]. Taking these factors into account, each woman will have a peak bone mass and a unique set of risk factors for bone loss that determines whether she will experience a non-traumatic fracture or osteoporosis. In postmenopausal women with breast cancer, the relative risks of osteoporotic fractures are higher than women without history of breast cancer [4]. …
Literature
1.
go back to reference Ramaswamy B, Shapiro CL (2003) Osteopenia and osteoporosis in women with breast cancer. Semin Oncol 30(6):763–775CrossRefPubMed Ramaswamy B, Shapiro CL (2003) Osteopenia and osteoporosis in women with breast cancer. Semin Oncol 30(6):763–775CrossRefPubMed
2.
go back to reference Kanis JA (2002) Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359(9321):1929–1936CrossRefPubMed Kanis JA (2002) Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359(9321):1929–1936CrossRefPubMed
3.
go back to reference Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19(4):385–397CrossRefPubMed Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19(4):385–397CrossRefPubMed
4.
go back to reference Chen Z, Maricic M, Aragaki AK, Mouton C, Arendell L, Lopez AM, Bassford T, Chlebowski RT (2009) Fracture risk increases after diagnosis of breast or other cancers in postmenopausal women: results from the Women’s Health Initiative. Osteoporos Int 20(4):527–536CrossRefPubMed Chen Z, Maricic M, Aragaki AK, Mouton C, Arendell L, Lopez AM, Bassford T, Chlebowski RT (2009) Fracture risk increases after diagnosis of breast or other cancers in postmenopausal women: results from the Women’s Health Initiative. Osteoporos Int 20(4):527–536CrossRefPubMed
5.
go back to reference Imai Y, Kondoh S, Kouzmenko A, Kato S (2010) Minireview: osteoprotective action of estrogens is mediated by osteoclastic estrogen receptor-alpha. Mol Endocrinol 24(5):877–885CrossRefPubMed Imai Y, Kondoh S, Kouzmenko A, Kato S (2010) Minireview: osteoprotective action of estrogens is mediated by osteoclastic estrogen receptor-alpha. Mol Endocrinol 24(5):877–885CrossRefPubMed
6.
go back to reference Gnant M, Mlineritsch B, Luschin-Ebengreuth G, Kainberger F, Kassmann H, Piswanger-Solkner JC, Seifert M, Ploner F, Menzel C, Dubsky P et al (2008) Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. Lancet Oncol 9(9):840–849CrossRefPubMed Gnant M, Mlineritsch B, Luschin-Ebengreuth G, Kainberger F, Kassmann H, Piswanger-Solkner JC, Seifert M, Ploner F, Menzel C, Dubsky P et al (2008) Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. Lancet Oncol 9(9):840–849CrossRefPubMed
7.
go back to reference Pant S, Shapiro CL (2008) Aromatase inhibitor-associated bone loss: clinical considerations. Drugs 68(18):2591–2600CrossRefPubMed Pant S, Shapiro CL (2008) Aromatase inhibitor-associated bone loss: clinical considerations. Drugs 68(18):2591–2600CrossRefPubMed
8.
go back to reference Molina JR, Barton DL, Loprinzi CL (2005) Chemotherapy-induced ovarian failure: manifestations and management. Drug Saf 28(5):401–416CrossRefPubMed Molina JR, Barton DL, Loprinzi CL (2005) Chemotherapy-induced ovarian failure: manifestations and management. Drug Saf 28(5):401–416CrossRefPubMed
9.
go back to reference Shapiro CL, Manola J, Leboff M (2001) Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol 19(14):3306–3311PubMed Shapiro CL, Manola J, Leboff M (2001) Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol 19(14):3306–3311PubMed
10.
go back to reference Davison KS, Siminoski K, Adachi JD, Hanley DA, Goltzman D, Hodsman AB, Josse R, Kaiser S, Olszynski WP, Papaioannou A et al (2006) Bone strength: the whole is greater than the sum of its parts. Semin Arthritis Rheum 36(1):22–31CrossRefPubMed Davison KS, Siminoski K, Adachi JD, Hanley DA, Goltzman D, Hodsman AB, Josse R, Kaiser S, Olszynski WP, Papaioannou A et al (2006) Bone strength: the whole is greater than the sum of its parts. Semin Arthritis Rheum 36(1):22–31CrossRefPubMed
11.
go back to reference Felsenberg D, Boonen S (2005) The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther 27(1):1–11CrossRefPubMed Felsenberg D, Boonen S (2005) The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther 27(1):1–11CrossRefPubMed
12.
13.
go back to reference Manolagas SC, Jilka RL (1995) Bone marrow, cytokines, and bone remodeling emerging insights into the pathophysiology of osteoporosis. N Engl J Med 332(5):305–311CrossRefPubMed Manolagas SC, Jilka RL (1995) Bone marrow, cytokines, and bone remodeling emerging insights into the pathophysiology of osteoporosis. N Engl J Med 332(5):305–311CrossRefPubMed
14.
go back to reference Kearns AE, Khosla S, Kostenuik PJ (2008) Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev 29(2):155–192CrossRefPubMed Kearns AE, Khosla S, Kostenuik PJ (2008) Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev 29(2):155–192CrossRefPubMed
16.
go back to reference Kostenuik PJ (2005) Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol 5(6):618–625CrossRefPubMed Kostenuik PJ (2005) Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol 5(6):618–625CrossRefPubMed
17.
18.
go back to reference Weitzmann MN, Pacifici R (2006) Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 116(5):1186–1194CrossRefPubMed Weitzmann MN, Pacifici R (2006) Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 116(5):1186–1194CrossRefPubMed
19.
go back to reference Imai Y, Youn M-Y, Kondoh S, Nakamura T, Kouzmenko A, Matsumoto T, Takada I, Takaoka K, Kato S (2009) Estrogens maintain bone mass by regulating expression of genes controlling function and life span in mature osteoclasts. Ann N Y Acad Sci 1173(S1):E31–E39CrossRefPubMed Imai Y, Youn M-Y, Kondoh S, Nakamura T, Kouzmenko A, Matsumoto T, Takada I, Takaoka K, Kato S (2009) Estrogens maintain bone mass by regulating expression of genes controlling function and life span in mature osteoclasts. Ann N Y Acad Sci 1173(S1):E31–E39CrossRefPubMed
20.
go back to reference Krum SA, Miranda-Carboni GA, Hauschka PV, Carroll JS, Lane TF, Freedman LP, Brown M (2008) Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival. EMBO J 27(3):535–545CrossRefPubMed Krum SA, Miranda-Carboni GA, Hauschka PV, Carroll JS, Lane TF, Freedman LP, Brown M (2008) Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival. EMBO J 27(3):535–545CrossRefPubMed
21.
go back to reference Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y et al (2007) Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell 130(5):811–823CrossRefPubMed Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y et al (2007) Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell 130(5):811–823CrossRefPubMed
22.
go back to reference Weitzmann MN, Pacifici R (2005) Role of the immune system in postmenopausal bone loss. Curr Osteoporos Rep 3(3):92–97CrossRefPubMed Weitzmann MN, Pacifici R (2005) Role of the immune system in postmenopausal bone loss. Curr Osteoporos Rep 3(3):92–97CrossRefPubMed
23.
go back to reference Weitzmann MN, Pacifici R (2007) T cells: unexpected players in the bone loss induced by estrogen deficiency and in basal bone homeostasis. Ann N Y Acad Sci 1116:360–375CrossRefPubMed Weitzmann MN, Pacifici R (2007) T cells: unexpected players in the bone loss induced by estrogen deficiency and in basal bone homeostasis. Ann N Y Acad Sci 1116:360–375CrossRefPubMed
24.
go back to reference Zallone A (2006) Direct and indirect estrogen actions on osteoblasts and osteoclasts. Ann N Y Acad Sci 1068:173–179CrossRefPubMed Zallone A (2006) Direct and indirect estrogen actions on osteoblasts and osteoclasts. Ann N Y Acad Sci 1068:173–179CrossRefPubMed
25.
go back to reference Weitzmann MN, Pacifici R (2005) The role of T lymphocytes in bone metabolism. Immunol Rev 208:154–168CrossRefPubMed Weitzmann MN, Pacifici R (2005) The role of T lymphocytes in bone metabolism. Immunol Rev 208:154–168CrossRefPubMed
26.
go back to reference Lea CK, Flanagan AM (1999) Ovarian androgens protect against bone loss in rats made oestrogen deficient by treatment with ICI 182, 780. J Endocrinol 160(1):111–117CrossRefPubMed Lea CK, Flanagan AM (1999) Ovarian androgens protect against bone loss in rats made oestrogen deficient by treatment with ICI 182, 780. J Endocrinol 160(1):111–117CrossRefPubMed
27.
go back to reference Fogelman I, Blake GM, Blamey R, Palmer M, Sauerbrei W, Schumacher M, Serin D, Stewart A, Wilpshaar W (2003) Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Osteoporos Int 14(12):1001–1006CrossRefPubMed Fogelman I, Blake GM, Blamey R, Palmer M, Sauerbrei W, Schumacher M, Serin D, Stewart A, Wilpshaar W (2003) Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Osteoporos Int 14(12):1001–1006CrossRefPubMed
28.
go back to reference Saarto T, Blomqvist C, Valimaki M, Makela P, Sarna S, Elomaa I (1997) Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients. J Clin Oncol 15(4):1341–1347PubMed Saarto T, Blomqvist C, Valimaki M, Makela P, Sarna S, Elomaa I (1997) Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients. J Clin Oncol 15(4):1341–1347PubMed
29.
go back to reference Crandall C, Petersen L, Ganz PA, Greendale GA (2004) Bone mineral density and adjuvant therapy in breast cancer survivors. Breast Cancer Res Treat 88(3):257–261CrossRefPubMed Crandall C, Petersen L, Ganz PA, Greendale GA (2004) Bone mineral density and adjuvant therapy in breast cancer survivors. Breast Cancer Res Treat 88(3):257–261CrossRefPubMed
30.
go back to reference Greep NC, Giuliano AE, Hansen NM, Taketani T, Wang HJ, Singer FR (2003) The effects of adjuvant chemotherapy on bone density in postmenopausal women with early breast cancer. Am J Med 114(8):653–659CrossRefPubMed Greep NC, Giuliano AE, Hansen NM, Taketani T, Wang HJ, Singer FR (2003) The effects of adjuvant chemotherapy on bone density in postmenopausal women with early breast cancer. Am J Med 114(8):653–659CrossRefPubMed
31.
go back to reference Goodwin PJ, Ennis M, Pritchard KI, Trudeau M, Hood N (1999) Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 17(8):2365–2370PubMed Goodwin PJ, Ennis M, Pritchard KI, Trudeau M, Hood N (1999) Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 17(8):2365–2370PubMed
32.
go back to reference Anderson RA, Themmen AP, Al-Qahtani A, Groome NP, Cameron DA (2006) The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum Reprod 21(10):2583–2592CrossRefPubMed Anderson RA, Themmen AP, Al-Qahtani A, Groome NP, Cameron DA (2006) The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum Reprod 21(10):2583–2592CrossRefPubMed
33.
go back to reference Shapiro CL, Phillips G, Van Poznak CH, Jackson R, Leboff MS, Woodard S, Lemeshow S (2005) Baseline bone mineral density of the total lumbar spine may predict for chemotherapy-induced ovarian failure. Breast Cancer Res Treat 90(1):41–46CrossRefPubMed Shapiro CL, Phillips G, Van Poznak CH, Jackson R, Leboff MS, Woodard S, Lemeshow S (2005) Baseline bone mineral density of the total lumbar spine may predict for chemotherapy-induced ovarian failure. Breast Cancer Res Treat 90(1):41–46CrossRefPubMed
34.
go back to reference Chen Z, Arendell L, Aickin M, Cauley J, Lewis CE, Chlebowski R (2008) Hip bone density predicts breast cancer risk independently of Gail score: results from the Women’s Health Initiative. Cancer 113(5):907–915CrossRefPubMed Chen Z, Arendell L, Aickin M, Cauley J, Lewis CE, Chlebowski R (2008) Hip bone density predicts breast cancer risk independently of Gail score: results from the Women’s Health Initiative. Cancer 113(5):907–915CrossRefPubMed
35.
go back to reference Termine JD, Wong M (1998) Post-menopausal women and osteoporosis: available choices for maintenance of skeletal health. Maturitas 30(3):241–245CrossRefPubMed Termine JD, Wong M (1998) Post-menopausal women and osteoporosis: available choices for maintenance of skeletal health. Maturitas 30(3):241–245CrossRefPubMed
36.
go back to reference Shapiro CL, Halabi S, Gibson G et al (2008) Effect of zoledronic acid (ZA) on bone mineral density (BMD) in premenopausal women who develop ovarian failure (OF) due to adjuvant chemotherapy (AdC): first results from CALGB trial 79809. J Clin Onc 26 (May 20 Suppl; abstract 512) Shapiro CL, Halabi S, Gibson G et al (2008) Effect of zoledronic acid (ZA) on bone mineral density (BMD) in premenopausal women who develop ovarian failure (OF) due to adjuvant chemotherapy (AdC): first results from CALGB trial 79809. J Clin Onc 26 (May 20 Suppl; abstract 512)
37.
go back to reference Gralow JR, Biermann JS, Farooki A, Fornier MN, Gagel RF, Kumar RN, Shapiro CL, Shields A, Smith MR, Srinivas S et al (2009) NCCN task force report: bone health in cancer care. J Natl Compr Cancer Netw 7(Suppl 3):S1–S32 (quiz S33–S35) Gralow JR, Biermann JS, Farooki A, Fornier MN, Gagel RF, Kumar RN, Shapiro CL, Shields A, Smith MR, Srinivas S et al (2009) NCCN task force report: bone health in cancer care. J Natl Compr Cancer Netw 7(Suppl 3):S1–S32 (quiz S33–S35)
Metadata
Title
Estrogen deficiency and bone loss in women with breast cancer
Author
Charles L. Shapiro
Publication date
01-10-2010
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-1099-1

Other articles of this Issue 3/2010

Breast Cancer Research and Treatment 3/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine