[en] Cancer treatment-induced bone loss (CTIBL) is one of the most important side effects of adjuvant antineoplastic treatment in hormone-dependent neoplasms. Chemotherapy, GnRH analogs and tamoxifen can induce marked bone loss in premenopausal women with early breast cancer. Aromatase inhibitors (AIs) are replacing tamoxifen as the preferred treatment for postmenopausal women. As a class effect, steroidal (exemestane) and non-steroidal (anastrozole and letrozole) AIs increase bone turnover and cause bone loss (4%-5% over 2 years). When compared to tamoxifen, the risk of getting a clinical fracture under AI treatment is increased by 35%-50%. In patients with prostate cancer, androgen deprivation therapy (ADT) increases bone turnover, reduces bone mass (4%-5% per year) and increases the fracture rate depending on the duration of therapy. Zoledronic acid can prevent accelerated bone loss induced by goserelin in premenopausal women, by letrozole in postmenopausal women and by ADT in men. More limited data indicate that weekly alendronate or risedronate could also be effective for preventing CTIBL. Initiation of therapy early, prior to the occurrence of severe osteoporosis, rather than after, may be more effective. Bisphosphonate treatment should be considered in osteoporotic but also in osteopenic patients if other risk factor(s) for fractures are present.
Disciplines :
General & internal medicine
Author, co-author :
Body, Jean-Jacques
Bergmann, P.
Boonen, S.
Boutsen, Y.
Devogelaer, Jean-Pierre
Goemaere, S.
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Rozenberg, S.
Kaufman, J. M.
Language :
English
Title :
Management of cancer treatment-induced bone loss in early breast and prostate cancer -- a consensus paper of the Belgian Bone Club.
Publication date :
2007
Journal title :
Osteoporosis International
ISSN :
0937-941X
eISSN :
1433-2965
Publisher :
Springer Science & Business Media B.V., Godalming, United Kingdom
Pfeilschifter, J., Diel, I.J., Osteoporosis due to cancer treatment: Pathogenesis and management (2002) J Clin Oncol, 18, pp. 1570-1593
Hoff, A.O., Gagel, R.F., Osteoporosis in breast and prostate cancer survivors (2005) Oncology, 19, pp. 651-658
Cooper, C., The crippling consequences of fractures and their impact on quality of life (1997) Am J Med, 103, pp. 12S-17S
Shapiro, C.L., Manola, J., Leboff, M., Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer (2001) J Clin Oncol, 19, pp. 3306-3311
Bruning, P.F., Pit, M.J., De Jong-Bakker, M., Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer (1990) Br J Cancer, 61, pp. 308-310
Buzdar, A.U., Hortobagyi, G., Update on endocrine therapy for breast cancer (1998) Clin Cancer Res, 4, pp. 527-534
Garrett, T.J., Vahdat, L.T., Kinne, D.W., Systemic adjuvant therapy of breast cancer (1997) J Surg Oncol, 64, pp. 167-172
Jonat, W., Kaufmann, M., Sauerbrei, W., Zoladex Early Breast Cancer Research Association Study. Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study (2002) J Clin Oncol, 20, pp. 4628-4635
Fogelman, I., Blake, G.M., Blamey, R., 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) (2003) Osteoporos Int, 14, pp. 1001-1006
Love, R.R., Mazess, R.B., Barden, H.S., Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer (1992) N Engl J Med, 326, pp. 852-856
Powles, T.J., Hickish, T., Kanis, J.A., Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women (1996) J Clin Oncol, 14, pp. 78-84
Winer, E.P., Hudis, C., Burstein, H.J., Chlebowski, R.T., American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for women with hormone receptor-positive breast cancer: Status report 2002 (2002) J Clin Oncol, 20, pp. 3317-3327
Winer, E.P., Hudis, C., Burstein, H.J., American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: Status report 2004 (2005) J Clin Oncol, 23, pp. 619-629
Smith, I.E., Dowsett, M., Aromatase inhibitors in breast cancer (2003) N Engl J Med, 48, pp. 2431-2442
Fisher, B., Costantino, J.P., Wickerham, D.L., Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study (1998) J Natl Cancer Inst, 90, pp. 1371-1388
McCloskey, E.V., Effects of third-generation aromatase inhibitors on bone (2006) Eur J Cancer, 42, pp. 1044-1051
Goss, P.E., Qi, S., Cheung, A.M., Hu, H., Effects of the F(7)steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats (2004) Clin Cancer Res, 10, pp. 5717-5723
Subar, M., Goss, P.E., Thomsen, T., Effects of steroidal and nonsteroidal aromatase inhibitors (AIs) on markers of bone turnover and lipid metabolism in healthy volunteers (2004) J Clin Oncol, 22, p. 8038. , 14S
Heshmati, H.M., Khosla, S., Robins, S.P., Role of low levels of endogenous estrogen in regulation of bone resorption in late postmenopausal women (2002) J Bone Miner Res, 17, pp. 172-178
McCloskey, E., Hannon, R., Lakner, G., The letrozole (L), exemestane (E) and anastrozole (A) pharmacodynamics (LEAP) trial: A direct comparison of bone biochemical measurements between aromatase inhibitors (AIs) in healthy postmenopausal women (2006) J Clin Oncol, 24, p. 555. , 18S
Eastell, R., Hannon, R.A., Cuzick, J., On behalf of the ATAC Trialists' Group. Effect of an aromatase inhibitor on BMD and bone turnover markers: 2-year results of the anastrozole, tamoxifen, alone or in combination (ATAC) Trial (18233230) (2006) J Bone Miner Res, 21, pp. 1215-1223
Geisler, J., Lonning, P.E., Krag, L.E., Changes in bone and lipid metabolism in postmenopausal women with early breast cancer after terminating 2-year treatment with exemestane: A randomized placebo-controlled study (2006) Eur J Cancer, 42, pp. 2968-2975
Cuzick, J., Forbes, J., Edwards, R., First results from the International Breast Cancer Intervention Study (IBIS-1): A randomiser prevention trial (2002) Lancet, 360, pp. 817-824
Fisher, B., Costantino, J.P., Wickerham, D.L., Tamoxifen for the prevention of breast cancer: Current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study (2005) J Natl Cancer Inst, 97, pp. 1652-1662
Baum, M., Buzdar, A., Cuzick, J., The ATAC (Arimidex, Tamoxifen Alone or in Combination) Trialists' Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: Results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses (2003) Cancer, 98, pp. 1802-1810
Thurlimann, B., Keshaviah, A., Coates, A.S., Breast International Group (BIG) 1-98 Collaborative Group. a comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer (2005) N Engl J Med, 353, pp. 2747-2757
Howell, A., Cuzick, J., Baum, M., ATAC Trialists' Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer (2005) Lancet, 365, pp. 60-62
Goss, P.E., Ingle, J.N., Martino, S., A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer (2003) N Engl J Med, 349, pp. 1793-1802
Perez, E.A., Josse, R.G., Pritchard, K.I., Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: A companion study to NCIC CTG MA-17 (2006) J Clin Oncol, 24, pp. 3629-3635
Coombes, R.C., Hall, E., Gibson, L.J., Intergroup Exemestane Study. a randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer (2004) N Engl J Med, 350, pp. 1081-1092
Jakesz, R., Jonat, W., Gnant, M., Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: Combined results of ABCSG trial 8 and ARNO 95 trial (2005) Lancet, 366, pp. 455-462
Lonning, P.E., Geisler, J., Krag, L.E., Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer (2005) J Clin Oncol, 23, pp. 5126-5137
Mincey, B.A., Duh, M.S., Thopmas, S.K., Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors (2006) Clinical Breast Cancer, 7, pp. 127-132
Martin, A.R., Sornay-Rendu, E., Chandler, J.M., The impact of osteoporosis on quality-of-life: The OFELY cohort (2002) Bone, 31, pp. 32-36
Padalecki, S.S., Carreon, M., Grubbs, B., Androgen deprivation enhances bone loss and prostate cancer metastases to bone: Prevention by zoledronic acid (2003) Oncology, 17, p. 32
Body, J.J., Bisphosphonates for malignancy-related bone disease: Current status, future developments (2006) Support Care Cancer, 14, pp. 408-418
Morris, C.A., Cheng, H., Cabral, D., Predictors of screening and treatment of osteoporosis: A structural review of the literature (2004) Endocrinologist, 14, pp. 70-75
Indications and reporting for dual-energy X-ray absorptiometry (2004) J Clin Densitom, 7, pp. 37-44. , Writing Group for the ISCD, Position Development Conference
Hillner, B.E., Ingle, J.N., Chlebowski, R.T., American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer (2003) J Clin Oncol, 21, pp. 4042-4057. , American Society of Clinical Oncology Erratum in: (2004) J Clin Oncol 22:1351
Saarto, T., Blomqvist, C., Valimaki, M., Makela, P., Sarna, S., Elomaa, I., 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 (1997) J Clin Oncol, 15, pp. 1341-1347
Delmas, P.D., Balena, R., Confravreux, E., Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: A double-blind, placebo-controlled study (1997) J Clin Oncol, 15, pp. 955-962
Gnant, M., Mlineritsch, B., Luschin-Ebengreuth, G., Zoledronic acid effectively prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: A report from the Austrian Breast and Colorectal Cancer Study Group (2007) J Clin Oncol, 25, pp. 820-828
Brufsky, A., Harker, W.G., Beck, J.T., Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer (2007) J Clin Oncol, 25, pp. 829-836
Moul, J.W., Contemporary hormonal management of advanced prostate cancer (1998) Oncology, 12, pp. 499-505
Robson, M., Dawson, N., How is androgen-dependent metastatic prostate cancer best treated? (1996) Hematol Oncol Clin North Am, 10, pp. 727-747
Eastell, R., Treatment of postmenopausal osteoporosis (1998) N Engl J Med, 338, pp. 736-746
Higano, C.S., Understanding treatments for bone loss and bone metastases in patients with prostate cancer: A practical review and guide for the clinician (2004) Urol Clin North Am, 31, pp. 331-352
Maillefert, J.F., Sibilia, J., Michel, F., Bone mineral density in men treated with synthetic gonadotropin-releasing hormone agonists for prostatic carcinoma (1999) J Urol, 161, pp. 1219-1222
Eriksson, S., Eriksson, A., Stege, R., Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogens (1995) Calcif Tissue Int, 57, pp. 97-99
Daniell, H.W., Dunn, S.R., Ferguson, D.W., Progressive osteoporosis during androgen deprivation therapy for prostate cancer (2000) J Urol, 163, pp. 181-186
Daniell, H.W., Osteoporosis after orchiectomy for prostate cancer (1997) J Urol, 157, pp. 439-444
Townsend, M.F., Sanders, W.H., Northway, R.O., Bone fractures associated with luteinizing hormone-releasing hormone agonists used in the treatment of prostate carcinoma (1997) Cancer, 79, pp. 545-550
Oefelein, M.G., Ricchuiti, V., Conrad, W., Skeletal fracture associated with androgen suppression induced osteoporosis: The clinical incidence and risk factors for patients with prostate cancer (2001) J Urol, 166, pp. 1724-1728
Smith, M.R., Boyce, S.P., Moyneur, E., Risk of clinical fracture after gonadotropin-releasing hormone agonist therapy for prostate cancer (2006) J Urol, 175, pp. 136-139
Shahinian, V.B., Kuo, Y.F., Freeman, J.L., Risk of fracture after androgen deprivation for prostate cancer (2005) N Engl J Med, 352, pp. 154-164
Smith, M.R., Finkelstein, J.S., McGovern, F.J., Changes in body composition during androgen deprivation therapy for prostate cancer (2002) J Clin Endocrinol Metab, 87, pp. 599-603
Van Staa, T.P., Leufkens, H.G., Abenhaim, L., Use of oral corticosteroids and risk of fractures (2000) J Bone Miner Res, 15, pp. 993-1000
Van Pottelbergh, I., Goemaere, S., Kaufman, J.M., Bioavailable estradiol and an aromatase gene polyorphism are determinants of bone mineral density changes in men over 70 years of age (2003) J Clin Endocrinol Metab, 88, pp. 3075-3081
Barrett-Connor, E., Mueller, J.E., Von Muhlen, D.G., Low levels of estradiol are associated with vertebral fractures in older men, but not women: The Rancho Bernardo Study (2000) J Clin Endocrinol Metab, 85, pp. 219-223
Bilezikian, J.P., Morishima, A., Bell, J., Increased bone mass as a result of estrogen therapy in a man with aromatase deficiency (1998) N Engl J Med, 339, pp. 599-603
Verhelst, J., Denis, L., Van Vliet, P., Endocrine profiles during administration of the new non-steroidal anti-androgen Casodex in prostate cancer (1994) Clin Endocrinol, 41, pp. 525-530
Smith, M.R., Goode, M., Zietman, A.L., Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: Effects on bone mineral density and body composition (2004) J Clin Oncol, 22, pp. 2546-2553
Diamond, T.H., Higano, C.S., Smith, M.R., Osteoporosis in men with prostate carcinoma receiving androgen-deprivation therapy: Recommendations for diagnosis and therapies (2004) Cancer, 100, pp. 892-899
Bilezikian, J.P., Osteoporosis in men (1999) J Clin Endocrinol Metab, 84, pp. 3431-3434
Smith, M.R., Fallon, M.A., Lee, H., Finkelstein, J.S., Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: A randomized controlled trial (2004) J Clin Endocrinol Metab, 89, pp. 3841-3846
Taxel, P., Fall, P.M., Albertsen, P.C., The effect of micronized estradiol on bone turnover and calciotropic hormones in older men receiving hormonal suppression therapy for prostate cancer (2002) J Clin Endocrinol Metab, 87, pp. 4907-4913
Smith, M.R., McGovern, F.J., Zietman, A.L., Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer (2001) N Engl J Med, 345, pp. 948-955
Diamond, T.H., Winters, J., Smith, A., The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade: A double blind, randomized, placebo-controlled crossover study (2001) Cancer, 92, pp. 1444-1450
Smith, M.R., Eastham, J., Gleason, D.M., Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer (2003) J Urol, 169, pp. 2008-2012
Michaelson, M.D., Kaufman, D.S., Lee, H., Randomized controlled trial of annual zoledronic acid to prevent gondotropin-releasing hormone agonist-induced bone loss in men with prostate cancer (2007) J Clin Oncol, 25, pp. 1038-1042
Greenspan, S.L., Wagner, J.M., Nelson, J.B., Alendronate prevents bone loss in men on androgen deprivation therapy for prostate cancer (2005) J Bone Miner Res, 20, p. 93. , Suppl 1
Bruder, J.M., Ma, J.Z., Wing, M., Effects of alendronate on bone mineral density in men with prostate cancer treated with androgen deprivation therapy (2006) J Clin Densitom, 9, pp. 431-437
Body, J.J., Dosing regimens and main adverse events of bisphosphonates (2001) Semin Oncol, 28, pp. 49-53. , Suppl 11
Chang, J.T., Green, L., Beitz, J., Renal failure with the use of zoledronic acid (2003) N Engl J Med, 349, pp. 1676-1679
Bamias, A., Kastritis, E., Bamia, C., Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: Incidence and risk factors (2005) J Clin Oncol, 23, pp. 8580-8587
Woo, S.B., Hellstein, J.W., Kalmar, J.R., Bisphosphonates and osteonecrosis of the jaws (2006) Ann Intern Med, 144, pp. 753-761
Bilezikian, J.P., Osteonecrosis of the jaw - Do bisphosphonates pose a risk? (2006) N Engl J Med, 355, pp. 2278-2281
Black, D.M., Delmas, P.D., Eastell, R., Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis (2007) N Engl J Med, 356, pp. 1809-1822
Goss, P.E., Emerging role of aromatase inhibitors in the adjuvant setting (2003) Am J Clin Oncol, 26, pp. 27-S33
Kanis, J.A., Borgstrom, F., De Laet, C., Assessment of fracture risk (2005) Osteoporos Int, 16, pp. 581-589
Guise, T.A., Bone loss and fracture risk associated with cancer therapy (2006) The Oncologist, 11, pp. 1121-1131
Chien, A.J., Goss, P.E., Aromatase inhibitors and bone health in women with breast cancer (2006) J Clin Oncol, 24, pp. 5305-5312
Body, J.J., Diel, I.J., Lichinitser, M.R., MF 4265 Study Group. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases (2003) Ann Oncol, 14, pp. 1399-1405
Body, J.J., Zoledronic acid: An advance in tumour bone disease and a new hope for osteoporosis (2003) Expert Opin Pharmacother, 4, pp. 567-580
Srinivas, S., Colocci, N., Bone related events in high risk prostate cancer (2006) J Urol, 176, pp. 50-S54. , 6 Pt 2
