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01.12.2008 | Review Article

Aromatase Inhibitor-Associated Bone Loss

Clinical Considerations

verfasst von: Shubham Pant, Dr Charles L. Shapiro

Erschienen in: Drugs | Ausgabe 18/2008

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Abstract

Aromatase inhibitors (AIs) are standard treatments for postmenopausal women with estrogen responsive breast cancers. The mechanism of AIs, inhibition of the aromatase enzyme that causes decreases in endogenous estrogens, is responsible for bone loss and increased fractures. Screening and prevention of AI-induced bone loss closely follows the standard recommendations for postmenopausal osteoporosis. Lifestyle changes such as increasing physical activity and weight-bearing exercise, stopping smoking, and taking adequate amounts of daily calcium and vitamin D promote bone and overall health. Bisphosphonates are specific inhibitors of osteoclasts and reduce bone loss in women treated with AIs. The optimal dose administration schedule and duration of bisphosphonate treatment for AI-induced bone loss remains undefined.

Winer EP, Hudis C, Burstein HJ, et al. 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. J Clin Oncol 2004; 23: 619–29PubMedCrossRef

Goldhirsch A, Wood WC, Gelber RD, et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer. Ann Oncol 2007; 18: 1133–44PubMedCrossRef

Brueggemeier R. Aromatase, aromatase inhibitors, and breast cancer. Am J Ther 2001; 8: 333–44PubMedCrossRef

Smith IE, Dowsett M. Aromatase inhibitors in breast cancer. N Engl J Med 2003; 348: 2431–42PubMedCrossRef

Confavreux CB, Fontana A, Guastalla JP, et al. Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole: revention with bisphosphonates. Bone 2007; 41: 346–52PubMedCrossRef

Lindsay R, Cosman F, Nieves J. Estrogen: effects and actions in osteoporosis. Osteoporos Int 1993; 3 Suppl. 1: 150–2CrossRef

O’Connell MB. Pharmacokinetic and pharmacologic variation between different estrogen products. J Clin Pharmacol 1995; 35 (9 Suppl.): 18–24S

Reginster JY, Sarlet N, Deroisy R, et al. Minimal levels of serum estradiol prevent postmenopausal bone loss. Calcif Tissue Int 1992; 51: 340–3PubMedCrossRef

Lindsay R, Hart DM, Aitken JM, et al. Long-term prevention of postmenopausal osteoporosis by oestrogen: evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet 1976; I: 1038–41CrossRef

10.

Gnant MFX, Mlineritsch B, Luschin-Ebengreuth G, et al. Zoledronic acid 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. J Clin Oncol 2007; 25: 820–8PubMedCrossRef

11.

Shapiro CL, Manola J, Leboff M. Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol 2001; 19: 3306–11PubMed

12.

Saarto T, Blomqvist C, Valimaki M, et al. 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 1997; 15: 1341–7PubMed

13.

Eastell R, Adams JE, Coleman RE, et al. Effect of anastrozole on bone mineral density: 5-year results from the Anastrozole, Tamoxifen, Alone or in Combination Trial 18233230. J Clin Oncol 2008; 26: 1051–7PubMedCrossRef

14.

Gnant MF, Mlineritsch B, Luschin-Ebengreuth G, et al. Zoledronic acid 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. J Clin Oncol 2007; 25: 820–8PubMedCrossRef

15.

Warming L, Hassager C, Christiansen C. Changes in bone mineral density with age in men and women: a longitudinal study. Osteoporos Int 2002; 13: 105–12PubMedCrossRef

16.

Nelson HD, Humphrey LL, Nygren P, et al. Postmenopausal hormone replacement therapy: scientific review. JAMA 2002; 288: 872–81PubMedCrossRef

17.

Eichner SF, Lloyd KB, Timpe EM. Comparing therapies for postmenopausal osteoporosis prevention and treatment. Ann Pharmacother 2003; 37: 711–24PubMedCrossRef

18.

Love RR, Mazess RB, Barden HS, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer [see comments]. N Engl J Med 1992; 326: 852–6PubMedCrossRef

19.

Felsenberg D, Boonen S. The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther 2005; 27: 1–11PubMedCrossRef

20.

Davison KS, Siminoski K, Adachi JD, et al. Bone strength: the whole is greater than the sum of its parts. Semin Arthritis Rheum 2006; 36: 22–31PubMedCrossRef

21.

Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling: emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995; 332: 305–11PubMedCrossRef

22.

Karsenty G, Ducy P. The hypothalamic control of bone mass, implication for the treatment of osteoporosis. Ann Endocrinol (Paris) 2006; 67: 123CrossRef

23.

Ramaswamy B, Shapiro CL. Osteopenia and osteoporosis in women with breast cancer. Semin Oncol 2003; 30: 763–75PubMedCrossRef

24.

Kearns AE, Khosla S, Kostenuik P. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev 2008; 29(2): 155–92PubMedCrossRef

25.

Boyce BF, Xing L. The RANKL/RANK/OPG pathway. Curr Osteoporos Rep 2007; 5: 98–104PubMedCrossRef

26.

Dougall WC, Chaisson M. The RANK/RANKL/OPG triad in cancer-induced bone diseases. Cancer Metastasis Rev 2006; 25: 541–9PubMedCrossRef

27.

Hofbauer LC, Neubauer A, Heufelder AE. Receptor activator of nuclear factor-kappaB ligand and osteoprotegerin: potential implications for the pathogenesis and treatment of malignant bone diseases. Cancer 2001; 92: 460–70PubMedCrossRef

28.

Kostenuik PJ. Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol 2005; 5: 618–25PubMedCrossRef

29.

Weitzmann MN, Pacifici R. Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 2006; 116: 1186–94PubMedCrossRef

30.

Geisler J, Lonning PE. Endocrine effects of aromatase inhibitors and inactivators in vivo: review of data and method limitations. J Steroid Biochem Mol Biol 2005; 95: 75–81PubMedCrossRef

31.

Simpson ER, Dowsett M. Aromatase and its inhibitors: significance for breast cancer therapy. Recent Prog Horm Res 2002; 57: 317–38PubMedCrossRef

32.

Dixon JM. Exemestane: a potent irreversible aromatase inactivator and a promising advance in breast cancer treatment. Expert Rev Anticancer Ther 2002; 2: 267–75PubMedCrossRef

33.

Lonning P. Pharmacology and clinical experience with exemestane. Expert Opin Investig Drugs 2000; 9: 1897–905PubMedCrossRef

34.

Geisler J. Breast cancer tissue estrogens and their manipulation with aromatase inhibitors and inactivators. J Steroid Biochem Mol Biol 2003; 86: 245–53PubMedCrossRef

35.

Geisler J, Haynes B, Anker G, et al. Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol 2002; 20: 751–7PubMedCrossRef

36.

Lamb HM, Adkins JC. Letrozole: a review of its use in postmen-opausal women with advanced breast cancer. Drugs 1998; 56: 1125–40PubMedCrossRef

37.

Wiseman LR, Adkins JC. Anastrozole: a review of its use in the management of postmenopausal women with advanced breast cancer. Drugs Aging 1998; 13: 321–32PubMedCrossRef

38.

Goss PE, Qi S, Josse RG, et al. The steroidal aromatase inhibitor exemestane prevents bone loss in ovariectomized rats. Bone 2004; 34: 384–92PubMedCrossRef

39.

Lonning PE, Geisler J, Krag LE, et al. 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. J Clin Oncol 2005; 23(22): 5126–37PubMedCrossRef

40.

National Cancer Institute. Phase III randomized adjuvant study of exemestane versus anastrozole in postmenopausal women with receptor-positive primary breast cancer [online]. Available from URL: http://www.cancer.gov/clinicaltrials/CANNCIC-MA27 [Accessed 2008 Oct 13]

41.

Khan MN, Khan AA. Cancer treatment-related bone loss: a review and synthesis of the literature. Curr Oncol 2008; 15 Suppl. 1: S30–40PubMedCrossRef

42.

Chowdhury S, Pickering LM, Ellis PA. Adjuvant aromatase inhibitors and bone health. J Br Menopause Soc 2006; 12: 97–103PubMedCrossRef

43.

McCloskey E. Effects of third-generation aromatase inhibitors on bone. Eur J Cancer 2006; 42: 1044–51PubMedCrossRef

44.

Perez EA. Safety of aromatase inhibitors in the adjuvant setting. Breast Cancer Res Treat 2007; 105 Suppl. 1: 75–89CrossRef

45.

Body JJ, Bergmann P, Boonen S, et al. Management of cancer treatment-induced bone loss in early breast and prostate cancer: a consensus paper of the Belgian Bone Club. Osteoporos Int 2007; 18: 1439–50PubMedCrossRef

46.

Eastell R. Aromatase inhibitors and bone. J Steroid Biochem Mol Biol 2007; 106: 157–61PubMedCrossRef

47.

Coates AS, Keshaviah A, Thurlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol 2007; 25: 486–92PubMedCrossRef

48.

Coombes RC, Kilburn LS, Snowdon CF, et al. Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 2007; 369: 559–70PubMedCrossRef

49.

Forbes JF, Cuzick J, Buzdar A, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 2008; 9: 45–53PubMedCrossRef

50.

Goss PE, Ingle JN, Martino S, et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA. 17. J Natl Cancer Inst 2005; 97: 1262–71CrossRef

51.

Jakesz R, Jonat W, Gnant M, et al. 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. Lancet 2005; 366: 455–62PubMedCrossRef

52.

Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354: 669–83PubMedCrossRef

53.

Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005; 293: 2257–64PubMedCrossRef

54.

Brown JP, Josse RG. 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ 2002; 167 (10 Suppl.): S1–34PubMed

55.

Hillner BE, Ingle JN, Chlebowski RT, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003; 21: 4042–57PubMedCrossRef

56.

Michaud LB, Goodin S. Cancer-treatment-induced bone loss, part 2. Am J Health Syst Pharm 2006; 63: 534–46PubMedCrossRef

57.

Coleman RE, Banks LM, Girgis SI, et al. Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. Lancet Oncol 2007; 8: 119–27PubMedCrossRef

58.

Perez EA, Josse RG, Pritchard KI, et al. 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. J Clin Oncol 2006; 24: 3629–35CrossRef

59.

Jones SE, Cantrell J, Vukelja S, et al. The effects of tamoxifen (T) or exemestane (E) on bone mineral density (BMD) after 1 year of adjuvant treatment of postmenopausal women with early breast cancer [abstract no. 610]. J Clin Oncol 2005; 23: 31S

60.

Eastell R, Hannon RA, Cuzick J, et al. 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). J Bone Miner Res 2006; 21: 1215–23PubMedCrossRef

61.

Khosla S, Riggs BL. Pathophysiology of age-related bone loss and osteoporosis. Endocrinol Metab Clin North Am 2005; 34: 1015–30, xiPubMedCrossRef

62.

Mazzuoli G, Acca M, Pisani D, et al. Annual skeletal balance and metabolic bone marker changes in healthy early postmenopausal women: results of a prospective study. Bone 2000; 26: 381–6PubMedCrossRef

63.

Seeman E. Pathogenesis of bone fragility in women and men. Lancet 2002; 359: 1841–50PubMedCrossRef

64.

Scifert-Klauss V, Link T, Heumann C, et al. Influence of pattern of menopausal transition on the amount of trabecular bone loss: results from a 6-year prospective longitudinal study. Maturitas 2006; 55: 317–24CrossRef

65.

Anonymous. Osteoporosis prevention, diagnosis, and therapy. NIH Consensus Statement 2000; 17: 1–45

66.

Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet 2002; 359: 1929–36PubMedCrossRef

67.

Kanis JA, Burlet N, Cooper C, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2008; 19(4): 399–428PubMedCrossRef

68.

Kanis JA, McCloskey EV, Johansson H, et al. A reference standard for the description of osteoporosis. Bone 2008; 42: 467–75PubMedCrossRef

69.

Kanis JA, Brazier JE, Stevenson M, et al. Treatment of established osteoporosis: a systematic review and cost-utility analysis. Health Technol Assess 2002; 6: 1–146PubMed

70.

Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 1995; 332: 767–73

71.

Cummings SR, Bates D, Black DM. Clinical use of bone densitometry: scientific review. JAMA 2002; 288: 1889–97PubMedCrossRef

72.

Brufsky A, Harker WG, Beck JT, et al. Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer. J Clin Oncol 2007; 25: 829–36PubMedCrossRef

73.

Brufsky A, Bosserman L, Caradonna R, et al. The effect of zoledronic acid on aromatase inhibitor-associated bone loss in postmenopausal woemn with early breast cancer receiving adjuvant letrozole: the Z-FAST study 36-month follow-up [abstract no. 27]. Breast Cancer Res Treat 2007; 106 Suppl. 1: S8

74.

NIH Consensus Development Panel on Osteoporosis Prevention DaT. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285: 785–95CrossRef

75.

Lester JE, Dodwell D, Horsman JM, et al. Current management of treatment-induced bone loss in women with breast cancer treated in the United Kingdom. Br J Cancer 2006; 94: 30–5PubMedCrossRef

76.

Schwartz AL, Winters-Stone K, Gallucci B. Exercise effects on bone mineral density in women with breast cancer receiving adjuvant chemotherapy. Oncol Nurs Forum 2007; 34: 627–33PubMedCrossRef

77.

Demark-Wahnefried W, Aziz NM, Rowland JH, et al. Riding the crest of the teachable moment: promoting long-term health after the diagnosis of cancer. J Clin Oncol 2005; 23(24): 5814–30PubMedCrossRef

78.

Demark-Wahnefried W, Pinto BM, Gritz ER. Promoting health and physical function among cancer survivors: potential for prevention and questions that remain. J Clin Oncol 2006; 24: 5125–31PubMedCrossRef

79.

Russell RG, Watts NB, Ebetino FH, et al. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 2008; 19: 733–9PubMedCrossRef

80.

Bundred NJ, Campbell ID, Davidson N, et al. Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST study results. Cancer 2008; 112(5): 1001–10PubMedCrossRef

81.

Aapro M. Improving bone health in patients with early breast cancer by adding bisphosphonates to letrozole: the Z-ZOEZO-FAST program. Breast 2006; 15 Suppl. 1: S30–40PubMedCrossRef

82.

Von Poznak C, Hannon RA, Clack G, et al. The SABRE (Study of Anastrazole with the Bisphosphonate RisedrontE) study: 12-month analysis [abstract no. 502]. Breast Cancer Res Treat 2007; 106: S37

83.

Bamias A, Kastritis E, Bamia C, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 2005; 23: 8580–7PubMedCrossRef

84.

Diel IJ, Bergner R, Grotz KA. Adverse effects of bisphosphonates: current issues. J Support Oncol 2007; 5: 475–82PubMed

85.

Mehrotra B. Safety profile of intravenous bisphosphonates. Semin Oncol 2007; 34 (6 Suppl. 4): S24–7PubMedCrossRef

86.

Pazianas M, Blumentals WA, Miller PD. Lack of association between oral bisphosphonates and osteonecrosis using jaw surgery as a surrogate marker. Osteoporos Int 2008; 19: 773–9PubMedCrossRef

87.

American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 2007; 65: 369–76CrossRef

88.

Weitzman R, Sauter N, Eriksen EF, et al. Critical review: updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients. Crit Rev Oncol Hematol 2006; 62: 148–52CrossRef

89.

Pazianas M, Miller P, Blumentals WA, et al. A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther 2007; 29: 1548–58PubMedCrossRef

90.

Bobba RS, Beattie K, Parkinson B, et al. Tolerability of different dosing regimens of bisphosphonates for the treatment of osteoporosis and malignant bone disease. Drug Saf 2006; 29: 1133–52PubMedCrossRef

91.

Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007; 356: 1809–22PubMedCrossRef

92.

Schwarz EM, Ritchlin CT. Clinical development of anti-RANKL therapy. Arthritis Res Ther 2007; 9 Suppl. 1: S7PubMedCrossRef

93.

Ellis G, Bone H, Chelebowski R, et al. A phase study of the effect of denosumab therapy on bone mineral density in women receiving aroamatase inhibitors for non metastatic breast cancer [abstract no. 47]. Breast Cancer Res Treat 2007; 101: S1CrossRef

Titel: Aromatase Inhibitor-Associated Bone Loss
Clinical Considerations
verfasst von: Shubham Pant
Dr Charles L. Shapiro
Publikationsdatum: 01.12.2008
Verlag: Springer International Publishing
Erschienen in: Drugs / Ausgabe 18/2008
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI: https://doi.org/10.2165/0003495-200868180-00005

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

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Aromatase Inhibitor-Associated Bone Loss

Clinical Considerations

Abstract

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

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