Prevention of bone loss with risedronate in breast cancer survivors: a randomized, controlled clinical trial
Tóm tắt
In postmenopausal women with low bone mass and hormone-receptor-positive breast cancer on an aromatase inhibitor, risedronate maintained skeletal health assessed by bone density and turnover markers. Women with the greatest decreases in bone turnover markers at 12 months had the greatest increases in bone density at 24 months. Aromatase inhibitors (AIs), adjuvant endocrine therapy for postmenopausal women with hormone-receptor-positive breast cancer, are associated with bone loss and fractures. Our objectives were to determine if (1) oral bisphosphonate therapy can prevent bone loss in women on an AI and (2) early changes in bone turnover markers (BTM) can predict later changes in bone mineral density (BMD). We conducted a 2-year double-blind, placebo-controlled, randomized trial in 109 postmenopausal women with low bone mass on an AI (anastrozole, letrozole, or exemestane) for hormone-receptor-positive breast cancer. Participants were randomized to once weekly risedronate 35 mg or placebo, and all received calcium plus vitamin D. The main outcome measures included BMD, BTM [carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type 1 procollagen (P1NP)], and safety. Eighty-seven percent completed 24 months. BMD increased more in the active treatment group compared to placebo with an adjusted difference at 24 months of 3.9 ± 0.7 percentage points at the spine and 3.2 ± 0.5 percentage points at the hip (both p < 0.05). The adjusted difference between the active treatment and placebo groups were 0.09 ± 0.04 nmol/LBCE for CTX and 23.3 ± 4.8 μg/mL for P1NP (both p < 0.05). Women with greater 12-month decreases in CTX and P1NP in the active treatment group had a greater 24-month increase in spinal BMD (p < 0.05). The oral therapy was safe and well tolerated. In postmenopausal women with low bone mass and breast cancer on an AI, the oral bisphosphonate risedronate maintained skeletal health.
Tài liệu tham khảo
Becker T, Lipscombe L, Narod S, Simmons C, Anderson GM, Rochon PA (2012) Systematic review of bone health in older women treated with aromatase inhibitors for early-stage breast cancer. J Am Geriatr Soc 60(9):1761–1767. doi:10.1111/j.1532-5415.2012.04107.x
Bauer M, Bryce J, Hadji P (2012) Aromatase inhibitor-associated bone loss and its management with bisphosphonates in patients with breast cancer. Breast Cancer (Dove Medical Press) 4:91–101. doi:10.2147/bctt.s29432
Hadji P (2010) Guidelines for osteoprotection in breast cancer patients on an aromatase inhibitor. Breast Care (Basel, Switzerland) 5(5):290–296. doi:10.1159/000321426
Greenspan SL, Brufsky A, Lembersky BC, Bhattacharya R, Vujevich KT, Perera S et al (2008) Risedronate prevents bone loss in breast cancer survivors: a 2 year, randomized, double-blind, placebo-controlled clinical trial. J Clin Oncol 26(16):2644–2652. doi:10.1200/JCO.2007.15.2967
Brufsky AM, Harker WG, Beck JT, Bosserman L, Vogel C, Seidler C et al (2012) Final 5-year results of Z-FAST trial: adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole. Cancer 118(5):1192–1201. doi:10.1002/cncr.26313
Llombart A, Frassoldati A, Paija O, Sleeboom HP, Jerusalem G, Mebis J et al (2012) Immediate Administration of zoledronic acid reduces aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer: 12-month analysis of the E-ZO-FAST trial. Clin Breast Cancer 12(1):40–48. doi:10.1016/j.clbc.2011.08.002
Gnant M, Mlineritsch B, Luschin-Ebengreuth G, Kainberger F, Kassmann H, Piswanger-Solkner JC 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):840–849. doi:10.1016/s1470-2045(08)70204-3
Van Poznak C, Hannon RA, Mackey JR, Campone M, Apffelstaedt JP, Clack G et al (2010) Prevention of aromatase inhibitor-induced bone loss using risedronate: the SABRE trial. J Clin Oncol 28(6):967–975. doi:10.1200/jco.2009.24.5902
Markopoulos C, Tzoracoleftherakis E, Koukouras D, Venizelos B, Zobolas V, Misitzis J et al (2012) Age effect on bone mineral density changes in breast cancer patients receiving anastrozole: results from the ARBI prospective clinical trial. J Cancer Res Clin Oncol 138(9):1569–1577. doi:10.1007/s00432-012-1233-z
Van Poznak C (2010) Managing bone mineral density with oral bisphosphonate therapy in women with breast cancer receiving adjuvant aromatase inhibition. Breast Cancer Res 12(3):110. doi:10.1186/bcr2584
Markopoulos C, Tzoracoleftherakis E, Polychronis A, Venizelos B, Dafni U, Xepapadakis G et al (2010) Management of anastrozole-induced bone loss in breast cancer patients with oral risedronate: results from the ARBI prospective clinical trial. Breast Cancer Res 12(2):R24. doi:10.1186/bcr2565
Sestak I, Singh S, Cuzick J, Blake GM, Patel R, Gossiel F et al (2014) Changes in bone mineral density at 3 years in postmenopausal women receiving anastrozole and risedronate in the IBIS-II bone substudy: an international, double-blind, randomised, placebo-controlled trial. Lancet Oncol 15(13):1460–1468. doi:10.1016/s1470-2045(14)71035-6
Sergi G, Pintore G, Falci C, Veronese N, Berton L, Perissinotto E et al (2012) Preventive effect of risedronate on bone loss and frailty fractures in elderly women treated with anastrozole for early breast cancer. J Bone Miner Metab 30(4):461–467. doi:10.1007/s00774-011-0341-1
Lester JE, Dodwell D, Purohit OP, Gutcher SA, Ellis SP, Thorpe R et al (2008) Prevention of anastrozole-induced bone loss with monthly oral ibandronate during adjuvant aromatase inhibitor therapy for breast cancer. Clin Cancer Res 14(19):6336–6342. doi:10.1158/1078-0432.ccr-07-5101
Henry NL, Azzouz F, Desta Z, Li L, Nguyen AT, Lemler S et al (2012) Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol 30(9):936–942. doi:10.1200/jco.2011.38.0261
Briot K, Tubiana-Hulin M, Bastit L, Kloos I, Roux C (2010) Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer: the ATOLL (articular tolerance of letrozole) study. Breast Cancer Res Treat 120(1):127–134. doi:10.1007/s10549-009-0692-7
Dawson-Hughes B, Jacques P, Shipp C (1987) Dietary calcium intake and bone loss from the spine in healthy postmenopausal women. Am J Clin Nutr 46:685–687
Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, Del Valle HB (eds) (2011) Dietary reference intakes for calcium and vitamin D. National Academies Press (US), Washington (DC)
Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S et al (2014) Clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int 25(10):2359–2381. doi:10.1007/s00198-014-2794-2
Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 4:368–381
Varney LF, Parker RA, Vincelette A, Greenspan SL (1999) Classification of osteoporosis and osteopenia in postmenopausal women is dependent on site-specific analysis. J Clin Densitom 2:275–283
Coleman RE, Banks LM, Girgis SI, Vrdoljak E, Fox J, Porter LS, et al (2005) Skeletal effect of exemestane in the Intergroup Exemestane Study (IES) 2 year bone mineral density (BMD) and bone biomarker data. Presented at 28th Annual San Antonio Breast Cancer Symposium
Howell A (2003) Effect of anastrozole on bone mineral density: 2-year results of the 'Arimidex' (anastrozole), Tamoxifen, Alone or in Combination (ATAC) trial. Presented at the San Antonio Breast Cancer Symposium 2003
Lonning PE, Geisler J, Krag LE, Erikstein B, Bremnes Y, Hagen AI et al (2005) 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 23:5126–5137
Brufsky A, Harker W, Beck J, Carroll R, Tan-Chiu E, Seidler C, et al (2005) Zoledronic acid (ZA) effectively inhibits cancer treatment-induced bone loss (CTIBL) in postmenopausal women (PMW) with early breast cancer (BCa) receiving adjuvant Letrozole (Let): 12 mos BMD results of the Z-FAST trial. Presented at the annual meeting of the American Society of Clinical Oncology (ASCO)
Rubin DB (1987) Multiple imputation for nonresponse in surveys. John Wiley & Sons, Ltd., New York, NY
Brufsky AM, Bosserman LD, Caradonna RR, Haley BB, Jones CM, Moore HC et al (2009) Zoledronic acid effectively prevents aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST study 36-month follow-up results. Clin Breast Cancer 9(2):77–85. doi:10.3816/CBC.2009.n.015
Valachis A, Polyzos NP, Coleman RE, Gnant M, Eidtmann H, Brufsky AM et al (2013) Adjuvant therapy with zoledronic acid in patients with breast cancer: a systematic review and meta-analysis. Oncologist 18(4):353–361. doi:10.1634/theoncologist.2012-0261
Lonning PE, Eikesdal HP (2013) Aromatase inhibition 2013: clinical state of the art and questions that remain to be solved. Endocr Relat Cancer 20(4):R183–R201. doi:10.1530/erc-13-0099
Mathew A, Brufsky A (2014) Bisphosphonates in breast cancer. Int J Cancer. doi:10.1002/ijc.28965
Ellis GK, Bone HG, Chlebowski R, Paul D, Spadafora S, Fan M et al (2009) Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study. Breast Cancer Res Treat 118(1):81–87. doi:10.1007/s10549-009-0352-y
Ellis GK, Bone HG, Chlebowski R, Paul D, Spadafora S, Smith J et al (2008) Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 26(30):4875–4882. doi:10.1200/jco.2008.16.3832
Greenspan SL, Parker RA, Ferguson L, Rosen HN, Maitland-Ramsey L, Karpf DB (1998) Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial. J Bone Miner Res 13:1431–1438
Greenspan SL, Rosen HN, Parker RA (2000) Early changes in serum N-telopeptide and C-telopeptide cross-linked collagen type 1 predict long-term response to alendronate therapy in elderly women. J Clin Endocrinol Metab 85:3537–3540