Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer: An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG. - 2025
Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer: An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG.
Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer. An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG-2.pdf
Aromatase Inhibitor; Bisphosphonate; Breast cancer; Denosumab; Fracture; Osteoporosis; Oncology
Abstract :
[en] [en] BACKGROUND: Women with hormone-responsive breast cancer who receive adjuvant endocrine treatment with aromatase inhibitors (AI) are known to be at higher fracture risk due to a marked increase in bone resorption. In 2017, several interdisciplinary cancer and bone societies involved in the management of women with AI-associated bone loss (AIBL) published a joint position statement comprising evidence-based recommendations and a practical management algorithm for the assessment of fracture risk and optimal treatment of this patient population.
PATIENTS AND METHODS: In order to provide updated recommendations that reflect recent advances in the assessment and management of AIBL since publication of the 2017 joint position statement, a systematic literature review was undertaken to identify relevant studies for analysis, including systematic reviews and meta-analyses. Individual trials identified were assessed for their level of evidence based on design, size, follow-up, and evaluation of safety, as well as the impact of bone directed treatments on breast cancer outcomes.
RESULTS: New evidence was combined with the existing recommendations to provide an updated joint position statement regarding fracture risk assessment and implementation of bone-directed therapy.
CONCLUSION: Current published literature, including recent clinical trial reports, systematic reviews and meta-analyses, continue to affirm the high risk of fractures in women with breast cancer who are receiving adjuvant AI treatment, a risk which has been observed to increase with the commonly used approach of extended duration AI therapy (>5 years). Risk factors for fracture and risk assessment in this patient population as well as the most suitable treatment modalities have been updated. Finally, the influence of bone protective treatments on breast cancer outcomes such as incidence of bone metastasis and breast cancer related overall survival have been included.
Disciplines :
Public health, health care sciences & services
Author, co-author :
Hadji, Peyman; Frankfurt Centre for Bone Health and Endocrinology, Frankfurt, Germany ; Philipps University of Marburg, Marburg, Germany
Aapro, Matty; Cancer Center, Clinique de Genolier, Switzerland
Al-Dagri, Nasser; Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
Alokail, Majed; Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
Biver, Emmanuel; Division of Bone Diseases Geneva University Hospitals and Faculty of Medicine Rue Gabrielle Perret-Gentil, Geneva, Switzerland
Body, Jean-Jacques; CHU Brugmann, Department of Medicine, Free University of Brussels, Brussels, Belgium
Brandi, Maria Luisa; Fondazione FIRMO, Florence, Italy ; Division of Endocrinology and Metabolism, McMaster University, Hamilton, Canada
Brown, Janet; Division of Clinical Medicine and Weston Park Cancer Centre, University of Sheffield, Sheffield, UK
Confavreux, Cyrille; University of Lyon, Bone Metastasis Expert Center (CEMOS) Cancer Institute of Hospices Civils de Lyon, Rheumatology Department, Centre Hospitalier Lyon Sud, Pierre Bénite, France ; Centre for Cancer Research Lyon (CRCL) - UMR INSERM 1052 CNRS 5286, University Claude Bernard Lyon 1, Lyon, France
Cortet, Bernard; Department of Rheumatology, CHU Lille and University of Lille, Lille, France
Drake, Matthew; Metabolic Bone Service, Hospital for Special Surgery, NY, USA
Ebeling, Peter; Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
Eriksen, Erik Fink; Pilestredet Park Specialist Centre and Faculty of Odontology, University of Oslo, Oslo, Norway
Fuleihan, Ghada El-Hajj; Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, Department of Medicine, American University of Beirut, Beirut, Lebanon
Guise, Theresa A; Department of Endocrine Neoplasia and Hormone Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Harvey, Nick ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé ; MRC Lifecourse Epidemiology Centre and NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK ; University Hospital Southampton NHS Foundation Trust, Southampton, UK
Kurth, Andreas; Orthopedic Institute Dr. Baron and Colleagues, Goethe University, Frankfurt am Main, Frankfurt, Germany
Langdahl, Bente; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark ; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Lems, Willem; Department of Rheumatology, Amsterdam UMC, Amsterdam, the Netherlands
Matijevic, Radmila; Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
McCloskey, Eugene; Centre for Metabolic Bone Diseases and the Mellanby Centre for Musculoskeletal Research, Division of Clinical Medicine, School of Medicine & Population Health, University of Sheffield, Sheffield, UK
Nappi, Rossella; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy ; Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause, IRCCS S. Matteo Foundation, Pavia, Italy
Palacios, Santiago; Palacios Clinic for Women's Health, Madrid, Spain
Pfeiler, Georg; Department of Gynecology and Gynecological Oncology, Medical University of Vienna, Vienna, Austria
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique ; Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
Rizzoli, René ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé ; Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
Santini, Daniele; Department of Medical Sciences and Biotechnology, University "Sapienza", UOC Medical Oncology, Rome, Italy
Tuzun, Sansin; Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey
Poznak, Catherine Van; Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA
Villiers, Tobias De; Mediclinic Panorama and Department of Gynecology, Stellenbosch University, Cape Town, South Africa
Zillikens, M Carola; Department of Internal Medicine, Erasmus MC Bone Center, Erasmus University Medical Center, Rotterdam, the Netherlands
Coleman, Robert; Weston Park Hospital and University of Sheffield, Sheffield, UK
Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer: An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG.
Wilkinson, L., Gathani, T., Understanding breast cancer as a global health concern. Br. J. Radiol., 95(1130), 2022, 20211033.
Ginsburg, O., Bray, F., Coleman, M.P., Vanderpuye, V., Eniu, A., Kotha, S.R., Sarker, M., Huong, T.T., Allemani, C., Dvaladze, A., Gralow, J., Yeates, K., Taylor, C., Oomman, N., Krishnan, S., Sullivan, R., Kombe, D., Blas, M.M., Parham, G., Kassami, N., Conteh, L., The global burden of women's cancers: a grand challenge in global health. Lancet, 2016.
Organization, 2024.
Caswell-Jin, J.L., Sun, L.P., Munoz, D., Lu, Y., Li, Y., Huang, H., Hampton, J.M., Song, J., Jayasekera, J., Schechter, C., Alagoz, O., Stout, N.K., Trentham-Dietz, A., Lee, S.J., Huang, X., Mandelblatt, J.S., Berry, D.A., Kurian, A.W., Plevritis, S.K., Analysis of Breast Cancer Mortality in the US-1975 to 2019. JAMA 331:3 (2024), 233–241.
Duffy, S., Vulkan, D., Cuckle, H., Parmar, D., Sheikh, S., Smith, R., Evans, A., Blyuss, O., Johns, L., Ellis, I., Sasieni, P., Wale, C., Myles, J., Moss, S., Annual mammographic screening to reduce breast cancer mortality in women from age 40 years: long-term follow-up of the UK Age RCT. Health Technol. Assess. 24:55 (2020), 1–24.
Diana, A., Carlino, F., Giunta, E.F., Franzese, E., Guerrera, L.P., Di Lauro, V., Ciardiello, F., Daniele, B., Orditura, M., Cancer Treatment-Induced Bone Loss (CTIBL): state of the art and proper management in breast cancer patients on endocrine therapy. Curr. Treat. Options Oncol., 22(5), 2021, 45.
Gold, T., Williams, S.A., Weiss, R.J., Wang, Y., Watkins, C., Carroll, J., Middleton, C., Silverman, S., Impact of fractures on quality of life in patients with osteoporosis: a US cross-sectional survey. J Drug Assess 8:1 (2019), 175–183.
Kuba, S., Niimi, R., Chiba, K., Matsumoto, M., Hara, Y., Fukushima, A., Tanaka, A., Akashi, M., Morita, M., Inamasu, E., Otsubo, R., Kanetaka, K., Osaki, M., Matsumoto, K., Eguchi, S., Chemotherapy effects on bone mineral density and microstructure in women with breast cancer. J. Bone Miner. Metab. 42:5 (2024), 591–599.
Kuba, S., Watanabe, K., Chiba, K., Matsumoto, M., Yamanouchi, K., Fukushima, A., Meng, X., Morita, M., Otsubo, R., Yano, H., Kanetaka, K., Osaki, M., Nagayasu, T., Eguchi, S., Adjuvant endocrine therapy effects on bone mineral density and microstructure in women with breast cancer. J. Bone Miner. Metab. 39:6 (2021), 1031–1040.
Hadji, P., Aapro, M.S., Body, J.J., Gnant, M., Brandi, M.L., Reginster, J.Y., Zillikens, M.C., Gluer, C.C., de Villiers, T., Baber, R., Roodman, G.D., Cooper, C., Langdahl, B., Palacios, S., Kanis, J., Al-Daghri, N., Nogues, X., Eriksen, E.F., Kurth, A., Rizzoli, R., Coleman, R.E., Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. J Bone Oncol 7 (2017), 1–12.
G. Early Breast Cancer Trialists' Collaborative, Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials, Lancet 386(10001) (2015) 1341–1352.
R. Coleman, P. Hadji, J.J. Body, D. Santini, E. Chow, E. Terpos, S. Oudard, O. Bruland, P. Flamen, A. Kurth, C. Van Poznak, M. Aapro, K. Jordan, E.G.C.E.a. clinicalguidelines@esmo.org, Bone health in cancer: ESMO Clinical Practice Guidelines, Ann Oncol 31(12) (2020) 1650–1663.
Burstein, H.J., Lacchetti, C., Griggs, J.J., Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. J. Oncol. Pract. 15:2 (2019), 106–107.
P.A. Francis, G.F. Fleming, I. Lang, E.M. Ciruelos, H.R. Bonnefoi, M. Bellet, A. Bernardo, M.A. Climent, S. Martino, B. Bermejo, H.J. Burstein, N.E. Davidson, C.E. Geyer, Jr., B.A. Walley, J.N. Ingle, R.E. Coleman, B. Muller, F. Le Du, S. Loibl, E.P. Winer, B. Ruepp, S. Loi, M. Colleoni, A.S. Coates, R.D. Gelber, A. Goldhirsch, M.M. Regan, S. Investigators, G. the International Breast Cancer Study, Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT, J Clin Oncol 41(7) (2023) 1370–1375.
Waqas, K., Lima Ferreira, J., Tsourdi, E., Body, J.J., Hadji, P., Zillikens, M.C., Updated guidance on the management of cancer treatment-induced bone loss (CTIBL) in pre- and postmenopausal women with early-stage breast cancer. J Bone Oncol, 28, 2021, 100355.
Kyvernitakis, I., Kostev, K., Hadji, P., The tamoxifen paradox-influence of adjuvant tamoxifen on fracture risk in pre- and postmenopausal women with breast cancer. Osteoporos Int. 29:11 (2018), 2557–2564.
Tseng, O.L., Spinelli, J.J., Gotay, C.C., Ho, W.Y., McBride, M.L., Dawes, M.G., Aromatase inhibitors are associated with a higher fracture risk than tamoxifen: a systematic review and meta-analysis. Ther Adv Musculoskelet Dis 10:4 (2018), 71–90.
Goss, P.E., Ingle, J.N., Ales-Martinez, J.E., Cheung, A.M., Chlebowski, R.T., Wactawski-Wende, J., McTiernan, A., Robbins, J., Johnson, K.C., Martin, L.W., Winquist, E., Sarto, G.E., Garber, J.E., Fabian, C.J., Pujol, P., Maunsell, E., Farmer, P., Gelmon, K.A., Tu, D., Richardson, H., Investigators, N.C.M.S., Exemestane for breast-cancer prevention in postmenopausal women. N. Engl. J. Med. 364:25 (2011), 2381–2391.
Cuzick, J., Sestak, I., Forbes, J.F., Dowsett, M., Knox, J., Cawthorn, S., Saunders, C., Roche, N., Mansel, R.E., von Minckwitz, G., Bonanni, B., Palva, T., Howell, A., I.-I. investigators, anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet 383:9922 (2014), 1041–1048.
Cuzick, J., Sestak, I., Forbes, J.F., Dowsett, M., Cawthorn, S., Mansel, R.E., Loibl, S., Bonanni, B., Evans, D.G., Howell, A., I.-I. investigators, use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial. Lancet 395:10218 (2020), 117–122.
Sestak, I., Blake, G., Patel, R., Cuzick, J., Howell, A., Coleman, R., Eastell, R., Off-treatment bone mineral density changes in postmenopausal women receiving anastrozole for 5 years: 7-year results from the IBIS-II prevention trial. Br. J. Cancer 124:8 (2021), 1373–1378.
F. Borgstrom, L. Karlsson, G. Ortsater, N. Norton, P. Halbout, C. Cooper, M. Lorentzon, E.V. McCloskey, N.C. Harvey, M.K. Javaid, J.A. Kanis, F. International Osteoporosis, Fragility fractures in Europe: burden, management and opportunities, Arch Osteoporos 15(1) (2020) 59.
Xiao, P.L., Cui, A.Y., Hsu, C.J., Peng, R., Jiang, N., Xu, X.H., Ma, Y.G., Liu, D., Lu, H.D., Global, regional prevalence, and risk factors of osteoporosis according to the World Health Organization diagnostic criteria: a systematic review and meta-analysis. Osteoporos Int. 33:10 (2022), 2137–2153.
Abreu, C., Dionísio, M.R., Silva, J.C., Costa, L., Cancer treatment-induced bone loss (CTIBL). Encyclopedia of Endocrine Diseases, 2019, 296–303.
Shapiro, C.L., Bone-modifying agents (BMAs) in breast cancer. Clin. Breast Cancer 21:5 (2021), e618–e630.
Lorentzon, M., Johansson, H., Harvey, N.C., Liu, E., Vandenput, L., McCloskey, E.V., Kanis, J.A., Osteoporosis and fractures in women: the burden of disease. Climacteric 25:1 (2022), 4–10.
Chang, C.H., Chen, S.J., Liu, C.Y., Fracture risk and adjuvant therapies in young breast cancer patients: a population-based study. PLoS One, 10(6), 2015, e0130725.
Lee, Y.K., Lee, E.G., Kim, H.Y., Lee, Y., Lee, S.M., Suh, D.C., Yoo, J.I., Lee, S., Osteoporotic fractures of the spine, hip, and other locations after adjuvant endocrine therapy with aromatase inhibitors in breast cancer patients: a meta-analysis. J. Korean Med. Sci., 35(46), 2020, e403.
Pedersini, R., Amoroso, V., Maffezzoni, F., Gallo, F., Turla, A., Monteverdi, S., Ardine, M., Ravanelli, M., Vassalli, L., Rodella, F., Formenti, A.M., Dalla Volta, A., Simoncini, E.L., Giustina, A., Maroldi, R., Berruti, A., Association of fat body mass with vertebral fractures in postmenopausal women with early breast cancer undergoing adjuvant aromatase inhibitor therapy. JAMA Netw. Open, 2(9), 2019, e1911080.
Goldvaser, H., Barnes, T.A., Seruga, B., Cescon, D.W., Ocana, A., Ribnikar, D., Amir, E., Toxicity of extended adjuvant therapy with aromatase inhibitors in early breast cancer: a systematic review and meta-analysis. J. Natl Cancer Inst., 110(1), 2018.
Qian, X., Li, Z., Ruan, G., Tu, C., Ding, W., Efficacy and toxicity of extended aromatase inhibitors after adjuvant aromatase inhibitors-containing therapy for hormone-receptor-positive breast cancer: a literature-based meta-analysis of randomized trials. Breast Cancer Res. Treat. 179:2 (2020), 275–285.
Martinez, P., Galve, E., Arrazubi, V., Sala, M.A., Fernandez, S., Perez, C.E., Arango, J.F., Torre, I., Impact of an osteoporosis specialized unit on bone health in breast cancer survivals treated with aromatase inhibitors. Reumatol Clin (engl Ed) 15:4 (2019), 211–217.
Leslie, W.D., Martineau, P., Bryanton, M., Lix, L.M., Which is the preferred site for bone mineral density monitoring as an indicator of treatment-related anti-fracture effect in routine clinical practice?. A Registry-Based Cohort Study, Osteoporos Int 30:7 (2019), 1445–1453.
Pedersini, R., Monteverdi, S., Mazziotti, G., Amoroso, V., Roca, E., Maffezzoni, F., Vassalli, L., Rodella, F., Formenti, A.M., Frara, S., Maroldi, R., Berruti, A., Simoncini, E., Giustina, A., Morphometric vertebral fractures in breast cancer patients treated with adjuvant aromatase inhibitor therapy: a cross-sectional study. Bone 97 (2017), 147–152.
Allbritton-King, J.D., Elrod, J.K., Rosenberg, P.S., Bhattacharyya, T., Reverse engineering the FRAX algorithm: clinical insights and systematic analysis of fracture risk. Bone, 159, 2022, 116376.
Leslie, W.D., Morin, S.N., Lix, L.M., Niraula, S., McCloskey, E.V., Johansson, H., Harvey, N.C., Kanis, J.A., Performance of FRAX in women with breast cancer initiating aromatase inhibitor therapy: a registry-based cohort study. J. Bone Miner. Res. 34:8 (2019), 1428–1435.
Prawiradilaga, R.S., Gunmalm, V., Lund-Jacobsen, T., Helge, E.W., Brons, C., Andersson, M., Schwarz, P., FRAX calculated without BMD resulting in a higher fracture risk than that calculated with BMD in women with early breast cancer. J. Osteoporos., 2018, 2018, 4636028.
Harvey, N.C., Gluer, C.C., Binkley, N., McCloskey, E.V., Brandi, M.L., Cooper, C., Kendler, D., Lamy, O., Laslop, A., Camargos, B.M., Reginster, J.Y., Rizzoli, R., Kanis, J.A., Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice. Bone 78 (2015), 216–224.
Rajan, R., Cherian, K.E., Kapoor, N., Paul, T.V., Trabecular bone score-an emerging tool in the management of osteoporosis. Indian J Endocrinol Metab 24:3 (2020), 237–243.
Mariotti, V., Page, D.B., Davydov, O., Hans, D., Hudis, C.A., Patil, S., Kunte, S., Girotra, M., Farooki, A., Fornier, M.N., Assessing fracture risk in early stage breast cancer patients treated with aromatase-inhibitors: an enhanced screening approach incorporating trabecular bone score. J Bone Oncol 7 (2017), 32–37.
Pedrazzoni, M., Casola, A., Verzicco, I., Abbate, B., Vescovini, R., Sansoni, P., Longitudinal changes of trabecular bone score after estrogen deprivation: effect of menopause and aromatase inhibition. J. Endocrinol. Invest. 37:9 (2014), 871–874.
Gazzotti, S., Aparisi Gomez, M.P., Schileo, E., Taddei, F., Sangiorgi, L., Fusaro, M., Miceli, M., Guglielmi, G., Bazzocchi, A., High-resolution peripheral quantitative computed tomography: research or clinical practice?. Br. J. Radiol., 96(1150), 2023, 20221016.
van den Bergh, J.P., Szulc, P., Cheung, A.M., Bouxsein, M., Engelke, K., Chapurlat, R., The clinical application of high-resolution peripheral computed tomography (HR-pQCT) in adults: state of the art and future directions. Osteoporos Int. 32:8 (2021), 1465–1485.
S. Lu, N.R. Fuggle, L.D. Westbury, O.B. M, G. Bevilacqua, K.A. Ward, E.M. Dennison, S. Mahmoodi, M. Niranjan, C. Cooper, Machine learning applied to HR-pQCT images improves fracture discrimination provided by DXA and clinical risk factors, Bone 168 (2023) 116653.
Panagiotakou, A., Yavropoulou, M., Nasiri-Ansari, N., Makras, P., Basdra, E.K., Papavassiliou, A.G., Kassi, E.N., Extra-skeletal effects of bisphosphonates. Metabolism, 110, 2020, 154264.
Kuznik, A., Pazdzierniok-Holewa, A., Jewula, P., Kuznik, N., Bisphosphonates-much more than only drugs for bone diseases. Eur. J. Pharmacol., 866, 2020, 172773.
Reid, I.R., Billington, E.O., Drug therapy for osteoporosis in older adults. Lancet 399:10329 (2022), 1080–1092.
Sing, C.W., Wong, A.Y., Kiel, D.P., Cheung, E.Y., Lam, J.K., Cheung, T.T., Chan, E.W., Kung, A.W., Wong, I.C., Cheung, C.L., Association of alendronate and risk of cardiovascular events in patients with hip fracture. J. Bone Miner. Res. 33:8 (2018), 1422–1434.
Sing, C.W., Kiel, D.P., Hubbard, R.B., Lau, W.C., Li, G.H., Kung, A.W., Wong, I.C., Cheung, C.L., Nitrogen-containing bisphosphonates are associated with reduced risk of pneumonia in patients with hip fracture. J. Bone Miner. Res. 35:9 (2020), 1676–1684.
Wolfe, F., Bolster, M.B., O'Connor, C.M., Michaud, K., Lyles, K.W., Colon-Emeric, C.S., Bisphosphonate use is associated with reduced risk of myocardial infarction in patients with rheumatoid arthritis. J. Bone Miner. Res. 28:5 (2013), 984–991.
Li, Y.Y., Gao, L.J., Zhang, Y.X., Liu, S.J., Cheng, S., Liu, Y.P., Jia, C.X., Bisphosphonates and risk of cancers: a systematic review and meta-analysis. Br. J. Cancer 123:10 (2020), 1570–1581.
Clezardin, P., Mechanisms of action of bisphosphonates in oncology: a scientific concept evolving from antiresorptive to anticancer activities. Bonekey Rep, 2, 2013, 267.
Bouvard, B., Confavreux, C.B., Briot, K., Bonneterre, J., Cormier, C., Cortet, B., Hannoun-Levi, J.M., Hennequin, C., Javier, R.M., Kerbrat, P., Lespessailles, E., Lesur, A., Mayeur, D., Paccou, J., Tremollieres, F., Vieillard, M.H., Debiais, F., French recommendations on strategies for preventing and treating osteoporosis induced by adjuvant breast cancer therapies. Joint Bone Spine 86:5 (2019), 542–553.
Shapiro, C.L., Van Poznak, C., Lacchetti, C., Kirshner, J., Eastell, R., Gagel, R., Smith, S., Edwards, B.J., Frank, E., Lyman, G.H., Smith, M.R., Mhaskar, R., Henderson, T., Neuner, J., Management of osteoporosis in survivors of adult cancers with nonmetastatic disease: ASCO clinical practice guideline. J. Clin. Oncol. 37:31 (2019), 2916–2946.
Eisen, A., Somerfield, M.R., Accordino, M.K., Blanchette, P.S., Clemons, M.J., Dhesy-Thind, S., Dillmon, M.S., D'Oronzo, S., Fletcher, G.G., Frank, E.S., Hallmeyer, S., Makhoul, I., Moy, B., Thawer, A., Wu, J.Y., Van Poznak, C.H., Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: ASCO-OH (CCO) guideline update. J. Clin. Oncol. 40:7 (2022), 787–800.
G. Early Breast Cancer Trialists' Collaborative, R. Coleman, T. Powles, A. Paterson, M. Gnant, S. Anderson, I. Diel, J. Gralow, G. von Minckwitz, V. Moebus, J. Bergh, K.I. Pritchard, J. Bliss, D. Cameron, V. Evans, H. Pan, R. Peto, R. Bradley, R. Gray, Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials, Lancet 386(10001) (2015) 1353–61.
Mei, M., Xiang, Z., Yang, J., Xiang, R., Efficacy of zoledronic acid for prevention of bone loss in early-stage breast cancer patients receiving adjuvant therapy: a meta-analysis of 13 randomized controlled trials. Curr. Probl. Cancer, 44(2), 2020, 100507.
Miyashita, H., Satoi, S., Kuno, T., Cruz, C., Malamud, S., Kim, S.M., Bone modifying agents for bone loss in patients with aromatase inhibitor as adjuvant treatment for breast cancer; insights from a network meta-analysis. Breast Cancer Res. Treat. 181:2 (2020), 279–289.
A. Bassatne, A. Bou Khalil, M. Chakhtoura, A. Arabi, C. Van Poznak, G. El-Hajj Fuleihan, Effect of antiresorptive therapy on aromatase inhibitor induced bone loss in postmenopausal women with early-stage breast cancer: A systematic review and meta-analysis of randomized controlled trials, Metabolism 128 (2022) 154962.
Adams, A., Jakob, T., Huth, A., Monsef, I., Ernst, M., Kopp, M., Caro-Valenzuela, J., Wockel, A., Skoetz, N., Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst. Rev., 7(7), 2024, CD013451.
Mazziotti, G., Pedersini, R., Vena, W., Cosentini, D., Carrone, F., Pigni, S., Simoncini, E.L., Torrisi, R., Zambelli, A., Farina, D., Balzarini, L., Lania, A.G., Berruti, A., Real-world effectiveness of denosumab and bisphosphonates on risk of vertebral fractures in women with breast cancer undergoing treatment with aromatase inhibitors. Calcif. Tissue Int. 111:5 (2022), 466–474.
Ramchand, S.K., Ghasem-Zadeh, A., Hoermann, R., White, S., Yeo, B., Francis, P.A., Xu, C.L.H., Coleman, O., Shore-Lorenti, C., Ebeling, P.R., Zajac, J.D., Seeman, E., Grossmann, M., Denosumab prevents bone loss and microarchitectural deterioration in premenopausal women with breast cancer receiving estradiol suppression therapy: a randomized controlled trial. J. Clin. Oncol., 2024.
Wilson, C., Bell, R., Hinsley, S., Marshall, H., Brown, J., Cameron, D., Dodwell, D., Coleman, R., Adjuvant zoledronic acid reduces fractures in breast cancer patients; an AZURE (BIG 01/04) study. Eur. J. Cancer 94 (2018), 70–78.
Brown, J., Paggiosi, M.A., Rathbone, E., Gregory, W., Bertelli, G., Din, O., McCloskey, E., Dodwell, D., Cameron, D., Eastell, R., Coleman, R., Prolonged bone health benefits for breast cancer patients following adjuvant bisphosphonate therapy: the BoHFAB study. J. Bone Miner. Res. 39:1 (2024), 8–16.
Murdoch, R., Mellar, A., Horne, A.M., Billington, E., Chan, P.L., Gamble, G.D., Reid, I.R., Effect of a three-day course of dexamethasone on acute phase response following treatment with zoledronate: a randomized controlled trial. J. Bone Miner. Res. 38:5 (2023), 631–638.
Jagpal, A., Saag, K.G., How to use bisphosphonates safely and optimally. Rheumatology (Oxford) 57:11 (2018), 1875–1876.
Fatoye, F., Smith, P., Gebrye, T., Yeowell, G., Real-world persistence and adherence with oral bisphosphonates for osteoporosis: a systematic review. BMJ Open, 9(4), 2019, e027049.
Anastasilakis, A.D., Makras, P., Yavropoulou, M.P., Tabacco, G., Naciu, A.M., Palermo, A., Denosumab discontinuation and the rebound phenomenon: a narrative review. J. Clin. Med., 10(1), 2021.
Tsourdi, E., Zillikens, M.C., Meier, C., Body, J.J., Gonzalez Rodriguez, E., Anastasilakis, A.D., Abrahamsen, B., McCloskey, E., Hofbauer, L.C., Guanabens, N., Obermayer-Pietsch, B., Ralston, S.H., Eastell, R., Pepe, J., Palermo, A., Langdahl, B., Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS. J. Clin. Endocrinol. Metab., 2020.
Lu, K.H., Wang, S.I., Yang, S.F., Denosumab withdrawal increases vertebral fracture and mortality risk compared with zoledronate. Eur. J. Endocrinol. 192:3 (2025), 180–190.
Kim, A.S., Girgis, C.M., McDonald, M.M., Osteoclast recycling and the rebound phenomenon following denosumab discontinuation. Curr. Osteoporos. Rep. 20:6 (2022), 505–515.
El-Masri, B.M., Andreasen, C.M., Laursen, K.S., Kofod, V.B., Dahl, X.G., Nielsen, M.H., Thomsen, J.S., Bruel, A., Sorensen, M.S., Hansen, L.J., Kim, A.S., Taylor, V.E., Massarotti, C., McDonald, M.M., You, X., Charles, J.F., Delaisse, J.M., Andersen, T.L., Mapping RANKL- and OPG-expressing cells in bone tissue: the bone surface cells as activators of osteoclastogenesis and promoters of the denosumab rebound effect. Bone Res., 12(1), 2024, 62.
Ferrari, S., Langdahl, B., Mechanisms underlying the long-term and withdrawal effects of denosumab therapy on bone. Nat. Rev. Rheumatol. 19:5 (2023), 307–317.
Persson, R., Hagberg, K.W., Pranschke, E., Vasilakis-Scaramozza, C., Jick, S., Treatment for osteoporosis and risk of osteonecrosis of the jaw among female patients in the United Kingdom clinical practice research datalink. Osteoporos Int. 36:1 (2025), 47–60.
Bedogni, A., Mauceri, R., Fusco, V., Bertoldo, F., Bettini, G., Di Fede, O., Lo Casto, A., Marchetti, C., Panzarella, V., Saia, G., Vescovi, P., Campisi, G., Italian position paper (SIPMO-SICMF) on medication-related osteonecrosis of the jaw (MRONJ). Oral Dis. 30:6 (2024), 3679–3709.
Yarom, N., Van Poznak, C.H., Epstein, J.B., Ottaviani, G., Matsuda, Y., Migliorati, C., Elad, S., MASCC/ISOO clinical practice statement: adjuvant bone-modifying agents in primary breast cancer patients - prevention of medication-related osteonecrosis of the jaw. Support Care Cancer, 32(8), 2024, 547.
Bertoldo, F., Eller-Vainicher, C., Fusco, V., Mauceri, R., Pepe, J., Bedogni, A., Palermo, A., Romeo, U., Guglielmi, G., Campisi, G., Medication related osteonecrosis (MRONJ) in the management of CTIBL in breast and prostate cancer patients. Joint Report by SIPMO AND SIOMMMS, J Bone Oncol, 50, 2025, 100656.
Nicolatou-Galitis, O., Schiodt, M., Mendes, R.A., Ripamonti, C., Hope, S., Drudge-Coates, L., Niepel, D., Van den Wyngaert, T., Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol 127:2 (2019), 117–135.
Black, D.M., Geiger, E.J., Eastell, R., Vittinghoff, E., Li, B.H., Ryan, D.S., Dell, R.M., Adams, A.L., Atypical femur fracture risk versus fragility fracture prevention with bisphosphonates. N. Engl. J. Med. 383:8 (2020), 743–753.
T. Strain, S. Flaxman, R. Guthold, E. Semenova, M. Cowan, L.M. Riley, F.C. Bull, G.A. Stevens, G. Country Data Author, National, regional, and global trends in insufficient physical activity among adults from 2000 to 2022: a pooled analysis of 507 population-based surveys with 5.7 million participants, Lancet Glob Health 12(8) (2024) e1232–e1243.
Green, J.R., Loppnow, A., Long-term bisphosphonate therapy: Benefits and risks. Curr. Osteoporos. Rep. 17:2 (2019), 153–161.
Black, D.M., Rosen, C.J., Schwarz, M., Bisphosphonates and the Treatment of Osteoporosis JAMA 318:24 (2017), 2447–2448.
Coleman, R., Metastasis prevention with bone-targeted agents: a complex interaction between the microenvironment and tumour biology. J. Bone Miner. Metab. 41:3 (2023), 290–300.
J.R. Gralow, W.E. Barlow, A.H.G. Paterson, L. M'Iao J, D.L. Lew, A.T. Stopeck, D.F. Hayes, D.L. Hershman, M.M. Schubert, M. Clemons, C.H. Van Poznak, E.C. Dees, J.N. Ingle, C.I. Falkson, A.D. Elias, M.J. Messino, J.H. Margolis, S.R. Dakhil, H.K. Chew, K.Z. Dammann, J.S. Abrams, R.B. Livingston, G.N. Hortobagyi, Phase III Randomized Trial of Bisphosphonates as Adjuvant Therapy in Breast Cancer: S0307, J Natl Cancer Inst 112(7) (2020) 698–707.
Moretti, L., Richelmi, L., Cosentini, D., Pedersini, R., Grisanti, S., Amoroso, V., Berruti, A., Lagana, M., Adjuvant denosumab for early breast cancer-evidence and controversy. Breast, 78, 2024, 103826.
M. Gnant, G. Pfeiler, P.C. Dubsky, M. Hubalek, R. Greil, R. Jakesz, V. Wette, M. Balic, F. Haslbauer, E. Melbinger, V. Bjelic-Radisic, S. Artner-Matuschek, F. Fitzal, C. Marth, P. Sevelda, B. Mlineritsch, G.G. Steger, D. Manfreda, R. Exner, D. Egle, J. Bergh, F. Kainberger, S. Talbot, D. Warner, C. Fesl, C.F. Singer, B. Austrian, G. Colorectal Cancer Study, Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial, Lancet 386(9992) (2015) 433–43.
Gnant, M., Frantal, S., Pfeiler, G., Steger, G.G., Egle, D., Greil, R., Fitzal, F., Wette, V., Balic, M., Haslbauer, F., Melbinger-Zeinitzer, E., Bjelic-Radisic, V., Artner-Matuschek, S., Kainberger, F., Ritter, M., Rinnerthaler, G., Sevelda, P., Bergh, J., Kacerovsky-Strobl, S., Suppan, C., Brunner, C., Deutschmann, C., Gampenrieder, S.P., Fohler, H., Jakesz, R., Fesl, C., Singer, C., Long-term outcomes of adjuvant denosumab in breast cancer. NEJM Evid, 1(12), 2022, EVIDoa2200162.
Coleman, R., Finkelstein, D.M., Barrios, C., Martin, M., Iwata, H., Hegg, R., Glaspy, J., Perianez, A.M., Tonkin, K., Deleu, I., Sohn, J., Crown, J., Delaloge, S., Dai, T., Zhou, Y., Jandial, D., Chan, A., Adjuvant denosumab in early breast cancer (D-CARE): an international, multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 21:1 (2020), 60–72.
