Real-World Effectiveness of Denosumab and Bisphosphonates on Risk of Vertebral Fractures in Women with Breast Cancer Undergoing Treatment with Aromatase Inhibitors

Gherardo Mazziotti1,2, Rebecca Pedersini3, Walter Vena3,4,5, Deborah Cosentini3, Flaminia Carrone4,6, Stella Pigni4, Edda Simoncini3, Rosalba Torrisi7, Alberto Zambelli7,6, Davide Farina8,9, Luca Balzarini10, Andrea Lania4,6, Alfredo Berruti3,8
1IRCCS Humanitas Research Hospital
2Humanitas University
3Medical Oncology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy
4Endocrinology, Diabetology and Andrology Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy
5Endocrinology and Diabetology Center, Humanitas Gavazzeni-Castelli, Bergamo, Italy
6Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
7Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Italy
8Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
9Radiology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy
10Department of Radiology, IRCCS Humanitas Research Hospital, Rozzano, Italy

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Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA 71:209–249

Hadji P, Aapro MS, Body JJ, Gnant M, Brandi ML, Reginster JY, Zillikens MC, Glüer CC, de Villiers T, Baber R, Roodman GD, Cooper C, Langdahl B, Palacios S, Kanis J, Al-Daghri N, Nogues X, Eriksen EF, Kurth A, Rizzoli R, Coleman RE (2017) 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 7:1–12

(EBCTCG) EBCTCG (2015) Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet (London, England) 386:1341–1352

Mazziotti G, Canalis E, Giustina A (2010) Drug-induced osteoporosis: mechanisms and clinical implications. Am J Med 123:877–884

Hadji P (2009) Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis. Crit Rev Oncol Hematol 69:73–82

Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet (London, England) 365:60–62

Lems WF, Paccou J, Zhang J, Fuggle NR, Chandran M, Harvey NC, Cooper C, Javaid K, Ferrari S, Akesson KE (2021) Vertebral fracture: epidemiology, impact and use of DXA vertebral fracture assessment in fracture liaison services. Osteoporos Int 32:399–411

Pedersini R, Monteverdi S, Mazziotti G, Amoroso V, Roca E, Maffezzoni F, Vassalli L, Rodella F, Formenti AM, Frara S, Maroldi R, Berruti A, Simoncini E, Giustina A (2017) Morphometric vertebral fractures in breast cancer patients treated with adjuvant aromatase inhibitor therapy: a cross-sectional study. Bone 97:147–152

Adachi JD, Adami S, Gehlbach S, Anderson FA Jr, Boonen S, Chapurlat RD, Compston JE, Cooper C, Delmas P, Díez-Pérez A, Greenspan SL, Hooven FH, LaCroix AZ, Lindsay R, Netelenbos JC, Wu O, Pfeilschifter J, Roux C, Saag KG, Sambrook PN, Silverman S, Siris ES, Nika G, Watts NB (2010) Impact of prevalent fractures on quality of life: baseline results from the global longitudinal study of osteoporosis in women. Mayo Clin Proc 85:806–813

Jalava T, Sarna S, Pylkkänen L, Mawer B, Kanis JA, Selby P, Davies M, Adams J, Francis RM, Robinson J, McCloskey E (2003) Association between vertebral fracture and increased mortality in osteoporotic patients. J Bone Miner Res 18:1254–1260

Shapiro CL, Van Poznak C, Lacchetti C, Kirshner J, Eastell R, Gagel R, Smith S, Edwards BJ, Frank E, Lyman GH, Smith MR, Mhaskar R, Henderson T, Neuner J (2019) Management of osteoporosis in survivors of adult cancers with nonmetastatic disease: ASCO clinical practice guideline. J Clin Oncol 37:2916–2946

Miyashita H, Satoi S, Kuno T, Cruz C, Malamud S, Kim SM (2020) 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 181:279–289

Bassatne A, Bou Khalil A, Chakhtoura M, Arabi A, Van Poznak C, El-Hajj Fuleihan G (2021) 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 128:154962

von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet (London, England) 370:1453–1457

Rossini M, Adami S, Bertoldo F, Diacinti D, Gatti D, Giannini S, Giusti A, Malavolta N, Minisola S, Osella G, Pedrazzoni M, Sinigaglia L, Viapiana O, Isaia GC (2016) Guidelines for the diagnosis, prevention and management of osteoporosis. Reumatismo 68:1–39

Dalla Volta A, Mazziotti G, Maffezzoni F, Grisanti S, Palumbo C, Pedersini R, Maroldi R, Berruti A (2020) Bone mineral density and FRAX score may not predict fracture risk in patients with cancer undergoing hormone deprivation therapies. J Clin Oncol 38:3363–3366

Mazziotti G, Vena W, Pedersini R, Piccini S, Morenghi E, Cosentini D, Zucali P, Torrisi R, Sporeni S, Simoncini EL, Maroldi R, Balzarini L, Lania AG, Berruti A (2022) Prediction of vertebral fractures in cancer patients undergoing hormone deprivation therapies: reliability of who fracture risk assessment tool (frax) and bone mineral density in real-life clinical practice. J Bone Oncol 33:100421

Clark EM, Carter L, Gould VC, Morrison L, Tobias JH (2014) Vertebral fracture assessment (VFA) by lateral DXA scanning may be cost-effective when used as part of fracture liaison services or primary care screening. Osteoporos Int 25:953–964

Griffith JF, Genant HK (2012) New advances in imaging osteoporosis and its complications. Endocrine 42:39–51

Engelke K, Stampa B, Steiger P, Fuerst T, Genant HK (2019) Automated quantitative morphometry of vertebral heights on spinal radiographs: comparison of a clinical workflow tool with standard 6-point morphometry. Arch Osteoporos 14:18

Crans GG, Genant HK, Krege JH (2005) Prognostic utility of a semiquantitative spinal deformity index. Bone 37:175–179

Schousboe JT, Shepherd JA, Bilezikian JP, Baim S (2013) Executive summary of the 2013 international society for clinical densitometry position development conference on bone densitometry. J Clin Densitom 16:455–466

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 19:385–397

Lindsay R, Pack S, Li Z (2005) Longitudinal progression of fracture prevalence through a population of postmenopausal women with osteoporosis. Osteoporos Int 16:306–312

Mirza F, Canalis E (2015) Management of endocrine disease: secondary osteoporosis: pathophysiology and management. Eur J Endocrinol 173:R131-151

Pedersini R, Amoroso V, Maffezzoni F, Gallo F, Turla A, Monteverdi S, Ardine M, Ravanelli M, Vassalli L, Rodella F, Formenti AM, Dalla Volta A, Simoncini EL, Giustina A, Maroldi R, Berruti A (2019) Association of fat body mass with vertebral fractures in postmenopausal women with early breast cancer undergoing adjuvant aromatase inhibitor therapy. JAMA Netw Open 2:e1911080

Mazziotti G, Lania AG, Canalis E (2022) Skeletal disorders associated with the growth hormone-insulin-like growth factor 1 axis. Nat Rev Endocrinol. https://doi.org/10.1038/s41574-022-00649-8

Lu H, Lei X, Zhao H, Elting L, Siricilla M, Ursani MA, Giordano SH, Suarez-Almazor M (2021) Bone mineral density at the time of initiating aromatase inhibitor therapy is associated with decreased fractures in women with breast cancer. J Bone Miner Res 36:861–871

Confavreux CB, Fontana A, Guastalla JP, Munoz F, Brun J, Delmas PD (2007) Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prev Bisphosphonates Bone 41:346–352

Pineda-Moncusí M, Garcia-Giralt N, Diez-Perez A, Servitja S, Tusquets I, Prieto-Alhambra D, Nogués X (2020) Increased fracture risk in women treated with aromatase inhibitors versus tamoxifen: beneficial effect of bisphosphonates. J Bone Miner Res 35:291–297

Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, Wette V, Balic M, Haslbauer F, Melbinger E, Bjelic-Radisic V, Artner-Matuschek S, Fitzal F, Marth C, Sevelda P, Mlineritsch B, Steger GG, Manfreda D, Exner R, Egle D, Bergh J, Kainberger F, Talbot S, Warner D, Fesl C, Singer CF (2015) Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet (London, England) 386:433–443

Sun S, Wang F, Dou H, Zhang L, Li J (2016) Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole. Onco Targets Ther 9:6029–6036

Eidtmann H, de Boer R, Bundred N, Llombart-Cussac A, Davidson N, Neven P, von Minckwitz G, Miller J, Schenk N, Coleman R (2010) Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST Study. Ann Oncol 21:2188–2194

Monda V, Lupoli GA, Messina G, Peluso R, Panico A, Villano I, Salerno M, Sessa F, Marciello F, Moscatelli F, Valenzano A, Molino L, Lupoli R, Fonderico F, Tortora A, Pisano A, Ruberto M, Gabriella M, Cavaliere G, Trinchese G, Mollica MP, Cipolloni L, Cibelli G, Monda M, Lupoli G, Messina A (2017) Improvement of bone physiology and life quality due to association of risedronate and anastrozole. Front Pharmacol 8:632

Buch-Larsen K, Jørgensen NR, Jensen LT, Andersson M, Schwarz P (2021) Denosumab vs. zoledronic acid treatment in post-menopausal breast cancer: a 2-year prospective observational study. Scand J Clin Lab Invest 81:425–431

van de Glind EM, Willems HC, Eslami S, Abu-Hanna A, Lems WF, Hooft L, de Rooij SE, Black DM, van Munster BC (2016) Estimating the time to benefit for preventive drugs with the statistical process control method: an example with alendronate. Drugs Aging 33:347–353

Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822

Barrionuevo P, Kapoor E, Asi N, Alahdab F, Mohammed K, Benkhadra K, Almasri J, Farah W, Sarigianni M, Muthusamy K, Al Nofal A, Haydour Q, Wang Z, Murad MH (2019) Efficacy of pharmacological therapies for the prevention of fractures in postmenopausal women: a network meta-analysis. J Clin Endocrinol Metab 104:1623–1630

Jacob L, Kostev K, Hadji P (2017) Prevalence of bisphosphonate therapy in women with breast cancer treated with aromatase inhibitors in Germany. Int J Clin Pharmacol Ther 55:394–396

Diacinti D, Del Fiacco R, Pisani D, Todde F, Cattaruzza MS, Diacinti D, Arima S, Romagnoli E, Pepe J, Cipriani C, Minisola S (2012) Diagnostic performance of vertebral fracture assessment by the lunar iDXA scanner compared to conventional radiography. Calcif Tissue Int 91:335–342

Szulc P (2018) Bone turnover: biology and assessment tools. Best practice & research. Clin Endocrinol Metab 32:725–738

Tsourdi E, Langdahl B, Cohen-Solal M, Aubry-Rozier B, Eriksen EF, Guañabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Zillikens MC (2017) Discontinuation of denosumab therapy for osteoporosis: a systematic review and position statement by ECTS. Bone 105:11–17

Osella G, Puglisi S, Alì A, Reimondo G, Terzolo M (2021) Multiple rebound-associated vertebral fractures after denosumab discontinuation: is prompt antiresorptive therapy always recommended, even when the risk of fracture seems low? A case report. Endocr Metab Immune Disord Drug Targets 21:2303–2306