Aromatase inhibitor-induced bone loss osteosarcopenia in older patients with breast cancer: effects of the RANK/RANKL system's inhibitor denosumab vs. bisphosphonates.
Aromatase inhibitor-induced bone loss
Bisphosphonates
Breast cancer
Inhibitors of RANK/RANKL system
Osteosarcopenia
Journal
Internal and emergency medicine
ISSN: 1970-9366
Titre abrégé: Intern Emerg Med
Pays: Italy
ID NLM: 101263418
Informations de publication
Date de publication:
02 Aug 2024
02 Aug 2024
Historique:
received:
26
01
2024
accepted:
03
07
2024
medline:
3
8
2024
pubmed:
3
8
2024
entrez:
2
8
2024
Statut:
aheadofprint
Résumé
The raising number of older patients who are diagnosed with breast cancer represents a significant medical and societal challenge. Aromatase inhibitors (AI), which are commonly utilized to treat this condition in these patients have significant adverse events on bone and muscle health. Falling estrogen production leads to an increase in RANKL secretion by osteoblasts with accelerated bone remodeling due to osteoclast activity. Furthermore, estrogen deficiency reduces skeletal muscle strength and mass. The humanized monoclonal antibody, denosumab, neutralizes RANKL, thereby inhibiting osteoclast formation, function and survival and ultimately exerting powerful anti-resorptive effects.. In this study, we report on the efficacy of denosumab in mitigating aromatase inhibitor-induced bone loss (AIBL) and sarcopenia in older women with breast cancer. From January 2022 to January 2023, we enrolled 30 patients (female sex, ≥ 65 years) diagnosed with non-metastatic breast cancer undergoing adjuvant endocrine therapy; patients received, as per clinical practice, primary bone prophylaxis with denosumab (60 mg via subcutaneous injection every 6 months) according to oncologic guidelines. This group was matched with 30 patients with non-metastatic breast cancer, who were treated with biphosphonates (BF) therapy (oral alendronate 70 mg/week). For each patient bone mineral density (BMD) and bone quality in terms of trabecular bone score (TBS) in addition to body composition and Relative Skeletal Muscle Index (RSMI) was assessed by bone densitometry at baseline and after one year of treatment. Significant improvements in TBS at the lumbar spine, RSMI and whole-body composition (arms, legs, and trunk) were observed in the denosumab group compared with the BF group. These findings underscore the role of denosumab as an effective strategy in managing AIBL and osteosarcopenia in older women with breast cancer and undergoing adjuvant endocrine therapy, which is crucial for improving quality of life, preventing functional decline, and optimizing treatment outcomes.
Identifiants
pubmed: 39095675
doi: 10.1007/s11739-024-03725-1
pii: 10.1007/s11739-024-03725-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).
Références
Rahib L, Wehner MR, Matrisian LM, Nead KT (2021) Estimated projection of US cancer incidence and death to 2040. JAMA Netw Open. 4(4):e214708. https://doi.org/10.1001/jamanetworkopen.2021.4708
doi: 10.1001/jamanetworkopen.2021.4708
pubmed: 33825840
pmcid: 8027914
Lodi M et al (2017) Breast cancer in elderly women and altered clinico-pathological characteristics: a systematic review. Breast Cancer Res Treat 166(3):657–668. https://doi.org/10.1007/s10549-017-4448-5
doi: 10.1007/s10549-017-4448-5
pubmed: 28803352
Eppenberger-Castori S et al (2002) Age-associated biomarker profiles of human breast cancer. Int J Biochem Cell Biol 34(11):1318–1330. https://doi.org/10.1016/s1357-2725(02)00052-3
doi: 10.1016/s1357-2725(02)00052-3
pubmed: 12200028
Carli P et al (2012) Target therapy in elderly breast cancer patients. Crit Rev Oncol Hematol 83(3):422–431. https://doi.org/10.1016/j.critrevonc.2011.12.004
doi: 10.1016/j.critrevonc.2011.12.004
pubmed: 22257652
Bjarnason NH, Hitz M, Jorgensen NR, Vestergaard P (2008) Adverse bone effects during pharmacological breast cancer therapy. Acta Oncol 47(4):747–754. https://doi.org/10.1080/02841860802001467
doi: 10.1080/02841860802001467
pubmed: 18465344
Gnant M et al (2015) Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 386(9992):433–443. https://doi.org/10.1016/S0140-6736(15)60995-3
doi: 10.1016/S0140-6736(15)60995-3
pubmed: 26040499
M S LeBoff et al.,”The clinician's guide to prevention and treatment of osteoporosis”, Osteoporos Int. 2022 Oct;33(10):2049–2102. https://doi.org/10.1007/s00198-021-05900-y . Epub 2022 Apr 28, https://doi.org/10.1007/s00198-021-05900-y
Hadji P et al (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. https://doi.org/10.1016/j.jbo.2017.03.001
doi: 10.1016/j.jbo.2017.03.001
pubmed: 28413771
pmcid: 5384888
Taiwan J (2018) A study of the value of trabecular bone score in fracture risk assessment of postmenopausal women. Obstet Gynecol. 57(3):389–393. https://doi.org/10.1016/j.tjog.2018.04.011
doi: 10.1016/j.tjog.2018.04.011
Qaseem A, Forciea MA, McLean RM, Denberg TD, Barry MJ, Cooke M, Fitterman N, Harris RP, Humphrey LL, Kansagara D, McLean RM, Mir TP, Schünemann HJ (2017) Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians (in Eng). Ann Intern Med 166:818–839. https://doi.org/10.7326/m15-1361
doi: 10.7326/m15-1361
pubmed: 28492856
Papapoulos S, Chapurlat R, Libanati C, Brandi ML, Brown JP et al (2012) Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension (in Eng). J Bone Miner Res 27:694–701. https://doi.org/10.1002/jbmr.1479
doi: 10.1002/jbmr.1479
pubmed: 22113951
Gnant M et al (2015) Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial (in Eng). Lancet 386:433–443
doi: 10.1016/S0140-6736(15)60995-3
pubmed: 26040499
Baron R et al (2011) Denosumab and bisphosphonates: different mechanisms of action and effects. Bone. 201148:677–692
doi: 10.1016/j.bone.2010.11.020
Marcadet L et al (2022) The roles of RANK/RANKL/OPG in cardiac, skeletal, and smooth muscles in health and disease. Front Cell Dev Biol. 26(10):903657. https://doi.org/10.3389/fcell.2022.903657
doi: 10.3389/fcell.2022.903657
Hadji P, Coleman RE, Wilson C et al (2016) Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European panel. Ann Oncol 27:379–390
doi: 10.1093/annonc/mdv617
pubmed: 26681681
Sözen T, Özışık L, Başaran N (2017) An overview and management of osteoporosis. Eur J Rheumatol 4:46–56
doi: 10.5152/eurjrheum.2016.048
pubmed: 28293453
Anand A et al (2022) European Working Group on Sarcopenia in Older People (EWGSOP2) criteria with population-based skeletal muscle index best predicts mortality in asians with cirrhosis. J Clin Exp Hepatol 12(1):52–60. https://doi.org/10.1016/j.jceh.2021.03.015
doi: 10.1016/j.jceh.2021.03.015
pubmed: 35068785
Jing Xu et al (2023) The recent progress of endocrine therapy-induced osteoporosis in estrogen-positive breast cancer therapy. Front Oncol. 7(13):1218206. https://doi.org/10.3389/fonc.2023.1218206
doi: 10.3389/fonc.2023.1218206
Cummings SR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 361:756–765. https://doi.org/10.1056/NEJMoa0809493
doi: 10.1056/NEJMoa0809493
pubmed: 19671655
McClung MR et al (2017) Effect of denosumab on trabecular bone score in postmenopausal women with osteoporosis. Osteoporos Int. https://doi.org/10.1007/s00198-017-4140-y
doi: 10.1007/s00198-017-4140-y
pubmed: 28748386
pmcid: 5391373
Di Gregorio S et al (2015) Comparison between different bone treatments on areal bone mineral density (aBMD) and bone microarchitectural texture as assessed by the trabecular bone score (TBS). Bone. 75:138–43. https://doi.org/10.1016/j.bone.2014.12.062
doi: 10.1016/j.bone.2014.12.062
pubmed: 25571842
Kirk B et al (2020) Osteosarcopenia: epidemiology, diagnosis, and treatment-facts and numbers. J Cachexia Sarcopenia Muscle. 11(3):609–618. https://doi.org/10.1002/jcsm.12567
doi: 10.1002/jcsm.12567
pubmed: 32202056
pmcid: 7296259
Bonnet N et al (2019) RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass. J Clin Invest. 129(8):3214–3223. https://doi.org/10.1172/JCI125915
doi: 10.1172/JCI125915
pubmed: 31120440
pmcid: 6668701
Slade L et al (2023) Bisphosphonates attenuate age-related muscle decline in Caenorhabditis elegans. J Cachexia Sarcopenia Muscle. 14(6):2613–2622. https://doi.org/10.1002/jcsm.13335
doi: 10.1002/jcsm.13335
pubmed: 37722921
pmcid: 10751425