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. 2024 Nov;19(8):2193-2199.
doi: 10.1007/s11739-024-03725-1. Epub 2024 Aug 2.

Aromatase inhibitor-induced bone loss osteosarcopenia in older patients with breast cancer: effects of the RANK/RANKL system's inhibitor denosumab vs. bisphosphonates

Andrea Casabella #  1 , Francesca Paladin #  2 , Claudia Bighin  3 , Silvia Ottaviani  2   3 , Cristina Marelli  4 , Marta Ponzano  4 , Alessio Signori  4 , Giuseppe Murdaca  5 , Maurizio Cutolo  3   6 , Luigi Molfetta  7 , Alessio Nencioni  2   3 , Sabrina Paolino #  8   9 , Lucia Del Mastro #  10   11 , Fiammetta Monacelli #  2   3
Affiliations

Aromatase inhibitor-induced bone loss osteosarcopenia in older patients with breast cancer: effects of the RANK/RANKL system's inhibitor denosumab vs. bisphosphonates

Andrea Casabella et al. Intern Emerg Med. 2024 Nov.

Abstract

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.

Keywords: Aromatase inhibitor-induced bone loss; Bisphosphonates; Breast cancer; Inhibitors of RANK/RANKL system; Osteosarcopenia.

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Conflict of interest statement

Declarations. Conflict of interest: All authors have no competing interests with any organization or entity with a financial interest in competition with the subject, matter or materials discussed in the manuscript. Ethical approval and consent to participate: This study was conducted in accordance with the Ethics Committee. Informed consent: Informed consent was waived because of the retrospective nature of the study and the analysis used anonymous clinical data.

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