Background: In recent years, a steady increase has been observed in the prevalence of elderly women affected by hormone-sensitive breast cancer. The standard therapy for this condition—aromatase inhibitors—is well known for its adverse effects on bone metabolism, which are particularly pronounced in postmenopausal women who are already characterized by skeletal fragility. Concurrently, growing attention has been devoted to to muscle health and to the concomitant presence of alterations in both bone and muscle metabolism, which in certain conditions lead to a state known as osteosarcopenia—a syndrome associated with adverse clinical outcomes such as increased risk of falls, fractures, and disability. Among the therapeutic strategies recommended by current guidelines to prevent or counteract Cancer Treatment–Induced Bone Loss (CTIBL), denosumab, a potent antiresorptive agent, plays a pivotal role. However, its potential effects on muscle tissue have been investigated only recently, with heterogeneous and sometimes conflicting results. Moreover, studies conducted in elderly patients with breast cancer treated with denosumab often lack data on geriatric phenotypes and comprehensive geriatric assessment (CGA)—both essential for appropriate clinical characterization of this population. Objectives: To evaluate the impact of denosumab on bone and muscle health in elderly women with breast cancer receiving aromatase inhibitors, to assess its potential effects on other geriatric domains, including frailty, to analyse treatment adherence rates and the main causes of non-compliance. Methods: We conducted a retrospective observational study involving patients attending the Oncogeriatrics Outpatient Clinic at IRCCS San Martino Hospital (Genoa) within the “Breast and Bone” project between April 2021 and September 2024. Inclusion criteria: women aged ≥65 years, with non-metastatic breast cancer under aromatase inhibitor therapy, followed for at least one year by our clinic, and who provided informed consent. Participants were divided into two subgroups: “Denosumab” group- patients who had initiated and continued denosumab treatment for at least one year, and “No Denosumab” group- patients who had never initiated denosumab or had received only one injection. For both groups, we analysed bone mineral density (BMD) in patients with two Dual Energy X-ray Absorptiometry (DXA) scans—one prior to therapy initiation and another after at least one year of treatment with denosumab. Collected data included medical history, osteoporosis risk factors, DXA T-scores for lumbar spine, total hip and femoral neck, occurrence of new fractures, biochemical markers of bone turnover when available, therapy-related adverse events, and multidimensional assessment with calculation of the Frailty Index (FI) score. Muscle function was evaluated using handgrip strength (HG) and Timed Up and Go (TUG) tests. Additionally, adherence data and reasons for non-adherence were recorded. Results: Between April 2021 and September 2025, 220 patients were evaluated within the “Breast and Bone” project. Of these, 120 met inclusion criteria: 80 in the “Denosumab” group and 40 in the “No Denosumab” group. The mean age was 76.9 years in both groups. In the “Denosumab” group (n=56 with paired DXA), a significant increase in BMD T-score was observed between baseline and follow-up: lumbar spine: mean +0.38, 95% CI 0.21–0.55 (normalized +0.19, CI 0.11–0.28), total hip: mean +0.33, 95% CI 0.18–0.49 (normalized +0.19, CI 0.11–0.28). In the “No Denosumab” group, a non-significant trend toward BMD decline was detected. The between-group differences in densitometric changes were statistically significant across all DXA sites. No significant variations were observed in muscle strength or gait speed between the two groups. Similarly, no statistically significant differences emerged in frailty trajectories or other CGA domains at 1- and 2-year follow-up. Adherence analysis: among the 40 patients in the “No Denosumab” group, 27 (22.5% of total) never initiated treatment due to: ongoing or planned dental procedures / dentist’s recommendation (7), fear or refusal of new therapies (19), hospitalization or worsening general condition (1). Of the remaining 13 who received only one injection, delays between indication and initiation were attributed to dental issues (3) or patient choice (8); 2 discontinued after the first dose upon dentist’s advice. No major adverse events or fractures were reported. In conclusion, denosumab confirmed its efficacy in improving BMD in elderly women with breast cancer, while its effects on sarcopenia appeared inconclusive, likely reflecting heterogeneity in patient phenotypes.
Denosumab and bone and muscle health in Older Women with Breast Cancer: A Geriatric Perspective
MUZYKA, MARIYA
2026-05-25
Abstract
Background: In recent years, a steady increase has been observed in the prevalence of elderly women affected by hormone-sensitive breast cancer. The standard therapy for this condition—aromatase inhibitors—is well known for its adverse effects on bone metabolism, which are particularly pronounced in postmenopausal women who are already characterized by skeletal fragility. Concurrently, growing attention has been devoted to to muscle health and to the concomitant presence of alterations in both bone and muscle metabolism, which in certain conditions lead to a state known as osteosarcopenia—a syndrome associated with adverse clinical outcomes such as increased risk of falls, fractures, and disability. Among the therapeutic strategies recommended by current guidelines to prevent or counteract Cancer Treatment–Induced Bone Loss (CTIBL), denosumab, a potent antiresorptive agent, plays a pivotal role. However, its potential effects on muscle tissue have been investigated only recently, with heterogeneous and sometimes conflicting results. Moreover, studies conducted in elderly patients with breast cancer treated with denosumab often lack data on geriatric phenotypes and comprehensive geriatric assessment (CGA)—both essential for appropriate clinical characterization of this population. Objectives: To evaluate the impact of denosumab on bone and muscle health in elderly women with breast cancer receiving aromatase inhibitors, to assess its potential effects on other geriatric domains, including frailty, to analyse treatment adherence rates and the main causes of non-compliance. Methods: We conducted a retrospective observational study involving patients attending the Oncogeriatrics Outpatient Clinic at IRCCS San Martino Hospital (Genoa) within the “Breast and Bone” project between April 2021 and September 2024. Inclusion criteria: women aged ≥65 years, with non-metastatic breast cancer under aromatase inhibitor therapy, followed for at least one year by our clinic, and who provided informed consent. Participants were divided into two subgroups: “Denosumab” group- patients who had initiated and continued denosumab treatment for at least one year, and “No Denosumab” group- patients who had never initiated denosumab or had received only one injection. For both groups, we analysed bone mineral density (BMD) in patients with two Dual Energy X-ray Absorptiometry (DXA) scans—one prior to therapy initiation and another after at least one year of treatment with denosumab. Collected data included medical history, osteoporosis risk factors, DXA T-scores for lumbar spine, total hip and femoral neck, occurrence of new fractures, biochemical markers of bone turnover when available, therapy-related adverse events, and multidimensional assessment with calculation of the Frailty Index (FI) score. Muscle function was evaluated using handgrip strength (HG) and Timed Up and Go (TUG) tests. Additionally, adherence data and reasons for non-adherence were recorded. Results: Between April 2021 and September 2025, 220 patients were evaluated within the “Breast and Bone” project. Of these, 120 met inclusion criteria: 80 in the “Denosumab” group and 40 in the “No Denosumab” group. The mean age was 76.9 years in both groups. In the “Denosumab” group (n=56 with paired DXA), a significant increase in BMD T-score was observed between baseline and follow-up: lumbar spine: mean +0.38, 95% CI 0.21–0.55 (normalized +0.19, CI 0.11–0.28), total hip: mean +0.33, 95% CI 0.18–0.49 (normalized +0.19, CI 0.11–0.28). In the “No Denosumab” group, a non-significant trend toward BMD decline was detected. The between-group differences in densitometric changes were statistically significant across all DXA sites. No significant variations were observed in muscle strength or gait speed between the two groups. Similarly, no statistically significant differences emerged in frailty trajectories or other CGA domains at 1- and 2-year follow-up. Adherence analysis: among the 40 patients in the “No Denosumab” group, 27 (22.5% of total) never initiated treatment due to: ongoing or planned dental procedures / dentist’s recommendation (7), fear or refusal of new therapies (19), hospitalization or worsening general condition (1). Of the remaining 13 who received only one injection, delays between indication and initiation were attributed to dental issues (3) or patient choice (8); 2 discontinued after the first dose upon dentist’s advice. No major adverse events or fractures were reported. In conclusion, denosumab confirmed its efficacy in improving BMD in elderly women with breast cancer, while its effects on sarcopenia appeared inconclusive, likely reflecting heterogeneity in patient phenotypes.
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