Fracture Risk Among Older Cancer Survivors Compared With Older Adults Without a History of Cancer

Abstract

ImportanceThe number of cancer survivors living in the US is projected to be 26.1 million by 2040. Cancer survivors may be at increased risk of bone fractures, but research is limited in several important ways.ObjectiveTo investigate the associations of cancer diagnoses, including time since diagnosis and stage at diagnosis, with risks of pelvic, radial, and vertebral fractures (separately and combined) among older cancer survivors and compared with fracture risk among older adults without a history of cancer. Secondarily, to examine differences in risk of fracture stratified by modifiable behaviors, treatment, and cancer type.Design, Setting, and ParticipantsThis longitudinal cohort study used data from 92 431 older adults in the US Cancer Prevention Study II Nutrition Cohort linked with 1999 to 2017 Medicare claims. Data were analyzed from July 15, 2021, to May 3, 2022.ExposuresCancer history, time since cancer diagnosis, and stage at cancer diagnosis.Main Outcomes and MeasuresHazard ratios (HRs) and 95% CIs for the risk of pelvic, radial, vertebral, and total frailty-related fractures were estimated using multivariate Cox proportional hazards regression. Stratification was used for secondary aims.ResultsAmong 92 431 participants (mean [SD] age, was 69.4 [6.0] years, 51 820 [56%] women, and 90 458 [97.9%] White], 12 943 participants experienced a frailty-related bone fracture. Compared with participants without a history of cancer, cancer survivors who were diagnosed 1 to less than 5 years earlier with advanced stage cancer had higher risk of fracture (HR, 2.12; 95% CI, 1.75-2.58). The higher fracture risk in cancer survivors with recent advanced stage diagnosis (vs no cancer) was driven largely by vertebral (HR, 2.46; 95% CI, 1.93-3.13) and pelvic (HR, 2.46; 95% CI, 1.84-3.29) fracture sites. Compared with cancer survivors who did not receive chemotherapy, survivors who received chemotherapy were more likely to have a fracture; this association was stronger within 5 years of diagnosis (HR, 1.31; 95% CI, 1.09-1.57) than 5 or more years after diagnosis (HR, 1.22; 95% CI, 0.99-1.51). Although the HR for risk of fracture was lower among physically active cancer survivors 5 or more years after diagnosis (HR, 0.76; 95% CI, 0.54-1.07), this result was not statistically significant, whereas current smoking was significantly associated with higher risk of fracture (HR, 2.27; 95% CI, 1.55-3.33).Conclusions and RelevanceFindings from this cohort study suggest that older adults with a history of cancer may benefit from clinical guidance on prevention of frailty-related fractures. If study findings are replicated, fracture prevention programs for survivors might include referrals for physical activity with cancer exercise professionals and smoking cessation programs.

Prevention and Co-Management of Breast Cancer-Related Osteoporosis Using Resveratrol

“…Likewise, common chemotherapeutic agents have been found in correlation with enhanced bone resorption in premenopausal BC patients [137], which is consistent with findings from a longitudinal cohort study (N = 92,431) [133].…”

“…These data demonstrate the tremendous positive impact of early diagnosis and effective treatment options. Nevertheless, it is crucial to evaluate potential side effects associated with BC therapies such as surgical oophorectomy, chemotherapy-induced ovarian failure, and anti-estrogenic hormone therapies, including aromatase inhibitors, on the maintenance of a high quality of life for cancer survivors [ 132 , 133 ].…”

Eribulin mesylate induces bone mass loss by promoting osteoclastic bone resorption in mice

“…Nonetheless, in vivo and in vitro studies have shown that cytotoxic chemotherapeutic agents such as epirubicin ( Huang et al, 2018 ), methotrexate ( Georgiou et al, 2012 ; Shandala et al, 2012 ), doxorubicin (DOX) ( Fan et al, 2017 ; Yao et al, 2020 ; Rana et al, 2013 ), cyclophosphamide ( Fan et al, 2017 ), and melphalan ( Chai et al, 2017 ) can induce bone loss through multiple mechanisms that do not involve hormone deprivation. While it is not yet clear to what extent these cytotoxic agents contribute to CTIBL in cancer survivors, a recent cohort study revealed that older cancer survivors who received chemotherapy had a higher risk of fragility fractures than older adults without cancer ( Rees-Punia et al, 2023 ). The results of this study indicate that chemotherapy has a significant impact on long-term bone health in cancer survivors and underlines the importance of understanding the effects and mechanisms of chemotherapeutic agents on CTIBL.…”