Cancer Survivors Found to Be at Greater Risk of Frailty-Related Bone Fractures

Factors such as chemotherapy treatment and a cancer diagnosis within the past 5 years were associated with a greater risk of frailty-related bone fractures among older cancer survivors, according to findings from a recent cohort study.

Cancer survivors have a significantly higher risk of frailty-related bone fractures for several years after diagnosis vs those without a history of cancer, according to findings from a recent study published in JAMA Oncology.

Older adults with a history of cancer were found to have a 57% greater risk of fractures in the first year after diagnosis (HR 1.57; 95% CI, 1.38-1.79) vs those without. The risk was especially elevated for those diagnosed with distant metastases 1 to 4 years prior to the study (HR 2.12; 95% CI, 1.75-2.58). This disparity in risk derived largely from vertebral (HR 2.46; 95% CI, 1.93-3.13) and pelvic (HR, 2.46; 95% CI 1.84-3.29) fractures. The risk of radial fracture meanwhile did not substantially vary based on history of cancer (HR 1.09; 95% CI, 0.64-1.87).

“Cancer survivors are at higher risk of bone fractures likely because of higher rates of osteoporosis coupled with low muscle mass, poor balance, and unexpected changes in gait,” the investigators wrote. “One novel finding in this study was the difference in risk by fracture site….[It] is important to understand the differences in risk by fracture site because each fracture type is associated with certain health care costs and risks of subsequent morbidity and mortality. Pelvic fractures, in particular, are highly associated with further health issues, including mortality, and account for nearly 77% of all costs incurred from incident fractures.”

Other relevant risk factors included treatment modality, lifestyle, and sex. Survivors of cancer who received chemotherapy were 31% more likely to have a fracture vs those who didn’t receive chemotherapy (HR 1.31; 95% CI, 1.09-1.57) in the first 4 years after diagnosis and 22% more likely 5 or more years beyond diagnosis (HR 1.22; 95% CI, 0.99-1.51). Additionally, survivors who were current smokers at the time of the study were more than twice as likely to have fractures (HR 2.27; 95% CI, 1.55-3.33) as those who never smoked. The risk of fracture was lower among physically active survivors 5 or more years after diagnosis (HR 0.76; 95% CI, 0.54-1.07), but this correlation was not statistically significant. Higher BMI (≥25) was also associated with lower risk of fracture for those with (HR 0.72; 95% CI, 0.62-0.85) and without (HR 0.78; 95% CI, 0.75-0.81) a history of cancer. Men were generally less likely to experience fractures than women, including in those without a history of cancer (HR 0.51; 95% CI, 0.48-0.54), in survivors 1 to 4 years after diagnosis (HR 0.53; 95% CI, 0.41-0.69), and in survivors 5 or more years beyond (HR, 0.74; 95% CI, 0.54-1.01), though the latter correlation was not statistically significant.

This longitudinal cohort study examined 92,413 eligible participants out of 116,355 adults who completed the 1999 Cancer Prevention Study II Nutrition Cohort survey and were linked with Medicare claims from 1999 to 2017. The vast majority of this study population were White (97.9%) and older than 60 years (95.8%) at the time of the survey. The median age was 69.4 years, and most participants were women (56%). Most either met (24.1%) or significantly exceeded (32.3%) the guidelines for moderate to vigorous physical activity, and most (54.2%) had a BMI of 25 or greater. Current smokers comprised 4.7% of the population, with former smokers comprising a further 48.6%.

Incident fractures affected 12,943 participants in total. The primary analysis only included first fractures because roughly 4% (n = 3793) of participants experienced more than one; further exploratory analyses assessed the risks related to multiple fractures.

“Future studies are needed that explore the associations of [moderate- to vigorous-intensity physical activity], strength training, smoking, alcohol use, or diet quality across the life course, both before and after diagnosis, with fracture risk in [survivors of cancer],” the investigators concluded, writing nonetheless that “[these] survivors, especially those who received chemotherapy or received a cancer diagnosis more recently (<5 years), may benefit from clinical guidance on frailty-related fracture prevention.”


Rees-Punia E, Newton CC, Parsons HM, et al. Fracture risk among older cancer survivors compared with older adults without a history of cancer. JAMA Oncol. Published online November 3, 2022. doi:10.1001/jamaoncol.2022.5153