Cancer survivors at greater risk for bone fractures late in life

Cancer survivors may be more susceptible to frailty-related bone fractures to the pelvis and vertebrae according to a study by American Cancer Society (ACS) researchers.

“Prior to our study, there was some evidence to suggest that cancer survivors may be at a higher risk of bone fractures,” says Erika Rees-Punia, PhD, MPH, senior principal scientist of the Department of Population Science at the ACS in Atlanta, Georgia. “But many prior studies focused on one cancer type, most often breast cancer only; combined all fracture sites together, even though we know that certain fracture sites, like hip and spine, are the costliest and the most likely to be associated with further morbidity and mortality down the road; and only studied cancer survivors immediately after treatment.” The study appears in JAMA Oncology (doi:10.1001/jamaoncol.2022.5153).

The participants in this study were from the ACS’s Cancer Prevention Study II (CPS-II) Nutrition Cohort (NC) and had provided demographic and lifestyle information in a series of questionnaires since 1992. Cancer incidence information was self-reported by the study participants and verified by the researchers via medical record abstraction and state cancer registries.

Because both CPS-II and Centers for Medicare & Medicaid Services claims databases include a patient’s Social Security number, name, sex, and date of birth, the researchers were able to link data provided to the ACS with Medicare inpatient, outpatient, and physician

claims files, which were used to identify incident pelvic, radial, and vertebral fractures when subjects were at least 65 years old.

“Linking CPS-II data with Medicare Claims data allows us to benefit from both datasets in one study,” says Dr Rees-Punia. “CPS-II has years of validated physical activity, smoking, and diet data (pre- and post-diagnosis for cancer survivors), while Claims data provide an opportunity to identify sites and dates of bone fractures without relying on self-reporting.”

Following cancer survivors for more than 15 years, the study included survivors of all cancer sites and explored the differences in fracture risk by three sites (wrist, pelvis, and vertebrae) that are associated with frailty. “This was important, as we indeed found that the risk of fracture was different by fracture site, and the risk of fracture was elevated for cancer survivors for many years after diagnosis and treatment,” Dr Rees-Punia says.

Participants were classified by their cancer history, including the time since diagnosis and the stage at diagnosis. The researchers then examined potential associations of these and other clinical characteristics with the number of pelvic, radial, and vertebral fractures.

“These analytic decisions align with those made in previous studies of bone health in cancer survivors and with other studies of cancer survivorship within CPS-II NC,” the researchers wrote.

This study used data from 92,431 of the more than 116,000 participants who completed a CPS-II questionnaire in 1999. In this analytic cohort, 56.1% (51,820) were female, and 43.9% (40,611) were male; 97.9% (90,458) were White, 1.1% (1037) were Black, and 1.0% (936) were classified as “all other races and ethnicities.” The mean age for all participants was 69.4 years at the study baseline.

Of these 92,431 study subjects, 12,943 experienced a frailty-related bone fracture. The researchers used multivariable Cox proportional hazards regression to demonstrate a significantly increased risk of frailty-related fractures (all three sites combined) occurring 1–5 years after the diagnosis of local-, regional-, or distant-stage cancer. The risk of frailty-related fractures of these bones overall was also significantly increased 5 or more years after the diagnosis of distant- (but not local- or regional-) stage cancer. The greatest excess risk was for pelvic fractures 1–5 years after a distant-stage diagnosis (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.84–3.29), for vertebral fractures 1–5 years after a distant-stage diagnosis (HR, 2.46; 95% CI, 1.93–3.13), and for pelvic fractures 5 or more years after a distant-stage diagnosis (HR, 1.84; 95% CI, 1.26–2.70).

In addition, survivors who received chemotherapy were significantly more likely than those who did not to have a frailty-related fracture 1–5 years after their diagnosis (HR, 1.31; 95% CI, 1.09–1.57) and 5 or more years after their diagnosis (HR, 1.22; 95% CI, 0.99–1.51). The researchers also found that the risk of a frailty-related fracture 5 or more years after diagnosis was associated with two modifiable factors. Smoking was significantly associated with a higher fracture risk (HR, 2.27; 95% CI, 1.55–3.33), and there was a nonsignificant suggestion that the combination of greater strength training and more aerobic physical activity at the time of diagnosis might be associated with lower risk (HR, 0.76; 95% CI, 0.54–1.07).

“While this study is not breaking new ground, it adds to the literature by addressing the risk of fractures among cancer survivors compared to those without cancer, overcoming some of the limitations of prior studies in the field,” says Larissa Nekhlyudov, MD, MPH, professor of medicine at the Harvard Medical School and Brigham and Women’s Hospital in Boston, Massachusetts.

“Oncologists and primary care clinicians caring for cancer survivors should be aware of the increased risk of fracture and counsel patients accordingly,” says Dr Nekhlyudov. She suggests fall risk reduction strategies including a holistic approach, such as the treatment of underlying predisposing conditions (e.g., osteoporosis and its associated risk factors, such as smoking and corticosteroids); addressing fall risk (e.g., a history of dizziness, pain, balance, weakness, and fatigue); conducting a physical examination (e.g., measuring orthostatic blood pressure); conducting cardiovascular, musculoskeletal, and neurological examinations and specific assessments (e.g., Timed Up & Go); reviewing medications (e.g., medications for blood pressure, corticosteroids, benzodiazepines, and narcotics); and assessing for cancer-related pain and neuropathy due to chemotherapy or other causes.

“There is no doubt that interventions for smoking cessation for all cancer survivors is critical,” says Dr Nekhlyudov. “Benefits of cancer rehabilitation and exercise physiology have also been clearly demonstrated, including a growing [body of] literature specifically focusing on those with advanced cancer.”