Older women who receive radiation therapy for cervical, rectal, or anal cancer have a substantially increased risk for pelvic fractures, according to an article in the November 23 issue of the Journal of the American Medical Association.

The lifetime risk of a hip fracture after 50 years of age for white women is estimated at 17 percent. Within the first year after a hip fracture, 10 percent to 20 percent more women die than expected for age. The number of deaths due to hip fractures is comparable with the number of deaths due to pancreatic cancer and is only slightly lower than the number of deaths due to breast cancer.

It is well recognized that therapeutic radiation can result in bone damage and may increase fracture risks. However, the risks have not been well studied. Because of the high baseline incidence of fractures in older people and the significant illness and death associated with fractures, even a small increase in the fracture rate would be an important finding.

Nancy Baxter, MD, PhD, and her American colleagues conducted a study to determine if women who undergo pelvic irradiation for pelvic malignancies (anal, cervical, or rectal cancers) have a higher rate of pelvic fracture than women with pelvic malignancies who do not undergo irradiation.

The researchers used Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked to insurance claims data. A total of 6,428 women aged 65 years and older diagnosed with pelvic malignancies from 1986 through 1999 were included.

The researchers found that the cumulative incidence of pelvic fractures was greater in the irradiated group than in the non-irradiated group for all three types of cancer diagnoses. Within the first five years of the study period, the incidence of pelvic fractures was 14.0 percent in the irradiated group versus 7.5 percent in the non-irradiated group for women with anal cancer, 8.2 percent in the irradiated group versus 5.9 percent in the non-irradiated group for women with cervical cancer, and 11.2 percent in the irradiated group versus 8.7 percent in the non-irradiated group for women with rectal cancer. The incidence of arm or spine fractures was similar in both groups.

“The observed hazard ratio for radiation therapy in women with anal cancer was 3.16. This value can be interpreted as a 3-fold increase in pelvic fracture risk for women with anal cancer who underwent radiation therapy (versus women who did not) at any given time. The observed hazard ratio for radiation therapy in women with cervical cancer was 1.66; in women with rectal cancer, 1.65. These values indicate a lesser effect, but are still consistent with a substantial increase in fracture risk,” the researchers wrote.

“Given the high baseline rate of fractures in women aged 65 years or older, the hazard ratio of 1.65 that we found in our study may represent an increased lifetime incidence of fractures from the baseline rate of 17 percent to 27 percent - a substantial and clinically significant absolute increase.”

“The high risk of pelvic fracture after radiation therapy for anal cancer may reflect the radiation therapy technique used to treat this disease. In the treatment of anal cancer, it is usually appropriate to treat the inguinal nodes because of the risk of disease at this site. Because of the location of these nodes with respect to the femoral head and neck, it has been difficult to treat these nodes well without concomitant irradiation of the femur, and thus the femoral heads are exposed to a relatively high irradiation dose in the treatment of anal cancer patients,” the authors noted.

The researchers noted that the study population (older, predominantly white women) was already at high risk for pelvic fractures; thus, results could not be generalized to other populations and study in other populations should follow.

In an accompanying editorial, William Small, Jr., MD, of Northwestern University, Chicago, and Lisa Kachnic, MD, of Boston University Medical Center, Boston, commented: “How should clinicians use the knowledge of an increased risk of pelvic fractures associated with radiotherapy- This potential morbidity should be discussed with the patient at the time of radiation oncology consultation and factored into informed decision making and informed consent regarding the use of radiotherapy. More important, patients who have received prior pelvic radiation must receive long-term follow-up examinations, and must be carefully assessed when pelvic pain appears.”

The editorial added that in addition to improved targeting of radiotherapy, clinicians should consider use of agents that reduce toxicity or improve osseous consistency or structure after radiotherapy.

“In conclusion, Baxter et al have provided compelling evidence for a significant increase in pelvic fracture risk with the use of pelvic radiotherapy as a component of definitive cancer management. The morbidity associated with pelvic fractures and the widespread use of pelvic radiotherapy make research into reducing such osseous effects a high priority,” the editorial concluded.