Any Fracture, Regardless of Location, Signals Increased Risk of Subsequent Fracture in Postmenopausal Women

Carolyn Crandall, MD

Researchers from UCLA are hopeful their recent study can serve as a warning for clinicians treating postmenopausal women and help inform guidelines in the future.

While previous research points to an increased risk of subsequent fracture following a hip or spine fracture, the UCLA-led analysis of more than 150,000 patients suggests any fracture, no matter the location, was associated with increased risk of any fracture in the future.

"Current clinical guidelines have only been emphasizing hip and spine fractures, but our findings challenge that viewpoint," said lead investigator Carolyn Crandall, MD, professor of medicine at the David Geffen School of Medicine at UCLA, in a statement. "By not paying attention to which types of fractures increase the risk of future fractures, we are missing the opportunity to identify people at increased risk of future fracture and counsel them regarding risk reduction.”

Despite posing a significant threat to overall health and quality of life, Crandall and colleagues noted a gap in research related colocations of subsequent fracture after initial fracture among postmenopausal women. With an interest in filling this apparent knowledge gap, investigators designed the current study as a prospective analysis of patients who were enrolled in the Women’s Health Initiative (WHI) from 1993-1998.

From the WHI, investigators obtained data related to more than 161,000 postmenopausal women aged 50-79 years from 40 centers across the US. After excluding women based on missing information and use of bisphosphonates, calcitonin, and/or raloxifene at baseline, investigators identified a cohort of 157,282 women for inclusion in the current study. Of these, 137,412 had complete covariate information.

Overall, the mean participant age was 63.1 (SD, 7.2) years, the mean BMI was 28.0 (SD, 5.9) kg/m2, and the mean follow-up duration was 15.4 (SD, 6.2) years. Investigators also noted 83% of participants self-identified as White.

In total, 47,126 (30%) participants experienced a fracture during the follow-up period. Compared to those who did not experience a fracture, those with incident fracture were older (P <.0001), more likely to be White (P <.0001), less likely to be using hormone therapy at baseline (P=.001), more likely to have experienced falls during the 12 months prior to baseline (P <.0001), and were more likely to report a prevalent fracture at baseline (P <.0001).

Upon analysis, investigators found risk of each type of subsequent fracture was increased after each type of initial fracture. Results suggested incident lower arm/wrist fracture was associated with significantly increased risk of subsequent fractures at upper arm/shoulder, upper leg, knee, lower leg/ankle, hip/pelvis, and spine, with adjusted hazard ratios ranging from 2.63 to 5.68.

Additionally, results indicated hip fracture risk was increased following a lower arm or wrist fracture (aHR, 4.80; 95% CI, 4.29-5.36), initial upper arm or shoulder fracture (aHR, 5.06; 95% CI, 4.39-5.82), initial upper leg fracture (aHR, 5.11; 95% CI, 3.91-6.67), initial knee fracture (aHR, 5.03; 95% CI, 4.20-6.03), initial lower leg/ankle fracture (aHR, 4.10; 95% CI, 3.58-4.68), and initial spine fracture (aHR, 6.69; 95% CI, 5.95-7.53).

Further analysis demonstrated the observed increases in risk were significant across all age groups. Investigators also pointed out risk of subsequent fracture appeared to be more pronounced among women self-identifying as non-Hispanic Black, Hispanic/Latina, and Asian/Pacific Islander compared to those self-identifying as non-Hispanic White.

Investigators cautioned clinicians to consider the limitations of their study before overinterpretation of its findings. These limitations included reliance on self-reporting of fractures, lack of information related to rib fractures, and limited availability of data related to bone mineral density.

This study, “After the initial fracture in postmenopausal women, where do subsequent fractures occur?,” was published in EClinical Medicine.