Red Blood Cell Width Predicts Hip Fracture Risk

Nancy A. Melville

September 26, 2019

ORLANDO, Florida — Red blood cell distribution width (RDW) — an easily assessed, valuable predictor of cardiovascular disease, mortality, and other aging-related diseases — shows strong accuracy in a novel use as a predictor of hip fracture, with accuracy approaching that of the best currently available prediction tools, new research shows.

"This is the first report [describing] red blood cell width and hip fracture risks," first author Kyoung Min Kim, MD, PhD, of the San Francisco Coordinating Center, California Pacific Medical Center Research Institute, told Medscape Medical News, following presentation of the findings from the Osteoporotic Fractures in Men (MrOS) study here at the American Society for Bone and Mineral Research (ASBMR) 2019 Annual Meeting.

"According to our results, RDW shows a very strong and consistent association with risks of hip fractures and all clinical fractures...[and] could have potential value in predicting future fractures," she said

And importantly, unlike potentially costly fracture assessment methods, "Most people already have their RDW values available in their medical records as part of a complete blood count, which is the most widely performed clinical test in routine clinical practice," she explained.

Session comoderator Elaine W. Yu, MD, director of the Bone Density Center at Massachusetts General Hospital, Boston, said the study is notable for being what is believed to be the first to describe RDW and fracture risk.

"That being said, RDW is associated with many chronic diseases and also with aging, so perhaps it is not surprising that it serves as a marker of skeletal fragility," she told Medscape Medical News, adding that it's "unclear whether there is a direct biologic mechanism that underlies this association."

"If the results can be validated in other cohorts, clinicians might be able to utilize these commonly performed tests to risk stratify older men who are at risk for osteoporotic fractures," Yu said.

Highest vs Lowest RDW Equals Triple the Risk of Hip Fracture

Red blood cells are produced in the bone marrow from hematopoietic stem cells and become more variable in size with age and some types of anemia, such as iron deficiency and B12 deficiency.

In addition to being associated with cardiovascular disease, higher RDWs have also been linked to renal insufficiency, dementia, and other outcomes; however, the biological mechanisms behind these relationships remain unknown, Kim noted.

To evaluate the potential role of RDW in fracture risk, Kim and colleagues obtained measures from 3635 older men, who were a mean age of 79.1 years, from the MrOS study.

Femoral neck bone mineral density (BMD) was also assessed.

Over an average 8.1 years of follow-up, there were 164 (5%) hip fractures among the men and 701 (19%) fractures overall. In addition, there were 1059 (29%) incident falls.

RDW values between 11% and 15% are considered in the normal range, with higher values indicative of more variation in size.

After adjusting for factors including age, body mass index, alcohol, and smoking, the results showed that a higher percentage RDW, compared with low, was a strong predictor of hip fracture.

Those in the highest tertile of RDW (value > 15.7%) versus the lowest (< 13.0%) had an almost threefold higher risk of hip fracture, for a hazard ratio of 2.8.

The analysis showed an increased risk of all clinical fractures associated with higher RDW values (P for trend = .01), and the incidence of falls was also increased (P for trend = .001).

But there was no relationship between RDW and BMD.

"We found that RDW provided a very strong and consistent association with hip and clinical fracture," which means it could be a simple, universal, and powerful measure to identify those at high risk, Kim concluded.

Study Limitations and Further Research

Yu noted, however, the lack of adjustment for renal function data, which could be a confounder. 

"The fact that RDW is not associated with bone density suggests that perhaps RDW is simply a marker for other comorbidities that increase fracture risk," she added.

Kim noted that the fact the study was all-male, not very diverse, and participants were older, might limit generalizability to younger people, women, or nonwhite groups.

However, although they are considering testing the theory in women, in reports of RDW in other clinical contexts, no gender differences have been observed, she noted.

And as such values are already available for many patients in medical charts, it might be worth taking a second look.

"Although further study is needed to confirm these findings, it would be worthwhile to check...values once, and if the patients (already) have higher risks of fractures and also have higher values of RDW, the physician should consider further assessment or treatment of osteoporosis," Kim said.

Separate Findings on Hip Fracture Risk With Anemia

In a separate finding, despite the known link between anemia and RDW, no significant link was seen between RDW values and hip fracture risk in patients with anemia (P = .19), a result that Kim described as intriguing.

But men with anemia (n = 714) had an almost twofold higher risk of hip fracture compared to those without (n = 2921), with a hazard ratio of 1.9 (P < .001).

"The primary purpose of this study was just to test RDW and hip fracture, but during the analyses, we found that anemia status also is a risk factor for fractures," Kim emphasized.

"The results of this study suggest that both anemia and high RDW serve as markers of skeletal fragility in older men," she concluded.

Kim and Yu have reported no relevant financial relationships.

ASBMR 2019 Annual Meeting. Presented September 21, 2019. Abstract 1069.

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