Higher erythropoietin (EPO) doses are associated with increased risk for hip fractures in patients receiving hemodialysis (HD), a new study finds.

Over the past 3 decades, hip fracture trends for patients receiving hemodialysis diverged from trends for the general population and appeared to follow EPO dosing patterns, investigators observed. Hip fracture rates among 747,832 patients receiving HD in USRDS datasets (1997-2013) increased from 12.0 per 1000 patient years in 1997 to 18.9 in 2004, then decreased to 13.1 by 2013. Concurrently, average EPO doses increased from 11,900 units/week in 1997 to 18,300 in 2004, then decreased to 8800 by 2013.

Compared with EPO doses less than 50 units/kg/week, doses of 50-149, 150-299, and 300 or more units/kg/week were associated with 8%, 22%, and 41% higher risk for hip fracture, respectively, Sukanya Suresh, PhD, MSc, of the National Institutes of Health in Bethesda, Maryland, and colleagues reported in the Journal of Bone and Mineral Research. The investigators corroborated these findings in a multivariable analyses of 128,941 patients in CROWNWeb datasets from 2013. Hip fracture risk increased 17%, 21%, and 45% at these respective EPO doses compared with the reference.


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These analyses also confirmed known hip fracture risk factors, including older age, female sex, White race, low serum albumin, and low body mass index. With respect to medications, proton pump inhibitors (PPIs), antiarrhythmics, cardiac stimulants, and antidepressants were associated with increased hip fracture risk, whereas cinacalcet, phosphate binders, and vitamin D correlated with decreased risk.

With respect to study limitations, the investigators noted that they could not analyze fibroblast growth factor 23, parathyroid hormone, bone-specific alkaline phosphatase, and vitamin D levels in relation to hip fracture risk.

According to Dr Suresh and colleagues, “findings of the present study provide further justification for minimizing the doses of EPO used to treat patients with renal failure and for avoiding high doses, using EPO to ameliorate rather than to correct anemia.”

Reference

Suresh S, Wright EC, Wright DG, Abbott KC, Noguchi CT. Erythropoietin treatment and the risk of hip fractures in hemodialysis patients. J Bone Miner Res. Published online May 5, 2021. doi:10.1002/jbmr.4297