Erythropoietin use linked to risk of hip fractures in dialysis patients: Study

Erythropoietin (EPO) is the primary regulator of bone marrow erythropoiesis. Mouse models have provided evidence that EPO also promotes bone remodeling and that EPO‐stimulated erythropoiesis is accompanied by bone loss independent of increased red blood cell production.

EPO has been used clinically for three decades to treat anemia in end‐stage renal disease, and notably, although the incidence of hip fractures decreased in the United States generally after 1990, it rose among hemodialysis patients coincident with the introduction and subsequent dose escalation of EPO treatment.

Given this clinical paradox and findings from studies in mice that elevated EPO affects bone health, the authors, Sukanya Suresh and colleagues from the Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA examined EPO treatment as a risk factor for fractures in hemodialysis patients.

Relationships between EPO treatment and hip fractures were analyzed using United States Renal Data System (USRDS) datasets and Consolidated Renal Operations in a Web‐enabled Network (CROWNWeb) datasets.

Fracture risks for patients treated with <50 units of EPO/kg/week were compared to those receiving higher doses by multivariable Cox regression.

The following findings were seen-

a. Hip fracture rates for 747,832 patients increased from 12.0 per 1000 patient to 18.9, then decreased to 13.1 in the later years.

b. Concomitantly, average EPO doses increased from 11,900 units/week to 18,300 in, then decreased to 8,800.

c. During this time, adjusted hazard ratios for hip fractures with EPO doses of 50–149, 150–299, and ≥ 300 units/kg/week compared to <50 units/kg/week were 1.08 (95% confidence interval [CI], 1.01–1.15), 1.22 (95% CI, 1.14–1.31), and 1.41 (95% CI, 1.31–1.52), respectively.

d. Multivariable analyses of 128,941 patients in CROWNWeb datasets replicated these findings.

Therefore, the authors concluded that "this study implicates EPO treatment as an independent risk factor for hip fractures in hemodialysis patients and supports the conclusion that EPO treatment may have contributed to changing trends in fracture incidence for these patients during recent decades."