Risk of bone fracture following saccharated ferric oxide in Japan

Intravenous (IV) iron is recommended for the treatment of iron deficiency anemia (IDA) when oral iron is ineffective or poorly tolerated, or when rapid iron replenishment is needed. However, specific IV iron formulations, including saccharated ferric oxide (SFO) and ferric carboxymaltose (FCM), are associated with increased rates of hypophosphatemia and subsequent osteomalacia. Clinical trials of these IV iron formulations were not sufficiently large or long enough to assess whether these effects translate into increased risk of fracture. This observational cohort study used claims data from a Japanese health insurance database between June 2018 and May 2021 to assess the risk of fracture following treatment with SFO in patients with IDA who were propensity score-matched (approximately 4:1) to controls who had anemia but were not treated with IV iron. Since kidney dysfunction partially protects against severe IV iron-induced hypophosphatemia, a secondary analysis was restricted to patients with normal kidney function. Of the patients treated with SFO, 29,037 were matched to 128,311 untreated controls. Treatment with SFO was associated with significantly higher risk of incident fracture compared with controls (hazard ratio [HR]: 1.154; 95% confidence interval [CI]: 1.088, 1.225; p < 0.0001). In patients with normal kidney function, the risk of fracture was increased in those who received higher cumulative doses of SFO. Patients with kidney dysfunction were also at significantly increased risk of fracture following SFO (HR: 1.512; 95% CI: 1.344, 1.702; p < 0.0001). These real-world data suggest that SFO, known to cause significant hypophosphatemia, also increases the risk of fracture.