A 60-year-old man with portal hypertensive gastropathy due to type C liver cirrhosis
developed severe bone pains, marked hypophosphatemia with inappropriately increased
urinary excretion of phosphate (%TRP; 9.6%), and hyperalkaline phosphatasia, after
intravenous administration of saccharated ferric oxide (SFO) at a dose of 80-240 mg/week
over a period of more than 5 years. The total iron infused was estimated to be more
than 25 g. On a diagnosis of SFO-induced osteomalacia, the infusion of iron was immediately
discontinued, and phosphate and vitamin D2 (1000 IU/day) were administered. Serum
levels of 25-OHD2 increased after 1 week, whereas levels of 1,25-(OH)2D2 did not increase
until 3 months later, accompanied by improvement of renal tubular reabsorption of
phosphate and gradual improvement of the bone pains. The patient has been doing well
for the last 2 years, with normal serum levels of phosphate, calcium, and alkaline
phosphatase, without any supplementation of phosphate, vitamin D, or iron-containing
agents. In primary culture of neonatal mouse renal tubules, in which 1,25-(OH)2D3
was produced from 25-OHD3 in response to PTH, SFO significantly inhibited PTH-induced
production of 1,25-(OH)2D3 at 30 mumol/L, which is attainable in the urine of patients
receiving a therapeutic intravenous dose of SFO. Furthermore, SFO decreased the calcium
content and inhibited 45Ca incorporation in cultured fetal mouse parietal bones at
3 mumol/L. Such SFO concentration may be transiently observed in the plasma of patients
receiving excessive intravenous doses of SFO for a prolonged period. These in vitro
findings together with the clinical observations suggest that SFO, after filtration
through the glomerulus and reabsorption in the proximal renal tubules, impaired proximal
renal tubular function, such as tubular reabsorption of phosphate and 1 alpha-hydroxylase
activity, leading to hypophosphatemic osteomalacia. Furthermore, it is highly likely
that SFO in the peripheral blood, when transferrin is saturated with iron, may impair
bone formation and aggravate osteomalacia. Although SFO-induced osteomalacia is reversible
simply by discontinuation of the agent, excessive and prolonged administration of
SFO should be avoided.