Although the incidence of serious adverse reactions remains low with administration of parenteral iron, hypophosphataemia is increasingly being recognised as an important complication, though it is often transient and asymptomatic. A postulated mechanism for hypophosphataemia is the reduced degradation of FGF-23, resulting in renal phosphate wasting and reduced synthesis of 1,25-hydroxy vitamin D.
We report two post-menopausal women who developed symptomatic hypophosphataemic osteomalacia with bone pain and multiple insufficiency fractures on a background of chronic gastrointestinal blood loss, necessitating monthly iron polymaltose infusions over 13- and 17-months, respectively. Respective blood tests revealed serum phosphate of 0.29 and 0.43 mmol/L [0.8 - 1.5mmol/L], 25-hydroxy vitamin D of 98 and 57 nmol/L, 1,25-dihydroxy vitamin D of 80 and 32 pmol/L [60 - 158], alkaline phosphatase of 302 and 125 U/L [30 - 130], with normal serum calcium and PTH. Urinary fractional phosphate excretion of the first patient was 24% [<5%] with TmP/GFR of 0.47 [0.87 - 1.4], consistent with renal phosphate wasting. Serum FGF-23 obtained from the second patient was 285 pg/mL [<54]. There was no biochemical evidence of Fanconi’s syndrome. Bone mineral density scans were in the osteoporotic range and whole body bone scans revealed increased uptake at multiple skeletal sites indicative of insufficiency fractures and in a pattern consistent with osteomalacia. Cessation of iron infusions resulted in clinical and biochemical improvement within 2-months.
The third case was a 25-year-old male with Crohn’s disease and iron deficiency anaemia who presented with severe hypophosphataemia (0.13 mmol/L) and generalised muscle weakness twelve days after a single dose of iron polymaltose. There was no arrhythmia on ECG. Serum calcium, PTH, 25-hydroxy and 1,25-hydroxy vitamin D were normal with supplementation. Fractional phosphate excretion was marginally elevated (6.5%), reflecting depleted phosphate stores. Bone mineral density scan was in the osteoporotic range. Following oral phosphate supplementation, serum phosphate and metabolic bone parameters normalised within 2-months. Vigilant prescribing of parenteral iron is needed to avoid clinically serious hypophosphataemia.