ferric-oxide--saccharated and Osteomalacia

Fibroblast growth factor 23 (FGF23) is an essential hormone for phosphate metabolism. It has been shown that intravenous administration of some iron formulations including saccharated ferric oxide induces hypophosphatemic osteomalacia with high FGF23 levels. On the other hand, iron deficiency promotes FGF23 and induces hypophosphatemia in patients with autosomal dominant hypophosphatemic rickets (ADHR). While iron and phosphate metabolism is connected, the detailed mechanism of this connection remains to be clarified.

Topics: Anemia, Iron-Deficiency; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucaric Acid; Humans; Hypophosphatemia; Injections, Intravenous; Iron; Osteomalacia; Phosphates; Renal Insufficiency, Chronic; Rickets, Hypophosphatemic

Some of the hypophosphatemic rickets/osteomalacia are caused by the increased bioactivity of FGF23, and classified into FGF23-mediated hypophosphatemic rickets/osteomalacia. This group includes various disorders such as X-linked, autosomal dominant and autosomal recessive hypophosphatemic rickets/osteomalacia, tumor-induced osteomalacia, and rickets/osteomalacia caused by the administration of iron polymaltose or saccharated ferric oxide. Measurement of serum levels of FGF23 is useful for diagnosis of these conditions. In the adult patients with FGF23-mediated hypophosphatemic rickets/osteomalacia, mineralizing enthesoopathy is an often observed complication.

Topics: Diagnosis, Differential; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucaric Acid; Humans; Osteomalacia; Phosphates; Rickets, Hypophosphatemic

In our country, calcium- or phosphate-deficient rickets/osteomalacia due to malnutrition are scarcely reported. However, osteomalacia induced by drugs, such as anti-epileptics, etidronate and saccharated ferric oxide (SFO) is occasionally reported. When SFO is repeatedly injected to patients with iron-deficient anemia for a prolonged period, a tiny amount of SFO is excreted into renal tubules, where it exerts toxic effects on renal phosphate reabsorption and 1alpha-hydroxylase activity, leading to hypophosphatemic osteomalacia. Furthermore, Fe accumulates on the calcification front, resulting in impairment of bone formation. Although the SFO-induced osteomalacia is reversible, SFO should be used according to instructions of the package inserts, since it is a very effective parental agent for patients with iron-deficient anemia.

Topics: Anticonvulsants; Etidronic Acid; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Osteomalacia

Saccharaed ferric oxide (SFO)-induced osteomalacia develops when excessive SFO infusions are administrated to patients with anemia for prolonged periods for a few years. The small particles and almost neutral saccharide of SFO filter through the glomerular tufts into the renal tubules, resulting in impairment of proximal renal tubular function, particularly renal reabsorption of phosphate and 1alpha-hydroxylase activity, resulting in decreased serum levels of phosphorus and active vitamin D, both of which lead to development of hypophosphatemic osteomalacia. Furthermore, SFO, at concentrations attainable in serum, exacerbates the osteomalacia by inhibiting bone formation directly. In contrast to itai-itai disease, another iatrogenic osteomalacia due to cadmium nephropathy [44], the proximal renal tubular function impairment induced by SFO is reversible simply by discontinuing the nephrotoxin, which is followed by improvement of all the clinical manifestations, except bone deformities. So far, SFO-induced osteomalacia, that is, SFO-induced osteopathy due to nephropathy, has been reported only in Japan, probably due to the lax surveillance system of the health insurance scheme. All physicians who prescribe SFO should be aware of its severe adverse effects. We hope that such iatrogenic osteomalacia caused by abusive infusion of SFO will never again be reported in our country.

Topics: Aged; Anemia, Iron-Deficiency; Anemia, Refractory; Animals; Calcitriol; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Hypophosphatemia; Iatrogenic Disease; Kidney Diseases; Male; Middle Aged; Osteomalacia; Phosphates

Saccharated ferric oxide has been shown to lead to elevation of fibroblast growth factor 23, hypophosphatemia, and, consequently, osteomalacia. Moreover, mineral imbalance is often observed in patients with short-bowel syndrome to some degree.. A 62-year-old woman with short-bowel syndrome related with multiple resections of small intestines due to Crohn disease received regular intravenous administration of saccharated ferric oxide. Over the course of treatment, she was diagnosed with tetany, which was attributed to hypocalcemia. Additional assessments of the patient revealed not only hypocalcemia, but also hypophosphatemia, hypomagnesemia, osteomalacia, and a high concentration of fibroblast growth factor 23 (314 pg/mL).. We diagnosed her with mineral imbalance-induced osteomalacia due to saccharated ferric oxide and short-bowel syndrome.. Magnesium replacement therapy and discontinuation of saccharated ferric oxide alone.. These treatments were able to normalize her serum mineral levels and increase her bone mineral density.. This case suggests that adequate evaluation of serum minerals, including phosphate and magnesium, during saccharated ferric oxide administration may be necessary, especially in patients with short-bowel syndrome.

Topics: Bone Density; Female; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucaric Acid; Hematinics; Humans; Hypocalcemia; Hypophosphatemia; Magnesium; Magnesium Deficiency; Middle Aged; Osteomalacia; Short Bowel Syndrome; Treatment Outcome; Withholding Treatment

CASE 1: An 80-year-old man presented at our hospital with pain in both knees.He had received continuous intravenous administration of saccharated ferric oxide (SFO) over a period of five years following a diagnosis of iron-deficiency anemia.Blood tests revealed hypophosphatemia (1.4 mg/dl) and high circulating levels of fibroblast growth factor 23 (FGF23) at 248.8 mg/dl.These findings led to the diagnosis of FGF23-related osteomalacia due to SFO administration.Accordingly, the treatment plan was first to discontinue SFO, which led to a decrease in pain and normalization of phosphorus and FGF23 after 1 month.CASE 2: A 63-year-old woman presented at our hospital with leg pain.She had undergone total gastrectomy for gastric cancer at 36 years of age.Blood tests revealed hypocalcemia (8.3 mg/dl) and hypophosphatemia (2.2 mg/dl), and 25(OH)D at no more than 5 pg/ml.Bone X-rays showed significantly diminished bone shadowing.These findings led to a diagnosis of vitamin D-deficient osteomalacia due to impaired absorption following total gastrectomy.For therapy, she was treated with 1 μg/day oral alfacalcidol.Two months after initiating treatment, the pain improved.. When a patient is diagnosed with unexplained pain, it is important to pay attention to the possibility of an iatrogenic etiology.

Topics: Aged, 80 and over; Anemia, Iron-Deficiency; Female; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Gastrectomy; Glucaric Acid; Humans; Hypophosphatasia; Iatrogenic Disease; Male; Middle Aged; Osteomalacia; Postoperative Complications; Vitamin D Deficiency

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Hypophosphatemia; Low Back Pain; Magnetic Resonance Imaging; Middle Aged; Osteomalacia; Pelvic Pain; Remission Induction; Treatment Outcome

A 44-year-old woman with iron deficiency anemia was on a continuous course of intravenous saccharated ferric oxide (SFO). She came to our hospital because of right hip joint pain. She was found to have hypophosphatemia caused by impaired phosphorus resorption and her fibroblast growth factor 23 (FGF-23) levels were elevated. Therefore, she was diagnosed with FGF-23-related osteomalacia due to SFO administration. Discontinuation of the SFO treatment rapidly improved the impaired phosphorus resorption and also normalized the blood levels of phosphorus and FGF-23. During the treatment with SFO, it is important to regularly measure the blood levels of phosphorus in order to prevent the occurrence of osteomalacia.

Topics: Absorptiometry, Photon; Adult; Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Female; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucaric Acid; Hematinics; Humans; Osteomalacia; Phosphorus; Time Factors; Treatment Outcome; Withholding Treatment

Topics: Aged; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucaric Acid; Hematinics; Humans; Hypophosphatemia; Male; Osteomalacia

Topics: Adult; Anemia; Duodenal Ulcer; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Iatrogenic Disease; Malabsorption Syndromes; Middle Aged; Osteomalacia

Topics: Adult; Anemia, Hypochromic; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Injections, Intravenous; Intestinal Diseases; Intestine, Small; Iron; Middle Aged; Osteomalacia; Ulcer