Parental Iron: A Rare Cause of Hypophosphatemia

Osteoporosis is the most common metabolic bone disease and is associated with many underlying causes. Laboratory evaluation is important to uncover causes of osteoporosis that may be treatable.

We report a case of hypophosphatemia in a patient on chronic ferric carboxymaltose injections (FCM) (Injectafer). which was corrected with phosphorus supplementation and changing to an alternative form of parental iron.

Case Description:

A 52-year-old male was referred to the UC San Diego Health endocrinology clinic in May 2017 for a new diagnosis of osteoporosis following an insufficiency foot fracture of the right second metatarsal. As per DXA on 4/17: right femur T-score was -2.9, left femur T-score of -2.5., and lumbar spine T -score of -2.8. (L1-L3). Patient has a history of congenital distal colonic venous malformation and esophageal varices resulting from congenital absence of the portal vein. He also has chronic anal fistulae resulting in hematochezia requiring chronic life-long iron infusions. Patient was diagnosed with MGUS at age 18 and was closely followed by hematology. He had been receiving IV iron infusions on regular basis since 1996, and in 2015 was switched to FCM.

In June 2017, laboratory analysis revealed a mild anemia with a hemoglobin of 11.5, and a normal metabolic panel and magnesium. His phosphorus was low at 2.5 (ref 2.7-4.5mg/dL). His PTH, TSH, calcitriol, magnesium, 25-OH vitamin D and testosterone levels were normal. His phosphorus level was then repeated three weeks later and found to be 0. 8. It was repeated, and the value remained the same. The patient was asymptomatic. Labs and urine were performed for all causes of hypophosphatemia (FGF-23, renal tubular defects, etc.) and all were negative. Patient was started on phosphorus supplementation with Sodium potassium phosphate two packets daily, which achieved normal phosphorus levels on subsequent testing. In February 2018 the patient was switched from FCM (Injectafer) to intravenous ferumoxytol (Feraheme).

His repeat DXA (6/2018) after one year of normal phosphorus levels on supplementation revealed an increase in his BMD from prior of 6.1% at the right femur (T-score -2.1),, 9% at the lumbar spine (T-score -2.1 (L1-L2), and no significant change at the left femur (T- score -1.9). His phosphorus supplementation was stopped in June 2018 and phosphorus was checked routinely and continued to remain normal.

Discussion:

Hypophosphatemia is a well-documented side effect of IV iron, particularly with ferric carboxymaltose iron (Injectafer) (FCM).

It is thought that FCM stimulates FGF-23 which induces renal phosphate wasting and suppresses calcitriol, thereby lowering serum phosphate. We recommend routinely monitoring patients’ phosphorus levels while on IV iron, and repleting aggressively. This case further suggests phosphorus repletion can ameliorate loss of BMD while on FCM. If long term IV iron is necessary, we suggest avoiding FCM as a formulation as it has been shown to cause more pronounced hypophosphatemia than other IV formulations. After discontinuation of FCM and switching to ferumoxytol our patient demonstrated a dramatic improvement in bone mineral density.