Table 1.

Recent hypophosphatemia cases reported in the scientific literature

Patient	Relevant history	Prior treatment	Presentation	Laboratory findings	Diagnosis
45-year-old man [46]	Crohn’s disease IDA	FCM total of 27 g over 3 years	Proximal muscle weakness Bilateral groin and shoulder pain	Hypophosphatemia (serum phosphate 0.46 mmol/L) Increased FEPi (46%) Elevated FGF23 (173 pg/mL) Normal PTH and 25-OH-vitamin D Mild hypocalcemia	Hypophosphatemia and osteomalacia with bilateral symmetric pseudofractures in the femur necks with IDA
38-year-old man [20]	Crohn’s disease IDA	FCM 1 g/month for 8 months	Bilateral hip pain with inability to walk Costal and sternal pain Multiple hip fractures of the femoral heads	Hypophosphatemia (serum phosphate 0.34 mmol/L) Elevated FGF23 (226 ng/L) Low calcium (1.97 mmol/L) Low 25-OH-vitamin D (18 ng/mL) Low 1,25(OH)2D (8 pg/mL) Normal PTH and calcinuria Phosphaturia 19.4 mmol/mmol of creatininuria Phosphate reabsorption rate 60%	FGF23-mediated osteomalacia
45-year-old man [47]	Crohn’s disease IDA	FCM Q8 weeks for 4 years	4-month history of progressive bone pain in ribs, spine, and feet Acute bone fractures of the ribs, femoral head, and metatarsals	Low 1,25(OH)2D (19 pmol/L) Elevated intact serum FGF23 (> 5 × ULN) History of hypophosphatemia (serum phosphate 0.21–0.80 mmol/L)	Hypophosphatemic osteomalacia
65-year-old woman [17]	IDA secondary to gastric antral vascular ectasia	Iron polymaltose 1 g/month for 13 months	2-year history of minimal trauma fractures of the wrist, ribs, sacrum, right pubis Compression fracture of the T6 vertebra Worsening generalized bone pain	Hypophosphatemia (serum phosphate 0.29 mmol/L) TmP/GFR (0.76) and fractional phosphate excretion (16%) consistent with renal phosphate wasting Normal urine calcium, pH, amino acid, glucose, and protein levels	Hypophosphatemic osteomalacia with multiple insufficiency fractures
58-year-old woman [17]	IDA secondary to hereditary hemorrhagic telangiectasia	Iron polymaltose 1 g/month for 17 months	6-month history of bone pain involving the chest wall, back, lower limb’s and arms Insufficiency fractures of the ribs Diffusely increased osteoblastic activity compatible with metabolic bone disease	Hypophosphatemia (serum phosphate 0.43 mmol/L) Low 1,25(OH)2D (32 pmol/L) Elevated PTH (8.3 pmol/L) Elevated FGF23 (285 pg/mL) TmP/GFR (0.48) and fractional phosphate excretion (24%) consistent with renal phosphate wasting	Severe hypophosphatemia and sacral and lumbar insufficiency fractures
73-year-old woman [18]	IDA secondary to gastric antral vascular ectasia	Total of 11 g FCM (as 1 g infusions) over a 2-year period	10-month history of upper and lower limb muscle pain, weakness, back pain, and deteriorating mobility without falls Bilateral insufficiency fractures of the sacral wings Degenerative changes Acute left L5 transverse process fracture and fracture of the lateral mass of sacrum	Hypophosphatemia (serum phosphate 0.27 mmol/L) Hypocalcemia (corrected calcium 2.04 mmol/L) Low 25-hydroxyvitamin D (32 nmol/L) Increased PTH 29.8 pmol/L and ALP (229 IU/L) Increased 24-h urinary phosphate excretion 92 mmol/day	Hypophosphatemia insufficiency fractures
42-year-old man [16]	Crohn’s disease Ileocecal resection and multiple surgical resections of the small intestine IDA	FCM 1 g/month for ca. 1.5 years	Diffuse skeletal pain (lumbar and thoracic spine, ribs, lower extremities), gait disturbance, and progressive loss of mobility Osteomalacia	Hypophosphatemia (serum phosphate 0.50 mmol/L) 24-h urine phosphate excretion indicative of renal phosphate wasting (524 mg) Serum calcium, PTH, and 25-hydroxyvitamin D within the reference range	FGF23-related hypophosphatemic osteomalacia
57-year-old man [19]	Crohn’s disease poorly responsive to multiple therapies 2 bowel resections IDA	26 monthly infusions of FCM 750 mg over about 2 years	1.5-year history of joint and bone pain Osteoporosis	Normo-calcemia with elevated alkaline phosphate and PTH, and low-normal phosphate level TmP/GFR suggestive of renal phosphate wasting Pseudofractures Osteomalacia	FCM-induced hypophosphatemia with autosomal dominant hypophosphatemic rickets precipitated by iron deficiency
38-year-old woman [15]	IDA—caused by heavy menstrual bleeding Vitamin D deficiency	FCM 500 mg (2 infusions) 4 and 3 weeks prior to presentation	Tiredness Diffused muscle pain Weakness	Hypophosphatemia (serum phosphate 0.23 mmol/L) Slightly low albumin-adjusted calcium (1.99 mmol/L) Low 1,25(OH)2D (12 μg/L) TmP/GFR (0.21 mmol/L) suggestive of renal wasting	FGF23-related hypophosphatemia and renal phosphate wasting
33-year-old woman [21]	IDA	FCM 750 mg (2 courses)	Fatigue and shortness of breath increasing over 3 weeks Mild tenderness in the thighs	Hypophosphatemia (serum phosphate 1.2 mg/dL) PTH 38.7 pg/mL 25(OH)vitamin D (22.0 ng/mL) C-terminal FGF-23 (116 RU/mL) Hyperphosphaturia (FEPi 99.76%)	Hypophosphatemia
45-year-old woman [48]	Post gastric bypass surgery	Oral iron supplementation (for about 5+ years at max doses) Iron sucrose (20 mg/mL monthly for ca. 10 months) Iron carboxymaltose (50 mg/mL monthly for 5 months)	Asthenia, weakness, and generalized muscle pain	Hypophosphatemia (serum phosphate 0.9 mg/dL) PTH 179 pg/mL Normal calcium, vitamin D, magnesium, plasma creatinine, and 24-h urine phosphorus	Hypophosphatemia
34-year-old woman [49]	IDA Laparoscopic subtotal colectomy	FCM (2 infusions 1 week apart; last infusion 6 days before surgery)	Significant decrease (of 0.29 mmol/L) in post-surgical phosphate levels led to prolongation of hospitalization	Hypophosphatemia (serum phosphate levels 0.37–0.58 mmol/L) Low levels of 1,25 (OH)2D Significantly increased FEPi (29.8%) suggestive of renal phosphate wasting	Renal phosphate wasting secondary to FGF23 excess
62-year-old woman [50]	Type 2 diabetes Arterial HTN NAFLD Severe asthenia	Oral iron supplementation Packed red blood cells FCM (initially 500 mg Q 2–3 months; most recently 500 mg Q 3 weeks)	Continued intense asthenia	Hypophosphatemia (serum phosphate level 0.61 mg/dL) Vitamin D deficiency FGF23 (427 RU/mL) All other laboratory parameters (including renal) normal	Severe hypophosphatemia
32-year-old woman [51]	Mixed connective tissue disorder Rheumatoid arthritis Systemic lupus erythematosus IDA Remote history of pulmonary embolism and CV accident	FCM 4 weeks prior to hospitalization	Fatigue Weakness Lightheadedness	Hypophosphatemia (serum phosphate 3.6 mg/dL at first FCM infusion) 1 week later serum phosphate 1 mg/dL (repleted with 21 mmol potassium phosphate) After 3rd FCM infusion, serum phosphate < 1 mg/dL	Severe hypophosphatemia
65-year-old man [52]	Hereditary hemorrhagic telangiectasia (Rendu–Osler–Weber syndrome) Chronic anemia due to intestinal blood loss and epistaxis Sensorineural deafness Type 2 diabetes Osteoporosis	Treated orally with ferrous sulfate for 15 years Monthly FCM treatment in prior 2 years	Bone pain in both shoulders, pelvis, and all 4 limbs: worsened with movement Required crutch and wheelchair Bone scans showed multiple hot spots CT confirmed multiple insufficiency fractures	Calcium, 9.2 mg/dL Phosphate 1.2 mg/L ALP 356 U/L 1,25(OH)2D 21.8 ng/mL (optimal > 30 ng/mL) 24-h urine calcium 46.8 mg, phosphate 0.44 g FEPi 5.9% cFGF23 > 419 RU/mL	FGF23-mediated hypophosphatemic osteomalacia

1,25 (OH)₂D 1,25-dihydrodroxyvitamin D, ALP alkaline phosphatase, cFGF23CT C-terminal FGF23 computed tomography, FCM ferric carboxymaltose, FEPi fractional excretion of phosphate, FGF23 fibroblast growth factor 23, HGB hemoglobin, HTN hypertension, IDA iron deficiency anemia, NAFLD non-alcoholic fatty liver disease, PINP procollagen type I N-terminal pro peptide, PTH pituitary thyroid hormone, TmP/GFR tubular maximum reabsorption of phosphate/glomerular filtration rate, ULN upper limit of normal