What is the treatment for hypophosphatemia (low phosphate levels)?

From the Guidelines

Low phosphate levels should be treated with oral phosphate supplements at a dose of 750-1,600 mg daily (based on elemental phosphorus) in 2-4 divided doses, as recommended by the most recent and highest quality study 1.

Treatment Approach

The treatment approach for low phosphate levels should prioritize the severity and underlying cause of the condition.

• For patients with X-linked hypophosphataemia (XLH), burosumab treatment is recommended in children and adolescents with growing skeletons, radiographic evidence of overt bone disease, and disease refractory to conventional therapy 1.
• Oral phosphate supplements should be given at a dose of 750-1,600 mg daily (based on elemental phosphorus) in 2-4 divided doses, with the dose increased gradually to avoid gastrointestinal adverse effects 1.
• Active vitamin D should be taken in combination with phosphate supplements to reduce osteomalacia and its consequences, and to improve oral health 1.

Monitoring and Adjustments

• Fasting serum phosphate levels should be monitored during the titration period between injections, ideally 7-11 days after the last injection, to detect hyperphosphataemia 1.
• The dose of burosumab should be titrated in 0.4mg/kg increments to raise fasting serum phosphate levels within the lower end of the normal reference range for age, to a maximum dosage of 2.0mg/kg body weight (maximum dose 90mg) 1.
• Burosumab should not be adjusted more frequently than every 4 weeks, and the dose should be discontinued if fasting serum phosphate level is above the upper range of normal 1.

Special Considerations

• In patients undergoing orthopaedic surgery, therapy might need to be discontinued if long-term bed rest and/or non-weight-bearing mobilization is anticipated to avoid hypercalciuria and/or hypercalcaemia due to increased bone resorption 1.
• Pregnant and lactating women with XLH should be treated with active vitamin D in combination with phosphate supplements if needed, and close biochemical monitoring should be performed 1.
• Normal calcium intake (minimum 1g per day) and a low-sodium diet are recommended to reduce calciuria and support weight control 1.

From the FDA Drug Label

INDICATIONS AND USAGE Sodium Phosphates Injection, USP, 3 mM P/mL is indicated as a source of phosphorus, for addition to large volume intravenous fluids, to prevent or correct hypophosphatemia in patients with restricted or no oral intake. CLINICAL PHARMACOLOGY Phosphorus in the form of organic and inorganic phosphate has a variety of important biochemical functions in the body and is involved in many significant metabolic and enzyme reactions in almost all organs and tissues Hypophosphatemia should be avoided during periods of total parenteral nutrition, or other lengthy periods of intravenous infusions The normal level of serum phosphorus is 3.0 to 4.5 mg/100 mL in adults; 4.0 to 7. 0 mg/100 mL in children.

Low phosphate treatment is indicated for patients with hypophosphatemia, which can be prevented or corrected with sodium phosphate injection.

• The treatment goal is to maintain normal serum phosphorus levels, which are 3.0 to 4.5 mg/100 mL in adults and 4.0 to 7.0 mg/100 mL in children.
• Sodium phosphate injection can be used to add phosphorus to large volume intravenous fluids in patients with restricted or no oral intake 2.
• It is also recommended to regularly monitor serum phosphorus levels and add appropriate amounts of phosphorus to infusions to maintain normal levels 2.

From the Research

Low Phosphate Treatment

• Low phosphate levels can be treated with phosphate supplements, which are indicated in patients who are symptomatic or have a renal tubular defect leading to chronic phosphate wasting 3.
• Oral phosphate supplements in combination with calcitriol are the mainstay of treatment for low phosphate levels 3.
• Parenteral phosphate supplementation is generally reserved for patients with life-threatening hypophosphatemia (serum phosphate < 2.0 mg/dL) 3.
• The rate and amount of phosphate replacement are empirically determined, and several algorithms are available 4.
• Treatment is tailored to symptoms, severity, anticipated duration of illness, and presence of comorbid conditions, such as kidney failure, volume overload, hypo- or hypercalcemia, hypo- or hyperkalemia, and acid-base status 4.

Phosphate Supplementation

• Phosphate replacement can be given either orally, intravenously, intradialytically, or in total parenteral nutrition solutions 4.
• Mild to moderate acute hypophosphatemia can usually be corrected with increased dietary phosphate or oral supplementation 4.
• Intravenous replacement is generally needed when significant comorbid conditions or severe hypophosphatemia with phosphate depletion exist 4.
• Chronic hypophosphatemia is typically treated with oral phosphate supplementation and active vitamin D 4.

Vitamin D and Phosphate Interactions

• Vitamin D plays an essential role in calcium and inorganic phosphate homeostasis, maintaining their optimal levels to assure adequate bone mineralization 5.
• The interaction of 1,25(OH)2D with its receptor (VDR) increases the efficiency of intestinal absorption of calcium and phosphate 5.
• Serum phosphate levels can influence 1,25(OH)2D and fibroblast growth factor 23 (FGF23) levels, and high phosphate concentrations can suppress vitamin D activation and stimulate parathyroid hormone (PTH) release 5.

Dietary Phosphate

• The Recommended Dietary Allowance (RDA) for phosphate in the U.S. is around 700 mg/day for adults, but many people consume almost double this amount 6.
• Excessive dietary phosphate consumption can lead to adverse health effects, including cardiovascular diseases, kidney diseases, and tumor formation 6.
• Nutritional education and better guidelines for reporting phosphate content on ingredient labels are necessary to help consumers make informed choices about their diets and minimize phosphate consumption 6.