X-Linked Familial Hypophosphatemia: A Case Report of 27-Year Old Male and Review of Literature.

X-linked hypophosphatemia (XLH) associated with short stature during childhood are mostly referred to the hospital and diagnosed as vitamin D deficiency rickets and received vitamin D before adulthood. A case is presented with clinical features of hypophosphatemia from childhood who did not seek medical care for diagnosis and treatment, nor did his mother or two brothers, who have short statures, bone pain, and fractures. The patient was assessed for sociodemographic, hematological, and biochemical parameters together with a genetic assessment. A DEXA scan and X-ray were done to determine the abnormalities and deformities of joints and bones despite clinical examination by an expert physician. All imaging, laboratory parameters, and the genetic study confirmed the diagnosis of XLH. A detailed follow-up of his condition was performed after the use of phosphate tablets and other treatments. X-linked hypophosphatemia needs a good assessment, care, and follow up through a complementary medical team including several specialties. Phosphate tablets in adulthood significantly affects clinical and physical improvement and prevention of further skeletal abnormality and burden on daily activity. The patients should be maintained with an adequate dose of phosphate for better patient compliance. More awareness is needed in society and for health professionals when conducting medical checkups during the presence of stress fractures, frequent dental and gum problems, rickets, short stature, or abnormality in the skeleton or walking to think of secondary causes such as hypophosphatemia. Further investigations including a visit to a specialist is imperative to check for the primary cause of these disturbances.

Hypophosphatemia related to intravenous iron therapy with ferric carboxymaltose: A case series.

OBJECTIVES: This case series would like to highlight hypophosphatemia related to ferric carboxymaltose and its adverse clinical consequences. BACKGROUND: Intravenous iron supplementation is a good alternative to oral iron replacement in iron deficiency anaemia due to its ability to correct iron deficit with minimal infusions without incurring the gastrointestinal side effects of oral iron replacement. Ferric carboxymaltose is one common formula for intravenous iron supplementation. However, an increasingly recognised adverse side-effect of intravenous ferric carboxymaltose is hypophosphatemia. There has been increasing reports and studies highlighting hypophosphatemia related to intra-venous iron therapy. Though initially thought to be transient and asymptomatic, recent studies have shown that persistent hypophosphatemia in iron therapy can result in debilitating disease including myopathy, fractures and osteomalacia. METHODS: A retrospective analysis of all patients who had ferric carboxymaltose was performed. RESULTS: We highlight 3 cases where hyposphatemia affected the clinical outcomes. CONCLUSION: With the increased use of IV iron it is important to be aware of the high potential for hypophosphatemia secondary to ferric carboxymaltose.

Impact of Intravenous Iron Substitution on Serum Phosphate Levels and Bone Turnover Markers-An Open-Label Pilot Study.

The association between intravenous iron substitution therapy and hypophosphatemia was previously reported in patients with iron deficiency anemia. However, the extent of hypophosphatemia is thought to depend on the type of iron supplementation. We hypothesized that the intravenous application of ferric carboxymaltose and iron sucrose leads to a different longitudinal adaptation in serum phosphate levels. In this open-label pilot study, a total of 20 patients with inflammatory bowel diseases or iron deficiency anemia were randomly assigned to one of two study groups (group 1: ferric carboxymaltose, n = 10; group 2: iron sucrose, n = 10). Serum values were controlled before iron substitution therapy, as well as 2, 4, and 12 weeks after the last drug administration. The primary objective of the study was the longitudinal evaluation of serum phosphate levels after iron substitution therapy with ferric carboxymaltose and iron sucrose. The secondary objective was the longitudinal investigation of calcium, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone, procollagen type 1 amino-terminal propeptide (P1NP), beta-CrossLaps (CTX), hemoglobin (Hb), iron, ferritin, and transferrin saturation levels. Two weeks after drug administration, phosphate levels were significantly lower (p < 0.001) in group 1 and ferritin levels were significantly higher (p < 0.001) in group 1. Phosphate levels (0.8-1.45 mmol/L) were below the therapeutic threshold and ferritin levels (10-200 ng/mL for women and 30-300 ng/mL for men) were above the therapeutic threshold in group 1. P1NP (15-59 µg/L) and CTX (<0.57 ng/mL) levels were above the therapeutic threshold in group 2. Four weeks after drug administration, significant differences were still observed between both study groups for phosphate (p = 0.043) and ferritin (p = 0.0009). All serum values except for Hb were within the therapeutic thresholds. Twelve weeks after drug administration, no differences were observed in all serum values between both study groups. Hb values were within the therapeutic threshold in both study groups. Serum 25(OH)D levels did not differ between both study groups throughout the whole study period and remained within the therapeutic threshold.

The efficacy and safety of burosumab in two patients with cutaneous skeletal hypophosphatemia syndrome.

Cutaneous skeletal hypophosphatemia syndrome (CSHS) is an ultra-rare mosaic disorder manifesting as skeletal dysplasia and FGF23-mediated hypophosphatemia, with some experiencing extra-osseous/extra-cutaneous manifestations, including both benign and malignant neoplasms. Like other disorders of FGF23-mediated hypophosphatemia including X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO), patients with CSHS have low serum phosphorus and active 1,25-dihydroxyvitamin D levels. Current treatment options for patients with CSHS include multiple daily doses of oral phosphorus and one or more daily doses of active vitamin D analog to correct the deficits. Recently, the fully human monoclonal antibody against FGF23 burosumab received US approval for the treatment of XLH and TIO, two rare diseases characterized by FGF23-mediated hypophosphatemia leading to rickets and osteomalacia. Given the similarities between the pathobiologies of these disorders and CSHS, we investigated the impact of burosumab on two patients, one pediatric and one adult, with CSHS who participated in separate, but similarly designed trials. In both the pediatric and adult patients, burosumab therapy was well-tolerated and contributed to clinically meaningful improvements in disease outcomes including normalization of phosphorus metabolism and markers of bone health, and improvements in skeletal abnormalities, fractures, and physical function. Reported adverse events were minimal, with only mild injection site reactions attributed to burosumab therapy. Together, these findings suggest that burosumab therapy is a promising therapeutic option for patients with CSHS.

Long-term use of burosumab for the treatment of tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral overproduction of FGF-23. Due to local recurrence, we describe the long-term efficacy and safety profile of burosumab, an anti-FGF-23 monoclonal antibody, in a TIO patient after three unsuccessfully surgical attempts. INTRODUCTION: TIO is a rare paraneoplastic syndrome caused by tumoral overproduction of fibroblast growth factor 23 (FGF23), resulting in hyperphospaturia, hypophosphatemia, and osteomalacia. Surgery is the only definitive treatment, but tumor can locally recur, even after years from primary surgery. Furthermore, some tumors cannot be removed by surgery due to their location. METHODS: We describe the case of a 54-year-old woman affected by recurrent TIO who, after three unsuccessful surgical attempts of tumor removal, was treated with burosumab, an anti-FGF-23 monoclonal antibody. RESULTS: The patient was referred to our Bone Unit after experiencing several fractures in different sites, both traumatic and non-traumatic. At the time of first evaluation, at the age of 46, serum-phosphate (SP) was 1.2 mg/dL (reference range (RR) 2.5-4.5), 24-h urinary phosphate was 842 mg (RR 400-1000), and intact-FGF-23 was 117 pg/mL (RR 25-45). Imaging showed a metabolic pre-sacral lesion that firstly underwent to exploratory laparotomy. Then, patient underwent to surgical excision of tumor. After 18 months of well-being, tumor relapsed and even the subsequent surgery was not able to completely remove it. Since 2015, patient was maintained in phosphorus supplements and 1,25(OH)2vitamin D3, but SP levels never normalized. In September 2019, she was started on burosumab, initially at the dose of 0.3 mg/kg/month, progressively increased to the current 0.8 mg/kg/month, with great improvement of pain, physical performance, and normalization of SP levels. Burosumab was temporary and cautionary discontinued for COVID-19 pneumonia, with a worsening of SP. After restart of burosumab, biochemistry returned to normal. CONCLUSIONS: To our knowledge, this is the first European patient affected by TIO treated with burosumab for more than 2 years. Burosumab is a promising therapy in the medical treatment of TIO refractory or not eligible for definitive surgery, with good efficacy and safety profile.

The efficacy and safety of different doses of calcitriol combined with neutral phosphate in X-linked hypophosphatemia: a prospective study.

The present study was the first prospective cohort evaluated the efficacy and safety of different doses of calcitriol in XLH children. The results suggested that a dose of 40 ng/kg/day calcitriol, compared with 20 ng/kg/day, was more effective in relieving the rickets, with similar safety outcomes. Further investigations were expected to set more dose groups. INTRODUCTION: Dose recommended for calcitriol in X-linked hypophosphatemia (XLH) varies in different studies. Therefore, we aimed to compare the efficacy as well as the safety of 20 ng/kg/d and 40 ng/kg/d calcitriol in Chinese XLH pediatrics population. METHODS: A 2-year, randomized, open-label, prospective study recruited 68 XLH children, which were randomized to receive either 40 ng/kg/day or 20 ng/kg/day calcitriol. Efficacy endpoints were the total Thacher ricket severity score (RSS) change from baseline to month 12 and 24, the difference in serum TALP level, fasting serum phosphate level, body height Z-score, and frequency of dental abscess. Safety assessments were done using renal ultrasound nephrocalcinosis grades (0-4), fasting serum and 24 h urine calcium level, and the occurrence of hyperparathyroidism. RESULTS: The decrease in the total RSS from baseline was more significant in the high-dose group at 12 (difference 0.87, p = 0.049) and 24 month (difference 1.23, p = 0.011). The serum TALP level was significantly lower in the high-dose group at 6 months. Pi level, height Z-score change, frequency of dental abscess and ratio of de novo nephrocalcinosis were comparable. A lower incidence of secondary hyperparathyroidism was seen in the high-dose group (p < 0.0001). CONCLUSION: For the first time in this prospective cohort, 40 ng/kg/d calcitriol was shown to be the more effective therapy in XLH children than the 20 ng/kg/d. Moreover, 40 ng/kg/d calcitriol was not associated with increasing adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 03,820,518.

Favorable effects of burosumab on tumor-induced osteomalacia caused by an undetectable tumor: A case report.

RATIONALE: Tumor-induced osteomalacia (TIO) is curable by tumor resection, but detection of the tumor can be challenging. Overproduction of fibroblast growth factor 23 (FGF23) by the tumor causes hypophosphatemia and consequently induces inappropriate bone turnover. Conventionally oral phosphate supplementation was the only treatment for TIO, but had risks of hypercalciuria and nephrocalcinosis. Burosumab, a human monoclonal anti-FGF23 antibody, was recently post-marketed in Japan against for FGF23-related hypophosphatemia. Herein, we present a case of TIO with undetectable tumor that was successfully treated with burosumab. PATIENT CONCERNS: A 47-year-old woman was forced to use a wheelchair because of pain in both feet. DIAGNOSIS: Laboratory findings showed hypophosphatemia, elevated bone markers, and high serum FGF23 without renal tubular defects. Imaging studies revealed bone atrophy in the feet, decreased bone density, and multiple pseudofractures in the talar, sacral, and L5 vertebral regions. After excluding drug-induced and hereditary osteomalacia, we diagnosed her as TIO. INTERVENTIONS: Comprehensive imaging studies and stepwise venous sampling failed to localize the tumor, and we started to administer subcutaneous burosumab. OUTCOMES: After administration of burosumab, her serum phosphate was normalized without phosphate supplementation within 2 months. Improvement of pseudofractures, relief of pain evaluated by a visual analog scale, and normalization of bone biomarkers were observed. The patient was able to stand by herself after 6 months administration of burosumab. LESSONS: This is the first report in clinical practice to demonstrate favorable effects of burosumab, including not only normalization of serum phosphate but also improvements of pseudofractures and subjective pain, in a patient with TIO and undetectable tumor.

Hungry Bone Syndrome After Living Donor Liver Transplant for Biliary Atresia.

Hungry bone syndrome is a rare but potentially lethal complication that is characterized by rapid, severe, long-lasting hypocalcemia and hypophosphatemia secondary to increased bone metabolism. We present a case of hungry bone syndrome after living donor liver transplant for biliary atresia. Following a failed Kasai procedure for biliary atresia, a 5-month-old boy underwent living donor liver transplant with reduced left lateral lobe from his father. Despite the oral administration of alfacalcidol, the patient exhibited severe craniotabes before the surgery. He developed severe hypocalcemia and hypophosphatemia im-mediately after liver transplant and required supplementation of calcium and phosphorus for 1 month thereafter. After serum levels of calcium and phosphate had normalized, there was a rapid increase in the serum bone-type alkaline phosphatase level, and the craniotabes subsided remarkably. To our knowledge, this is the world's first reported case of hungry bone syndrome after liver transplant for cholestatic cirrhosis. It underscores the importance of strict nutritional and electrolyte management in the perioperative period. A prompt diagnosis and correction of hungry bone syndrome are imperative to prevent the associated significant morbidity and mortality.

Efficacy and Safety of Phosphate Enema as a therapeutic agent in Hypophosphatemia in Critically Ill Children.

The aim of the study was to evaluate the safety and efficacy of oral administration of phosphorous enema in hypophosphatemia (HP) in critically ill children admitted in the pediatric intensive care unit (PICU) of The Indus Hospital, Karachi, from September 2018 to August 2019. This was a retrospective review of 31 critically ill children with hypophosphatemia who received 1 ml/kg/day of phosphate enema through nasogastric tube or orally for phosphate replacement, with serial phosphorus level monitoring along with observation for its side effects. The results showed that the rise of serum phosphorus level was observed in all cases and 64.5% of cases achieved target phosphorus level with no adverse reactions observed. Sample size although limited, it is safe to state that oral phosphate enema is safe and effective for correction of hypophosphatemia in critically ill children. Key Words: Hypophosphatemia, Enema, Pediatric intensive care unit.

Refractory hypophosphatemia following ferric carboxymaltose administration.

Hypophosphatemia is a rare side effect of intravenous iron replacement. Urinary phosphate wasting due to increased FGF23 is the most likely mechanism. Here, we present a case of intractable hypophosphatemia in a 32-year-old female patient with history of ulcerative colitis (UC), who was primarily hospitalized due to UC flare-up. Her urinary fractional excretion of phosphate was inappropriately elevated at 70%. A careful history revealed that she had been treated with ferric carboxymaltose 2 weeks prior to hospitalization, leading to a diagnosis of iron-induced hypophosphatemia. She was treated with 5 weeks of intravenous sodium phosphate since she did not tolerate oral supplementation. In conclusion, clinicians should be aware of iron-induced hypophosphatemia and be cautious when prescribing intravenous iron.

New Therapies for Hypophosphatemia-Related to FGF23 Excess.

FGF23 is a hormone produced by osteocytes in response to an elevation in the concentration of extracellular phosphate. Excess production of FGF23 by bone cells, or rarely by tumors, is the hormonal basis for several musculoskeletal syndromes characterized by hypophosphatemia due to renal phosphate wasting. FGF23-dependent chronic hypophosphatemia causes rickets and osteomalacia, as well as other skeletal complications. Genetic disorders of FGF23-mediated hypophosphatemia include X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR), fibrous dysplasia of bone, McCune-Albright syndrome, and epidermal nevus syndrome (ENS), also known as cutaneous skeletal hypophosphatemia syndrome (CSHS). The principle acquired form of FGF23-mediated hypophosphatemia is tumor-induced osteomalacia (TIO). This review summarizes current knowledge about the pathophysiology and clinical presentation of the most common FGF23-mediated conditions, with a focus on new treatment modalities. For many decades, calcitriol and phosphate supplements were the mainstay of therapy. Recently, burosumab, a monoclonal blocking antibody to FGF23, has been approved for treatment of XLH in children and adults, and an active comparator trial in children has shown good efficacy and safety for this drug. The remainder of FGF23-mediated hypophosphatemic disorders continue to be treated with phosphate and calcitriol, although ongoing trials with burosumab for treatment of tumor-induced osteomalacia show early promise. Burosumab may be an effective treatment for the remainder of FGF23-mediated disorders, but clinical trials to support that possibility are at present not available.

Symptomatic hypocalcemia following a single dose of zoledronic acid in a patient with bone metastases secondary to breast cancer.

INTRODUCTION: The use of bisphosphonates is increasing, for treatment of hypercalcemia and pain in cancer, and post-menopausal osteoporosis and also to decrease the risk of skeletal morbidity in multiple myeloma and metastatic breast cancer. CASE REPORT: A single dose of zoledronic acid was administered for hypercalcemia in a 54-year-old woman breast cancer patient with extensive bone metastasis. After the first dose, the patient developed symptomatic hypocalcemia.Management and outcome: Simultaneous hypocalcemia, hypophosphatemia, and vitamin D deficiency were detected in the patient. In the symptomatic process, intravenous, then oral replacement was performed. DISCUSSION: There is a need for taking precautionary measures such as vitamin D, serum phosphorus and, calcium monitoring and supplementation to prevent life-threatening complications, such as symptomatic hypocalcemia, especially in populations with vitamin D deficiency like ours.

Ferric carboxymaltose (Ferinject®) associated hypophosphataemia: case report illustrating the need for increased awareness to minimise incidence and risk.

Ferric carboxymaltose (Ferinject®) is an infusion administered for the treatment of iron deficiency anaemia. A number of previous case reports have shown the occurrence of hypophosphataemia after Ferinject® treatment, supposedly managed though high dose phosphate therapy. This case report highlights the risk associated with, and futility of, managing this adverse effect through high dose phosphate infusion. A review of the available literature suggests that if hypophosphataemia develops as a result of Ferinject®, through upregulation of the renal protein Fibroblast Growth Factor-23, it cannot be readily reversed and on average persists for circa 50 days. Acute medical units should be aware of this - likely underreported - adverse effect, and avoid treating these hypophosphataemic patients with high dose phosphate since it can compound symptoms.

The Association of Hypophosphatemia With Resistant Lactic Acidosis in Critical Care Illness.

Critically ill patients are known to have a variety of electrolyte abnormalities. Lactic acidosis can frequently be seen secondary to shock states and is usually treated with aggressive volume resuscitation. Interestingly, hypophosphatemia is a potential cause of resistant lactic acidosis, which may not be as commonly identified or considered. We present a case of a 42-year-old man admitted twice over a span of 6 months with an elevated lactate level that did not resolve with volume resuscitation. It was ultimately determined that his lactic acidosis was due to hypophosphatemia after ruling out other potential causes. Phosphate replacement therapy resulted in the normalization of his lactate. In the literature, multiple theories have indicated the association of hypophosphatemia with lactic acidosis though no prior cases exist supporting a direct relationship. In this case, we set forth to evaluate the complicated relationship between all of these factors and to highlight the importance of early detection and treatment of hypophosphatemia, which may be beneficial in treating lactic acidosis.

Resistant iron-induced hypophosphatemia following colorectal surgery.

Iron-induced hypophosphatemia represents an increasingly recognised complication of iron infusion. A 34-year-old woman presented for surgical management of her colorectal cancer. Post-operative blood tests revealed severe hypophosphatemia, resistant to oral phosphate supplementation and large volumes of intravenous phosphate replacement. Further questioning and biochemical investigation led to the recognition of iron-induced hypophosphatemia as a contributory cause, secondary to iron infusion administered as part of pre-operative optimisation. Early consideration, diagnosis and management of this complication has the potential to reduce fluid burden associated with intravenous phosphate supplementation and optimise post-operative care.

Denosumab improves clinical manifestations of hypophosphatemic osteomalacia by adefovir-induced Fanconi syndrome: a case report.

BACKGROUND: Adefovir dipivoxil is a nucleotide analogue that is approved for treatment of chronic hepatitis B. Adefovir dipivoxil is associated with proximal tubular dysfunction, resulting in Fanconi syndrome, which can cause secondary hypophosphatemic osteomalacia. We describe a case of a patient with hypophosphatemic osteomalacia secondary to Fanconi syndrome induced by adefovir dipivoxil concomitantly with osteoporosis in whom clinical symptoms were improved by adding denosumab (a human monoclonal antibody targeting the receptor activator of nuclear factor-κB ligand) to preceding administration of vitamin D3. CASE PRESENTATION: A 60-year-old Japanese man had been receiving low-dose adefovir dipivoxil (10 mg/day) to treat chronic hepatitis B for approximately 5 years. He presented to an orthopedic surgeon with severe pain of the right hip and no trauma history, and fracture of the neck of the right femur was identified. In addition, 99mTc-hydroxymethylene diphosphate scintigraphy revealed significantly abnormal uptake in the bilateral ribs, hips, and knees, and he was therefore referred to our university hospital for evaluation of multiple pathological fractures. We diagnosed hypophosphatemic osteomalacia due to Fanconi syndrome induced by adefovir dipivoxil therapy. Although we reduced the patient's adefovir dipivoxil dose and added calcitriol (active vitamin D3), he did not respond and continued to complain of bone pain. Several bone resorption markers and bone-specific alkaline phosphatase were also persistently elevated. Therefore, we added denosumab to vitamin D3 supplementation for treatment of excessive bone resorption. Two months after initiation of denosumab, his hip and knee pain was relieved, along with a decrease in serum alkaline phosphatase and some bone resorption markers. CONCLUSIONS: Although denosumab is not generally an appropriate treatment for acquired Fanconi syndrome, it may be useful for patients who have hypophosphatemic osteomalacia due to adefovir dipivoxil-induced Fanconi syndrome associated with excessive bone resorption. However, clinicians should keep in mind that if denosumab is administered to patients with hypophosphatemic osteomalacia accompanied by excessive bone resorption, adequate vitamin D and/or phosphate supplementation should be done before administration of denosumab.

Phosphate supplementation for hypophosphatemia during continuous renal replacement therapy in adults.

BACKGROUND: Hypophosphatemia is common during continuous renal replacement therapy (CRRT) in critically ill patients and can cause generalized muscle weakness, prolonged respiratory failure, and myocardial dysfunction. This study aimed to investigate the efficacy and safety of adding phosphate to the dialysate and replacement solutions to treat hypophosphatemia occurring in intensive CRRT in critically ill patients. METHODS: We retrospectively analyzed 73 patients treated with intensive CRRT (effluent flow ≥35 ml/kg/hr) in the intensive care unit. The control group (group 1, n = 22) received no phosphate supplementation. The treatment groups received dialysate and replacement solution phosphate supplementation at 2.0 mmol/L (group 2, n = 26) or 3.0 mmol/L (group 3, n = 25). RESULTS: The CRRT-induced hypophosphatemia incidence was 59.0%. Correction of hypophosphatemia with phosphate supplementation changed the mean serum phosphorus levels to 1.24 ± 0.37 and 1.44 ± 0.31 mmol/L in groups 2 and 3, respectively (p = .02). The time required for correction was 1.65 ± 0.80 and 1.39 ± 1.43 days for groups 2 and 3, respectively and was significantly longer in group 2 (p = .02). After supplementation, hypophosphatemia, and hyperphosphatemia both occurred in 7% of group 2. Group 3 developed no hypophosphatemia, but 20% developed hyperphosphatemia. The serum phosphate levels in hyperphosphatemia cases returned to normal within 2.0 days (group 2) and 1.0 day (group 3) after stopping phosphate supplementation. CONCLUSION: Phosphate supplementation effectively corrected CRRT-induced hypophosphatemia in critically ill patients with an acute kidney injury. The use of 2 mmol/L phosphate is appropriate in patients with CRRT-induced hypophosphatemia, but a different concentration could be required to prevent hypophosphatemia at the start of CRRT.

Early Hypophosphatemia in High-Risk Preterm Infants: Efficacy and Safety of Sodium Glycerophosphate From First Day on Parenteral Nutrition.

BACKGROUND: Early hypophosphatemia is common in premature infants ≤1250 g. The aim of this study was to assess the frequency and severity of hypophosphatemia after sodium glycerophosphate supplementation from first day of life in parenteral nutrition and to address the safety of this practice. METHODS: Prospective cohort study of infants ≤1250 g birth weight born in a tertiary-care level neonatal intensive care unit and supplied with sodium glycerophosphate from the first day of life. Primary outcome was the presence of hypophosphatemia (<4 mg/dL) on the first week. Data were compared with our 2014 prospective subcohort of infants ≤1250 g receiving phosphate after 48 hours of life and morbidity with that of our 2016 retrospective cohort of ≤1250 g. RESULTS: Fifty-four neonates were included. The frequency of hypophosphatemia was 29.6%. Only 1 patient presented hypophosphatemia <2 mg/dL. Mild hypokalemia was found in 8 patients (50%). No cases of hypernatremia were observed. Patients with hypophosphatemia had significantly lower gestational age (27.4 vs 28.8 weeks, P = .032) and lower z-score birth weight (-1.68 vs -0.47; P = .001). When compared with the 2014 subcohort, we found a lower frequency of hypophosphatemia (29.6% vs 69.2%; P = .008) and a lower rate of samples with hypophosphatemia (20.4% vs 51.4%; P = .0002) and critical hypophosphatemia (0.68% vs 11.4%, P = .0005). No differences were found in morbidity or mortality. CONCLUSIONS: Sodium glycerophosphate supplementation in parenteral nutrition from the first day of life significantly decreased the frequency of hypophosphatemia. No adverse events were reported.

Efficacy and safety of a phosphate replacement strategy for severe hypophosphatemia in the ICU.

BACKGROUND: Experience with individualized phosphate replacement is limited in patients with severe hypophosphatemia. This study compares the efficacy and safety of an individualized regimen of serum phosphate < 0.4 mmol/l treatment in ICU patients to patients with moderate hypophosphatemia (0.4-0.6 mmol/l). METHODS: This retrospective cohort study included 36 patients with severe and 35 patients with moderate hypophosphatemia. Supplementation dose was calculated according to the equation: phosphate dose (in mmol) = 0.5 x body weight x (1.25 - [serum phosphate]). Sodium-potassium-phosphate was infused at a rate of 10 mmol/hour. Blood samples were taken at baseline and the next morning at 06.00 hrs. RESULTS: Serum phosphate rose to a level > 0.40 mmol/l in all patients with severe hypophosphatemia. Serum phosphate increased to > 0.60 mmol/l in 56% of patients with severe hypophosphatemia and in 86% of patients with moderate hypophosphatemia (p = 0.01). Mild hyperphosphatemia was observed in one patient only (1.53 mmol/l), hyperkalemia was observed in three patients (all three had severe hypophosphatemia, average potassium after supplementation was 5.2 ±; 0.2 mmol/l) and serum calcium levels remained unchanged in both groups. CONCLUSION: Individualized phosphate replacement was effective and safe for both moderate and severe hypophosphatemia, but was more accurate in moderate hypophosphatemia.

Suitability of oral administration of monosodium phosphate, disodium phosphate, and magnesium phosphate for the rapid correction of hypophosphatemia in cattle.

BACKGROUND: Hypophosphatemia is commonly associated with disease and decreased productivity in dairy cows particularly in early lactation. Oral supplementation with phosphate salts is recognized as suitable for the rapid correction of hypophosphatemia. Little information is available about the differences in efficacy between salts used for oral phosphorus supplementation. OBJECTIVES: Comparison of efficacy of oral administration of NaH2 PO4 , Na2 HPO4 , and MgHPO4 in treating hypophosphatemia in cattle. ANIMALS: 12 healthy dairy cows in the fourth week of lactation in their second to fifth lactation. METHODS: Randomized clinical study. Phosphorus deficient, hypophosphatemic cows underwent a sham treatment and were afterwards assigned to 1 of 3 treatments-NaH2 PO4 , Na2 HPO4 , or MgHPO4 (each provided the equivalent of 60 g of phosphorus). Blood samples were obtained immediately before and repeatedly after treatment. RESULTS: Treatment with NaH2 PO4 and Na2 HPO4 resulted in rapid and sustained increases of plasma phosphate concentrations ([Pi]). Significant effects were apparent within 1 hour (NaH2 PO4 : P = .0044; Na2 HPO4 : P = .0077). Peak increments of plasma [Pi] of 5.33 mg/dL [5.26-5.36] and 4.30 mg/dL [3.59-4.68] (median and interquartile range) were reached after 7 and 6 hours in animals treated with NaPH2 PO4 and Na2 HPO4 , respectively, whereas treatment with MgHPO4 led to peak increments 14 hours after treatment (3.19 mg/dL [2.11-4.04]). CONCLUSIONS AND CLINICAL IMPORTANCE: NaH2 PO4 and Na2 HPO4 are suitable to rapidly correct hypophosphatemia in cattle. Because of the protracted and weaker effect, MgHPO4 cannot be recommended for this purpose. Despite important differences in solubility of NaH2 PO4 and Na2 HPO4 only small plasma [Pi] differences were observed after treatment.