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Bone Jan 2022Contemporary intravenous iron formulations allow administration of high doses of elemental iron and enable correction of total iron deficit in one or two infusions. An... (Review)
Review
Contemporary intravenous iron formulations allow administration of high doses of elemental iron and enable correction of total iron deficit in one or two infusions. An important but underappreciated complication of certain formulations is hypophosphatemia caused by increased secretion of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). The pathophysiology of FGF23-induced hypophosphatemia due to certain intravenous iron formulations has been recently investigated in prospective clinical trials. To reach the correct diagnosis, clinicians must recognize the typical clinical manifestations of intravenous iron-induced hypophosphatemia and identify a specific pattern of biochemical changes (hyperphosphaturic hypophosphatemia triggered by high FGF23 that causes low 1,25 (OH) vitamin D, hypocalcemia and secondary hyperparathyroidism). Physicians and patients should be aware of hypophosphatemia as a common complication of intravenous iron therapy and monitor serum phosphate concentrations in patients receiving repeated doses of specific intravenous iron formulations. Symptoms of hypophosphatemia are associated with severity and duration. Persistent hypophosphatemia can occur with iron therapy and can cause debilitating diseases including myopathy, osteomalacia and fractures. This review summarizes the current understanding of the iron-phosphate axis as well as complications of intravenous iron-induced hypophosphatemia.
Topics: Anemia, Iron-Deficiency; Fibroblast Growth Factors; Humans; Hypophosphatemia; Iron; Osteomalacia; Prospective Studies
PubMed: 34534708
DOI: 10.1016/j.bone.2021.116202 -
The Journal of Clinical Endocrinology... Dec 2022Hypophosphatemic rickets typically presents in infancy or early childhood with skeletal deformities and growth plate abnormalities. The most common causes are genetic...
Hypophosphatemic rickets typically presents in infancy or early childhood with skeletal deformities and growth plate abnormalities. The most common causes are genetic (such as X-linked hypophosphatemia), and these typically will result in lifelong hypophosphatemia and osteomalacia. Knowledge of phosphate metabolism, including the effects of fibroblast growth factor 23 (FGF23) (an osteocyte produced hormone that downregulates renal phosphate reabsorption and 1,25-dihydroxyvitamin-D (1,25(OH)2D) production), is critical to determining the underlying genetic or acquired causes of hypophosphatemia and to facilitate appropriate treatment. Serum phosphorus should be measured in any child or adult with musculoskeletal complaints suggesting rickets or osteomalacia. Clinical evaluation incudes thorough history, physical examination, laboratory investigations, genetic analysis (especially in the absence of a guiding family history), and imaging to establish etiology and to monitor severity and treatment course. The treatment depends on the underlying cause, but often includes active forms of vitamin D combined with phosphate salts, or anti-FGF23 antibody treatment (burosumab) for X-linked hypophosphatemia. The purpose of this article is to explore the approach to evaluating hypophosphatemic rickets and its treatment options.
Topics: Adult; Child; Child, Preschool; Humans; Familial Hypophosphatemic Rickets; Osteomalacia; Fibroblast Growth Factors; Rickets, Hypophosphatemic; Hypophosphatemia; Phosphates
PubMed: 35981346
DOI: 10.1210/clinem/dgac488 -
Journal of Bone and Mineral Research :... Jul 2011X-linked hypophosphatemia (XLH) is the prototypic disorder of renal phosphate wasting, and the most common form of heritable rickets. Physicians, patients, and support... (Review)
Review
X-linked hypophosphatemia (XLH) is the prototypic disorder of renal phosphate wasting, and the most common form of heritable rickets. Physicians, patients, and support groups have all expressed concerns about the dearth of information about this disease and the lack of treatment guidelines, which frequently lead to missed diagnoses or mismanagement. This perspective addresses the recommendation by conferees for the dissemination of concise and accessible treatment guidelines for clinicians arising from the Advances in Rare Bone Diseases Scientific Conference held at the NIH in October 2008. We briefly review the clinical and pathophysiologic features of the disorder and offer this guide in response to the conference recommendation, based on our collective accumulated experience in the management of this complex disorder.
Topics: Familial Hypophosphatemic Rickets; Genetic Diseases, X-Linked; Humans; Practice Guidelines as Topic; Radiography
PubMed: 21538511
DOI: 10.1002/jbmr.340 -
Critical Care (London, England) 2010Currently no evidence-based guideline exists for the approach to hypophosphatemia in critically ill patients. (Review)
Review
INTRODUCTION
Currently no evidence-based guideline exists for the approach to hypophosphatemia in critically ill patients.
METHODS
We performed a narrative review of the medical literature to identify the incidence, symptoms, and treatment of hypophosphatemia in critically ill patients. Specifically, we searched for answers to the questions whether correction of hypophosphatemia is associated with improved outcome, and whether a certain treatment strategy is superior.
RESULTS
Incidence: hypophosphatemia is frequently encountered in the intensive care unit; and critically ill patients are at increased risk for developing hypophosphatemia due to the presence of multiple causal factors.
SYMPTOMS
hypophosphatemia may lead to a multitude of symptoms, including cardiac and respiratory failure.
TREATMENT
hypophosphatemia is generally corrected when it is symptomatic or severe. However, although multiple studies confirm the efficacy and safety of intravenous phosphate administration, it remains uncertain when and how to correct hypophosphatemia.
OUTCOME
in some studies, hypophosphatemia was associated with higher mortality; a paucity of randomized controlled evidence exists for whether correction of hypophosphatemia improves the outcome in critically ill patients.
CONCLUSIONS
Additional studies addressing the current approach to hypophosphatemia in critically ill patients are required. Studies should focus on the association between hypophosphatemia and morbidity and/or mortality, as well as the effect of correction of this electrolyte disorder.
Topics: Critical Illness; Humans; Hypophosphatemia; Incidence; Intensive Care Units; Phosphates; Prevalence
PubMed: 20682049
DOI: 10.1186/cc9215 -
Nature Reviews. Drug Discovery Mar 2009The family of fibroblast growth factors (FGFs) regulates a plethora of developmental processes, including brain patterning, branching morphogenesis and limb development.... (Review)
Review
The family of fibroblast growth factors (FGFs) regulates a plethora of developmental processes, including brain patterning, branching morphogenesis and limb development. Several mitogenic, cytoprotective and angiogenic therapeutic applications of FGFs are already being explored, and the recent discovery of the crucial roles of the endocrine-acting FGF19 subfamily in bile acid, glucose and phosphate homeostasis has sparked renewed interest in the pharmacological potential of this family. This Review discusses traditional applications of recombinant FGFs and small-molecule FGF receptor kinase inhibitors in the treatment of cancer and cardiovascular disease and their emerging potential in the treatment of metabolic syndrome and hypophosphataemic diseases.
Topics: Animals; Cardiovascular Diseases; Fibroblast Growth Factors; Homeostasis; Humans; Hypophosphatemia; Metabolic Syndrome; Neoplasms; Receptors, Fibroblast Growth Factor
PubMed: 19247306
DOI: 10.1038/nrd2792 -
Frontiers in Endocrinology 2021X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the gene lead to elevated... (Review)
Review
X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidisciplinary group of Belgian experts convened to discuss translation of international best available evidence into locally feasible consensus recommendations. Patients with XLH may present to a wide array of primary, secondary and tertiary care physicians, among whom awareness of the disease should be raised. XLH has a very broad differential-diagnosis for which clinical features, biochemical and genetic testing in centers of expertise are recommended. Optimal care requires a multidisciplinary approach, guided by an expert in metabolic bone diseases and involving (according to the individual patient's needs) pediatric and adult medical specialties and paramedical caregivers, including but not limited to general practitioners, dentists, radiologists and orthopedic surgeons. In children with severe or refractory symptoms, FGF23 inhibition using burosumab may provide superior outcomes compared to conventional medical therapy with phosphate supplements and active vitamin D analogues. Burosumab has also demonstrated promising results in adults on certain clinical outcomes such as pseudofractures. In summary, this work outlines recommendations for clinicians and policymakers, with a vision for improving the diagnostic and therapeutic landscape for XLH patients in Belgium.
Topics: Alkaline Phosphatase; Antibodies, Monoclonal, Humanized; Belgium; Consensus; Familial Hypophosphatemic Rickets; Fibroblast Growth Factor-23; Humans; Hypophosphatemia; Interdisciplinary Communication; Mutation; Osteomalacia; PHEX Phosphate Regulating Neutral Endopeptidase; Severity of Illness Index; Societies, Medical; Treatment Outcome; Vitamin D
PubMed: 33815294
DOI: 10.3389/fendo.2021.641543 -
Acta Haematologica 2019As the adverse effects of iron deficiency are better recognized, the use of oral and intravenous iron has increased dramatically. Oral iron is often poorly tolerated,... (Review)
Review
As the adverse effects of iron deficiency are better recognized, the use of oral and intravenous iron has increased dramatically. Oral iron is often poorly tolerated, with up to 70% or more of patients noting gastrointestinal issues; this may affect adherence to therapy. In addition, many patients will not respond to oral iron due to their underlying illness. Intravenous iron is being used more frequently to replete iron stores. True anaphylaxis is very rare, but complement-mediated infusion reactions may be seen in up to 1 in every 200 patients. Previous concerns about intravenous iron increasing the risk of infection or cardiovascular disease are unfounded.
Topics: Administration, Intravenous; Administration, Oral; Anemia, Iron-Deficiency; Cardiovascular Diseases; Humans; Hypophosphatemia; Iron; Risk Factors
PubMed: 30970354
DOI: 10.1159/000496966 -
Journal of Pediatric Gastroenterology... Dec 2023Refeeding syndrome (RS) is characterized by electrolyte imbalances that can occur in malnourished and abruptly refed patients. Typical features of RS are... (Review)
Review
Refeeding syndrome (RS) is characterized by electrolyte imbalances that can occur in malnourished and abruptly refed patients. Typical features of RS are hypophosphatemia, hypokalemia, hypomagnesemia, and thiamine deficiency. It is a potentially life-threatening condition that can affect both adults and children, although there is scarce evidence in the pediatric literature. The sudden increase in food intake causes a shift in the body's metabolism and electrolyte balance, leading to symptoms such as weakness, seizures, and even heart failure. A proper management with progressive increase in nutrients is essential to prevent the onset of this condition and ensure the best possible outcomes. Moreover, an estimated incidence of up to 7.4% has been observed in pediatric intensive care unit patients receiving nutritional support, alone or as an adjunct. To prevent RS, it is important to carefully monitor feeding resumption, particularly in severely malnourished individuals. A proper strategy should start with small amounts of low-calorie fluids and gradually increasing the calorie content and amount of food over several days. Close monitoring of electrolyte levels is critical and prophylactic use of dietary supplements such as thiamine may be required to correct any imbalances that may occur. In this narrative review, we aim to provide a comprehensive understanding of RS in pediatric clinical practice and provide a possible management algorithm.
Topics: Humans; Child; Refeeding Syndrome; Malnutrition; Nutritional Support; Water-Electrolyte Imbalance; Hypophosphatemia; Electrolytes
PubMed: 37705405
DOI: 10.1097/MPG.0000000000003945 -
Journal of Internal Medicine Mar 2023Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients present with... (Review)
Review
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by mesenchymal tumors that secrete fibroblast growth factor 23 (FGF23). Patients present with progressive bone pain, muscle weakness, and fragility fractures. TIO is characterized by hypophosphatemia, excess renal phosphate excretion, and low/inappropriately normal 1,25-dihydroxyvitamin D (1,25(OH) D) levels. Rarity and enigmatic clinical presentation of TIO contribute to limited awareness among the medical community. Accordingly, appropriate diagnostic tests may not be requested, leading to delayed diagnosis and poorer patient outcomes. We have developed a global guidance document to improve the knowledge of TIO in the medical community, enabling the recognition of patients with TIO and appropriate referral. We provide recommendations aiding diagnosis, referral, and treatment, helping promote a global standard of patient management. We reviewed the literature and conducted a three-round Delphi survey of TIO experts. Statements were drafted based on published evidence and expert opinions (≥70% consensus required for final recommendations). Serum phosphate should be measured in patients presenting with chronic muscle pain or weakness, fragility fractures, or bone pain. Physical examination should establish features of myopathy and identify masses that could be causative tumors. Priority laboratory evaluations should include urine/serum phosphate and creatinine to assess renal tubular reabsorption of phosphate and TmP/GFR, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D, 1,25(OH) D, and FGF23. Patients with the clinical/biochemical suspicion of TIO should be referred to a specialist for diagnosis confirmation, and functional imaging should be used to localize causative tumor(s). Recommended treatment is tumor resection or, with unresectable/unidentifiable tumors, phosphate salts plus active vitamin D, or burosumab.
Topics: Humans; Phosphates; Hypophosphatemia; Paraneoplastic Syndromes; Fractures, Bone; Pain; Fibroblast Growth Factors
PubMed: 36511653
DOI: 10.1111/joim.13593 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2021The refeeding syndrome (RFS) has been recognized as a potentially life-threatening metabolic complication of re-nutrition, but the definition widely varies and, its... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
The refeeding syndrome (RFS) has been recognized as a potentially life-threatening metabolic complication of re-nutrition, but the definition widely varies and, its incidence is unknown. The aim of this systematic review and meta-analyses was to estimate the incidence of RFS in adults by considering the definition used by the authors as well as the recent criteria proposed by the American Society of Parenteral and Enteral Nutrition (ASPEN) consensus. Furthermore, the incidence of refeeding hypophosphatemia (RH) was also assessed.
METHODS
Four databases were systematically searched until September 2020 for retrieving trials and observational studies. The incidences of RFS and RH were expressed as percentage and reported with 95% confidence intervals (CI).
RESULTS
Thirty-five observational studies were included in the analysis. The risk of bias was serious in 16 studies and moderate in the remaining 19. The incidence of RFS varied from 0% to 62% across the studies. No substantial change in the originally reported incidence of RFS was found by applying the ASPEN criteria. Similarly, the incidence of RH ranged between 7% and 62%. In the subgroup analyses, inpatients from Intensive Care Units (ICUs) and those initially fed with >20 kcal/kg/day seemed to have a higher incidence of both RFS (pooled incidence = 44%; 95% CI 36%-52%) and RH (pooled incidence = 27%; 95% CI 21%-34%). However, due to the high heterogeneity of data, summary incidence measures are meaningless.
CONCLUSION
The incidence rate of both RFS and RH greatly varied according to the definition used and the population analyzed, being higher in ICU inpatients and in those with increased initial caloric supply. Therefore, a universally accepted definition for RFS, taking different clinical contexts and groups of patients into account, is still needed to better characterize the syndrome and its approach.
Topics: Consensus; Humans; Hypophosphatemia; Incidence; Observational Studies as Topic; Practice Guidelines as Topic; Refeeding Syndrome
PubMed: 34134001
DOI: 10.1016/j.clnu.2021.04.023