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Endocrine Practice : Official Journal... Oct 2022Phosphate plays a critical and diverse role in human physiology. In addition to its importance in skeletal mineralization, it is essential for energy homeostasis, enzyme... (Review)
Review
Phosphate plays a critical and diverse role in human physiology. In addition to its importance in skeletal mineralization, it is essential for energy homeostasis, enzyme function, and cell membrane integrity. These diverse functions of phosphate provide an explanation for the range of symptoms and clinical manifestations observed in patients with both acute and chronic causes of hypophosphatemia. Normal phosphate homeostasis involves several major systems, including the gastrointestinal tract, bones, and kidneys. Phosphate balance is maintained directly and indirectly by 1α,25-dihydroxyvitamin D, parathyroid hormone, and the osteocyte-derived phosphatonin fibroblast growth factor 23. This review discusses normal phosphate homeostasis, the clinical manifestations and causes of hypophosphatemia, and an approach to establish a diagnosis and appropriate management.
Topics: Bone and Bones; Fibroblast Growth Factors; Humans; Hypophosphatemia; Osteomalacia; Parathyroid Hormone; Phosphates
PubMed: 35940468
DOI: 10.1016/j.eprac.2022.07.005 -
Best Practice & Research. Clinical... Mar 2024
Topics: Humans; Osteomalacia; Familial Hypophosphatemic Rickets; Rickets, Hypophosphatemic; Phosphates
PubMed: 38238129
DOI: 10.1016/j.beem.2024.101859 -
International Journal of Molecular... Nov 2022Among bone-material qualities, mineralization is pivotal in conferring stiffness and toughness to the bone. Osteomalacia, a disease ensuing from inadequate... (Review)
Review
Among bone-material qualities, mineralization is pivotal in conferring stiffness and toughness to the bone. Osteomalacia, a disease ensuing from inadequate mineralization of the skeleton, is caused by different processes leading to decreased available mineral (calcium and/or phosphate) or enzymatic alterations. Vitamin D deficiency, which remains the major cause of altered mineralization leading to inadequate intestinal calcium and phosphate absorption, may be also associated with other conditions primarily responsible for abnormal mineralization. Given the reality of widespread vitamin D inadequacy, a full biochemical assessment of mineral metabolism is always necessary to rule out or confirm other conditions. Both too-high or too-low serum alkaline phosphatase (ALP) levels are important for diagnosis. Osteomalacic syndrome is reversible, at least in part, by specific treatment. Osteomalacia and bone mineralization themselves constitute largely unexplored fields of research. The true prevalence of the different forms of osteomalacia and the recovery after proper therapy have yet to be determined in the real world. Although non-invasive techniques to assess bone mineralization are not available in clinical practice, the systematic assessment of bone quality could help in refining the diagnosis and guiding the treatment. This review summarizes what is known of osteomalacia recent therapeutic developments and highlights the future issues of research in this field.
Topics: Humans; Calcium; Osteomalacia; Vitamin D Deficiency; Vitamin D; Phosphates
PubMed: 36499221
DOI: 10.3390/ijms232314896 -
Journal of Bone and Mineral Research :... Apr 2021Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate...
Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T-CL201 is an ongoing, open-label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X-linked hypophosphatemia post-enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p < 0.0001). Most measures of osteomalacia were improved at week 48: osteoid volume/bone, osteoid thickness, and mineralization lag time decreased; osteoid surface/bone surface showed no change. Of 249 fractures/pseudofractures detected across 14 patients at baseline, 33% were fully healed and 13% were partially healed at week 144. Patients reported a reduction in pain and fatigue and an increase in physical health. Two patients discontinued: one to treat an adverse event (AE) of neoplasm progression and one failed to meet dosing criteria (receiving minimal burosumab). Sixteen serious AEs occurred in seven patients, and there was one death; all serious AEs were considered unrelated to treatment. Nine patients had 16 treatment-related AEs; all were mild to moderate in severity. In adults with TIO, burosumab exhibited an acceptable safety profile and was associated with improvements in phosphate metabolism and osteomalacia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..
Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Osteomalacia; Paraneoplastic Syndromes; Quality of Life
PubMed: 33338281
DOI: 10.1002/jbmr.4233 -
Vnitrni Lekarstvi 2023Osteomalacia with characteristic histomorphometric, radiographic, laboratory and clinical features is a prominent syndrome of disturbed bone mineralisation in adulthood....
Osteomalacia with characteristic histomorphometric, radiographic, laboratory and clinical features is a prominent syndrome of disturbed bone mineralisation in adulthood. From an etiological point of view, osteomalacia is usually caused by substrate (calcium, phosphate) deficiency, presence of excess mineralization inhibitors or deficiency or ineffectivness of mineralization facilitator (vitamin D). In proportion to the high number of congenital and acquired causes of osteomalacia, its clinical and laboratory picture is heterogeneous and rarely fully expressed. The treatment of a particular case is determined by the cause of osteomalacia and may (but does not necessarily) include correction of the underlying disease, administration of calcium and various forms of vitamin D, as well as orthopaedic interventions. For some of the hereditary forms, biological or replacement therapy is prospectively available. The article attempts to cover the whole range of osteomalacia variants, mentioning a fact discussed only in recent years - the occurrence of oligosymptomatic, incompletely expressed forms.
Topics: Humans; Osteomalacia; Calcium; Vitamin D; Vitamin D Deficiency; Syndrome; Vitamins
PubMed: 37468295
DOI: 10.36290/vnl.2023.048 -
Kidney International Nov 2022
Topics: Humans; Osteomalacia; Paraneoplastic Syndromes
PubMed: 36272746
DOI: 10.1016/j.kint.2022.04.042 -
Endocrine Practice : Official Journal... Jul 2020
Topics: Aged; Fanconi Syndrome; Female; Humans; Osteomalacia
PubMed: 33471651
DOI: 10.4158/EP-2019-0433 -
Clinical Calcium Oct 2007Rickets/osteomalacia is a disorder causing mineralization defect and bone and skeletal fragility, although production of bone matrix proteins and their architecture is... (Review)
Review
Rickets/osteomalacia is a disorder causing mineralization defect and bone and skeletal fragility, although production of bone matrix proteins and their architecture is not impaired. The disease is called rickets and osteomalacia in children during skeletal development and in adults, respectively. Pathophysiology in rickets/osteomalacia is defect in vitamin D actions and/or hypophosphatemia. Vitamin D deficiency, inability of activation of vitamin D in vivo or functional derangement in vitamin D receptor is involved in impaired actions of vitamin D. Common causes of hypophosphatemia are excessive actions of fibroblast growth factor (FGF) 23 and renal tubular dysfunction. Among them FGF23 could be a principal regulator for phosphate metabolism, and many investigators are engaged in exploration of physiological and pathophysiological roles of FGF23 in human.
Topics: Adult; Child; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Osteomalacia; Rickets; Vitamin D Deficiency
PubMed: 17906401
DOI: No ID Found -
Vnitrni Lekarstvi 2021Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome typically caused by small endocrine tumors that secrete fibroblast growth factor 23(FGF23). TIO is...
Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome typically caused by small endocrine tumors that secrete fibroblast growth factor 23(FGF23). TIO is clinically characterized by progressive muskuloskeletal pain, fatigue, proximal muscle weakness, and multiple fractures that lead to long-term disability. Due to the non-specific symptoms of the disease, it may take several years for them to be properly diagnosed and treated, so it is important to better inform about this rare paraneoplastic syndrome.
Topics: Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Osteomalacia; Pain; Paraneoplastic Syndromes
PubMed: 35459330
DOI: No ID Found -
Wiener Medizinische Wochenschrift (1946) 2004Although rickets and osteomalacia posed a serious health problem in industrialised countries a hundred years ago, these diseases are now rarely found, and when, usually... (Comparative Study)
Comparative Study Review
Although rickets and osteomalacia posed a serious health problem in industrialised countries a hundred years ago, these diseases are now rarely found, and when, usually in certain risk groups. In underdeveloped countries, rickets is still a major public health problem due to inadequate calcium intake by children. In our highly developed countries, elderly people--especially when institutionalised in nursing homes--are at a very high risk of developing osteomalacia, often combined with pre-existing osteoporosis, with its high impact on mobility and life expectancy in this section of the population. In this review, the common mechanisms involved in developing rickets or osteomalacia are identified and therapeutic measures are reported. Rare causes of osteomalacia due to congenital errors in metabolism or genetic defects are also discussed.
Topics: Aged; Calcium, Dietary; Child; Cross-Sectional Studies; Developed Countries; Developing Countries; Humans; Incidence; Nutritional Requirements; Osteomalacia; Rickets; Risk Factors; Vitamin D
PubMed: 15106892
DOI: 10.1007/s10354-004-0054-3