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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 -
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 -
Bailliere's Clinical Endocrinology and... Apr 1997Osteomalacia is a generalized bone disorder characterized by impairment of mineralization, leading to accumulation of unmineralized matrix or osteoid in the skeleton.... (Review)
Review
Osteomalacia is a generalized bone disorder characterized by impairment of mineralization, leading to accumulation of unmineralized matrix or osteoid in the skeleton. The classical clinical features of osteomalacia include musculoskeletal pain, skeletal deformity, muscle weakness and symptomatic hypocalcaemia. In childhood the features of osteomalacia are accompanied by rickets, with widening of the epiphyses and impaired skeletal growth. The major cause of osteomalacia is vitamin D deficiency, which is most often due to reduced cutaneous production of vitamin D in housebound elderly people, immigrants to Northern countries and women who adopt strict dress codes which prohibit exposure of uncovered skin. Vitamin D deficiency osteomalacia may also occur with malabsorption, liver disease and anticonvulsant therapy. Less commonly, osteomalacia may result from abnormal vitamin D metabolism, resistance to the action of vitamin D, hypophosphataemia or toxic effects on osteoblast function.
Topics: Calcium; Female; Humans; Hypophosphatemia; Male; Metabolism, Inborn Errors; Osteomalacia; Vitamin D; Vitamin D Deficiency
PubMed: 9222490
DOI: 10.1016/s0950-351x(97)80569-1 -
Best Practice & Research. Clinical... Mar 2024Tumor-induced osteomalacia (TIO) is rare paraneoplastic syndrome of hypophosphatemic osteomalacia, caused by phosphaturic factors secreted by small mesenchymal origin... (Review)
Review
Tumor-induced osteomalacia (TIO) is rare paraneoplastic syndrome of hypophosphatemic osteomalacia, caused by phosphaturic factors secreted by small mesenchymal origin tumors with distinct pathological features, called 'phosphaturic mesenchymal tumors'. FGF23 is the most well-characterized of the phosphaturic factors. Tumors are often small and located anywhere in the body from head to toe, which makes the localisation challenging. Functional imaging by somatostatin receptor-based PET imaging is the first line investigation, which should be followed with CT or MRI based anatomical imaging. Once localised, complete surgical excision is the treatment of choice, which brings dramatic resolution of symptoms. Medical management in the form of phosphate and active vitamin D supplements is given as a bridge to surgical management or in inoperable/non-localised patients. This review provides an overview of the epidemiology, pathophysiology, pathology, clinical features, diagnosis, and treatment of TIO, including the recent advances and directions for future research in this field.
Topics: Humans; Neoplasms, Connective Tissue; Osteomalacia; Mesenchymoma; Paraneoplastic Syndromes
PubMed: 37935612
DOI: 10.1016/j.beem.2023.101834 -
Kidney International Nov 2022
Topics: Humans; Osteomalacia; Paraneoplastic Syndromes
PubMed: 36272746
DOI: 10.1016/j.kint.2022.04.042 -
Best Practice & Research. Clinical... Mar 2024
Topics: Humans; Osteomalacia; Familial Hypophosphatemic Rickets; Rickets, Hypophosphatemic; Phosphates
PubMed: 38238129
DOI: 10.1016/j.beem.2024.101859 -
Endocrine-related Cancer Jun 2011Tumor-induced osteomalacia (TIO) is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is... (Review)
Review
Tumor-induced osteomalacia (TIO) is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is high blood levels of the recently identified phosphate and vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23). In TIO, FGF23 is secreted by mesenchymal tumors that are usually benign, but are typically very small and difficult to locate. FGF23 acts primarily at the renal tubule and impairs phosphate reabsorption and 1α-hydroxylation of 25-hydroxyvitamin D, leading to hypophosphatemia and low levels of 1,25-dihydroxy vitamin D. A step-wise approach utilizing functional imaging (F-18 fluorodeoxyglucose positron emission tomography and octreotide scintigraphy) followed by anatomical imaging (computed tomography and/or magnetic resonance imaging), and, if needed, selective venous sampling with measurement of FGF23 is usually successful in locating the tumors. For tumors that cannot be located, medical treatment with phosphate supplements and active vitamin D (calcitriol or alphacalcidiol) is usually successful; however, the medical regimen can be cumbersome and associated with complications. This review summarizes the current understanding of the pathophysiology of the disease and provides guidance in evaluating and treating these patients. Novel imaging modalities and medical treatments, which hold promise for the future, are also reviewed.
Topics: Algorithms; Animals; Diagnosis, Differential; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Neoplasms; Neoplasms, Connective Tissue; Osteomalacia; Paraneoplastic Syndromes; Phosphates
PubMed: 21490240
DOI: 10.1530/ERC-11-0006 -
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 -
Calcified Tissue International Oct 2022Tumor-induced osteomalacia (TIO) is a rare and largely underdiagnosed paraneoplastic condition. Previous reviews often reported incomplete data on clinical aspects,... (Review)
Review
Tumor-induced osteomalacia (TIO) is a rare and largely underdiagnosed paraneoplastic condition. Previous reviews often reported incomplete data on clinical aspects, diagnosis or prognosis. The aim of this study was to present a systematic clinical review of all published cases of TIO. A search was conducted in Pubmed, Embase, Web of Science from inception until April 23rd, 2020. We selected case reports and case series of patients diagnosed with TIO, with information on tumor localization and serum phosphate concentration. Two reviewers independently extracted data on biochemical and clinical characteristics including bone involvement, tumor localization and treatment. 468 articles with 895 unique TIO cases were included. Median age was 46 years (range 9 months-90 years) and 58.3% were males. Hypophosphatemia and inappropriately low or normal 1,25-dihydroxyvitamin D levels, characteristic for TIO, were present in 98% of cases. Median tumor size was 2.7 cm (range 0.5 to 25.0 cm). Serum fibroblast growth factor 23 was related to tumor size (r = 0.344, P < 0.001). In 32% of the cases the tumor was detected by physical examination. Data on bone phenotype confirmed skeletal involvement: 62% of cases with BMD data had a T-score of the lumbar spine ≤ - 2.5 (n = 61/99) and a fracture was reported in at least 39% of all cases (n = 346/895). Diagnostic delay was longer than 2 years in more than 80% of cases. 10% were reported to be malignant at histology. In conclusion, TIO is a debilitating disease characterized by a long diagnostic delay leading to metabolic disturbances and skeletal impairment. Increasing awareness of TIO should decrease its diagnostic delay and the clinical consequences.
Topics: Delayed Diagnosis; Female; Fibroblast Growth Factors; Humans; Hypophosphatemia; Male; Osteomalacia; Paraneoplastic Syndromes
PubMed: 35857061
DOI: 10.1007/s00223-022-01005-8 -
Annals of Internal Medicine Dec 1978Recently acquired knowledge about vitamin D metabolism has improved our understanding in different varieties of osteomalacia. Many new causes of osteomalacia continue to... (Review)
Review
Recently acquired knowledge about vitamin D metabolism has improved our understanding in different varieties of osteomalacia. Many new causes of osteomalacia continue to be found. Radiologic and biochemical changes are not always characteristic and may occasionally be misleading. Bone biopsy after a double tetracycline label is helpful in differentiating osteomalacia from high bone turnover conditions and is recommended in most patients with a generalized rarefying skeletal disorder. Even if the underlying disease state cannot be corrected, effective therapy is available in most varieties of osteomalacia. The newer metabolites of vitamin D should soon be generally available to the medical profession. Their use will make treatment of osteomalacia more individualized and specific.
Topics: Bone Development; Calcium; Humans; Hydroxycholecalciferols; Hydroxylation; Kidney; Liver; Malabsorption Syndromes; Osteoblasts; Osteomalacia; Phosphates; Vitamin D; Vitamin D Deficiency
PubMed: 363010
DOI: 10.7326/0003-4819-89-6-966