Materiały źródłowe

• #1 Rickets – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562285/

  Rickets is a condition characterized by a defect in mineralization of the epiphyseal plates. […] Defective mineralization can lead to rickets and/or osteomalacia. Rickets is characterized by a defect in mineralization and the widening of the epiphyseal plates. Osteomalacia, however, is a defect in the mineralization of the bone matrix. […] Any defect in osteoid mineralization may cause rickets. […] Calcium and phosphorus are required for the normal matrix mineralization. Reduction in these minerals causes abnormal mineralization. […] Low serum calcium, either from its low intake or from vitamin D deficiency, causes a compensatory increase in the PTH, which subsequently causes hypophosphatemia. Low serum phosphate, in turn, inhibits the apoptosis of chondrocytes and thereby accumulation of hypertrophic chondrocytes. Eventually, abnormal growth of the cartilaginous epiphyseal plate occurs. This results in many of the clinical manifestations as well as the radiological changes (widening of epiphysis) of rickets.

• #1 Overview of rickets in children – UpToDate

  https://www.uptodate.com/contents/overview-of-rickets-in-children

  Normal bone growth and mineralization require adequate calcium and phosphate, the two major nutritional elements that constitute the crystalline component of bone. Deficient mineralization can result in rickets and/or osteomalacia. Rickets refers to deficient mineralization at the growth plate, as well as architectural disruption of this structure. Osteomalacia refers to impaired mineralization of the bone matrix. Rickets and osteomalacia usually occur together as long as the growth plates are open; only osteomalacia occurs after the growth plates have fused. […] An overview of the pathogenesis, clinical presentation, and the differential diagnosis of rickets is presented here. […] Mineralization defects are classified according to the predominant mineral deficiency: […] Calcipenic rickets is caused by calcium deficiency, which usually is due to insufficient intake of vitamin D or failure to metabolize dietary vitamin D into its active form. […] Phosphopenic rickets is characterized by low serum levels of phosphorus, usually caused by renal phosphate wasting and, less commonly, by nutritional phosphorus deficiency.

• #1 Rickets | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/rickets?lang=us

  Rickets, less commonly known as rachitis, refers to deficient mineralization of the growth plate in the pediatric population. In contrast, osteomalacia refers to deficient mineralization of the bone matrix, which co-occurs with rickets but can also occur even after growth plate closure, in adults. […] Abnormalities in calcium-phosphate homeostasis disrupt endochondral ossification at open physes. The etiologies can be classified by whether the initial abnormality is inadequate calcium absorption or excessive phosphate excretion, termed „calcipenic” and „phosphopenic” rickets, respectively. […] Calcipenic rickets etiologies are the most common: vitamin D deficiency (most common cause) due to diet, insufficient sun exposure, and/or malabsorption; dietary calcium deficiency; defective vitamin D metabolism: mutation in CYP27B1 gene, which encodes the renal 1-alpha-hydroxylase enzyme (vitamin D dependent rickets type 1); 25-hydroxylase deficiency (very rare); hereditary vitamin D resistance: mutation in VDR gene, which encodes the vitamin D receptor (vitamin D dependent rickets type 2). […] Phosphopenic rickets etiologies are usually associated with elevated circulating fibroblast growth factor 23 (FGF23) levels and/or renal tubule disorders: hereditary hypophosphatemic rickets (vitamin D resistant rickets); tumor-induced (oncogenic) rickets; Fanconi syndrome.

• #1 Rickets: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/985510-overview

  Rickets is a disease of growing bone that is unique to children and adolescents. It is caused by a failure of osteoid to calcify in a growing person. Failure of osteoid to calcify in adults is called osteomalacia. […] Vitamin D deficiency rickets occurs when the metabolites of vitamin D are deficient. Less commonly, a dietary deficiency of calcium or phosphorus may also produce rickets. […] Calcitriol acts at 3 known sites to tightly regulate calcium metabolism: (1) it promotes absorption of calcium and phosphorus from the intestine; (2) it increases reabsorption of phosphate in the kidney; and, (3) it acts on bone to release calcium and phosphate. Calcitriol may also directly facilitate calcification. These actions result in an increase in the concentrations of calcium and phosphorus in extracellular fluid.

• #1 Rickets/Osteomalacia. The function and mechanism of vitamin D action. – The Commonwealth Scientific and Industrial Research Organisation (CSIRO)

  http://discovery.csiro.au/discovery/fulldisplay/cdi_pubmed_primary_30269113/61CSIRO_INST:CSIRO

  The antirickets factor vitamin D exhibits its action through activation of vitamin D receptor(VDR). The active form of vitamin D, 1α,25-dihydroxyvitamin D3[1,25(OH)2D3], is a potent VDR ligand, and contributes to the maintenance of calcium homeostasis by enhancing intestinal calcium absorption, renal calcium reabsorption and bone resorption. 1,25(OH)2D3 also regulates bone formation, phosphorus metabolism and vitamin D metabolism. Experimental and epidemiological evidence has shown vitamin D actions on cellular proliferation and differentiation, immunity and inflammation, and cardiovascular function. Vitamin D derivatives and VDR ligands may be useful for the treatment of osteoporosis, malignancy, autoimmune and inflammatory disease and cardiovascular disease as well as rickets and osteomalacia.

• #1 Osteomalacia & Rickets – Free Sketchy Medical Lesson

  https://www.sketchy.com/medical-lessons/osteomalacia-rickets

  The mechanisms that influence bone mineralization are essential in understanding bone pathologies like osteomalacia. In osteomalacia and rickets, the underlying mechanism involved decreased mineralization of osteoid, leading to an accumulation of unmineralized collagen matrix while maintaining preserved bone mass. […] Vitamin D deficiency commonly underlies impaired bone mineralization, resulting in calcium and phosphate deficiency. […] The hypocalcemia that arises from vitamin D deficiency triggers secondary hyperparathyroidism, which increases bone resorption to increase calcium, eventually leading to demineralization. This culminates in osteomalacia in adults and rickets in children. […] Osteomalacia and rickets are both conditions resulting from impaired bone mineralization. Osteomalacia occurs in adults and is marked by decreased mineralization of osteoid, the proteinaceous matrix primarily made of type I collagen. On the other hand, rickets affects children and is characterized by defective mineralization of the type II hyaline cartilage in the epiphyseal growth plates of long bones.

• #1

  https://www.jci.org/articles/view/29449

  The epidemic scourge of rickets in the 19th century was caused by vitamin D deficiency due to inadequate sun exposure and resulted in growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. […] Vitamin D deficiency has again become an epidemic in children, and rickets has become a global health issue. In addition to vitamin D deficiency, calcium deficiency and acquired and inherited disorders of vitamin D, calcium, and phosphorus metabolism cause rickets. […] Vitamin D deficiency is the most common cause of rickets. Vitamin D deficiency prevents the efficient absorption of dietary calcium and phosphorus. […] The poor absorption of calcium causes a decrease in serum-ionized calcium levels. This is immediately recognized by the calcium sensor in the parathyroid glands, resulting in an increase in the expression, synthesis, and secretion of parathyroid hormone (PTH).

• #1 Pathogenesis and diagnostic criteria for rickets and osteomalacia — Proposal by an expert panel supported by Ministry of Health, Labour and Welfare, Japan, The Japanese Society for Bone and Mineral Research and The Japan Endocrine Society [Opinion]

  https://www.jstage.jst.go.jp/article/endocrj/62/8/62_EJ15-0289/_article

  Rickets and osteomalacia are diseases characterized by impaired mineralization of bone matrix. […] Recent investigations revealed that the causes for rickets and osteomalacia are quite variable. […] On the other hand, there are no standard criteria to diagnose rickets or osteomalacia nationally and internationally. Therefore, we summarize the definition and pathogenesis of rickets and osteomalacia, and propose the diagnostic criteria and a flowchart for the differential diagnosis of various causes for these diseases. […] We hope that these criteria and flowchart are clinically useful for the proper diagnosis and management of patients with these diseases.

• #1 SciELO Brazil – New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia

  https://www.scielo.br/j/aem/a/7jZq4smd34mLHd6pNk7vyZd/

  Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. […] Different molecular mechanisms overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. […] If there is not enough phosphorus, the chondrocytes do not go into apoptosis, and osteoid accumulates without mineralization, resulting in growth retardation, rickets, and osteomalacia. […] The inactivation of PHEX mutations results in increased synthesis and secretion of FGF-23, causing phosphaturia, hypophosphatemia, and inappropriately low concentrations of 1,25(OH)2D3.

• #1 Rickets – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/rickets/symptoms-causes/syc-20351943

  Rickets is the softening and weakening of bones in children, often because of an extreme and prolonged vitamin D or calcium deficiency. Rare inherited problems also can cause rickets. […] Vitamin D helps a child’s body absorb calcium and phosphorus from food. Not enough vitamin D makes it hard to maintain proper calcium and phosphorus levels in bones, which can cause rickets. […] Your child’s body needs vitamin D to absorb calcium and phosphorus from food. Rickets can occur if your child’s body doesn’t get enough vitamin D or has problems using vitamin D properly. Occasionally, not getting enough calcium or lack of calcium and vitamin D can cause rickets. […] Some children are born with or develop medical problems that affect the way their bodies absorb vitamin D. Some examples include: Celiac disease, Inflammatory bowel disease, Cystic fibrosis, Kidney problems.

• #1 Hereditary hypophosphatemic rickets: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hereditary-hypophosphatemic-rickets/

  Hereditary hypophosphatemic rickets is a disorder related to low levels of phosphate in the blood (hypophosphatemia). Phosphate is a mineral that is essential for the normal formation of bones and teeth. […] In adults, hypophosphatemia is characterized by a softening of the bones known as osteomalacia. […] Hereditary hypophosphatemic rickets is characterized by a phosphate imbalance in the body. Among its many functions, phosphate plays a critical role in the formation and growth of bones in childhood and helps maintain bone strength in adults. Phosphate levels are controlled in large part by the kidneys. The kidneys normally excrete excess phosphate in urine, and they reabsorb this mineral into the bloodstream when more is needed. However, in people with hereditary hypophosphatemic rickets, the kidneys cannot reabsorb phosphate effectively and too much of this mineral is excreted from the body in urine. As a result, not enough phosphate is available in the bloodstream to participate in normal bone development and maintenance. […] The resulting overactivity of this protein reduces phosphate reabsorption by the kidneys, leading to hypophosphatemia and the related features of hereditary hypophosphatemic rickets.

• #1 Disorders of Calcification: Osteomalacia and Rickets | Oncohema Key

  https://oncohemakey.com/disorders-of-calcification-osteomalacia-and-rickets/

  The architecture of the bone cells and matrix in osteomalacic bone is usually normal. […] Hypomineralized periosteocytic lesions have been observed in some affected individuals with hypophosphatemic rickets. […] The persistence of this defect in patients in whom the abnormality in bone mineralization was corrected with therapy supports the hypothesis that osteocyte function may be abnormal. […] In contrast, there are clear abnormalities in the cells of the rachitic growth plate. […] The characteristic changes occur in the maturation zone of hypertrophic chondrocytes, whereas the resting and proliferative zones show normal histologic features. […] In the maturation zone, the number of cells per column is increased, and the cells are irregularly aligned. […] This is also accompanied by an increase in the transverse diameter, which may extend beyond the ends of the bone, resulting in characteristic cupping or flaring.

• #1

  https://www.orthobullets.com/basic-science/9033/osteomalacia

  Osteomalacia is a metabolic bone disease where defective mineralization results in a large amount or unmineralized osteoid. […] Diagnosis is made based on a thorough evaluation of serum labs, clinical features, and radiographic findings. […] Treatment involves medical management with Vitamin D supplementation and resolving the underlying etiology. […] Mechanism includes a qualitative defect as opposed to a quantitative defect like osteoporosis. […] The following conditions predispose a patient to osteomalacia: vitamin-D deficient diets, malabsorption e.g. celiac disease, renal osteodystrophy, hypophosphatemia, chronic alcoholism, and tumors (tumor-induced osteomalacia). […] Characteristic histology includes widely separated osteoid seams. […] Treatment involves large doses of oral vitamin D (1000IU/day) and treating the underlying cause.

• #1 Pathology Outlines – Rickets / osteomalacia

  https://www.pathologyoutlines.com/topic/bonerickets.html

  Defect in matrix mineralization due to Vitamin D disturbance (deficiency, abnormal metabolism or calcium deficiency) […] Causes accumulation of unmineralized bone matrix […] Various causes related to decreased serum calcium or phosphorus, including rare inborn errors of metabolism or common chronic renal failure; also phosphaturic mesenchymal tumor […] Associated with vague, generalized bone pain or muscle weakness (due to hypocalcemia) […] Rickets: children with irregular, broadened, cup shaped epiphyseal growth plates around knee and wrist […] Osteomalacia: adults, bone formed during remodeling is undermineralized, causes osteopenia and fractures […] Hypophosphatemia: usually due to renal tubular defect, diuretics, hyperparathyroidism; rarely due to a vascular tumor […] Adults: wide, noncalcified matrix surrounding disorganized bone trabeculae; junction between osteoid and mineralized bone is irregular and granular; may be increased bone volume […] Children: thickened, poorly defined growth plate, particularly on metaphyseal side; tongues of uncalcified cartilage may extend into metaphysis; wide osteoid seams.

• #1 Osteomalacia and Rickets | Concise Medical Knowledge

  https://www.lecturio.com/concepts/osteomalacia-and-rickets/

  Rickets and osteomalacia are disorders of decreased bone mineralization. Rickets affects the cartilage, while osteomalacia affects the sites of bone turnover in children and adults. Although most cases of rickets and osteomalacia are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Rickets and osteomalacia can be caused by deficiencies in vitamin D, calcium, or phosphorus, or by abnormalities in bone matrix deposition. […] Vitamin D-related (most common): Vitamin D deficiency is manifested clinically as rickets in children and osteomalacia in adults. Osteomalacia can occur if new osteoid is qualitatively or quantitatively abnormal, insufficient calcium and phosphate are present, or there is inadequate activity of alkaline phosphatase.

• #1

  https://link.springer.com/article/10.1007/s00774-015-0698-7

  Rickets and osteomalacia are diseases characterized by impaired mineralization of bone matrix. Recent investigations have revealed that the causes of rickets and osteomalacia are quite variable. […] On the other hand, there are no standard criteria to diagnose rickets or osteomalacia nationally and internationally. Therefore, we summarize the definition and pathogenesis of rickets and osteomalacia, and propose diagnostic criteria and a flowchart for the differential diagnosis of various causes of these diseases. We hope that these criteria and the flowchart are clinically useful for the proper diagnosis and management of these diseases.

• #2 [Pathophysiology in rickets/osteomalacia] – PubMed

  https://pubmed.ncbi.nlm.nih.gov/17906401/

  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. […] 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.

• #2 Rickets – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562285/

  Inhibited mineralization rickets occurs when there is a defect in growth plate mineralization in the presence of normal calcium and phosphate concentrations. It may result from several predisposing factors including, hereditary hypophosphatasia, medications (first-generation bisphosphonates), and toxicities from aluminum and fluoride.

• #2 Osteomalacia and Rickets | Concise Medical Knowledge

  https://www.lecturio.com/concepts/osteomalacia-and-rickets/

  In the absence of mineralization, the growth plate cartilage accumulates and becomes disorganized, and the growth plate thickens. Accumulation of unmineralized osteoid in the metaphysis eventually leads to bowing and deformation of bones. Osteoclasts resorb the old bone while osteoblasts lay down new osteoid. Osteomalacia can occur if new osteoid is qualitatively or quantitatively abnormal. […] Osteomalacia can occur if calcification is influenced by drugs (e.g., aluminum, fluoride). Inhibitors of mineralization include etidronate, fluoride, aluminum, and iron.

• #2 Rickets: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/985510-overview

  In the vitamin D deficiency state, hypocalcemia develops, which stimulates excess secretion of parathyroid hormone. In turn, renal phosphorus loss is enhanced, further reducing deposition of calcium in the bone. […] Excess parathyroid hormone also produces changes in the bone similar to those occurring in hyperparathyroidism. Early in the course of rickets, the calcium concentration in the serum decreases. After the parathyroid response, the calcium concentration usually returns to the reference range, though phosphorus levels remain low. […] Intestinal malabsorption of fat and diseases of the liver or kidney may produce the clinical and secondary biochemical picture of nutritional rickets. […] Studies have noted that disorders of increased fibroblast growth factor 23 (FGF-23) function are associated with rickets.

• #2

  https://www.jci.org/articles/view/29449

  An inadequate calcium-phosphorus product (Ca+2 HPO42) leads to a defect in bone mineralization that causes rickets in children and osteomalacia in adults. […] Vitamin D deficiency causes global poor mineralization of the skeleton. Clinical and radiological bone manifestations predominate in areas of rapid bone growth, including the long bone epiphyses and the costochondral junctions. […] The skeletal manifestations of rickets represent only the tip of the vitamin D deficiency iceberg. Vitamin D deficiency in utero and during the first year of life has devastating consequences and may imprint on the child’s life chronic diseases that will shorten his/her life span.

• #2

  https://link.springer.com/article/10.1007/s11914-017-0383-y

  The underlying mechanism of all forms of rickets is low serum phosphate resulting in reduced apoptosis of hypertrophic chondrocytes in the growth plate and reduced mineralisation of primary spongiosa in the metaphysis (new bone). In NR, hypophosphataemia is created by secondary hyperparathyroidism. Osteomalacia constitutes defective mineralisation of existing (old) bone during the remodelling process and therefore always goes along with rickets in growing children (open growth plates) and occurs ubiquitously in bones of adults or adolescents (closed growth plates). […] Low calcium intake and/or low vitamin D (from lack of sunshine exposure) are the leading causes of body calcium deprivation worldwide and their combined deficiency accelerates bone demineralisation. […] Hypophosphataemia increases the formation of poorly mineralised osteoid (osteomalacia) alongside a rise in serum alkaline phosphatase (ALP) and causes the growth plate abnormality known as rickets.

• #2 Nutritional Rickets and Osteomalacia in the Twenty-first Century: Revised Concepts, Public Health, and Prevention Strategies | springermedizin.de

  https://www.springermedizin.de/nutritional-rickets-and-osteomalacia-in-the-twenty-first-century/12441620

  Rickets constitutes the defective mineralisation of growth plates. The underlying mechanism of all forms of rickets is low serum phosphate resulting in reduced apoptosis of hypertrophic chondrocytes in the growth plate and reduced mineralisation of primary spongiosa in the metaphysis (new bone). In NR, hypophosphataemia is created by secondary hyperparathyroidism. Osteomalacia constitutes defective mineralisation of existing (old) bone during the remodelling process and therefore always goes along with rickets in growing children (open growth plates) and occurs ubiquitously in bones of adults or adolescents (closed growth plates). Therefore, osteomalacia is not just a disease of adults, but the main reason for long bone bowing deformities and fractures in children with rickets, as poor mineralisation reduces bone stiffness. Low calcium intake and/or low vitamin D (from lack of sunshine exposure) are the leading causes of body calcium deprivation worldwide and their combined deficiency accelerates bone demineralisation.

• #2

  https://www.orthobullets.com/basic-science/9031/rickets

  Bone resorption leads to increased alkaline phosphatase levels. […] In Vitamin D-resistant rickets, there is an inability of renal tubules to absorb phosphate, which is caused by mutations in genes such as PHEX and FGF23. […] This leads to impaired osteocyte maturation and bone mineralization, and increased levels of FGF23.

• #2 Frontiers | Diagnosis, treatment, and management of rickets: a position statement from the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology

  https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1383681/full

  The excessive production of FGF23 reduces tubular phosphate reabsorption and 1α-hydroxylase activity and stimulates renal 24-hydroxylase activity. […] The reduced TmP/GFR ratio found in patients with hypophosphatemic rickets is due to an overproduction or reduced degradation of fibroblast growth factor 23 (FGF23). […] The measurement of FGF23 may be useful to identify the FGF23-mediated from the non-FGF23-mediated hypophosphatemic disorders.

• #2 Bone Mineralization and Related Disorders: Practice Essentials, Vitamin D Metabolism, Pathophysiology

  https://emedicine.medscape.com/article/985766-reference

  FGF-23 has been implicated in the renal phosphate wasting in tumor-induced osteomalacia and autosomal dominant hypophosphatemic rickets. Mutations in the gene that codes for the main renal sodium-phosphate cotransporter (NPT2a) have been reported in some patients with familial renal calcium stones and hypophosphatemia owing to a decrease in renal phosphate reabsorption. These patients have hypercalciuria and elevated levels of 1,25(OH)2 vitamin D3.

• #2 SciELO Brazil – New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia

  https://www.scielo.br/j/aem/a/7jZq4smd34mLHd6pNk7vyZd/

  Different molecular mechanisms overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to the reduction or loss of PHEX can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate. […] The conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D metabolites or analogs as replacement therapy, with a phosphorus dosage of 20 to 40 mg/kg/day administered three to five times daily and a calcitriol dosage of 20 to 30 ng/kg/day. […] Burosumab, a recombinant fully human monoclonal antibody that binds to FGF-23, inhibits FGF-23 signaling and could reverse the effects of excess FGF-23, promoting increased phosphate levels, improved bone mineralization, and reduced morbidity in both conditions, XLH and TIO.

• #2 Rickets – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/rickets/symptoms-causes/syc-20351943

  Factors that can increase a child’s risk of rickets include: Darker skin pigmentation, Mother’s vitamin D deficiency during pregnancy, Northern latitudes, Premature birth, Medicines, Exclusive breastfeeding. […] If not treated, rickets can lead to: Failure to grow, Bone deformities, Dental defects, Seizures. […] Exposure to sunlight provides the best source of vitamin D. During most seasons, 10 to 15 minutes of exposure to the sun near midday is enough. But if you have brown or Black skin, if it’s winter, or if you live in northern latitudes, you might not be able to get enough vitamin D from sun exposure. […] To prevent rickets, make sure your child eats foods that contain vitamin D naturally fatty fish such as salmon and tuna, fish oil, and egg yolks or that have been fortified with vitamin D.

• #2

  https://journals.lww.com/indjem/fulltext/2012/16020/hypophosphatemic_rickets.6.aspx

  XLH rickets occurs due to inactivating mutations in PHEX which encodes a metalloprotease that cleaves small peptide hormones. […] The severity of the disease and specific clinical manifestations are variable even among members of the same family. […] In addition to the mineralization defect induced by hypophosphatemia, an intrinsic osteoblast defect also contributes to the bone disease and does not appear to respond to conventional treatment. […] Biochemical evaluation would reveal low serum phosphorus, normal calcium, normal or slightly elevated PTH, and decreased TMP/GFR (calculated by nomogram). […] Current standard of care is phosphate replacement in the form of phosphate mixture and with 1,25(OH)2D3 or 1-OHD3. […] Phosphate and calcitriol treatment leads to concurrent increases in circulating FGF23 concentrations, which may diminish therapeutic effect or contribute to complications of therapy. […] This is an acquired and paraneoplastic disorder caused due to humoral products known as phosphatonins produced by the tumors. […] Complete surgical removal of the underlying tumor provides definitive cure. Hence, it is important to localize the underlying tumor.

• #2 SciELO Brazil – Hypophosphatemic rickets and osteomalacia Hypophosphatemic rickets and osteomalacia

  https://www.scielo.br/j/abem/a/CYpssMfJYVZ6rKbvCbJk4dd/?format=html&lang=en

  Studies of the 3 main types of hypophosphatemic rickets (XHR, ADHR and TIO) suggest a common pathophysiologic underlying mechanism: hyperphosphaturia secondary to reduction of tubular phosphate reabsorption. Researches on these diseases indicate the existence of a metabolic bone-renal axis capable to regulate the phosphorus homeostasis and the bone mineralization. FGF-23 seems to have a central role on this axis through its phosphaturic action and its autocrine action on osteoblasts, modulating, thus, bone mineralization. Alterations in FGF-23 metabolism, due to inhibition of its proteolytic cleavage or to its increased resistance to proteolysis, trigger disturbances in phosphorus homeostasis and in bone-mineral metabolism.

• #2 Osteomalacia Is Not a Single Disease

  https://www.mdpi.com/1422-0067/23/23/14896

  The deposition of organized hydroxyapatite crystals in the bone matrix is the key event of biomineralization. […] This dynamic process is regulated by multiple soluble paracrine and endocrine factors, an adequate amount of matrix deposited by osteoblasts, enzymes, availability of substrates, and a low concentration of mineralization inhibitors. […] Classically, mineralization disorders were classified as “vitamin D-dependent” or “vitamin D-resistant” states, based on the response to treatment with vitamin D metabolites. […] Calcium and/or phosphate deficiency, excess of mineralization inhibitors, or hormonal excess/defects can lead to altered mineralization. […] Prolonged and severe vitamin D deficiency leads to both calcium and phosphate inadequacy. […] Additional types of osteomalacia are identified as vitamin D-resistant, since the replacement of vitamin D or its analogs does not correct the mineralization defect.

• #2 Disorders Of Calcification: Osteomalacia and Rickets | Clinical Gate

  https://clinicalgate.com/disorders-of-calcification-osteomalacia-and-rickets/

  The mechanism of defective mineralization is not the same in all disorders associated with osteomalacia and rickets, and biochemical indices such as serum levels of calcium and phosphorus also differ. Moreover, the relative imbalance in matrix synthesis and its mineralization varies depending on the underlying disease mechanism. […] The major driving force for mineralization is the concentration of inorganic phosphate (Pi), which at normal sites of mineralization is derived predominantly from the plasma. Therefore, control of Pi reabsorption in the renal tubular lumen is the most important process regulating mineralization. […] Acidosis resulting from a number of different causes has been associated with osteomalacia. The mechanism of bone loss and the mineralization defects are complex and not completely understood.

• #2 Disorders of Calcification: Osteomalacia and Rickets | Oncohema Key

  https://oncohemakey.com/disorders-of-calcification-osteomalacia-and-rickets/

  In experimental rickets, the water content of the growth plate is increased, and a number of metabolic abnormalities have been observed, including decreased glycogen content and an altered pattern of glycolysis. […] In normal bone, the mineralization front is seen at the junction of the osteoid seam and newly mineralized bone. […] In normal persons, the osteoid seam/bone junctions fluoresce intensely; in osteomalacia, the fluorescence is less well defined or even absent. […] In addition to impaired matrix mineralization, matrix biosynthesis may be abnormal in osteomalacia. […] Osteoblast function may be impaired in many forms of human rickets and osteomalacia, which may result in abnormal matrix formation. […] Notably, the hydroxylation of certain collagen lysyl residues is increased in vitamin D-deficient bone, as well as in other experimental hypocalcemic states.

• #3 Osteomalacia and rickets – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/osteomalacia-and-rickets/

  Osteomalacia and rickets are disorders of bone mineralization. Osteomalacia and rickets are caused by insufficient calcium, phosphate depletion, and/or direct inhibition of bone mineralization. The most common cause of both disorders is vitamin D deficiency. […] The causes of osteomalacia and rickets involve at least one of the following mechanisms: Calcipenic rickets, Phosphopenic rickets, Direct inhibition of mineralization impaired bone mineralization. Impaired bone mineralization can affect both existing bone matrix (osteomalacia) and, if growth plates are still open, new bone formation (rickets). […] Low phosphate is present in both calcipenic and phosphopenic forms of osteomalacia and rickets.

• #4

  https://link.springer.com/article/10.1007/s11914-017-0383-y

  Depending on the duration and severity of maternal vitamin D deficiency, the unsupplemented infant is at high risk of presenting in the first few days or months of life with hypocalcaemic complications. These include seizures, tetany and dilated cardiomyopathy which may result in cardiac failure and death. […] Hypophosphataemic complications include muscle weakness leading to hypotonia and delayed development, craniotabes, large fontanelles and bony deformities which usually present in the first 18 months of life. […] Diagnosis is based on clinical findings (long bone deformities, enlargement of wrists and costochondral junctions), typical biochemical abnormalities (increased ALP and PTH) and radiological changes of rickets (cupping, splaying and fraying of metaphyses, widened growth plates and low bone mass).

• #5

  https://link.springer.com/article/10.1007/s11914-017-0383-y

  Osteomalacia in girls can cause pelvic deformities and lead to obstructed labour later in life. […] The global consensus recommendations provide guidance both for clinicians and policy makers on the prevention of rickets, and infants, pregnant women and dark-skinned individuals should be at the core of any policies.

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