Osteomalacia and Rickets

Introduction to osteomalacia and rickets Osteomalacia and rickets are a bone disease characterized by a newly formed bone mineralization disorder, which results in the accumulation of non-mineralized bone-like tissue (osteoid), softening of the bone, and bone pain. A series of clinical symptoms and signs such as bone deformities and fractures, the causes of the disease are various, mainly divided into four categories: 1 vitamin D nutritional deficiency. 2 Vitamin D is deficient in metabolic activity. 3 The mineral content of the bone mineralization site is lacking. 4 bone cells, bone matrix disorders. Before puberty, that is, the damage of the long bone growth plate before the closure to the closure period is rickets. In adults, the bone mineralization damage after the closure of the epiphysis growth plate is called osteomalacia. Mineral deficiency in bone mineralization is a major role in mineralization and re-construction of bone growth. Vitamin D and PTH play an important role. Their role is to maintain a normal mineralized environment of calcium, phosphorus and magnesium, and maintain bone. Adequate supply of minerals to meet all aspects of the needs and healthy growth of bones, mineralization and re-construction, if for a variety of reasons the body intake of calcium, phosphorus, magnesium and other mineralized substances are insufficient or lost from the intestines, kidneys, even Vitamin D and PTH are normal, and bone metabolism abnormalities or mineralization disorders may occur, leading to osteomalacia and rickets. The formation of bone is an orderly and complex process. During the earliest stage of new bone formation, the organic phase is the production of matrix or osteoid. The matrix or osteoid is secreted by various glycoproteins, mucopolysaccharides and osteoblasts. Collagen composition, collagen is the basis of bone strength, mineral deposition of the stent, mainly contains high concentrations of hydroxyproline and hydroxylysine, after the formation of collagen fibers, cross-texture occurs in the cross-polymerization, and finally these polymerized parts are connected to each other. It is the maturation process, the mineralization of the matrix is initially related to collagen, the mineralization process must begin after the osteoids mature, the calcium salt crystals are deposited between the collagen units, and the crystals are formed in the matrix between the collagen fibers in the later mineralization stage. Calcium is precipitated in bone tissue in the form of amorphous calcium phosphate and hydroxyapatite, which makes the bone hard. Therefore, the mineralization of bone is not only related to the deposition of inorganic minerals such as calcium, phosphorus and magnesium, but also with bone matrix and production. The osteoblasts of collagen are closely related, and the disorder of bone matrix and osteoblasts will inevitably affect the speed and quality of bone mineralization, leading to softening of bone. basic knowledge The proportion of illness: 0.003% Susceptible people: good for children Mode of infection: non-infectious Complications: vitamin D deficiency in children, hand, foot and ankle syndrome, throat, bone softening and rickets

Osteomalacia and the cause of rickets

Mineralization of bone is a very complex process, from the basic chondrocytes, the formation of bone matrix, the supply of raw calcium, phosphorus, magnesium to the stability of the local internal environment, hormones such as parathyroid hormone (PTH), l, 25- (OH) 2D3, the regulation of calcitonin (CT), failure of any link can affect the mineralization of bone and lead to rickets and osteomalacia.

There are many causes of osteomalacia and rickets. Vitamin D deficiency is the main cause in a large number of countries before the 1970s, especially in developing countries. In recent years, with the improvement of people's nutritional status and living conditions, the disease has been recognized. Improvement and prevention, nutritional vitamin D deficiency rickets and osteomalacia are significantly reduced, and hereditary, metabolic defects caused by rickets and osteomalacia will become more important reasons, with the improvement of testing techniques and molecular biology Application, the latter may become the main direction of future research, due to the complexity of rickets and osteomalacia, leading to rickets and osteomalacia may have multiple factors at the same time, so the book for the cause of rickets and osteomalacia and The classification is more confusing, and this article is grouped into 4 categories.

The disease is characterized by the fact that the newly formed bone matrix cannot be mineralized in a normal way. Mineralization of the bone is a complex process involving calcium, phosphorus metabolism, osteoblast function and acid-base environment of mineralized parts. Factors, causing osteomalacia and rickets mainly include the following aspects:

Vitamin D deficiency (20%):

Vitamin D plays an important role in the body's calcium and phosphorus metabolism. It can promote the absorption of calcium and phosphorus in the small intestine, increase the absorption of calcium and phosphorus in the renal tubules, stimulate the absorption of bone calcium, and mobilize bone salts under the synergistic effect of PTH. Dissolving; maintaining the normal concentration of calcium and phosphorus in the blood, is conducive to the deposition of bone salt in the bone, and promotes the formation of new bone. Therefore, vitamin D deficiency and metabolic disorders are important causes of rickets and osteomalacia, causing There are many reasons for vitamin D deficiency, including:

(1) Insufficient sunshine: It is estimated that when exposed to sunlight, people can produce 6 U of vitamin D3 per square centimeter of skin per hour. Normal daylight can produce vitamin D of 310-100 g per day. If there is sufficient calcium and phosphorus diet, Prevent the occurrence of rickets and osteomalacia, but many factors can affect the amount of sunshine and UV absorption, such as seasons, temperature, air pollution, etc., the season can significantly affect the amount of sunshine and vitamin D, in winter, spring due to sun exposure The amount of 25-(OH)D3 is more than the average daily solar radiation. With the development of industry, industrial smoke and coal dust pollution further reduce the useful ultraviolet light. In fact, the disease may be air. The first example of a polluting disease, in addition, skin pigmentation, traditional clothing habits, and reduced outdoor activities are also important causes of reduced sun exposure. Skin pigmentation can lead to a reduction in UV absorption, in the cold regions or near the equator to avoid cold. Or the hot sun shines over the baby, Asian girls and women are used to staying in the house, wearing traditional The habit of closing the curtains in the room and the squatting room can make the mother and children less exposed to sunlight. In recent years, the cities are increasingly crowded, the buildings are dense, the floors are rapidly increasing, the street sunshine is gradually reduced, people are working hard, outdoor activities are reduced, especially many Older people have longer lifespans and metabolic decay in their bodies, and fewer mobility activities result in less out-of-life activities, which lead to nutritional vitamin D deficiency, rickets and osteomalacia or subclinical osteomalacia.

(2) Insufficient intake: Some children in the United States have reported rickets caused by vegetarian diet. In some areas, flour contains higher amounts of phytate and lignin. Phytate can bind calcium and zinc to increase their excretion. Lignin can form a complex with bile acid, which affects the absorption of vitamin D, and can cause rickets.

(3) gastrointestinal lesions and postoperative often accompanied by malabsorption of vitamin D; biliary tract diseases such as biliary cirrhosis, biliary obstruction affects the absorption of fat, also affects the absorption of fat-soluble vitamin D; pancreatic dysfunction can also cause vitamins D absorption is reduced.

(4) Malabsorption: Many causes of vitamin D deficiency are small intestine, hepatobiliary dysfunction, pancreatic disease with intestinal malabsorption, and vitamin D loss not only include oral vitamin D, but also Endogenous products, including: gastrectomy, small bowel resection or bypass anastomosis, Crohn's disease, gluten dystrophy, regional enteritis, diverticulum multiple dystrophy, stagnation (blind) ring syndrome, hard Skin disease, pancreatic exocrine deficiency, pancreatic duct adhesion obstruction, chronic steatorrhea, biliary obstruction, obstruction of the extrahepatic bile duct, congenital biliary atresia, etc., UK report that 25% of patients with small bowel bypass have osteomalacia histology Evidence, and there is a decrease in 25-(0H)D3 levels, but X-ray findings of osteomalacia are less common, and osteomalacia is also one of the surgical complications of partial gastrectomy (usually Bi-type II), but reported The incidence of bone disease varies greatly. Edd compares the radiological examination of patients who have undergone gastrectomy and peptic ulcer without surgery. It shows that the former group has obvious lesions in the mineralization of the thoracic and lumbar vertebrae, and 5.8% of the patients have disease. Sexual fractures, most of the previous studies considered that in gastrointestinal dystrophy and hepatobiliary disorders, an important common feature of vitamin D deficiency is interference with the intestinal hepatic circulation of 25-(0H)D3, but recent studies by Clement et al. show that 25-(OH) The intestinal and hepatic circulation of D3 is negligible, so the intestinal hepatic circulation of 25-(OH)D3 is responsible for the vitamin D deficiency. There is no unified statement. For the absorption of vitamin D, bile salts are necessary, and biliary obstruction is necessary. Such as congenital biliary atresia, extrahepatic bile duct obstruction, etc. have decreased vitamin D levels, pancreatic disease with absorption disorder, the incidence of osteomalacia is not many, 25-(OH)D3 levels are also different, but they can have significant hypocalcemia With secondary parathyroidism, in short, gastrointestinal, hepatobiliary diseases caused by rickets and osteomalacia, often the result of multiple factors, in addition to vitamin D absorption disorders, often accompanied by calcium, phosphorus, magnesium malabsorption In addition, the reduction of sun exposure, chronic diarrhea caused by systemic malnutrition, can affect vitamin D levels and bone mineralization, as well as the drug cholestyramine can bind bile acid in the intestine, increasing the risk of bone softening, even It exceeds the primary disease treatment.

(5) It is not uncommon for women with relatively high vitamin D requirements to cause osteomal softening in the end of pregnancy and lactation, especially in Asia, which may be related to the tradition of the region's many children. The end-stage and lactation period are not related to the customs, the customs of doors and windows are closed, and the calcium content of the mother is greatly increased by pregnancy and breastfeeding. The bones of newborn babies contain about 23g of calcium and 14g of phosphorus. Most of these minerals are in pregnancy. At the end of the period, the mother receives 300-500 mg of calcium per day. If the mother does not have a large amount of vitamin D synthesis and a sufficient amount of calcium supplement, it is easy to cause osteomalacia. Infants, especially premature babies are also Vitamin D needs to increase in the period of time. In addition to artificially fed babies due to the imbalance of calcium and phosphorus intake, it is easy to suffer from rickets. Recent studies have shown that vitamin D content in breast milk is only 40-50 U/L, and water-soluble vitamin D sulfate activity is only 1 % to 5%, can not prevent the occurrence of rickets, and then puberty (11 to 17 years old) bone development is vigorous, plasma 25-(0H)D3 is flat and low, and this period often overlooks the survival D supplement, is an important cause of late-onset rickets.

Defects in vitamin D metabolism (16%):

The main pathogenesis of this type of disease is not due to the deficiency of maternal vitamin D, but due to the metabolic disorder in the process of the conversion of maternal vitamin D into active vitamin D. There are many reasons, including congenital genetic defects, acquired diseases and drugs. The synthesis of 25-(OH)2D3 is reduced, and a series of damage caused by target organ receptor defects, many pathological mechanisms are still not very clear. With the development of molecular biology, this type of disease will become the main research. Object.

Decreased production of 25-(OH)D3 in the liver: a decrease in 25-(OH)D3 can directly lead to a decrease in the synthesis of 1,25-(OH)2D3, causing rickets and osteomalacia, and a decrease in 25-(OH)D3, one is Due to the lack of maternal vitamin D, it is a nutritional vitamin D deficiency, which has been discussed previously; the second is due to the reduction of maternal vitamin D2 and D3 to 25-(0H)D3 levels, and the liver is vitamin D for 25 hydroxylation. The main site, in a variety of liver diseases, including severe chronic alcoholic hepatitis, cirrhosis, chronic active hepatitis and primary biliary cirrhosis, can lead to a decrease in 25-(OH)D3 production and 1,25 -(OH)2D3 levels are reduced, affecting bone mineralization. The bone disease caused by this condition is also called "hepatic bone dystrophy". Many patients are asymptomatic, but histology is found to have osteoporosis and osteomalacia. As mentioned above, liver and biliary diseases often lead to cholestasis, reduced bile salts, and can also cause malabsorption of vitamin D, and protein synthesis disorders in liver disease. The reduction of binding protein of vitamin D and active vitamin D also affects its transport function. Cholestyramine can bind to endogenous 25-(OH)D3, plus The 25-(0H)D3 in the blood is reduced, so the cause of osteomalacia in liver diseases may be multifaceted. Iong et al found that although the level of 25-(0H)D3 in most untreated liver patients can be significantly reduced, With sufficient ultraviolet radiation, the level will be normal, similar situations can also occur in premature infants, especially low-weight immature children, whose birth weight is often less than 1000g, the number of months of pregnancy is less than 28 weeks, due to liver 25 hydroxylation The function is still immature, resulting in a decrease in the concentration of 25-(OH)D3 in the blood. Osteopathy often occurs 12 weeks after birth and can be prevented and treated by administering vitamin D.

Phosphorus metabolism disorder (20%):

Phosphorus is an important bone salt component. 80%-85% of the body's phosphorus is deposited in bones, combined with calcium to form hydroxyapatite crystals. Phosphorus deficiency (insufficient intake or malabsorption) and metabolic disorders are also caused by rickets and bones. An important cause of softening, such as X-linked anti-vitamin D hypophosphatemic rickets (as X-linked dominant hereditary disease) or secondary to other lesions such as tumors can also cause hypophosphatemia.

(1) Rickets and osteomalacia caused by antiepileptic drugs

Since Wright first raised the blood alkaline phosphatase in patients treated with antiepileptic drugs in 1965, anti-epileptic drugs have been known to cause rickets and osteomalacia, but the incidence reports vary, mostly in 15% to 20%. %, these drugs mainly include phenytoin and phenobarbital. It has been confirmed that patients treated with acetophenone have a decrease in the level of 25-(0H)D3, acetazolamide, and glumide. Can) induce aggravation of osteomalacia, the mechanism of rickets and osteomalacia is not completely clear, but most people believe that:

1 This kind of medicine can induce liver microsomal mixed oxidase system, accelerate the metabolism of vitamin D3,25-(0H)D3 and l,25-(OH)2D3. In recent years, some people think that the reduction of 1,25-(OH)2D3 It is due to the drug-induced hepatic cell smoothing endoplasmic reticulum hyperplasia and vitamin D metabolism diversion, the production of active metabolites is reduced.

2 This class of drugs can reduce liver 25-hydroxylase activity.

3 phenytoin can reduce intestinal calcium absorption and decrease the activity of vitamin D-dependent calcium-binding protein. Phenytoin is the most important drug leading to rickets and osteomalacia.

4 Because the level of vitamin D deficiency is not consistent with the degree of osteomalacia, it is believed that this type of drug can partially inhibit the reaction of bone and intestine to active vitamin D products, and it is agreed that The dose and course of treatment of the drug are directly related to the degree of lesions of rickets and osteomalacia. The drug causes no manifestation of bone lesions and X-ray signs.

The bone disease can be prevented and treated by administering vitamin D 5000-10000 U/week or 25-(OH)D3 20 g/d, which can improve biochemical and X-ray signs abnormalities and reduce the incidence of fractures, and introduce new anti-epileptic drugs. Derivatives of carbame-cepime and valproic acid such as dpakote may replace phenytoin and phenobarbital, but whether these new drugs cause osteomalacia and rickets need to be observed again, the blood urinary calcium should be regularly checked, due to hypocalcemia It can aggravate seizures, which in turn increases the dose of anti-epileptic drugs, further aggravating bone damage.

(2) hereditary vitamin D-dependent rickets: it is a rare hereditary disease, due to defects in congenital renal 1-hydroxylase, resulting in the inability of 25(OH)D3 to be converted to 1,25-(OH)2D3 , so that bone mineralization disorders, so also known as pseudo-vitamin D deficiency rickets type I, the disease is mostly autosomal recessive inheritance, onset from 3 to 12 months after birth, also have autosomal dominant inheritance and in late childhood The onset of the disease suggests that the genetic heterogeneity of the disease is characterized by hypocalcemia, hypophosphatemia, and increased alkaline phosphatase. It is often secondary to parathyroidism. The bone lesions of rickets may be severe or rapidly progressing. There are permanent permanent enamel dysplasia and amino aciduria. The level of 25-(OH)D3 in the blood is increased or normal, and the concentration of 1,25-(OH)2D3 is very low.

(3) rickets and osteomalacia (renal osteopathy) caused by chronic kidney disease: also known as renal osteodystrophy, which is an important cause of rickets and osteomalacia, and has its characteristic manifestations and histology A group of diseases that are characterized by calcium, phosphorus metabolism disorders, metabolic acidosis, reduction of 1,25-(OH)2D3, secondary lesions caused by parathyroidism, etc. Caused by chronic kidney disease, including chronic glomerulonephritis, chronic pyelonephritis, kidney stones, kidney tuberculosis, urinary tract obstruction, etc., the pathogenesis is currently considered to be mainly the following: 1 mainly due to chronic kidney disease leading to nephron (or The decrease of renal cell mass) impairs the activity of 1-hydroxylase in the kidney, and the conversion of 25-(OH)2D3 to 1,25-(0H)2D3 decreases, causing bone mineralization disorder. 2 Recently, studies have shown that the kidney Phosphorus retention in parenchymal cells is also one of the main factors affecting the activation of 25-(OH)D3 in renal tissue. Hyperphosphatemia caused by chronic renal failure can further inhibit 1-hydroxylase and interfere with PTH, 1,25-(OH)2D3. Synergistic action in bone inhibits PTH-mediated calcium ascending, Decreased intestinal calcium absorption, decreased blood calcium levels, 3 hypocalcemia, high blood phosphorus, 1,25-(OH)2D3 reduction can lead to increased PTH secretion and secondary hyperparathyroidism, 1,25-( OH) 2D3 levels decrease and the amount of binding to parathyroid receptors decreases, the inhibition of PTH is weakened, PTH is decomposed during renal failure, excretion is reduced, and PIH levels are also increased, so the resulting bone resorption increases, fibrocystic osteitis, etc. Secondary parathyroid bone lesions are more common and more severe than other types of rickets and osteomalacia. 4 Metabolic acidosis in chronic renal failure, accumulation of H in body fluids, and calcium bicarbonate is also buffered. Bone loses a large amount of calcium in the regulation of acid-base balance, and mineralization is inhibited when the mineralization site pH is <7.6; acidosis can interfere with 1-hydroxylase activity, resulting in 1,25-(OH)2D3 production. The speed is slowed down and affects the sensitivity of target cells to hormone vitamin D; acidosis can also excite PTH and increase bone resorption.

In short, the complex effects of various factors lead to a series of bone lesions, histological features not only the changes of rickets and osteomalacia caused by hormone vitamin D deficiency; osteoporosis caused by secondary hyperparathyroidism, bone resorption Increase, even the performance of fibrocystic osteitis; there are bone hardening and soft tissue calcification caused by high blood phosphorus, calcium, phosphorus, etc., so X-ray performance is a mixture of these three, but in different patients may be a certain More obvious, children with uremic bone disease may be due to the bone growth period, the demand for vitamin D and calcium is larger, the rickets performance is more obvious and the height growth is hindered, and the X-ray surface has a bone softening change, Signs of osteopetrosis, which is characteristic of renal osteodystrophy, can be characterized by increased regional bone density, mostly located in the cortical bone of the spine, under the pelvis and long bones; and cancellous bone trabeculae can be characterized by osteomalacia. The transillumination is reduced, the blur is unclear, the bone structure is like a glassy shape, and the vertebrae vertebral body has a characteristic sandwich-like changethe upper and lower layers are increased in density, and the middle 1/3 density is reduced, which is more common in the lumbar vertebrae. There are different degrees of subperiosteal bone resorption, biochemical indicators change blood calcium, blood phosphorus increased, alkaline phosphatase increased, urinary hydroxyproline increased, 25-(0H)D3 level normal, 1,25-( OH) 2D3 level is significantly reduced, the clinical manifestations according to the cause, the age of the patient, the severity of the primary disease and the diet Ca, P, protein content and treatment, the treatment form can vary greatly, and X-ray signs and There is no good correlation between laboratory tests, and dialysis and kidney transplantation without timely supplementation of calcium or vitamin D can be used to increase the degree of osteomalacia and rickets, and to use large doses in kidney transplantation, nephrotic syndrome or immune diseases. Glucocorticoids also cause a further decline in bone mineral content, with steroid-related avascular necrosis of the femoral head.

(4) hypoparathyroidism and pseudohypoparathyroidism: Many studies have discussed the important role of PTH on vitamin D. PTH can directly act on kidney cells, enhancing l-hydroxylase activity and promoting The synthesis of l,25-(OH)2D3 can be expected to be associated with abnormal vitamin D metabolism in hypoparathyroidism and pseudohypoparathyroidism, and it has been confirmed in clinical cases to examine such patients. Indeed, the level of 1,25-(OH)2D3 is decreased, while the 25-(0H)D3 level is normal, revealing that the process of converting 25-(0H)D3 to 1,25-(0H)2D3 is impaired. Treatment also shows that if vitamin D and 25-(0H)D3 are used, a larger pharmacological dose is required to correct hypocalcemia, while a physiological dose of 1,25-(0H)2D3 can achieve a similar response. Hyperphosphatemia in hypoparathyroidism and pseudohypoparathyroidism also have toxic effects on the production of active vitamin D, but in this type of disease, due to decreased plasma levels or normal PTH levels, bone pairs It has no reaction, which reduces the activity of bone cells, and there is very little bone matrix construction. Therefore, bone mineralization defects are not common. See, in patients with pseudohypoparathyroidism, one of them is a kidney-responsive bone-insensitive type, which is easily misdiagnosed as osteomalacia. Because this type of bone cells does not respond to PTH, PTH cannot mobilize bone salt to dissolve. Maintain normal blood calcium levels, low blood calcium leads to secondary hyperparathyroidism, and renal tubules respond to PTH, which reduces renal reabsorption of phosphorus and loses a large amount of phosphate. As a result, patients have hand and foot spasm, hypocalcemia, and hypophosphatemia. Urinary calcium is not high, urinary phosphorus is increased, but blood alkaline phosphatase is normal, PTH is high, X-ray film shows normal or increased bone density.

Patients with idiopathic hypoparathyroidism are susceptible to chronic fungal infections. At this time, ketoconazole is commonly used to inhibit the synthesis of 1,25-(OH)2D3, and long-term use requires an increase in the dose of vitamin D.

(5) Hereditary vitamin D resistance rickets: also known as vitamin D-dependent rickets type II or pseudo-vitamin D-deficient rickets type II, because of clinical characteristics and genetic characteristics similar to type I, has been considered a disease in the past Different types, it was later found that the patient's blood 1,25 in -(0H)2D3 is not low, but significantly increased; the activity is also normal, but can not play a role in anti-caries, given large doses of vitamin D treatment, poor efficacy, showing The disease is not a hormone deficiency and an abnormality of the hormone itself, but the target organ is resistant or insensitive to 1,25-(0H)2D3. The cause may be due to genetic factors such as alfacalcidol receptor or post-receptor level. There are a variety of abnormalities, the genetic characteristics are autosomal recessive, and there is a family tendency. Recently, cell culture studies from these patients have revealed a series of functional defects of the 1,25-(0H)2D3 receptor, and studies have confirmed Some patients lack 1,25-(0H)2D3 receptors or have defects in receptor-linked 1,25-(0H)2D3, and Hughes et al reported a vitamin in one of two families of hereditary vitamin D-resistant rickets. D receptor pair DN Abnormal binding of A, confirmed that the vitamin D receptor gene point mutation caused by more than one year after birth, there are delays, manifested as progressive rickets bone changes, growth retardation, mental retardation, and more than half of patients Accompanied by congenital alopecia, due to vitamin D hormone should not, immune function is affected, prone to various infections and skin fungal infections, biochemical indicators are dependent on rickets type I, and may have increased PTH, blood 25- (0H D3 is normal or slightly increased, 1,25-(0H)2D3 is significantly increased, and 24,25-(OH)2D3 is decreased.

Acidosis (10%):

There are many causes of acidosis. The common causes of chronic acidosis are uremia and renal tubular acidosis caused by various causes. Renal tubular acidosis can be divided into primary and secondary, primary kidney. Tube acidosis such as Debre-DeToni-Fanconi syndrome, Lignac-Fanconi syndrome, Love's syndrome, etc. Secondary renal tubular acidosis is mainly secondary to various chronic diseases such as chronic pyelonephritis, Sjogren's syndrome, Systemic lupus erythematosus, hyperthyroidism, hyperparathyroidism, etc., renal tubular incapable of normal exchange of hydrogen ions, loss of carbonate, causing low sodium, hypokale acidosis accompanied by urinary alkalization Can cause rickets and osteomalacia.

Mineral deficiency (16%):

Mineral deficiency in bone mineralization is a major role in mineralization and re-construction of bone growth. Vitamin D and PTH play an important role. Their role is to maintain a normal mineralized environment of calcium, phosphorus and magnesium, and maintain bone. Adequate supply of minerals to meet all aspects of the needs and healthy growth of bones, mineralization and re-construction, if for a variety of reasons the body intake of calcium, phosphorus, magnesium and other mineralized substances are insufficient or lost from the intestines, kidneys, even Vitamin D and PTH are normal, and bone metabolism abnormalities or mineralization disorders may occur, leading to osteomalacia and rickets.

(1) Calcium deficiency syndrome: Calcium is the most important mineral element in bone formation. The amount of bone calcium accounts for 99% of the total calcium of the human body. From fetal bone formation to adult bone reconstruction, a certain amount of calcium is consumed every day, but In different physiological state, the amount of calcium required is 240-900mg per day for adults, 360-500mg for adults, and at least double the amount of calcium required for pregnancy and lactation. Therefore, it is generally said that calcium is insufficient for any cause. Or intestinal calcium, excessive loss of urinary calcium will affect bone development and reconstruction, leading to poor mineralization, but due to the body's own regulation, including the adjustment of the three major calcium-promoting hormones, often the adjustment of blood calcium, especially ionized calcium, Under normal conditions of metabolism, there is generally no obvious hypocalcemia and severe rickets and osteomalacia, but calcium deficiency rickets with high plasma levels of 1,25-(OH)2D3 may occur in the following three cases.

1 Premature infants with few surviving bones grow rapidly, requiring more calcium than the calcium supplied by the intestine. A few people believe that intestinal calcium absorption does not respond to 1,25-(OH)2D3.

2 rickets occur in fast-growing puberty, and calcium in the diet is low (as in Bantu children in Africa), in which compensatory increases in blood PTH and 1,25-(OH)2D3, Keep blood calcium normal.

3 In the low-calcium diet, accompanied by high fluoride intake (high fluoride area), blood calcium can be reduced, partial osteomalacia, and secondary hyperparathyroidism.

(2) Chronic hypophosphatemia: Some scholars have suggested that rickets and osteomalacia can be divided into two categories from biochemical characteristics, one is low calcium rickets, characterized by low blood calcium, and some may be accompanied Low blood phosphorus; the other type is hypophosphatemic rickets, normal or mildly reduced blood calcium, the latter treated with calcium and vitamin D, the effect is not good, sometimes need a large dose of vitamin D, it is also called hypophosphatemia Vitamin D rickets and osteomalacia, it can be seen that phosphorus plays an important role in metabolic bone disease. Phosphorus can promote bone matrix synthesis and bone mineral deposition, promote bone formation, and phosphorus also affects bone regulation. Tissue culture shows that reducing the concentration of phosphate in the culture medium promotes bone resorption, increases the concentration of phosphate, and inhibits bone resorption; the decrease of phosphate also leads to abnormal structure and function of bone cells, and the lack of phosphate can cause rickets And osteomalacia, but there are also blood phosphorus low bone lesions are not obvious, therefore, the pathogenesis of hypophosphatemia anti-vitamin D rickets and osteomalacia may be multifaceted, may also have vitamin D activity defects, leading to slow There are many reasons for hypophosphatemia: such as X-linked familial hypophosphatemia and other forms of congenital hypophosphatemia, renal tubular acidosis, Fanconi syndrome and Wilson's disease, Lowe syndrome and other systemic metabolism. Sexual diseases, tumor-induced osteomalacia and a large amount of aluminum hydroxide gel, low-phosphorus solution in blood perfusion or long-term intravenous nutrition, can cause a large amount of phosphorus loss or insufficient intake, hypophosphatemic rickets and bone The most important features of softening are: low blood phosphorus, normal or decreased blood calcium, and obvious muscle weakness. Some patients have obvious bone disease, but also have severe muscle weakness, which limits their activity and upper limbs. Inability to raise, can not comb the hair; lower limbs weakness, can not stand up on their own after squatting, gait or duck step, can not walk longer distance, phosphorus deficiency can also affect cell energy metabolism, leading to muscle cells, white blood cells, Red blood cell dysfunction, anorexia, respiratory dysfunction, tachycardia, migratory body pain, etc., but it should be noted that the reduction of blood phosphorus is sometimes not completely consistent with the degree of bone lesions, in the hypophosphatemia Disease, osteomalacia and who simply do not give a phosphorus supplement of vitamin D can not effectively improve bone lesions.

(3) X-linked familial hypophosphatemia: also known as hereditary or familial hypophosphatemic vitamin D-resistant rickets (VDRR), X-linked familial hereditary rickets or osteomalacia, a congenital disease Most of them are X-linked dominant dominant, with family history, but also have sporadic forms and X-linked recessive inheritance, autosomal dominant or recessive inheritance reports, lesions are mainly due to renal proximal tubules to phosphorus reabsorption The absorption of phosphorus by the intestines is reduced, resulting in a decrease in blood phosphorus and a bone change caused by rickets. However, the mechanism of phosphorus loss in the kidney and intestine is unclear, which may be related to abnormal phosphorus transport in the membrane. Some people think that the phosphorus and protein in the kidney and intestine may be affected. The control of the same gene locus, the defect of this gene makes the phosphorus-operating protein abnormal, the urinary phosphorus is lost too much, and the intestinal phosphorus absorption is reduced, resulting in the uncorrectable hypophosphatemia. Recently, Harriet et al found that the mice suffering from the disease have chromosomes. The Hyp mutation, the high affinity of the renal proximal tubule brush border, the low-capacity Na-P cotransport and its mRNA are significantly reduced, while the gene expression product of the Hyp site may regulate Na-P Gene Reducing its transcription or increasing the destruction of transcripts, eventually reducing Na-P, resulting in reduced renal reabsorption of phosphorus, and found that the patient's plasma 25-(0H)D3 and iPTH are normal, while 1,25- The concentration of (OH)2D3 is decreased, so it is believed that the cause of the disease may be the deficiency of renal 1-hydroxylase reaction, the calcitriol synthesis is impaired, and the age of onset is from 6 months after birth to old age. Differences, most of which are evident during childhood, may be relieved with the closure of the growth plate, but recurrence of common symptoms in the elderly, adulterally milder, or asymptomatic, but with histological evidence of persistent osteomalacia, male The degree of bone lesions is heavier. Some female patients may have only hypophosphatemia. The typical manifestations are short stature, deformed lower limbs, delayed bone age, muscle weakness and decreased muscle tone, rickets, and genetic heterogeneity. It is obvious that children can have skull fusion, a few people have neurogenic deafness, X-ray signs are basically the same as nutritional vitamin D deficiency rickets and osteomalacia, but some X-ray signs have contradictory points, There is an increase in bone mineral content, although mineralization is lacking, but a large number of bone-like aggregates can lead to sclerosing disorders, especially the central axis bone, calcification of the pelvis can involve the waist, ankle, caudal ligament, in the muscle ligament There may be new bone formation at the attachment. Biochemical examination indicates normal blood calcium, increased urinary phosphorus, normal or elevated alkaline phosphatase, and no amino aciduria.

(4) damage to the renal tubules of severe tubular damage can lead to rickets and osteomalacia: although it is also a category of renal osteopathy, but also with glomerular bone disease (or uremic osteopathy) Obviously different characteristics, it is not parallel with the degree of renal failure. In the case of good renal function, obvious bone disease can occur, biochemical characteristics are accompanied by obvious hypophosphatemia, kidney phosphorus, and normal blood calcium. Or only mildly reduced, AKP increased, bone lesions vary in performance, severe patients from childhood can have obvious rickets bone disease, mild damage to adulthood to show osteomalacia, can also be secondary to parathyroidism, appear Obvious bone decalcification, osteoporosis or fibrocystic osteitis, bone deformity and pathological fracture, other manifestations of renal tubular acidosis, may have high chloride acidosis, hypokalemia, muscle weakness and limbs soft palate The proximal trabecular dysfunction may be accompanied by amino aciduria, diabetes, phosphoric acid and polyuria, and some may also have high urinary calcium, kidney stones and proteinuria, and finally lead to renal failure.

There are many causes of renal tubular damage, such as primary renal tubular damage, such as primary renal tubular acidosis is an autosomal dominant genetic disease, the pathogenesis of the distal convoluted tubule, the collection tube active secretion of H ability decreased or near The varicose veins absorb the HC03-disorder, as well as Fanconi syndrome, which is also a congenital tubular dysfunction. It is an autosomal recessive hereditary disease, mainly involving the proximal convoluted tubules, leading to a decrease in renal tubular reabsorption function. Urine (with or without cystineuria), diabetes, phosphate urine, uric acid and bicarbonate urine may be associated with cysteine deposition in systemic tissues in infants and childhood, with no adult cases Cystine deposition, and then secondary to various causes such as infection, heavy metal poisoning, expired tetracycline, streptozotocin, cresol and other drug poisoning; congenital systemic metabolic defects (cystine disease, galactose blood Syndrome, glycogen accumulation syndrome, liver and kidney genetic tyrosineuria, hereditary fructose intolerance, hepatolenticular degeneration and eye and brain syndrome; immune disease (amyloidosis, Sjogren synthesis) Excess) Sexual myeloma; radiation factors, etc., can cause secondary renal tubular dysfunction, can also cause secondary Fanconi syndrome, renal tubular damage caused by bone disease, in addition to the previous hypophosphatemia, acidosis In addition, the reduction and activity of 1,25-(OH)2D3 products are currently considered to be reduced, and bone lesions can be prevented by administering alfacalcidol (calcium triol), some simple renal tubular acidosis, Bone lesions can also be prevented by administering enough sodium bicarbonate [5 ~ 15mmoL / (kg · d)] to correct the blood pH to normal, this treatment can also prevent osteomalacia caused by acidosis after ureteral sigmoid anastomosis.

(5) neoplastic osteomalacia: also known as tumor-associated osteomalacia, tumor-induced hypophosphatemic osteomalacia rickets, clinical features similar to low-phosphorus vitamin D-resistant rickets osteomalacia, it was in 1959 by Prader In one report, an 11-year-old girl developed severe rickets and hypophosphatemia in a year, high urinary phosphorus with giant cell tumor of ribs, and rickets recovered after tumor resection. So far, nearly 100 cases have been reported, and related tumors can occur in Adults and children, located in soft tissue or bone, most commonly benign tumors of mesodermal tissue, Nuovo et al. 372 cases found that bone tumors accounted for 56.3%, half in long bones, followed by skull and including mandible, paranasal sinus, ethmoid sinus Bone neoplasms; 43.05% are soft tissue tumors, more common in the lower limbs, can be located in the skin, tumors are mostly benign, hemangiomas, angiosarcoma, fibroangioma, bone mesenchymal tumors, multiple neurofibromas, chondromas, giant cells Tumor, osteoblastoma and non-neoplastic diseases (fibrous dysplasia and malignant multiple myeloma, breast cancer, prostate cancer, oat cell cancer, etc.), most of the tumors are small, flat 1 to 4 cm, the minimum is 0.5 cm, and the maximum is 15 cm. The clinical features are hypophosphorus rickets and osteomalacia in healthy children or adults. The radiological features of rickets and osteomalacia may also progress. Severe muscle weakness, proximal myopathy, lower back, chest ribs and foot pain, pelvis, spine, limb deformities and pathological fractures, laboratory tests: normal blood calcium, low blood phosphorus, increased urinary phosphorus, PTH And calcitonin normal, 25-(0H)D3 normal, 1,25-(0H)2D3 often decreased, blood alkaline phosphatase increased, urinary HOP increased, and there were reports of amino aciduria, diabetes, rickets, bone softening and tumor The performance can occur at the same time, but also can be separated for several years. The bone softening performance of rickets can be earlier than that of tumor discovery for 1 to 13 years, with an average of 5 years. Therefore, the idiopathic and sporadic osteomalacia plaques diagnosed in the past may have some cases. That is, neoplastic osteomalacia rickets, the pathogenesis of the disease is still not very clear, most scholars believe that the tumor may release a factor or substance, directly acting on the renal proximal convoluted tubules, inhibiting the absorption of phosphorus, Reduced blood phosphorus, increased urinary phosphorus, and found that the extract of tumor cells can directly inhibit the activity of l-hydroxylase in the kidney, while the intracellular cAMP does not increase, indicating that this substance is different from PTH, many cases The report also confirmed the abnormality of vitamin D and the decrease of 25-(OH)D3. Recent studies have also shown that the extract of this type of tumor is a peptide substance, non-fat soluble, heat-resistant, anti-trypsin, molecular weight At 8 ~ 25kD, it can inhibit the absorption of phosphorus by Na-P co-transport on the brush border of proximal tubular epithelial cells, and can also change the function of proximal tubules, resulting in a series of pathological changes. In short, for many clinical tumors It is very important to be associated with carcinogenesis of rickets, and this damage should be carefully sought in the diagnosis of hypophosphatemic anti-vitamin D rickets.

Excision of these tumors, osteomalacia and rickets can be cured without treatment. When no tumor is found or the malignant tumor cannot be removed, it is necessary to supplement both phosphorus and alfacalcidol. The dose and method are lower than X-linked familial. Phosphemia.

(6) Magnesium deficiency syndrome: Magnesium is closely related to bone metabolism. Magnesium in bone tissue accounts for 60% to 70% of total magnesium in human body. In animal experiments, growth plate obstruction is observed when magnesium is deficient, and the tarsal plate is narrowed, almost no Chondrocytes, trabecular bones also disappeared, matrix proteins, mucopolysaccharide loss, collagen synthesis disorders, Smith et al. In 1972, found that magnesium-deficient immature rats had significant bone mineral reduction and growth stopped at the proximal end of the tibia. In 1973, the Nielsen study concluded that the concentration of extracellular magnesium can regulate the formation of calcification of immature bones and the conversion of non-crystalline salts to hydroxyapatite. The effects of magnesium on vitamin D levels are reported in different cases. In more studies, nearly half of the patients had decreased blood l,25-(OH)2D3, and most of them had 25-(0H)D3 deficiency. Therefore, the role of magnesium in metabolic bone disease has received more and more attention. Magnesium is widely present inO.5mmol/d 0.7mmol/LD1974Reddy2X0.5mg%0.74mg%D23MgCl 210mmoL/d121975Rwpado12(6.9mg/d1)(0.25mmol/L)D

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(2)1961Frame60DNelson42

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(3)SchmidX

(4)()()PTHD(desferrioxamine)

(5)

1-D0H-F-;;

1-125-(0H)2D3

99%

Other factors (2%):

Pathogenesis

Pathogenesis

DDD(<40)1.751.87mmol/L(77.5mg/dl)0.881.0mol/L(3.54.0mg/dl)(12)

2. Pathology

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1.DD3D80%20%50%2030mg/(kg·d)500mg/d5001000mg/d21550mg

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3.

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DD

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(2)24h50mg

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2.

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(2)DD25-(OH)D3(750ng/m1736ng/ml)125-(OH)2D3(2545pg/ml2162.4pg/m1)D25-(OH)D3125-(OH)2D3D1-25-(0H)D3125-(OH)2D3D125-(OH)2D3(2)

3.X

(1)X51010

(2)Looser(Milkman)X15mm

4.

X

5.

3(MAR)(MTT)1012715µm12%MAR0.61.0µm/d20µm20%()

DPaget

Diagnostic criteria

X

Rickets

(1)

(2)

(3)()

(4)

(5)Harrison

(6)

X

2.

3.X

4.

[2.22.7mmol/L(911mg/dl)];[0.91.3mmol/L(2.84mg/dl)][1.31.9mmol/L(46mg/dl)]<30(40)(1530)200µg/LD25-(OH)D3[12200nmol/L(580ng/ml)];125-(0H)2D3[40160pmol/L(1665pg/ml)]()

5.X

There is no special change in the early X-ray of osteomalacia. Most patients have different degrees of osteoporosis, bone density decreases, the long cortical bone becomes thinner, some have pathological fractures, and severe X-ray shows anterior and posterior curvature of the spine and vertebral body. Severe decalcification and atrophy, biconcave deformity, pelvic stenosis, pseudo-fracture (also known as Looser belt); can be considered as a feature of X-ray changes in adult osteomalacia, decalcification of banded bone, length on X-ray films Light-transmissive tapes ranging from a few millimeters to a few centimeters are generally perpendicular to the bone surface. These light-transmissive bands are often bilateral and symmetrical, especially at the pubic, ischial, femoral neck, rib and shoulder rim. As typical.

Differential diagnosis

DD 3µg(120U)D

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XX

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