Osteomalacia protein

Light increases the concentration of a specific Ca " ion transport protein in the enterocytes of small intestine to increase ion uptake. This increases the Ca " ion concentration in the plasma which is required for mineralisation of bone. A deficiency of the vitamin/hormone results in osteomalacia (i.e. a deficiency of mineral in the bone), also known as rickets in children. The growth of the skeleton and the role of vitamin D is discussed in Appendix 15.2. 

Vitamin D-binding protein and its associated vitamin are lost in nephrotic urine. Biochemical abnormalities in nephrotic patients (children and adults) include hypocalcemia, both total (protein-bound) and ionized hypocalciuria, reduced intestinal calcium absorption and negative calcium balance reduced plasma 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol and, surprisingly, also 1,25-dihydroxycholecalciferol and blunted response to parathormon (PTH) administration and increased PTH levels. Clinically, both osteomalacia and hyperparathyroidism have been described in nephrotic patients, more commonly in children than in adults, but bone biopsies are commonly normal, and clinically significant bone disease is very rare in nephrotic subjects. There is, however, evidence that patients with renal failure accompanied by nephrotic range proteinuria may be particularly prone to develop renal osteodystrophy. 

A classic example of essential metal deficiency resulting from nonessential metal exposure is Itai itai disease. Cadmium pollution in the Jinzu River basin in Japan resulted in severe nephrotoxicity in approximately 184 people. Renal tubule damage caused excessive loss of electrolytes and small proteins from the urine. In severe cases, urinary Ca loss was so severe that bone Ca was mobilized, resulting in osteomalacia. Renal tubular defects persisted for life and induced hypophosphatemia, hyperuricemia, and hyperchloremia, which are characteristic biochemical features of Itai-itai disease (see Section 21.6.1). 

Q13 Osteomalacia and osteoporosis are complications of celiac disease. The mineral in bone is mainly calcium phosphate a supply of calcium is therefore needed for bone growth and replacement. Calcium is absorbed by active mechanisms in the duodenum and jejunum, facilitated by a metabolite of vitamin D. It is also passively absorbed in the ileum and specific calcium binding proteins are present in the intestinal epithelial cells. Loss of absorptive cells and calcium binding proteins markedly decreases calcium uptake and limits its availability for bone growth and repair. 

Vitamin status can be assessed by a direct test for the levels of 25-(OHin the serum, This competitive binding test involves three components (1) a serum sample, (2) radioactive 25-hydroxy[ Hjvitamin Dj, and (3) vitamin D-binding protein. The source of vitamin D-binding protein may be sheep serum. The functional tests for deternrination of vitamin D irvdude the diagnostic tests for rickets and osteomalacia. A test for osteomalacia, for example, may include measurement of the width of the osteoid in a bone biopsy. The osteoid is described later. 

Vitamin D deficiency in adults cannot affect the epiphyseal plate, as it has disappeaced, but it can prevent normal mineralization of the osteoid layer in bone that turns over. In vitamin D deficiency the osteoclasts continue to create tunnels and pits in the bone. The osteoblasts continue to synthesize the protein matrix however, complete mineralization of the osteoid may not occur. The result is osteomalacia - This disease may present as bone pain about the hips. Osteomalacia can be diagnosed using a bone biopsy, A sample is taken from the iliac crest — the hip bone. An abnormally wide osteoid is indicative of the disease. X-rays can also be used to diagnose osteomalacia, which is characterized by arrays or zones of tiny fractures in sucli bones as the pelvis and femur. 

Over the years, problems have arisen as a result of the presence of significant amounts of aluminium in parenteral nutrition solutions in particular they have been held responsible for hypercalciuria and its consequences (54). Parenterally administered aluminium bypasses the gastrointestinal tract, which normally serves as a protective barrier to aluminium entry into the blood. In the past, aluminium contamination of casein hydrolysate, which was used as a source of protein in parenteral nutrition solutions, was associated with low-turnover osteomalacia and with encephalopathy in uremic patients. Premature infants are still at risk of aluminium accumulation as a result of prolonged parenteral nutrition (as are patients receiving plasmapheresis with albumin contaminated in its preparation with aluminium). Metabolic bone disease can result (54). 

Vitamin D is a fat soluble vitamin related to cholesterol. In the skin, sunlight spontaneously oxidizes cholesterol to 7-dehydrocholesterol. 7-Dehydrocholesterol spontaneously isomerizes to cholecalciferol (vitamin D3), which is oxidized in the liver to 25-hydroxy cholecalciferol and, under the influence of PTH in the kidney, to 1,25-dihy-droxy cholecalciferol (calcitriol), the active form of vitamin D. Vitamin D induces the expression of calcium ion transport proteins (calbindins) in intestinal epithelium, osteoclasts, and osteoblasts. Calbindins and transient receptor potential channels (TRPV) are responsible for the uptake of calcium from the diet. In children, the absence of sunlight provokes a deficiency of vitamin D, causing an absence of calbindins and inadequate blood calcium levels. Osteoid tissue cannot calcify, causing skeletal deformities (rickets). In the elderly, there is a loss of intestinal TRPV receptors and decreased calbindin expression by vitamin D. In both cases, the resultant low blood calcium levels cause poor mineralization during bone remodeling (osteomalacia). Rickets is the childhood expression of osteomalacia. Osteoclast activity is normal but the bone does not properly mineralize. In osteoporosis, the bone is properly mineralized but osteoclasts are overly active. 

A variety of endocrine effects have been reported Inhibition of vasopressin release has been observed in patients with inappropriate secretion of this hormone. Hyperglycemia and glycosuria appear to be due to inhibition of insulin secretion. Osteomalacia has been attributed to altered metabolism of vitamin D and the attendant inhibition of intestinal Ca absorption. Phenytoin also increases the metabolism of vitamin K and reduces the concentration of vitamin K-dependent proteins that are important for normal metabolism in bone, perhaps explaining why the osteo-... 

Shoop et al. (1998) studied the behavior of aluminum in urine to understand the role of Al in diseases, such as dialysis, dementia, and osteomalacia, which are of major concern to patients with end-stage renal failure. Non-protein- and protein-bound Al species were separated using a cation-exchange resin followed by NAA of Al. The total Al content was determined by RNAA. It was concluded that the majority of Al is bound to protein. 

A condition which clinically resembles osteomalacia. It differs from osteomalacia, however, in that it is due to a primary loss of the proteinaceous bone matrix with a resultant secondary loss of bone calcium. It can occur as part of the general process of ageing, or in conditions such as hyperthyroidism, acromegaly, Cushing s syndrome (because of the effects of thyroxine, growth hormone and cortisol on protein metabolism) and malabsorption (due to deficient amino acid absorption). Serum calcium, phosphate and alkaline phosphatase levels are normal, unlike osteomalacia. 

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