Mineralization of bone

D Calciferol Maintenance of calcium balance enhances intestinal absorption of Ca and mobilizes bone mineral Rickets = poor mineralization of bone osteomalacia = bone demineralization... 

Boivin G, Lips P, Ott SM, Harper KD, Sarkar S, Pinette KV, et al. (2003) Contribution of raloxifene and calcium and vitamin D3 supplementation to the increase of the degree of mineralization of bone in postmenopausal women. J Clin Endocrinol Metab 88 4199-4205... 

The development and maintenance of healthy bone depends in part on an adequate supply of dietary calcium. Although phosphate is absolutely required for the mineralization of bone, it is abundant in the diet. If one gets enongh to eat, one gets enough phosphate. The same is not necessarily trne for calcinm and many people snpplement their diet with a preparation of calcium, frequently calcinm glnconate or calcium citrate. More follows below about the chemistry of bone when we get to a consideration of calcium. 

Vitamin D is really a small family of closely related molecnles that prevent the bone disease rickets in children and osteomalacia in adnlts. In both cases, inadeqnate mineralization of bone results in bone deformation and weakness. Calcinm, Ca +, homeostasis is one goal of vitamin D activity, a goal it shares with parathyroid hormone and calcitonin. Calcium is intimately involved in bone mineralization and distnrbances of calcium levels in the blood can resnlt in inadeqnate bone mineralization or excessive calcification of other tissues. 

Calcium Mineralization of bone and teeth synaptic transmission muscle contraction blood clotting Men women 1000 mg/d... 

A. Pharmacokinetics Pamidronate is administered intravenously. All of the other bisphosphonates are orally active, although less than ten percent of the administered dose is absorbed. Food significantly interferes with absorption. Bisphosphonates should be administered with six to eight ounces of water at least one hour before eating breakfast. The bisphosphonates are rapidly cleared from the plasma, primarily because they avidly bind to hydroxyapatite mineral of bone. Once bound to bone they are cleared over a period of months to years. Elimination from the body is solely through renal clearance, and the bisphosphonates should not be given to individuals with severe renal impairment. 

Further evidence that C-25 and C-l hydroxylation are the activation steps of vitamin D3, and that C-24/C-23 and C-23/C-26-lactone metabolic conversions do not produce physiologically important products is with the use of side-chain fluoridated analogues of 25-OH-D3 [87, 88], Studies with these analogues were prompted by assertions that 24-hydroxylated or lactone metabolites are involved or required for such biological actions as mineralization of bone [89], suppression of parathyroid hormone secretion [90], cartilage metabolism [91], and embryonic development in the chick [92]. It is well established that plasma 24,25-(OH)2D3 concentrations (2-5 ng/ml) are approximately 50 times greater than those of l,25-(OH)2D3. Even so,... 

Q7 Calcium is present in both intracellular fluid (ICF) and ECF, but the concentration in the ECF is twice as high as that in the ICF. Calcium is found in both ionized and bound forms, and Ca2+ homeostasis is mainly controlled by parathyroid hormone, which increases absorption of calcium in the intestine and reabsorption in the nephron. Calcitonin also affects ECF calcium concentration by promoting renal excretion when there is an excess of calcium in the body. The normal kidney filters and reabsorbs most of the filtered calcium however, in renal disease this is reduced and blood calcium decreases. Calcium and phosphate imbalance can occur in patients with renal failure, leading to osteomalacia (defective mineralization of bone). Osteomalacia is mainly due to reduced production of 1,25-dihydroxycholecalciferol, an active form of vitamin D metabolized in the kidney. Deficiency of 1,25-dihydroxycholecalciferol reduces the absorption of calcium salts by the intestine. 

Potassium (K+) and calcium (Ca2+) levels in blood are affected by renal failure. High K+ leads to muscle weakness and may cause cardiac rhythm disturbance. The low blood Ca2+ leads to defective mineralization of bones (osteomalacia)... 

Vaughn D. J. (1984) The influence of bone cells on the formation, and mineralization, of bone matrix. Phil. Trans. Roy. Soc. London B 304, 453-454. 

The clinical manifestations of serum phosphate depletion depend on the length and degree of the deficiency. Moderate hypophosphatemia of 1.5 to 2,4 mg/dL (0.48 to 0.77 mmol/L) is usually not associated with clinical signs and symptoms (unless chronic, when osteomalacia or rickets develops). Plasma concentrations less than 1.5 mg/dL (0.48 mmol/L) may produce clinical manifestations. Because phosphate is necessary for the formation of ATP, glycolysis and cellular function are impaired by low intracellular phosphate concentrations. Muscle wealmess, acute respiratory failure, and decreased cardiac output may occur in phosphate depletion. At very low serum phosphate (<1 mg/dL or <0.32 mmol/L), rhabdomyolysis may occur. Phosphate depletion in erythrocytes decreases erythrocyte 2,3-diphosphoglycerate, which causes tissue hypoxia because of increased affinity of hemoglobin for oxygen. Severe hypophosphatemia (serum phosphate concentration <0.5 mg/dL [<0.16 mmol/L]) may result in hemolysis of the red blood cells. Mental confusion and frank coma also may be secondary to the low ATP and tissue hypoxia. If hypophosphatemia is chronic, impaired mineralization of bone produces rickets in children and osteomalacia in adults. 

Metabolic bone diseases result from a partial uncoupling or imbalance between bone resorption and formation. Decreased bone mass, or osteopenia, is more common than abnormal increases of bone mass. The most prevalent metabolic bone diseases are osteoporosis, osteomalacia and rickets, and renal osteodystrophy. Osteoporosis, the most prevalent metabolic bone disease in developed countries, is characterized by loss of bone mass, microarchitectural deterioration of bone tissue, and increased risk of fracture. Rickets and osteomalacia, which are more common in the less-developed countries, are characterized by defective mineralization of bone matrix. Renal osteodystrophy is a complex condition that develops in response to abnormalities of the endocrine and excretory functions of the kidneys. These three metabolic bone diseases and Paget s disease, a localized bone disease, are discussed below followed by laboratory markers of bone metabolism. 

Several disorders have already been discussed the following are additional disorders of calcium and phosphorus homeostasis. In rickets in children and osteomalacia in adults, there is failure of mineralization of osteoid, with consequent softening of bones. In rickets, there is defective mineralization of bone and of the cartilaginous matrix... 

Other chronic disorders cause osteomalacia. " " Phosphate depletion from low dietary intake, phosphate-binding antacids, and oncogenic osteomalacia (potentially phosphaturic effect) can cause osteomalacia. Hypophosphatasia is an inborn error of metabolism in which deficient activity of alkaline phosphatase causes impaired mineralization of bone matrix. Acidosis from renal dysfunction, distal renal tubular acidosis, hypergammaglobulinemic states (e.g., multiple myeloma), and drugs (e.g., chemotherapy) compromises bone mineralization. Renal tubular disorders secondary to Fanconi s syndrome, hereditary diseases (e.g., Wilson s disease, a defect in copper metabolism), acquired disease (e.g., myeloma), and toxins (e.g., lead) cause osteomalacia to varying degrees. Chronic wastage of phosphorus and/or calcium limits mineralization, which may be further compromised by acidosis and secondary hyperparathyroidism. 

Crystalline hydroxyapatites are the major mineral of bones and teeth in a matrix of the protein collagen. The hydroxyls reside in chaimels running along the crystal c-axis which provide easy access to the external environment. Hydroxyapatites in vivo are usually described as poorly crystalline, calcium deficient and containing carbonate substitutions. The carbonate substitutions can occur at both the hydroxyl and the phosphate... 

Osteomalacia in childhood is known as ricketts and leads to soft bones with characteristic deformities. In adults there is generalized reduction in mineralization of bone matrix and symptoms of bone pain and tenderness. 

The mineralization of bone. Shown are the bone matrix (collagen/proteoglycan). osteoblasts (bone mineralization), and osteoclasts (bone resorption in response to decreased blood calcium). 

Christoffersen J, Christoffersen MR, Kibalczyc W, Andersen FA (1989) A contribution to the understanding of the formation of calcium phosphates. J Ciyst Growth 94 767-777 Christoffersen J, Landis WJ (1991) A contribution with review to the description of mineralization of bone and other calcified tissues in vivo. Anatom Rec 230 435-450 Christoffersen J, Rostmp E, Christoffersen MR (1991) Relation between interfacial surface-tension of electrolyte ciystals in aqueous suspension and their solubility—A simple derivation based on surface nucleation. J Cryst Growth 113 599-605... 

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