Bone formation and resorption

Bone remodelling, which continues throughout adult life, is necessary for the maintenance of normal bone structure and requires that bone formation and resorption should be balanced. Bone remodelling occurs in focal or discrete packets know as bone multicellular unit (BMU). In this process, both bone formation and resorption occur at the same place so that there is no change in the shape of the bone. After a certain amount of bone is removed as a result of osteoclastic resorption and the osteoclasts have moved away from the site, a reversal phase takes place in which a cement line is laid down. Osteoblasts then synthesize matrix, which becomes mineralised. The BMU remodeling sequence normally takes about 3 months to produce a bone structure unit (Fig. 2). 

Bone is divided into trabecular and cortical components, with each further divided into surface bone, bone volume, and bone cavity (marrow compartment). Deposition of americium is assumed to occur from plasma directly to bone surfaces, whereas elimination from bone occurs by transfer from the bone surface or volume to the marrow cavity, and then from the marrow cavity to plasma (Figure 3-6). Transfers of americium within the cortical or trabecular bone compartments are modeled based on assumptions about rates of bone formation and resorption, which are assumed to be vary with age, but are equal within a given age group (Leggett et al. 1982). Movement of americium to the marrow compartment is determined by the bone resorption rate, whereas, movement from the bone surface to the bone volume is assumed to occur by burial of surface deposits with new bone and is determined by the bone formation rate. During growth, bone formation and resorption are assumed to occur at different sites within bone therefore, the rate of removal of americium from the bone surface is approximated by the sum of the bone resorption rate (represented in the model by the movement of americium to the marrow compartment) and the rate of bone... 

Three hormones serve as the principal regulators of calcium and phosphate homeostasis parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and the steroid vitamin D (Figure 42-2). Vitamin D is a prohormone rather than a true hormone, because it must be further metabolized to gain biologic activity. PTH stimulates the production of the active metabolite of vitamin D, l,25(OH)2D. l,25(OH)2D, on the other hand, suppresses the production of PTH. l,25(OH)2D stimulates the intestinal absorption of calcium and phosphate. l,25(OH)2D and PTH promote both bone formation and resorption in part by stimulating the proliferation and differentiation of osteoblasts and osteoclasts. Both... 

Bone formation and resorption are influenced by several protein factors. For example, IGF-I stimulates formation of bone, but EGF promotes breakdown.256 Additional bone-derived growth factors and morphogenetic factors also have been described.256 257 A cartilage-inducing factor has been identified as TGF-p.258... 

Baylink, D., and Wergedal, J. Bone formation and resorption by osteocytes. In Cellular mechanism for calcium transfer and homeostasis (eds. G. Nichols, Jr. and R. H. Wasser-man). New York and London Acad. Press 1971, 257-289. 

PTH works with two other primary hormones— calcitonin and vitamin D—in regulating calcium homeostasis. These three hormones, as well as several other endocrine factors, are all involved in controlling calcium levels for various physiologic needs. How these hormones interact in controlling normal bone formation and resorption is of particular interest to rehabilitation specialists. Regulation of bone mineral homeostasis and the principal hormones involved in this process are presented in the following section. 

Paget disease Excessive bone formation and resorption (turnover] leads to ineffective remodeling and structural abnormalities within the bone Calcitonin, bisphosphonates... 

Kushida, K., Takahashi, M., Kawana, K., and Inoue, T. 1995. Comparison of markers for bone formation and resorption in premenopausal and postmenopausal subjects, and osteoporosis... 

Frost HM. Could some biomechanical effects of growth hormone help to explain its effects on bone formation and resorption Bone. 1998 23 395-398. 

Hsieh Y-F, Silva MJ. In vivo fatigue loading of the rat ulna induces both bone formation and resorption and leads to time-related changes in bone mechanical properties and density. J Orthop Res. 2002 20 764-771. 

Preanalyticai and analytical variables significantly reduce the usefulness of measurements of markers of bone formation and resorption. The long-term, within-individual variability of urine markers is generally higher (15% to 60%) than that of serum markers (5% to ioo/o).3i> i >345.550,586... 

Marie PJ, Hot M. 1986. Short-term effects of fluoride and strontium on bone formation and resorption in the mouse. Metabolism 35(6) 547-551. 

Of the total amount of calcium in the human body, most (about 1 kg) is stored in the bones, whereas only 1 g is found in the circulatory system. Cellular Ca++ level is strictly controlled by hormones, cytokines and growth factors, and exerts an effect on bone formation and resorption by osteoblasts and osteoclasts, respectively (Raisz, 1988 Canalis et al., 1988, 1989 Suda et al.,... 

Ladlow, J. R, W. E. Hoffman, G. J. Breur, D. C. Richardson, and M.J. AUen. 2002. Biological variability in serum and urinary indices of bone formation and resorption in dogs. Calcified Tissue International 70 186-193. 

BONE PGs are strong modulators of bone metabolism. PGE stimulates bone formation and resorption through osteoblastic and osteoclastic activities affecting bone strength and composition. 

Marie PJ. Strontium ranelate a novel mode of action optimizing bone formation and resorption. Osteoporosis Int 2005 16(Suppl 1) S7-S10. 

Hoal-Van Helden EG, Epstein, Victor TC et al 1999 Mannose-binding protein B aUele confers protection against tuberculous meningitis. Pediatr Res 45 459—464 Ke HZ, Qi H, Weidema AF et al 2003 Deletion of the P2X7 nucleotide receptor reveals its regulatory roles in bone formation and resorption. Mol Endocrinol 17 1356—367 Khakh BS, North RA 2006 P2X receptors as cell-surface ATP sensors in health and disease. Nature 442 527-532... 

Osteoblast and osteoclast cells are responsible for bone formation and resorption, respectively. Calcium and phosphate are the two minerals that are essential for normal bone formation. Osteoblasts secrete a calcifiable matrix which contains minerals, collagen, and also small amount of non-collagenous proteins including osteopontin, osteonectin, bone sialoprotein, and osteocalcin (Gay et ah, 2000). The function of osteoclast is to remove bone tissue by removal of its mineralized matrix and breaking up the organic bone (90% collagen). An increase in the number of osteoclast cells and their function normally induces bone osteoporosis, indicating that osteoclast plays a pivotal role in bone homeostasis (Miyamoto and Suda, 2003). 

One of the important natural product investigations from marine algae is to focus on the pharmaceutically important compounds that can be applied in bone health. Osteoporosis is one of the bone diseases caused by an imbalance between bone formation and resorption. Promotion of osteoblast differentiation is one of the best therapeutic ways to combat osteoporosis. Osteoblasts are the cells responsible for bone formation by increasing the proliferation of the osteoblastic lineage or inducing differentiation of the... 

Bone metabolism is characterized by two opposing activities bone formation and bone resorption (Martin, 2002). Once formed, the bones in adulfs are confinuously remodeled, and the remodeling rate is between 2% and 10% of the skeletal mass per year. Bone mass depends on the balance between resorption and formation within the remodeling unit. As osteoporosis is characterized by a decrease in bone mass with deterioration in the architecture of bones, it is the result of an imbalance between bone formation and resorption. 

Mineral balance Changes in calcium metabolism and bone turnover have been evaluated in 20 post-pubertal men with idiopathic generalized epilepsy after 12 months of valproate monotherapy and in 20 post-pubertal sex- and age-matched healthy controls [331 ]. Both markers of bone formation and resorption were significantly higher than baseline in those who took valproate. 

Some conflicting statements have been made concerning the relative potencies of compounds possessing of the 24 R)- and 24(iS)-configuration in the vitamin D3 side chains. DeLuca (185) claims that both synthetically derived 24-hydroxyvitamin D3 isomers stimulate intestinal calcium transport almost equally well in the rat and has shown that the 24(S)-isomer has little or no activity in bone calcium resorption or in bone formation, whereas the 24(/ )-isomer is almost as active as 25-hydroxyvitamin D3 in these in vivo tests. However, Atkins (7) claims that both diastereo-isomers of 24,25-dihydroxyvitamin D3 are potent stimulators of bone resorption in tissue culture and there is no significant difference between the (R)- and (5)-forms. Boris (24) recently also showed that both 24 R)-and 24(/S)-isomers of la,24,25-trihydroxyvitamin D3 promote bone mineralization almost equally well in cockerels. Whether the differentiation of the 24(i )- and 24(5)-diastereoisomers in bone formation and resorption occurs only in the absence of the la- and the 25-hydroxy substituents is not known at this time, but it seems unlikely. 

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