Bone formation and

The calcification of atherosclerotic plaques may be induced by osteopontin expression, since osteopontin is a protein with a well-characterized role in bone formation and calcification. Vascular smooth muscle cell migration on osteopontin is dq endent on the integrin av 33 and antagonists of av 33 prevent both smooth muscle cell migration and restenosis in some animal model [8]. 

Bone metabolism comprises the processes of bone formation and bone resorption, the key actions by which skeletal mass, structure and quality are accrued and maintained throughout life. In the mature skeleton, anabolic and catabolic actions are mostly balanced due to the tight regulation of the activity of bone forming ( osteoblast) and bone resorbing ( osteoclast) cells through circulating osteotropic hormones and locally active cytokines. 

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). 

Statins lower plasma cholesterol levels by inhibiting HMG-CoA reductase in the mevalonate pathway (Fig. 4). Some research has shown that certain statins (but not all) stimulate BMP-2 expression in osteoblasts, increase bone formation and mimic N-BP in that they inhibit bone resorption. The use of statins in osteoporosis is presently being investigated. 

The most dramatic consequence of sHPT is alterations in bone turnover and the development of ROD. Other complications of CKD can also promote ROD. Metabolic acidosis decreases bone formation and aluminum toxicity causes aluminum uptake into bone in place of calcium, weakening the bone structure. The pathogenesis of sHPT and ROD are depicted in Fig. 23-5. 

It is important to monitor vitamin D therapy aggressively to assure that PTH levels are not oversuppressed. Oversuppression of PTH levels can induce adynamic bone disease, which manifests as decreased osteoblast and osteoclast activity, decreased bone formation, and low bone turnover. 

Under normal circumstances, the skeleton undergoes a dynamic process of bone remodeling. Bone tissue responds to stress and injury through continuous replacement and repair. This process is completed by the basic multicellular unit, which includes both osteoblasts and osteoclasts. Osteoclasts are involved with resorption or breakdown of bone and continuously create microscopic cavities in bone tissue. Osteoblasts are involved in bone formation and continuously mineralize new bone in the cavities created by osteoclasts. Until peak bone mass is achieved between the ages of 25 and 35, bone formation exceeds bone resorption for an overall increase in bone mass. Trabecular bone is more susceptible to bone remodeling in part owing to its larger surface area. 

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... 

The kinetics of bone formation and remodeling are important factors in the overall biokinetics of lead. 

PHB has been claimed to have piezo-electric properties similar to those of natural bone, giving it potential as biodegradable fixative plates that could actually stimulate bone formation and consequently promote the healing of the patient [117]. Furthermore, PHB has been used to produce non-woven patches for pericardium repair following open-heart surgery. 

C.T. Brighton, G. Friedlaender and J.M. Lane, Bone formation and repair. AAOS (1994). 

Miller, J., Horner, A., Stacy, T., Lowrey, C., Lian, J., Stein, G., Nuckolls, G. and Speck, N. (2002) The core binding factor beta subunit is required for bone formation and hematopoietic maturation. Nat Genet 22, 645-649. 

Osteoblasts (top) deposit collagen, as well as Ca "" and phosphate, and thereby create new bone matter, while osteoclasts (bottom) secrete H"" ions and collagenases that locally dissolve bone (bone remodeling). Osteoblasts and osteoclasts mutually activate each other by releasing cytokines (see p. 392) and growth factors. This helps keep bone formation and bone breakdown in balance. 

Osteomalacia is the condition in which bone becomes demineralised due to deficiency of vitamin D. In this condition parathyroid hormone (PTH) acts on the bone to maintain serum calcium, resulting in demineralisation. Serum calcium is usually normal or slightly low alkaline phosphatase levels are high, reflecting excessive osteoblast activity, and serum phosphate falls as an effect of PTH on the kidney. The same condition in children results in defects in long bone formation, and is termed rickets. 

K. Yamaguchi, E. Segi, T. Tsuboyama, M. Matsushita, K. Ito, Y. Ito, etal. Stimulation of bone formation and prevention of bone loss by prostaglandin E EP4 receptor activation, Proc. Natl. Acad. Sci. USA 99 (2002) 4580. 

A study in 500 Australian women (aged 40 to 80 years) has shown that higher isoflavone intakes are associated with higher concentrations of bone alkaline phosphatase, a short-term marker of bone formation and turnover. 

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... 

Typical changes in bone mineral density with time after the onset of menopause, with and without treatment. In the untreated condition, bone is lost during aging in both men and women. Fluoride, strontium (Sr2+), and parathyroid hormone (PTH) promote new bone formation and can increase bone mineral density in subjects who respond to it throughout the period of treatment, although PTH also activates bone resorption. In contrast, estrogen, calcitonin, and bisphosphonates block bone resorption. This leads to a transient increase in bone mineral density because bone formation is not initially decreased. However, with time, both bone formation and bone resorption are decreased with these pure antiresorptive agents, and bone mineral density reaches a new plateau. 

The charge neutralizing theory of calcification suggests a fundamental role of organic anions, e. g. sulfated mucopolysaccharides, in regulating bone formation and in retardation of atherosclerosis328). 

---