Normal Bone Remodeling

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). 

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. 

The bone disease osteoporosis results when an imbalance occurs in the normal course of bone remodeling, a dynamic and highly regulated... 

Parfitt AM (2004) What is the normal rate of bone remodeling Bone 35 1-3... 

Calcium is the major mineral component of bone and normal repair and remodelling of bone is reliant on an adequate supply of this mineral. Calcium uptake in the gut, loss through the kidneys and turnover within the body are controlled by hormones, notably PTH and 1,25 dihydroxy cholecalciferol (1,25 DHCC or 1,25 dihydroxy vitamin D3 or calcitriol). Refer to Figure 8.12 for a summary of the involvement of PTH and vitamin D3 in controlling plasma calcium concentration. These two major hormones have complementary actions to raise plasma calcium concentration by promoting uptake in the gut, reabsorption in the nephron and bone resorption. Other hormones such as thyroxine, sex steroids and glucocorticoids (e.g. cortisol) influence the distribution of calcium. 

Both cortical and trabecular bone are continuously remodeled through the formation of a bone-modeling unit (BMU), or cutter-cone this process involves activation of osteoclasts, leading to resorption of bone by osteoclasts and formation of new bone by osteoblasts on the site of the old, resorbed bone (Fig. 7) (Martin and Burr, 1989). Under normal physiological conditions (i.e., in the absence of either growth or disease) the dynamics of bone remodeling maintain bone homeostasis throughout a person s lifetime. 

Vitamin A is an essential fat-soluble compound acquired from the diet. The parent form of vitamin A is all-iram-retinol. Vitamin A is needed to maintain normal vision, normal reproduction (including spermatogenesis, conception, and placenta formation), and normal cell differentiation (including bone remodeling, maintenance of differentiated epithelial linings and skin, em-... 

Osteoblasts and osteoclasts are involved in the bone remodeling process. One can easily see that certain parts of bone must be eroded and lesorbed in the growing infant or child. Ihe skull, for example, must be resorbed to make room for the growing brain. The osteoclast adheres to the bone and secretes acid in its zone of contact with the bone, A pH of about 3 may be produced in this zone of contact. Normally, bone mineral is very insoluble in water. An attempt to dissolve hydroxyapatite in water at pH 7 results in a solution of calcium ions with a concentration of about 0,1 mM. Bone mineral can, however, be dissolved in acid. Apparently, the bone mineral dissolved in the acid secreted in the region of contact can result in a solution of calcium reaching about 40 mA4- The osteoclast is distinguished by its ruffled bonder... 

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. 

Children are particularly vulnerable to excess strontium because the immature skeleton has a high rate of bone remodeling, and strontium adversely affects bone development in several ways, as demonstrated in animal studies. In chickens and rats, excess strontium suppresses the activation of vitamin D3 in the kidney, which severely reduces the expression of calbindin D mRNA and the translation of calbindin D protein in the duodenum (Armbrecht et al. 1979, 1998 Omdahl and DeLuca 1972). As a result, duodenal absorption of calcium is reduced. Strontium also binds directly to hydroxyapatite crystals, which may interfere with the normal crystalline structure of bone in rats (Storey 1961). In addition, excess strontium may prevent the normal maturation of chondrocytes in the epiphyseal plates of long bones of rats (Matsumoto 1976). Excess strontium apparently interferes with the mineralization of complexed acidic phospholipids that is thought to help initiate the formation of hydroxyapatite crystals in developing bone (Neufeld and Boskey 1994). As a result, affected bone contains an excess of complexed acidic... 

Involutional (primary) osteoporosis is the manifestation of a metabolic bone disease in which the amount of normally mineralized bone matrix in affected patients has been reduced to a level below that of the normal population of the same age and sex. The disease is certainly of multifactorial origin, since genetic (Seeman etal. 1989), mechanical (e.g.. Frost 1988), nutritional (e.g., Hegsted 1986), and hormonal factors (e.g., Melton and Riggs 1988) can cause the severe impairment of the bone remodeling process (Eriksen etal. 1994) which underlies the observed reduction in bone mass and microarchitectural deterioration of bone tissue that lead to an increased risk of fractures at typical sites of the skeleton (for a definition, see Anonymous 1993)... 

Normal bone remodeling processes occur around calcium phosphate cement with osteoclastic resorption removing bone followed by deposition of new bone directly on the resorption line (Yuan et al. 2000). Bone growth on pre-hardened cement situated in muscle tissue suggests that bone cement is osteoinductive. 

---