Mineralized versus nonmineralized components

While cortical and cancellous bone are architecturally different, they are similar at the molecular and biochemical level. Bone is composed of cells and extracellular matrix (ECM). The cells produce and control the production and removal of bone. The mechanical properties of bone are derived from the composition of the ECM as well as the geometric and architectural characteristics resulting from the way this tissue is distributed in space.

The ECM has mineralized and nonmineralized components. The nonmineralized component is known as os-teoid. It is produced and secreted by osteoblasts. The mineralized component is made up of a crystalline material known as calcium hydroxyapatite. The important elements of this material are calcium and phosphate ions. The serum levels of these ions are tightly controlled by various mechanisms that influence bone metabolism and, in turn, bone mass.

Osteoid is made up of both collagenous and noncol-lagenous proteins. The predominant protein is type I collagen. In general, the collagenous portion of bone is responsible for its tensile strength. The greater the collagen concentration, the higher tensile and shear strength will be. Other noncollagenous proteins include osteonectin, osteo-pontin, and other various compounds. These noncollage-nous proteins affect many of the cellular activities in bone such as the ability of bone cells to attach to the ECM.

The mineralized portion of bone determines its com-pressive strength. With greater concentrations of calcium, compressive strength increases. Processes that diminish the levels of either bone mineral or collagen substantially decrease the ability of bone to withstand respective loads.

Bones fail and fractures occur when ultimate stress levels are exceeded. Stress is a property defined as an internal resistance to an externally applied load. Tensile and compressive stresses are the result of loads/forces acting along the same line (Fig. 2). Tensile forces act away from each other, while compressive forces act towards each other. Shear forces act towards each other in different, but parallel, planes. Bone can fail under tension, compression, or shear. The relative amounts of mineralized and nonmineralized bone influence its behavior under various loading patterns. Bone fails more easily under shear and ten

Fig. 2 The three basic types of stress that bone must endure are tension, compression, and shear. Tension is produced by forces acting in the same plane but away from each other. Compression is produced by forces acting in the same plane but towards each other. Shear is produced by two forces acting towards each other but in two different planes

Fig. 2 The three basic types of stress that bone must endure are tension, compression, and shear. Tension is produced by forces acting in the same plane but away from each other. Compression is produced by forces acting in the same plane but towards each other. Shear is produced by two forces acting towards each other but in two different planes sile forces, while it is strongest in compression. This is true for both cortical and trabecular bone.

These concepts can be illustrated with a simple analogy. Take, for example, a column of bricks stacked one on top of each other, but each connected to its neighbor by a strong rubber band. If one picks up the top brick, while the bottom brick is held fixed to the ground, the bricks will begin to separate, but only as far as the elasticity of the rubber bands will allow it. The rubber bands act like the long fibrils of collagen in bone. Eventually, if the column of bricks is stretched long enough, one of the rubber bands will break. It can be imagined, however, that this would not take an excessive amount of force. Now, consider placing a load on top of the column of bricks. As bricks are used in a similar manner to build a house, they can sustain great loads. One could stand on the column of bricks without fear of the bricks crushing or crumbling. The bricks act like the calcium/mineral component of bone. With this example, it can be understood that (1) the mineral component is responsible for compressive strength, (2) the collagen is responsible for tensile strength, and (3) much greater compressive loads can be endured than tensile loads before failure.

Using the same analogy, shear strength can be illustrated as well. If one were to push the top brick to the right and the bottom brick to the left, the resistance to failure would be from two sources. One would be the elastic tethering effect of the rubber bands. The other would be the friction between the two bricks. Thus shear force would be influenced by both the collagenous and mineral components of bone. In this way, one might also understand why shear strength is dramatically less than compressive strength.

Fig. 3 Bone mineralization is initiated at sites known as holes and pores. Holes are located between the ends of juxtaposed collagen molecules. Pores are formed longitudinally between collagen molecules

Cellular control of bone mass: osteoblasts and osteoclasts

Osteoblasts are bone-forming cells. They both secrete osteoid and conduct its mineralization. The collagen fibrils within the osteoid are arranged into linear columns, forming pores and holes (Fig. 3). It is at these sites that mineralization is initiated. Osteoblasts have receptors for several factors that are known to control bone metabolism, most notably parathyroid hormone (PTH) and 1,25-dihydroxy-vitamin D. Osteoblasts appear to influence the activity of osteoclasts, which suggests that the former may ultimately be in control of both bone formation and resorption.

Recent data have increased the available knowledge of how osteoblasts regulate bone remodeling and resorption. Lacey et al. [13] found that exposing bone marrow cells and osteoblasts to substances like PTH, prostaglandin E2, and 1,25-dihydroxyvitamin D3 stimulated osteoclast differentiation and osteoclast activity. This former is effected by expression of an osteoclast differentiation factor known as RANK ligand (receptor activator of NF-kB ligand). RANK ligand binds to a receptor located on the surface of osteoclast precursors. When macrophage colony stimulating factor, a cytokine also produced by bone marrow stro-mal cells and osteoblasts, binds to its receptor, known as c-fms, the precursor cell then matures into a functioning preosteoclast. This causes an increase in the number of osteoclasts and thus, more bone resorption. To further activate bone resorption, RANK ligand can bind RANK on mature, differentiated osteoclasts. Osteoprotegerin, which is the product of a distinct gene from RANK, inhibits differentiation of osteoclasts by binding RANK as a so-called decoy receptor and preventing its interaction with its lig-and [13].

Osteoclasts are bone-resorbing cells. They have several features that make them an ideal vehicle for this func tion. They have a ruffled border with extensive membrane folding that increases their metabolically active surface area. The cells effect bone resorption by the release of protons (H+) via a carbonic anhydrase-dependent proton pump. This lowers the pH of (i.e., acidifies) the region surrounding the cell, which in turn activates specific acid proteases. These proteases then break down the bone within the extracellular matrix. The multinucleated osteo-clasts reside within bone resorption cavities or pits known as Howship's lacunae, which can be recognized on microscopic examination. Osteoclasts do not have receptors for PTH or 1,25-dihydroxyvitamin D. Therefore, these factors appear to influence osteoclastic activity through mechanisms mediated via the osteoblast binding.

Osteocytes are osteoblasts that have terminally divided. Histologically, they are surrounded by, or trapped within, mineralized bone. Metabolically, they are relatively inactive, with a high nucleus-to-cytoplasm ratio. In view of their radiating processes that extend from the cell border to infiltrate the surrounding canaliculi, it is postulated that osteocytes may transmit signals between the bone cells [9, 19]. However, their role still remains unclear.

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