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Office of the Surgeon general (US). Bone Health and Osteoporosis: A Report that the surgeon General. Rockville (MD): Office that the Surgeon basic (US); 2004.


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The bony skeleton is a remarkable organ that offer both a structural function, providing mobility, support, and also protection because that the body, and a reservoir function, together the storehouse for essential minerals.
During childhood and also adolescence bones space sculpted by a process called modeling, which enables for the development of brand-new bone at one site and also the remove of old bone from another site in ~ the exact same bone. This procedure allows separation, personal, instance bones to grow in size and also to change in space.
Much of the cellular task in a bone consists of removal and also replacement at the very same site, a process called remodeling. The remodeling process occurs transparent life and becomes dominant by the moment that bone reaches its top mass (typically by the beforehand 20s). Remodeling continues throughout life so that most of the adult skeleton is replaced around every 10 years.
Both genes and also the environment contribute to bone health. Some elements of bone health are identified largely by genes, and also errors in signaling by these gene can result in bear defects. Exterior factors, such as diet and physical activity, room critically vital to bone health and wellness throughout life, and also these determinants can it is in modified.
The development of the skeleton, its solution to mechanically forces, and its function as a mineral storehouse room all dependency on the suitable functioning of a number of systemic or turn around hormones that respond to changes in blood calcium and phosphorus. If calcium or phosphorus space in quick supply, the regulating hormones take them the end of the bone come serve crucial functions in other systems of the body. Too plenty of withdrawals deserve to weaken the bone.
Many things have the right to interfere through the breakthrough of a strong and healthy and balanced skeleton. Genetic abnormalities can develop weak, slim bones, or bones that are too dense. Nutritional deficiencies can result in the development of weak, poorly mineralized bone. Countless hormonal disorders deserve to also affect the skeleton. Lack of exercise, immobilization, and smoking can additionally have negative effects on bone mass and also strength.
Osteoporosis, the most usual bone disease, frequently does no manifest till late in life, when bone loss starts due come bone malfunction and decreased levels of bone formation. Loss of bone mass leader to the breakthrough of structure abnormalities the make the skeleton much more fragile.

The function of this thing is to provide an summary of bone biology the will help the reader to understand:


While dealing with a subject that is extremely technical in nature, this chapter attempts to explain bone biological in terms that a lay human being can generally understand. It is plan to provide the reader with the background required to know the basis for few of the preventive, diagnostic, and treatment philosophies related come bone disease that are discussed in detail later in this report. Those interested in a an ext detailed review of bone biology and bone an illness can consult any type of of a variety of recent texts (Bilezikian et al. 2001, Marcus et al. 2001, Favus 2003).


Why perform We have Bones?

The bony skeleton is a remarkable organ that offer both a structure function—providing mobility, support, and also protection because that the body—and a reservoir function, as the storehouse for necessary minerals. The is not a static organ, but is constantly transforming to far better carry out its functions. The development of the bony skeleton likely started many eons ago, when pets left the calcium-rich ocean, very first to live in new water where calcium was in short supply, and also then on dry land whereby weight bearing put much higher stress ~ above the skeleton. The style of the skeleton is remarkably adapted to provide adequate strength and mobility so the bones execute not break once subjected to considerable impact, even the loads placed on bone during vigorous physical activity. The form or framework of bone is at least as essential as its fixed in giving this strength.

The skeleton is likewise a storehouse for 2 minerals, calcium and also phosphorus, the are vital for the work of various other body systems, and also this storehouse need to be referred to as upon in times of need. The maintenance of a consistent level that calcium in the blood and an enough supply of calcium and also phosphorus in cell is critical for the function of every body organs, but particularly for the nerves and muscle. Therefore, a complicated system that regulatory hormones has occurred that help to keep adequate offers of this minerals in a range of situations. This hormones action not only on bone however on other tissues, such together the intestine and also the kidney, to control the supply of these elements. Therefore one reason that bone health and wellness is challenging to keep is the the skeleton is all at once serving two various functions that are in competition through each other. First, bone have to be responsive to transforms in mechanically loading or load bearing, both of i m sorry require strong bones that have ample offers of calcium and also phosphorus. As soon as these aspects are in short supply the regulation hormones take them the end of the bone come serve an essential functions in various other systems that the body. Thus the skeleton can be likened to a bank where we have the right to deposit calcium or phosphorus and also then withdraw them later on in times of need. However, too plenty of withdrawals weaken the bone and can result in the most typical bone disorder, fractures.

Both the quantity of bone and its architecture or shape are identified by the mechanical pressures that action on the skeleton. Much of this is identified genetically so the each species, consisting of humans, has a skeleton that is adapted to its functions. However, there have the right to be great variation within a species, so the some people will have solid bones and others will have weak bones, largely because of distinctions in their genes (Huang et al. 2003). Moreover, bone mass and also architecture are additional modified transparent life as these functions and also the mechanical forces required to satisfy them change. In other words, skeleton will weaken if they room not subjected to adequate amounts of loading and also weight bearing for adequate periods of time. If they space not (such together in the weightless problem of room travel), quick bone loss can occur. In other words, similar to muscle, that is “use it or shed it” through bone together well. Whereas the amount and architecture that the bones have the right to be improved by mechanical loading. However, as defined in chapter 6, some types of exercise might be much better than rather in increase the skeleton.

To respond to its double roles of support and also regulation the calcium and also phosphorus, and to repair any type of damage to the skeleton, bone is continuous changing. Old bone breaks under and brand-new bone is created on a continuous basis. In fact, the tissue of the skeleton is replaced numerous times during life. This calls for an exquisitely regulated regulatory system that involves specialized cells that communicate with each other. This cells must respond to countless different signals, both internal and external, mechanical and hormonal, and systemic (affecting the entirety skeleton) and local (affecting just a small an ar of the skeleton). The is not surprising that through so many different jobs to perform and so many different factors regulating how the skeleton grows, adapts, and responds to an altering demands, over there are numerous ways the these processes can go astray.


How skeletal Work

Bone is a composite material, consist of of crystals the mineral bound come protein. This provides both strength and also resilience so the the skeleton can absorb impact without breaking. A structure made only of mineral would be an ext brittle and break much more easily, while a structure made just of protein would certainly be soft and also bend as well easily. The mineral step of bone consists of little crystals containing calcium and also phosphate, referred to as hydroxyapatite. This mineral is bound in an orderly manner come a matrix that is consisted of largely of a solitary protein, collagen. Collagen is make by bone cells and also assembled as long thin rods comprise three intertwined protein chains, which space then assembled right into larger yarn that are strengthened by chemical connections between them. Other proteins in bone can help to combine the collagen matrix even further and to manage its ability to tie mineral. Very small changes in the shape of the bone can act top top the cells within bone (the osteocytes), which develop chemical signals that allow the skeleton come respond to transforms in mechanical loading. Abnormalities in the collagen frame can take place as a an outcome of a hereditary disorder called osteogenesis imperfecta, if the fail of mineral deposition can be the result of rickets and osteomalacia, problems that result in significant weakening that the skeleton (see below and Chapter 3).

To provide the body v a structure that is both light and also strong, bones space hollow. The outer dense shell is dubbed cortical bone, which makes up around three-quarters the the total skeletal mass. Within the cortical shell is a fine network of connecting plates and rods referred to as trabecular bone that provides up the remaining 25 percent (Figure 2-1). Most bones space hollow structures in i beg your pardon the outer cortical bone shell specifies the form of the bone. This cortical covering is essential because it gives strength, sites because that firm attachment of the tendons, and also muscles and also protection without too much weight. The inside trabecular network has actually two necessary functions. It gives a huge bone surface for mineral exchange. In addition, trabecular bone help to maintain skeletal strength and integrity, as it is particularly abundant in the spine and at the ends of the lengthy bones, web page that are under constant stress indigenous motion and weight-bearing. Fractures are usual at these sites as soon as the bone is dilute (Kontulainen, Sievanen et al. 2003). The rods and plates of trabecular bone room aligned in a sample that provides maximal stamin without too lot bulk, much in the way that architects and engineers architecture buildings and bridges. The shape and also size that both cortical and trabecular bone have the right to respond to different kinds the stress developed by physics activity. Because that example, in most people the cortex that their leading arm is bigger than that of your non-dominant arm. The distinction in cortex dimension is also larger for tennis players and also other athletes who consistently use a dominant arm in your sporting activities. Bones execute not occupational in isolation, however rather are component of the musculoskeletal system, providing the “lever” that allows muscles to relocate (by pulling ~ above the lever). Hence muscle task is important for the normal role of the bone. When the mechanical force created by muscle is lost—for example, in patients with muscular dystrophy or paralysis—bone mass and also strength are likewise rapidly lost. Plenty of bones in the skeleton also have connecting joints that administer greater flexibility of movement. This joints room sites of an excellent mechanical stress and also are topic to injury and also to degeneration with aging. The most common form of share degeneration is osteoarthritis, a painful, degenerative condition that affects the hip, knees, neck, lower back, and/or tiny joints of the hand. This joint diseases result from very different causes and also require very different monitoring than carry out bone diseases, and also consequently they room not extended in this report. Yet it is vital to identify that the bones, joints, and muscles are the key parts the an incorporated “musculoskeletal system.” difficulties with any one component of this mechanism can influence the various other components. Thus, weakness of the muscles have the right to lead to loss the bone and also joint damage, if degeneration the the joints leader to changes in the underlying bone, such together the bony spurs or protuberances that take place in osteoarthritis.


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How Bones adjust Throughout Life

Throughout life, bones change in size, shape, and position. 2 processes overview these changes—modeling and remodeling. As soon as a bone is developed at one site and broken under in a different site that shape and position is changed. This is referred to as modeling (Figure 2-2). However, lot of the cellular activity in a bone is composed of removal and replacement at the same site, a procedure called remodeling. The remainder of this section describes why and also how these processes occur.


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Figure 2-2

Modeling and Remodeling. Note: In modeling, osteoblast and also osteoclast action are not linked and rapid transforms can occur in the amount, shape, and position that bone. In remodeling, osteoblast action is coupled to prior osteoclast action. Net transforms in (more...)


Why We require Modeling and also Remodeling

During childhood and adolescence bones room sculpted through modeling, which allows for the formation of new bone at one site and also the remove of old bone from one more site within the exact same bone (Seeman 2003) (Figure 2-2). This procedure allows individual bones to grow in size and also to transition in space. Throughout childhood skeletal grow because resorption occurs within the bone while formation of new bone occurs on its external (periosteal) surface. In ~ puberty the bones gain thicker since formation can occur on both the outer and inner (endosteal) surfaces. As people get older, resorption wake up on inner surface while development occurs on external surfaces, which have the right to partially compensate because that the ns of strength due to the thinning that the cortex. The size and also shape of the skeleton follows a genetic program, however can be greatly affected by the loading or affect that occurs with physical activity. At some point bones achieve a shape and size that fits finest to your function. In other words, “form adheres to function.”

The remodeling procedure occurs throughout life and also becomes the dominant process by the time that bone will its height mass (typically by the beforehand 20s). In remodeling, a tiny amount that bone top top the surface ar of trabeculae or in the inner of the cortex is removed and then replaced at the very same site (Figure 2-2). The remodeling process does not change the shape of the bone, however it is nevertheless critical for bone health, for a selection of reasons. First, remodeling repairs the damage to the skeleton the can result from recurring stresses through replacing tiny cracks or deformities in areas of cabinet damage. Remodeling likewise prevents the accumulation of too lot old bone, which can lose that resilience and become brittle. Remodeling is additionally important because that the function of the skeleton together the financial institution for calcium and also phosphorus. Resorption (the process of breaking down bone), specifically on the surface ar of trabecular bone, deserve to supply essential calcium and also phosphorus once there is a deficiency in the diet or for the requirements of the fetus during pregnancy or one infant during lactation. Once calcium and phosphorus supplies are ample the development phase the remodeling deserve to take up these minerals and replenish the bank.

Modeling and also remodeling continue throughout life for this reason that most of the adult skeleton is replaced about every 10 years. When remodeling predominates by beforehand adulthood, modeling can still occur specifically in response to weakening that the bone. For this reason with aging, if excessive amounts of bone are removed from the inside, some new bone deserve to be laid under on the outside, hence preserving the mechanical stamin of the bone regardless of the lose of bone mass.


How Modeling and also Remodeling Occur

The procedure of structure the skeleton and continuously reshaping it to respond come internal and external signals is lugged out by committed cells that deserve to be set off to type or failure bone. Both modeling and also remodeling involve the cell that form bone called osteoblasts and also the cell that failure bone, called osteoclasts (Figure 2-3). In remodeling there is an important local interaction between osteoblasts or your precursors (the cells the will develop into osteoblasts by acquiring more devoted functions—a process called differentiation) and also osteoclasts or their precursors. Since remodeling is the main method that bone changes in adults and also abnormalities in remodeling space the primary cause of bone disease, that is critically essential to understand this process. In addition, recent research has listed exciting information around these cell interactions.


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Figure 2-3

Bone Remodeling. Note: The sequence of activation, resorption, reversal, and also formation is shown here. The activation step relies on cell of the osteoblast lineage, one of two people on the surface ar of the bone or in the marrow, acting on blood cell precursors (more...)


Osteoblasts are derived from precursor cells the can likewise be engendered to come to be muscle, fat or cartilage; however, under the right conditions these cells change (or differentiate) to type new bone, producing the collagen that forms the scaffolding or bone matrix. This calcium- and phosphate-rich mineral is added to the matrix to kind the hard, however resilient, tissue that is healthy bone. Osteoblasts lay down bone in orderly class that add strength to the matrix. Some of the osteoblasts are hidden in the procession as the is being produced and also these space now called osteocytes. Others stay as slim cells that cover the surface and are dubbed lining cells. Osteocytes are the most countless cells in bone and also are extensively associated to each other and also to the surface ar of osteoblasts by a network of little thin extensions. This network is an important for the ability of bone come respond to mechanically forces and injury. When the skeleton is subjected to influence there is fluid movement about the osteocytes and the long-cell expansions that gives signals to the bone cells on the surface ar to transform their activity, either in terms of changes in bone resorption or formation. Fail of the osteoblasts to make a regular matrix occurs in a congenital disorder the the collagen molecule dubbed osteogenesis imperfecta. Inadequate bone procession formation additionally occurs in osteoporosis, an especially in the type of osteoporosis developed by an excess of the adrenal hormones called glucocorticoid-induced osteoporosis. This type of osteoporosis differs from major osteoporosis and also most other develops of secondary osteoporosis due to the fact that with glucocorticoid-induced osteoporosis inhibition the bone formation is the leading mechanism for weakening of the skeleton.

The osteoclasts remove bone by dissolve the mineral and also breaking down the matrix in a procedure that is dubbed bone resorption. The osteoclasts come from the very same precursor cells in the bone marrow that produce white blood cells. This precursor cells can also circulate in the blood and be accessible at various sites in require of bone breakdown. Osteoclasts are developed by blend of little precursor cells right into large, highly active cells with numerous nuclei. These large cells have the right to fasten onto the bone, seal turn off an area ~ above the surface, and also develop a region of intense activity in i beg your pardon the cell surface ar is very irregular, referred to as a ruffled border. This ruffled border contains transport molecule that carry hydrogen ion from the cells to the bone surface where they deserve to dissolve the mineral. In addition, packets that enzymes room secreted indigenous the ruffled border that can failure the matrix. Too much bone malfunction by osteoclasts is crucial cause that bone fragility not just in osteoporosis, but also in other bone illness such together hyperparathyroidism, Paget’s disease, and fibrous dysplasia (see thing 3). Inhibitors the osteoclastic bone break down have been developed to act these obstacle (see chapter 9).

Removal and also replacement that bone in the remodeling cycle wake up in a closely orchestrated succession that entails communication in between cells that the osteoblast and also osteoclast lineages (Hauge, Qvesel et al. 2001; Parfitt 2001). That is managed by local and also systemic factors that control bone remodeling to satisfy both that is structural and also metabolic functions. The activation that this procedure involves one interaction between cells of the osteoblastic lineage and also the precursors the will come to be osteoclasts. What stops this procedure is no known, yet the osteoclasts machinery clearly slows down and also the osteoclasts dice by a process that is referred to as programmed cabinet death. For this reason the quantity of bone removed deserve to be controlled by altering the price of production of brand-new osteoclasts, blocking your activity, or transforming their life span. Most present treatments because that osteoporosis occupational by slowing down osteoclastic bone break down through use of antiresorptive agents.

The activation and also resorption phases are adhered to by a short reversal step (Everts, Delaisse et al. 2002). Throughout the reversal step the resorbed surface ar is all set for the subsequent development phase, in part by developing a thin layer the protein, affluent in sugars, i beg your pardon is called the cement line and also helps type a strong bond in between the old bone and the newly created bone.

These three phases are relatively rapid, probably lasting just 2 come 3 weeks in humans. The final phase that bone formation takes much longer, lasting approximately 3 or 4 months. Thus energetic remodeling at many sites can weaken the bone for a considerable duration of time (even if formation records up eventually), as plenty of defects type in the bony framework that have actually not yet been filled. Formation is carried out by huge active osteoblasts that lay down succeeding layers of procession in an orderly manner the provides added strength. The enhancement of minerals to the collagenous matrix completes the process of making strong bone. Any type of error in this complex process have the right to lead to bone disease.

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Since remodeling serves both the structural and also metabolic attributes of the skeleton, it have the right to be stimulated both through the hormone that control mineral metabolism and by mechanically loads and local damage acting through regional factors. Repair of local damages is an essential function of remodeling. In time repeated little stresses ~ above the skeleton have the right to produce locations of defective bone, termed micro-damage. Replacement of that damaged bone by remodeling restores bone strength. Signals because that these responses room probably developed by the network the osteocytes and osteoblasts, which, with their multiple connections, can detect changes in the stress placed upon bone and in the health of the small areas that micro-damage. Components that affect the formation, activity, and life expectancy of osteoclasts and osteoblasts together they construct from precursor cells can affect the remodeling cycle. Drugs have been developed that plot in these ways, with the goal of reduce bone lose or boosting bone formation and maintaining bones health.