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


The bony skeleton is a remarkable organ that offer both a structure function, providing mobility, support, and protection because that the body, and also a reservoir function, together the storehouse for crucial minerals.
During childhood and adolescence bones room sculpted through a process called modeling, which allows for the formation of new bone in ~ one site and also the remove of old bone from one more site within the very same bone. This process allows individual bones to thrive in size and also to transition in space.
Much of the cellular task in a bone is composed of removal and replacement in ~ the very same site, a procedure called remodeling. The remodeling procedure occurs transparent life and also becomes dominant by the moment that bone get its top mass (typically by the at an early stage 20s). Remodeling proceeds throughout life so that many of the adult skeleton is replaced around every 10 years.
Both genes and the environment contribute to bone health. Some elements of bone health and wellness are figured out largely by genes, and errors in signaling through these gene can an outcome in birth defects. Outside factors, such together diet and also physical activity, room critically important to bone wellness throughout life, and also these factors can be modified.
The expansion of the skeleton, its an answer to mechanical forces, and also its role as a mineral storehouse are all dependency on the ideal functioning of a number of systemic or turn around hormones that respond to changes in blood calcium and also phosphorus. If calcium or phosphorus room in short supply, the regulation hormones take it them the end of the bone come serve critical functions in other systems the the body. Too many withdrawals can weaken the bone.
Many things deserve to interfere v the breakthrough of a solid and healthy and balanced skeleton. Hereditary abnormalities can create weak, slim bones, or skeleton that room too dense. Nutritional deficiencies can an outcome in the formation of weak, poorly mineralized bone. Countless hormonal disorders can also affect the skeleton. Absence of exercise, immobilization, and also smoking can additionally have negative effects on bone mass and strength.
Osteoporosis, the most common bone disease, generally does no manifest till late in life, as soon as bone loss begins due come bone malfunction and lessened levels of bone formation. Lose of bone mass leader to the development of structure abnormalities that make the skeleton much more fragile.

The objective of this thing is to provide an synopsis of bone biology the will aid the leader to understand:

While handling a topic that is extremely technical in nature, this thing attempts to describe bone biology in terms that a lay human being can normally understand. It is plan to provide the reader with the background required to recognize the communication for some of the preventive, diagnostic, and also treatment ideologies related come bone condition that are discussed in information later in this report. Those interested in a more detailed testimonial of bone biology and bone condition can consult any of a variety of recent messages (Bilezikian et al. 2001, Marcus et al. 2001, Favus 2003).

Why perform We have Bones?

The bony skeleton is a remarkable organ that serves both a structure function—providing mobility, support, and also protection for the body—and a reservoir function, together the storehouse for essential minerals. It is not a static organ, but is constantly transforming to far better carry the end its functions. The development of the bony skeleton likely began many eons ago, when animals left the calcium-rich ocean, an initial to live in new water whereby calcium to be in quick supply, and then on dry land where weight bearing put much better stress top top the skeleton. The architecture of the skeleton is remarkably adjusted to carry out adequate strength and mobility so that bones do not break when subjected to substantial impact, even the loads inserted on bone throughout vigorous physical activity. The form or structure of bone is at least as important as its massive in providing this strength.

The skeleton is likewise a storehouse for two minerals, calcium and phosphorus, the are vital for the to work of various other body systems, and this storehouse have to be dubbed upon in times of need. The maintain of a continuous level that calcium in the blood and also an sufficient supply of calcium and also phosphorus in cell is an important for the role of every body organs, but an especially for the nerves and muscle. Therefore, a complex system that regulatory hormone has developed that help to maintain adequate supplies of these minerals in a selection of situations. These hormones act not just on bone but on other tissues, such as the intestine and also the kidney, to control the supply of these elements. For this reason one factor that bone wellness is challenging to keep is that the skeleton is concurrently serving two various functions that room in competition with each other. First, bone must be responsive to transforms in mechanical loading or load bearing, both of i m sorry require solid bones that have ample gives of calcium and also phosphorus. As soon as these facets are in short supply the regulation hormones take it them the end of the bone to serve an essential functions in other systems of the body. Hence the skeleton deserve to be likened come a bank where we can deposit calcium or phosphorus and then retract them later in time of need. However, too many withdrawals threaten the bone and can cause the most usual bone disorder, fractures.

Both the quantity of bone and also its design or shape are established by the mechanical pressures that plot on the skeleton. Much of this is identified genetically so that each species, consisting of humans, has actually a skeleton the is adapted to the functions. However, there deserve to be an excellent variation in ~ a species, so that some individuals will have strong 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 more modified throughout life as these functions and the mechanically forces required to meet them change. In various other words, skeleton will weaken if they are not subjected to adequate amounts of loading and also weight bearing for enough periods of time. If they are not (such as in the weightless condition of space travel), rapid bone loss can occur. In other words, as with muscle, that is “use the or shed it” v bone together well. Conversely, the amount and architecture that the bones deserve to be enhanced by mechanical loading. However, as defined in thing 6, some varieties of exercise may be better than others in strengthening the skeleton.

To respond to its double roles that support and regulation that calcium and also phosphorus, as well as to repair any damage come the skeleton, bone is continually changing. Old bone breaks down and brand-new bone is formed on a continuous basis. In fact, the tissue of the skeleton is replaced plenty of times throughout life. This requires an exquisitely regulated regulatory device that involves dedicated cells that connect with every other. This cells need to respond to numerous different signals, both internal and also external, mechanical and also hormonal, and systemic (affecting the totality skeleton) and also local (affecting just a small region of the skeleton). It is not surprising that through so many different tasks to perform and also so plenty of different determinants regulating exactly how the skeleton grows, adapts, and also responds to transforming demands, there are many ways the these processes deserve to go astray.

How skeletal Work

Bone is a composite material, consist of of crystals of mineral bound to protein. This offers both strength and resilience so that the skeleton can absorb influence without breaking. A structure made only of mineral would be more brittle and break more easily, while a structure made just of protein would certainly be soft and also bend too easily. The mineral phase of bone is composed of small crystals comprise calcium and phosphate, referred to as hydroxyapatite. This mineral is bound in one orderly manner come a matrix that is consisted of largely that a single protein, collagen. Collagen is make by bone cells and assembled as long thin rods comprise three intertwined protein chains, which space then assembled into larger fibers that space strengthened by chemistry connections in between them. Other proteins in bone can aid to combine the collagen matrix also further and also to regulate its capacity to bind mineral. Very little changes in the form of the bone can act top top the cells within bone (the osteocytes), which create chemical signals that permit the skeleton come respond to changes in mechanical loading. Abnormalities in the collagen frame can take place as a result of a hereditary disorder called osteogenesis imperfecta, if the fail of mineral deposition have the right to be the result of rickets and osteomalacia, conditions that an outcome in marked weakening the the skeleton (see below and also Chapter 3).

To provide the body with a frame that is both light and also strong, bones space hollow. The outer thick shell is called cortical bone, which makes up roughly three-quarters the the full skeletal mass. Within the cortical covering is a fine network that connecting plates and also rods called trabecular bone that makes up the continuing to be 25 percent (Figure 2-1). Many bones are hollow frameworks in i beg your pardon the outer cortical bone shell specifies the form of the bone. This cortical shell is essential due to the fact that it offers strength, sites because that firm attachments of the tendons, and also muscles and also protection without extreme weight. The within trabecular network has actually two crucial functions. It gives a large bone surface ar for mineral exchange. In addition, trabecular bone help to keep skeletal strength and also integrity, together it is an especially abundant in the spine and at the end of the lengthy bones, website that are under continuous stress from motion and weight-bearing. Fractures are typical at this sites when the bone is weakened (Kontulainen, Sievanen et al. 2003). The rods and also plates the trabecular bone room aligned in a pattern that provides maximal stamin without too much bulk, much in the means that architects and engineers design buildings and bridges. The shape and size of both cortical and trabecular bone deserve to respond to various kinds that stress produced by physical activity. Because that example, in most civilization the cortex that their dominant arm is larger than that of your non-dominant arm. The distinction in cortex size is even larger because that tennis players and other athletes who on regular basis use a leading arm in their sporting activities. Bones execute not job-related in isolation, yet rather are component of the musculoskeletal system, providing the “lever” that permits muscles to move (by pulling top top the lever). Hence muscle activity is necessary for the normal role of the bone. When the mechanically force developed by muscle is lost—for example, in patients through muscular dystrophy or paralysis—bone mass and strength are also rapidly lost. Many bones in the skeleton likewise have connecting joints that provide greater flexibility of movement. This joints are sites of good mechanical stress and also are topic to injury and to degeneration through aging. The many common type of share degeneration is osteoarthritis, a painful, degenerative problem that affects the hip, knees, neck, lower back, and/or tiny joints of the hand. This joint diseases an outcome from really different causes and require very different monitoring than perform bone diseases, and consequently they are not spanned in this report. Yet it is important to identify that the bones, joints, and also muscles are the key parts of an incorporated “musculoskeletal system.” difficulties with any type of one component of this device can influence the other components. Thus, weak of the muscles deserve to lead to loss the bone and also joint damage, while degeneration that the joints leader to transforms in the basic bone, such as the bony spur or protuberances that take place in osteoarthritis.


How Bones readjust Throughout Life

Throughout life, bones readjust in size, shape, and also position. Two processes guide these changes—modeling and remodeling. When a bone is formed at one site and broken down in a various site that shape and also position is changed. This is dubbed modeling (Figure 2-2). However, much of the cellular task in a bone consists of removal and replacement in ~ the same site, a procedure called remodeling. The remainder the this section describes why and also how these procedures occur.


Figure 2-2

Modeling and also Remodeling. Note: In modeling, osteoblast and also osteoclast activity are no linked and also rapid changes can happen in the amount, shape, and position of bone. In remodeling, osteoblast action is coupled to front osteoclast action. Net changes in (more...)

Why We need Modeling and Remodeling

During childhood and also adolescence bones space sculpted by modeling, which allows for the development of brand-new bone at one site and the remove of old bone from another site within the very same bone (Seeman 2003) (Figure 2-2). This process allows separation, personal, instance bones to grow in size and to change in space. Throughout childhood bones grow due to the fact that resorption occurs inside the bone while development of new bone occurs on its external (periosteal) surface. In ~ puberty the bones gain thicker since formation can happen on both the outer and inner (endosteal) surfaces. As human being get older, resorption occurs on inner surface while development occurs on outer surfaces, which deserve to partially compensate because that the loss of strength as result of the thinning of the cortex. The size and also shape of the skeleton adheres to a genetic program, however can it is in greatly influenced by the loading or impact that occurs v physical activity. Ultimately bones attain a shape and size that fits best to your function. In other words, “form adheres to function.”

The remodeling procedure occurs throughout life and becomes the dominant process by the moment that bone will its peak mass (typically by the early 20s). In remodeling, a tiny amount of bone ~ above the surface of trabeculae or in the inner of the cortex is removed and then replaced at the exact same site (Figure 2-2). The remodeling process does not readjust the shape of the bone, however it is nevertheless an important for bone health, because that a range of reasons. First, remodeling repairs the damages to the skeleton that can result from recurring stresses through replacing little cracks or deformities in areas of cabinet damage. Remodeling additionally prevents the build-up of too lot old bone, which have the right to lose that resilience and also become brittle. Remodeling is also important for the duty of the skeleton together the financial institution for calcium and also phosphorus. Resorption (the process of breaking under bone), specifically on the surface ar of trabecular bone, can supply necessary calcium and phosphorus as soon as there is a deficiency in the diet or for the requirements of the fetus during pregnancy or an infant throughout lactation. When calcium and phosphorus provides are ample the development phase of remodeling deserve to take up these minerals and replenish the bank.

Modeling and remodeling continue throughout life therefore that most of the adult skeleton is replaced around every 10 years. While remodeling predominates by at an early stage adulthood, modeling deserve to still occur specifically in response to weakening of the bone. Thus with aging, if excessive amounts of bone are gotten rid of from the inside, some new bone have the right to be laid down on the outside, therefore preserving the mechanical stamin of the bone regardless of the lose of bone mass.

How Modeling and also Remodeling Occur

The process of building the skeleton and continuously reshaping it come respond come internal and also external signals is carried out by dedicated cells that can be caused to kind or break down bone. Both modeling and remodeling indicate the cells that form bone referred to as osteoblasts and also the cells that breakdown bone, called osteoclasts (Figure 2-3). In remodeling over there is an essential local interaction in between osteoblasts or their precursors (the cells the will develop into osteoblasts by obtaining more specialized functions—a procedure called differentiation) and osteoclasts or your precursors. Due to the fact that remodeling is the main method that bone alters in adults and also abnormalities in remodeling room the primary reason of bone disease, it is critically important to recognize this process. In addition, current research has detailed exciting information around these cell interactions.


Figure 2-3

Bone Remodeling. Note: The succession of activation, resorption, reversal, and formation is illustrated here. The activation step depends on cells of the osteoblast lineage, either on the surface of the bone or in the marrow, exhilaration on blood cell precursors (more...)

Osteoblasts are obtained from precursor cells the can likewise be engendered to become muscle, fat or cartilage; however, under the right conditions these cells change (or differentiate) to type new bone, developing the collagen that develops the scaffolding or bone matrix. This calcium- and phosphate-rich mineral is added to the procession to kind the hard, yet 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 that is being produced and also these room now referred to as osteocytes. Others continue to be as slim cells the cover the surface and are dubbed lining cells. Osteocytes room the most plenty of cells in bone and are extensively linked to each other and also to the surface of osteoblasts by a network of tiny thin extensions. This network is an essential for the ability of bone come respond to mechanical forces and injury. Once the skeleton is subjected to affect there is fluid movement approximately the osteocytes and the long-cell extensions that offers signals come the bone cells on the surface ar to transform their activity, either in terms of changes in bone resorption or formation. Failure of the osteoblasts to make a typical matrix wake up in a congenital disorder the the collagen molecule referred to as osteogenesis imperfecta. Insufficient bone procession formation also occurs in osteoporosis, particularly in the type of osteoporosis produced by an overfill of the adrenal hormones called glucocorticoid-induced osteoporosis. This kind of osteoporosis differs from major osteoporosis and most other creates of second osteoporosis since with glucocorticoid-induced osteoporosis inhibition the bone development is the leading mechanism for weakening the the skeleton.

The osteoclasts remove bone by dissolve the mineral and breaking down the matrix in a process that is dubbed bone resorption. The osteoclasts come from the exact same precursor cells in the bone marrow that create white blood cells. This precursor cells can also circulate in the blood and be obtainable at different sites in require of bone breakdown. Osteoclasts are created by fusion of small precursor cells into large, highly energetic cells with countless nuclei. These large cells have the right to fasten onto the bone, seal turn off an area ~ above the surface, and also develop a an ar of intense activity in which the cell surface ar is highly irregular, dubbed a ruffled border. This ruffled border consists of transport molecule that carry hydrogen ion from the cells to the bone surface ar where they have the right to dissolve the mineral. In addition, packets of enzymes room secreted native the ruffled border the can breakdown the matrix. Extreme bone break down by osteoclasts is an essential cause that bone fragility not just in osteoporosis, but additionally in other bone conditions such as hyperparathyroidism, Paget’s disease, and also fibrous dysplasia (see chapter 3). Inhibitors of osteoclastic bone breakdown have been emerged to act these disorders (see chapter 9).

Removal and replacement that bone in the remodeling cycle occurs in a carefully orchestrated sequence that involves communication in between cells of the osteoblast and also osteoclast lineages (Hauge, Qvesel et al. 2001; Parfitt 2001). That is controlled by local and systemic components that control bone remodeling to meet both that structural and also metabolic functions. The activation that this procedure involves an interaction between cells that the osteoblastic lineage and the precursors that will become osteoclasts. What stop this process is not known, but the osteoclasts machinery clearly slows down and also the osteoclasts dice by a procedure that is called programmed cabinet death. Therefore the amount of bone removed can be managed by changing the rate of manufacturing of new osteoclasts, blocking your activity, or altering their life span. Most existing treatments because that osteoporosis work-related by slowing under osteoclastic bone break down through usage of antiresorptive agents.

The activation and also resorption phases are followed by a brief reversal step (Everts, Delaisse et al. 2002). Throughout the reversal phase the resorbed surface is ready for the subsequent formation phase, in part by developing a slim layer the protein, well-off in sugars, i m sorry is dubbed the cement line and helps kind a solid bond between the old bone and also the newly formed bone.

These three phases are relatively rapid, probably lasting just 2 to 3 mainly in humans. The last phase that bone development takes lot longer, lasting as much as 3 or 4 months. Thus active remodeling at plenty of sites have the right to weaken the bone for a considerable duration of time (even if formation captures up eventually), as many defects form in the bony structure that have actually not yet been filled. Formation is brought out by large active osteoblasts that lay down succeeding layers of procession in one orderly manner the provides included strength. The addition of mineral to the collagenous matrix completes the process of making solid bone. Any type of error in this complicated process can lead to bone disease.

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Since remodeling offer both the structural and also metabolic attributes of the skeleton, it can be created both by the hormone that manage mineral metabolism and also by mechanical loads and local damage acting through neighborhood factors. Fix of local damages is vital function that remodeling. Over time repeated small stresses ~ above the skeleton have the right to produce locations of defective bone, termed micro-damage. Replacement of the damaged bone through remodeling restores bone strength. Signals because that these responses room probably developed by the network that osteocytes and also osteoblasts, which, through their lot of connections, have the right to detect alters in the stress put upon bone and also in the health of the tiny areas the micro-damage. Factors that impact the formation, activity, and also life span of osteoclasts and osteoblasts as they develop from precursor cell can affect the remodeling cycle. Drugs have been developed that act in these ways, through the score of reducing bone ns or raising bone formation and maintaining skeleton health.