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5.5: Bone Growth, Remodeling, and Repair - Biology

5.5: Bone Growth, Remodeling, and Repair - Biology



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Break a Leg

Did you ever break a leg or other bone, like the man looking longingly at the water in this swimming pool? Having a broken bone can really restrict your activity. Bones are very hard, but they will break, or fracture if enough force is applied to them. Fortunately, bones are highly active organs that can repair themselves if they break. Bones can also remodel themselves and grow. You’ll learn how bones can do all of these things in this concept.

Bone Growth

Early in the development of a human fetus, the skeleton is made almost entirely of cartilage. The relatively soft cartilage gradually turns into hard bone through ossification. Ossification is a process in which bone tissue is created from cartilage. The steps in which bones of the skeleton form from cartilage are illustrated in Figure (PageIndex{2}). The steps include the following:

  1. Cartilage “model” of bone forms; this model continues to grow as ossification takes place.
  2. Ossification begins at a primary ossification center in the middle of the bone.
  3. Ossification then starts to occur at secondary ossification centers at the ends of the bone.
  4. The medullary cavity forms and will contain red bone marrow.
  5. Areas of ossification meet at epiphyseal plates, and articular cartilage forms. Bone growth ends.

Primary and Secondary Ossification Centers

When bone forms from cartilage, ossification begins with a point in the cartilage called the primary ossification center. This generally appears during fetal development, although a few short bones begin their primary ossification after birth. Ossification occurs toward both ends of the bone from the primary ossification center, and it eventually forms the shaft of the bone in the case of long bones.

Secondary ossification centers form after birth. Ossification from secondary centers eventually forms the ends of the bones. The shaft and ends of the bone are separated by a growing zone of cartilage until the individual reaches skeletal maturity.

Skeletal Maturity

Throughout childhood, the cartilage remaining in the skeleton keeps growing and allows for bones to grow in size. However, once all of the cartilage has been replaced by bone and fusion has taken place at epiphyseal plates, bones can no longer keep growing in length. This is the point at which skeletal maturity has been reached. It generally takes place by age 18 to 25.

The use of anabolic steroids by teens can speed up the process of skeletal maturity, resulting in a shorter period of cartilage growth before fusion takes place. This means that teens who use steroids are likely to end up shorter as adults than they would otherwise have been.

Bone Remodeling

Even after skeletal maturity has been attained, bone is constantly being resorbed and replaced with new bone in a process known as bone remodeling. In this lifelong process, mature bone tissue is continually turned over, with about 10 percent of the skeletal mass of an adult being remodeled each year. Bone remodeling is carried out through the work of osteoclasts, which are bone cells that resorb bone and dissolve its minerals; and osteoblasts, which are bone cells that make the new bone matrix.

Bones remodeling serves several functions. It shapes the bones of the skeleton as a child grows, and it repairs tiny flaws in the bone that result from everyday movements. Remodeling also makes bones thicker at points where muscles place the most stress on them. In addition, remodeling helps regulate mineral homeostasis because it either releases minerals from bones into the blood or absorbs minerals from the blood into bones. The figure below shows how osteoclasts in bones are involved in calcium regulation.

The action of osteoblasts and osteoclasts in bone remodeling and calcium homeostasis is controlled by a number of enzymes, hormones, and other substances that either promote or inhibit the activity of the cells. In this way, these substances control the rate at which bone is made, destroyed, and changed in shape. For example, the rate at which osteoclasts resorb bone and release calcium into the blood is promoted by parathyroid hormone (PTH) and inhibited by calcitonin, which is produced by the thyroid gland (Figure (PageIndex{3})). The rate at which osteoblasts create new bone is stimulated by growth hormone, which is produced by the anterior lobe of the pituitary gland. Thyroid hormone and sex hormones (estrogens and androgens) also stimulate osteoblasts to create new bone.

Bone Repair

Bone repair, or healing, is the process in which a bone repairs itself following a bone fracture. You can see an X-ray of bone fracture in Figure (PageIndex{4}). In this fracture, the humerus in the upper arm has been completely broken through its shaft. Before this fracture heals, a physician must push the displaced bone parts back into their correct positions. Then the bone must be stabilized — for example, with a cast and/or pins surgically inserted into the bone — until the bone’s natural healing process is completed. This process may take several weeks.

The process of bone repair is mainly determined by the periosteum, which is the connective tissue membrane covering the bone. The periosteum is the primary source of precursor cells that develop into osteoblasts, which are essential to the healing process. Bones heal as osteoblasts form new bone tissue.

Although bone repair is a natural physiological process, it may be promoted or inhibited by several factors. For example, fracture repair is likely to be more successful with adequate nutrient intake. Age, bone type, drug therapy, and pre-existing bone disease are additional factors that may affect healing. Bones that are weakened by diseases, such as osteoporosis or bone cancer, are not only likely to heal more slowly but are also more likely to fracture in the first place.

Feature: Myth vs. Reality

Bone fractures are fairly common, and there are many myths about them. Knowing the facts is important because fractures generally require emergency medical treatment.

Myth: A bone fracture is a milder injury than a broken bone.

Reality: A bone fracture is the same thing as a broken bone.

Myth: If you still have a full range of motion in a limb, then it must not be fractured.

Reality: Even if a bone is fractured, the muscles and tendons attached to it may still be able to move the bone normally. This is especially likely if the bone is cracked but not broken into two pieces. Even if a bone is broken all the way through, the range of motion may not be much affected if the bones on either side of the fracture remain properly aligned.

Myth: A fracture always produces a bruise.

Reality: Many but not all fractures produce a bruise. If a fracture does produce a bruise, it may take several hours or even a day or more for the bruise to appear.

Myth: Fractures are so painful that you will immediately know if you break a bone.

Reality: Ligament sprains and muscle strains are also very painful, sometimes more painful than fractures. Additionally, every person has a different pain tolerance. People with high pain tolerance may continue using a broken bone in spite of the pain.

Myth: You can tell when a bone is fractured because there will be very localized pain over the break.

Reality: A broken bone is often accompanied by injuries to surrounding muscles or ligaments. As a result, the pain may extend far beyond the location of the fracture. The pain may be greater directly over the fracture, but the intensity of the pain may make it difficult to pinpoint exactly where the pain originates.

Review

  1. Outline how bone develops from early in the fetal stage through the age of skeletal maturity.
  2. Describe the process of bone remodeling. When does it occur?
  3. What purposes does bone remodeling serve?
  4. Define bone repair. How long does this process take?
  5. Explain how bone repair occurs.
  6. Identify factors that may affect bone repair.
  7. Parts of bone that have not yet become ossified are made of _________.
  8. If there is a large region between the primary and secondary ossification centers in a bone, is the person young or old? Explain your answer.
  9. The region where the primary and secondary ossification centers meet is called the ________________.
  10. True or False. Most bones are made entirely of cartilage at birth.
  11. True or False. A broken bone is the same as a bone fracture.
  12. If bones can repair themselves, why are casts and pins sometimes needed?
  13. Which bone cell type causes the release of calcium to the bloodstream when calcium levels are low?
  14. Which tissue and bone cell type are mainly involved in bone repair after a fracture?
  15. Describe one way in which hormones are involved in bone remodeling.

The biology of normal bone remodelling

During life, bone undergoes modelling and remodelling in order to grow or change shape. Bone modelling is the process by which bones change shape or size in response to physiologic influences or mechanical forces that are encountered by the skeleton, while bone remodelling takes place so that bone may maintain its strength and mineral homeostasis. During early childhood, both bone modelling (the formation and shaping of bone) and bone remodelling (the replacement or renewal of old bone) occur. The predominant process in childhood is bone modelling, while in adulthood bone remodelling predominates. The exception to this is after a fracture when we see massive increases in bone formation. During childhood and adolescence growth occurs in the bones longitudinally and radially, while in the growth plates it occurs longitudinally, thus promoting growth in size. Cartilage first proliferates in the epiphyseal and metaphyseal areas of long bones before undergoing mineralisation to form new bone.

Keywords: bone remodelling osteoblast osteoclasts osteocytes.


Bone remodeling, normal and abnormal: a biological basis for the understanding of cancer-related bone disease and its treatment

Remodeling the cyclical replacement of old bone by new, serves to maintain its mechanical and metabolic functions. In each cycle a circumscribed volume of bone is removed by osteoclastic resorption and subsequently replaced by osteoblastic formation at the same location. Remodeling is carried out by elongated structures known as basic multicellular units (BMU) that travel through or across the surface of bone. Each BMU lasts about six months, with continued sequential recruitment of new osteoclasts and osteoblasts. Abnormal bone remodeling involves some combination of loss of directional control, increase in number of remodeling cycles and incomplete replacement. In metastatic bone disease, tumor cells find the hematopoietic bone marrow conducive to their survival and growth, because they can manipulate the local cytokine network to increase recruitment of osteoclasts from local precursors and so increase bone resorption. The effect on bone formation is biphasic an initial increase is due partly to the normal evolution of the BMU, and partly to the induction of reparative woven bone formation. Later, normal BMU-based bone formation may fall to subnormal levels. In some tumors, a generalized increase in osteoclast recruitment and decline in bone formation are the systemic responses to one or more agents released by tumor cells into the circulation, of which the most frequent is parathyroid hormone-related peptide, but in both metastatic and non-metastatic disease, the cellular events in bone are essentially the same. Cancer-related bone disease is amenable to treatment with drugs that inhibit osteoclast recruitment, of which the bisphosphonates are the most effective. Treatment should be started before there has been irreparable damage to bone structure and before the onset of hypercalcemia. Although bisphosphonates remain in bone for a long time, adverse effects are very unlikely within the patient's lifetime.


What is Bone Remodeling? (with pictures)

Bone remodeling is a continuous process of bone resorption and formation for the purpose of maintaining normal bone mass. Normal bone mass indicates healthy bones that are strong and free from problems like osteoporosis. This process goes on inside the human body as long as the person is living. Cells that play important roles in it are osteoclasts, which are responsible for bone resorption osteoblasts, which are vital in the formation of bones and osteocytes, which send the signals that bones are being exposed to stress or injury.

Constant remodeling allows bones to perform their many functions, including structural support to the whole body and important storage sites of calcium. With bone remodeling, the body is also able to repair small bone fractures that occur from daily physical activities. Old bone is being replaced by new bone during the remodeling cycle. In adults, this occurs at a rate of about 10% each year. This is a natural process to ensure maintenance of normal bone mass as a person ages.

The remodeling cycle usually starts when injury or mechanical stresses occur in bones. Growth hormones stimulate the production of osteoclasts, which then release enzymes capable of dissolving the bone matrix, creating pits in most bone surfaces. Their lifespan is approximately two weeks, and then they die naturally through a programmed process of cell death, or apoptosis.

Osteoblasts are stimulated by growth hormones as well. They are responsible for filling the pits created by osteoclasts in bone surfaces. As the bone matrix thickens, osteoblasts incorporate minerals such as calcium and phosphorus into the bone in a process known as mineralization. After their lifespan of about three months, most mature into osteocytes, which reside mostly in the bone matrix and are the ones that give signals of mechanical stress and injury to growth hormones. Other osteoblasts become lining cells in the bone surfaces and are responsible for the release of calcium into the blood stream, while still others die naturally.

The actions of osteoclasts, osteoblasts, and osteocytes are regulated by prohormones and hormones inside the body. These include vitamin D, parathyroid hormone (PTH), calcitonin, testosterone, and estrogen. Any derangement in the actions of these chemicals can lead to certain medical conditions. For example, some studies indicate estrogen deficiency in menopausal women can cause a delay in cell death of most osteoclasts, thus exposing bones to their enzymatic actions longer and promoting osteoporosis.


DIRECT FRACTURE HEALING

Direct healing does not commonly occur in the natural process of fracture healing. This since it requires a correct anatomical reduction of the fracture ends, without any gap formation, and a stable fixation. However, this type of healing is often the primary goal to achieve after open reduction and internal fixation surgery. When these requirements are achieved, direct bone healing can occur by direct remodeling of lamellar bone, the Haversian canals and blood vessels. Depending on the species, it usually takes from a few months to a few years, before complete healing is achieved. 37

Contact Healing

Primary healing of fractures can either occur through contact healing or gap healing. Both processes involve an attempt to directly re-establish an anatomically correct and biomechanically competent lamellar bone structure. Direct bone healing can only occur when an anatomic restoration of the fracture fragments is achieved and rigid fixation is provided resulting in a substantial decrease in interfragmentary strain. Bone on one side of the cortex must unite with bone on the other side of the cortex to re-establish mechanical continuity. If the gap between bone ends is less than 0.01 mm and interfragmentary strain is less than 2%, the fracture unite by so-called contact healing. 41 Under these conditions, cutting cones are formed at the ends of the osteons closest to the fracture site. 22 The tips of the cutting cones consist of osteoclasts which cross the fracture line, generating longitudinal cavities at a rate of 50� μm/day. These cavities are later filled by bone produced by osteoblasts residing at the rear of the cutting cone. This results in the simultaneous generation of a bony union and the restoration of Haversian systems formed in an axial direction. 23, 37 The re-established Haversian systems allow for penetration of blood vessels carrying osteoblastic precursors. 15, 21 The bridging osteons later mature by direct remodelling into lamellar bone resulting in fracture healing without the formation of periosteal callus.

Gap Healing

Gap healing differs from contact healing in that bony union and Haversian remodelling do not occur simultaneously. It occurs if stable conditions and an anatomical reduction are achieved, although the gap must be less than 800 μm to 1 mm. 23 In this process the fracture site is primarily filled by lamellar bone oriented perpendicular to the long axis, requiring a secondary osteonal reconstruction unlike the process of contact healing. 39 The primary bone structure is then gradually replaced by longitudinal revascularized osteons carrying osteoprogenitor cells which differentiate into osteoblasts and produce lamellar bone on each surface of the gap. 41 This lamellar bone, however, is laid down perpendicular to the long axis and is mechanically weak. This initial process takes approximately 3 and 8 weeks, after which a secondary remodelling resembling the contact healing cascade with cutting cones takes place. Although not as extensive as endochondral remodelling, this phase is necessary in order to fully restore the anatomical and biomechanical properties of the bone. 41


Osteogenesis and bone remodeling: A focus on growth factors and bioactive peptides

Bone is one of the most frequently transplanted tissues. The bone structure and its physiological function and stem cells biology were known to be closely related to each other for many years. Bone is considered a home to the well-known systems of postnatal mesenchymal stem cells (MSCs). These bone resident MSCs provide a range of growth factors (GF) and cytokines to support cell growth following injury. These GFs include a group of proteins and peptides produced by different cells which are regulators of important cell functions such as division, migration, and differentiation. GF signaling controls the formation and development of the MSCs condensation and plays a critical role in regulating osteogenesis, chondrogenesis, and bone/mineral homeostasis. Thus, a combination of both MSCs and GFs receives high expectations in regenerative medicine, particularly in bone repair applications. It is known that the delivery of exogenous GFs to the non-union bone fracture site remarkably improves healing results. Here we present updated information on bone tissue engineering with a specific focus on GF characteristics and their application in cellular functions and tissue healing. Moreover, the interrelation of GFs with the damaged bone microenvironment and their mechanistic functions are discussed.

Keywords: bone tissue engineering growth factors mesenchymal stem cells.


Plasma spraying for thermal barrier coatings: processes and applications

5.4.1 Application in biomaterials

A biomaterial is a material in contact with fluids, cells and tissues of the living body utilised to evaluate, repair or replace any tissue or organ of the body. 13 A prerequisite for any synthetic material implanted in the body is that it should have good mechanical strength, high chemical stability, high corrosion resistance, very low toxicity and high biocompatibility. 13 Metals such as titanium, titanium alloys, stainless steel and CoCr-based alloys are popularly used as implant materials for their superior properties in terms of static and dynamic mechanical strength. In the past few years, researchers have been trying to improve on these mechanical properties and to develop new series of materials that can guarantee not only superior mechanical performance but also an excellent biological response. For this purpose, different materials have been produced to meet almost every conceivable need. Yet not all the problems connected with these implants, such as distance cell migration, breakage, stress shielding, reactivities and growth restriction, have been solved. 14 Moreover, the surface of the metal implant can become corroded and discolored and in some instances release metallic elements to the surrounding tissues when used in the corrosive environment of a human body. Ti–6Al–4 V alloys show many desirable features, such as biocompatibility, high corrosion resistance, excellent strength-to-weight ratio and so on, and they have been widely used in aerospace and orthopedic applications. Their corrosion resistance can be attributed to a passivation layer on the surface. However, it can be easily worn out and wear-corrosion failure can occur because of electric cell reactions between the passivated and non-passivated layers. 15

Biomedical coatings generally have to satisfy specific requirements such as high crystallinity, high coating adhesion and suitable porosity. 16 It is necessary to enhance biocompatibility, accelerate post-operative healing and improve adhesions. Coatings have specific functions ranging from improving fixation by establishing strong interfacial bonds, shielding the metallic implant from environmental attack or leaching effects, promoting fast tissue growth and interaction by the presence of a catalyst material and minimising adverse reaction by the provision of a biocompatible material.

Bone is mainly composed of mineral components, water and collagen fibers. A schematic anatomical view of a long bone is shown in Fig. 5.3 . 17 The major subphase of the mineral consists of submicroscopic crystals of an apatite of calcium and phosphate, resembling HA in its crystal structure. A typical wet cortical bone is composed of 22 wt% organic matrix, 69 wt% mineral and 9 wt% water. It has been known that HA can form strong biological bonds with bony tissue without the presence of soft fibrous tissues. The provision of a high-calcium and phosphorus-rich environment promotes rapid bone formation within the vicinity of the HA implant. HA also establishes strong interfacial bonds with titanium implants. Its excellent biointegration makes it an ideal choice for use in orthopedic and dental applications. 18 Some authors claimed that HA may act as a biological barrier to reduce toxic responses caused by the release of metallic ions from the metal substrate into the bone. 19

5.3 . Organization of a typical bone.

The chemical formula of HA is presented as Ca4(I)Ca6(II)(PO4)6(OH)2 (Ca10(PO4)6(OH)2). The Ca(I) atoms are on the fourfold symmetry 4(f) position and the Ca(II) atoms are in the sixfold symmetry 6(h) position. 19 The OH groups occupy disordered positions above and below the triangles formed by the Ca(II) atoms. The disorder of the OH groups gives rise to a ‘macroscopic’ space group P63/m (as determined by X-ray diffractometry), which is lost at the level of the individual columns. 20

As shown in Figs 5.4 and 5.5 , biological HA has a hexagonal lattice with the space group of P63/m 21 with dimension a = b = 9.432 Å and c = 6.881 A. The apatite structure of HA is represented by two sets of hexagonal cells shown in Fig. 5.5 : OH atoms, represented by the solid dots, form the HA unit cell and Ca atoms, represented by the open dots, form a smaller hexagonal cell (without an indentical point in the center). The size ratio of the HA unit cell to the Ca cell is about 3 . The crystal data of HA and some other physical properties are shown in Table 5.1 . The ideal Ca:P ratio of HA is 10:6 and the calculated density is 3.21 g/cm.

5.4 . Crystal structure of HA: 21 a = b = 9.418 Å and c = 6.884 Å.


Abstract

Fracture healing is a complex event that involves the coordination of a variety of different processes. Repair is typically characterized by four overlapping stages: the initial inflammatory response, soft callus formation, hard callus formation, initial bony union and bone remodeling. However, repair can also be seen to represent a juxtaposition of two distinct forces: anabolism or tissue formation, and catabolism or remodeling. These anabolic/catabolic concepts are useful for understanding bone repair without giving the false impression of temporally distinct stages that operate independently. They are also relevant when considering intervention.

In normal bone development, bone remodeling conventionally refers to the removal of calcified bone tissue by osteoclasts. However, in the context of bone repair there are two phases of tissue catabolism: the removal of the initial cartilaginous soft callus, followed by the eventual remodeling of the bony hard callus. In this review, we have attempted to examine catabolism/remodeling in fractures in a systematic fashion. The first section briefly summarizes the traditional four-stage view of fracture repair in a physiological manner. The second section highlights some of the limitations of using a temporal rather than process-driven model and summarizes the anabolic/catabolic paradigm of fracture repair. The third section examines the cellular participants in soft callus remodeling and in particular the role of the osteoclast in endochondral ossification. Finally, the fourth section examines the effects of delaying osteoclast-dependent hard callus remodeling and also poses questions regarding the crosstalk between anabolism and catabolism in the latter stages of fracture repair.


Section Summary

Bone, or osseous tissue, is connective tissue that includes specialized cells, mineral salts, and collagen fibers. The human skeleton can be divided into long bones, short bones, flat bones, and irregular bones. Compact bone tissue is composed of osteons and forms the external layer of all bones. Spongy bone tissue is composed of trabeculae and forms the inner part of all bones. Four types of cells compose bony tissue: osteocytes, osteoclasts, osteoprogenitor cells, and osteoblasts. Ossification is the process of bone formation by osteoblasts. Intramembranous ossification is the process of bone development from fibrous membranes. Endochondral ossification is the process of bone development from hyaline cartilage. Long bones lengthen as chondrocytes divide and secrete hyaline cartilage. Osteoblasts replace cartilage with bone. Appositional growth is the increase in the diameter of bones by the addition of bone tissue at the surface of bones. Bone remodeling involves the processes of bone deposition by osteoblasts and bone resorption by osteoclasts. Bone repair occurs in four stages and can take several months.


Conclusion

The recent explosion of knowledge concerning systemic and local regulation of bone remodeling should lead to new approaches to the diagnosis and treatment of skeletal disorders. In particular, the newer methods in molecular and cellular biology should enable us to define the abnormalities in cells of the osteoblastic and osteoclastic lineages that lead to bone disease and to develop new approaches based on a fuller understanding of the pathogenetic mechanisms in these disorders.

Lowell P. Weicker, Jr. General Clinical Research Center, University of Connecticut Health Center, MC-2806, 263 Farmington Ave., Farmington, CT 06030. Fax 960-679-1856 e-mail [email protected]

Nonstandard abbreviations: PTH, parathyroid hormone IGF, insulin-like growth factor OPG, osteoprotegerin and IL, interleukin.

Some of the work described in this review was supported by the NIH (Grant AM18063) and by the General Clinical Research Center (Grant MO1RR06192). I thank Barbara Capella for technical assistance.


Watch the video: Knochenwachstum - Schulfilm Biologie (August 2022).