CHAPTER 6   SKELETAL SYSTEM:

BONE TISSUE

 

 

Osteology--study of bone & treatment of bone disorders

 

6 FUNCTIONS OF BONE--P. 172

 

Anatomy--structure of a long bone

Parts of a typical long bone are listed and discussed on p. 172 – 173

                                        Figure 6.1  P. 173

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

HISTOLOGY OF BONE TISSUE

Bone (osseous tissue) is a form of CT. It contains a large amount of matrix with widely separated cells. Bone matrix is:

    25% protein (collagen) fibers (organic)

    25% water  (inorganic)

    50% crystallized mineral salts  (inorganic)

 

 

bone matrix contains abundant inorganic mineral salts. The most abundant one is calcium phosphate. It combines with smaller amounts of calcium hydroxide and forms crystals of hydroxyapatite. These crystals combine with calcium carbonate and ions of magnesium, potassium, and sulfate. These salts are deposited in a network of collagen fibers and, initiated by osteoblasts, the whole mass hardens (calcification). Calcification cannot occur without the collagen fibers. First the minerals must get in tiny spaces between fibers and then crystallize (harden)

 

       Hardness of bone—due to mineral salts (inorganic)

       Tensile strength of bone—means it holds together and is not brittle—due to collagen fibers (organic)

 

 

CELLS OF BONE

     1. Osteogenic cells—stem cells derived from mesenchyme--can undergo mitosis. Some remain and continue to divide; some differentiate into osteoblasts. Found in the periosteum, the endosteum and canals in bone that contain blood vessels.

 

     2. Osteoblasts--cells that form bone--do not undergo mitosis. Secrete collagen and other organic components and actually build all new bone. If we need more osteoblasts, they must develop from osteogenic cells.

 

     3. Osteocytes--mature bone cells that are derived from osteoblasts. Principle cells of bone tissue. No mitosis. As osteoblasts secrete bone matrix they surround themselves, leaving only a tiny space they occupy, and mature into osteocytes, which do not secrete matrix. Osteocytes carry on daily cellular activities of bone--exchange of nutrients & wastes, etc.

 

     4. Osteoclasts--develop from fusion of many monocytes (phagocytic white blood cells) and settle in the endosteum. Function is bone resorption (breakdown of matrix).

.

 

Despite appearances, bone is not completely solid. All types of bone have tiny spaces to provide channels for the blood vessels that supply it. Depending on size and distribution of spaces, bone tissue may be classified as compact or spongy.

 

1. Compact (dense) bone—80% of skeleton--contains fewest spaces and therefore is the strongest type of bone. Forms the external layer of all bones and almost all of the diaphyses of long bones, which gives great strength to allow the long bones to resist the stress of weight and movement.

 

Compact bone is highly organized into a concentric ring structure, which allows nutrients and O2 to reach all osteocytes with an absolute minimum of spaces.

 

 

 

 

 

 

 

 

 

 

 

Central canal--open space containing blood vessels—these run longitudinally

Concentric lamellae--rings of calcified matrix

Lacunae--tiny spaces in matrix located between rings--each completely filled with an osteocyte

Canaliculi ("little canals")--radiate out from central canals to lacunae and also connect some lacunae with each other. Contain ECF and processes (extensions) of osteocytes. Nutrients diffuse through these canals.

 

Intersitital lamellae (fragments of older osteons) fill spaces between concentric lamellae. Circumferential lamellae encircle the bone just beneath the periosteum or encircle the medullary cavity.

 

Blood vessels from the periosteum reach the central canals through perforating (Volkmann’s) canals, which run transversely. 

 

 

2. Spongy bone tissue—20% of skeleton--contains more spaces and has less strength. Does not contain osteons--consists of lamellae arranged in an irregular latticework made of thin plates of bone called trabeculae. Spaces between trabeculae are small but macroscopic, and are filled with red marrow, which produces blood cells. Osteocytes are found on superficial surfaces of lacunae. Blood vessels from the periosteum penetrate spongy bone and provide blood that circulates through the marrow cavities.

 

Spongy bone is lighter in weight than compact. Its numerous spaces between trabeculae provide the safest possible location for the red bone marrow, which must continue to produce large numbers of blood cell throughout life. 

 

Spongy bone makes up most of short, flat and irregular bones (under a thin layer of compact bone) and almost all of the epiphyses of long bones. Blood cells are formed mostly in red marrow of spongy bone of the:

     Hipbones

     Ribs

     Sternum

     Vertebrae

     Skull

     Epiphyses of some long bones

 

 

BLOOD SUPPLY

Bone tissue has a rich blood supply. Blood vessels pass into bones from the periosteum.

 

1. Usually a large artery called the nutrient artery penetrates the diaphysis of a long bone near the center, entering through an opening called the nutrient foramen. The nutrient artery reaches the medullary cavity and divides into proximal and distal branches. These supply the red bone marrow and the inner part of the compact bone of the diaphysis. Eventually, tiny branches reach the haversian canals.

 

2. Smaller arteries from the periosteum also enter the diaphysis at many points through perforating (Volkmann’s) canals. These supply the outer part of the compact bone of the diaphysis.

 

3. Epiphyses and metaphyses are supplied by arteries in those areas, which also supply associated joints.

 

Corresponding veins drain the blood away.

1. Sometimes a nutrient vein accompanies the nutrient artery.

2. Many small veins are usually found in the epiphyses & metaphyses

3. Many very small periosteal veins complete the job

 

Nerves accompany blood vessels deep into the bone and nerves are also found in the periosteum.

                               Figure 6.4  P. 177

 

 

 

      

PHYSIOLOGY OF OSSIFICATION

FORMATION OF BONES IN THE EMBRYO, FETUS, INFANT AND CHILD (BUILDING BONE FOR THE FIRST TIME)

The embryo first forms a skeleton made of mesenchymal cells, which are shaped somewhat like bones.  The mesenchyme is replaced mostly by hyaline cartilage with some areas formed by fibrous CT membranes. These are also shaped more or less like the finished bones will be. Both of these tissues are derived from mesenchyme. This is complete by the 6th week and the formation of bone (ossification or osteogenesis) begins at that point. Two kinds of bone formation take place:

 

1. Intramembranous ossification--formation of bone directly on or within the fibrous membranes. Forms most of the flat bones of the skull, the mandible and the clavicles. This type has no cartilage model involved.

 

     a. Mesenchyme cells cluster in the fibrous membrane, differentiate into osteogenic cells and then into osteoblasts. This cluster is known as a center of ossification and a large number form, scattered over the membrane.

     b. The osteoblasts secrete a collagenous fiber network in which Ca salts are deposited.

     c. As a cluster of osteoblasts becomes completely surrounded by matrix, the plate of bone thus formed is called a trabecula and trapped osteoblasts become osteocytes.       

     d. Trabeculae fuse into the latticework of spongy bone and spaces fill with red bone marrow. Blood vessels grow into the space between trabeculae.

     e. The original fibrous membrane condenses and becomes the periosteum

     f. Some of the surface layers of spongy bone are reorganized into compact bone.

 

2. Endochondral ossification--replacement of hyaline cartilage by bone. This forms most of the bones of the body. It is best observed in long bones and the tibia is most often used as the typical example.     

 

     a. Mesenchyme cells become chondroblasts, which produce a hyaline cartilage model of the bone. A membrane called the perichondrium develops around the cartilage model. The cartilage model grows with the baby. Cartilage "bones" are solid.

      b. Always at a point in the middle of the diaphysis, steps begin which will lead to ossification. Some cartilage cells enlarge and burst, raising the pH of the cartilage matrix and causing it to calcify.

     c. Remaining cartilage cells can no longer receive nutrients (by diffusion) so they also die.

     d. In this same area, a nutrient artery penetrates into the cartilage model. This stimulates osteogenic cells in the perichondrium to differentiate into osteoblasts.

     e. The osteoblasts lay down a thin shell of bone called the periosteal bone collar under the perichondrium, still in the center of the diaphysis.     

     f. The part of the perichondrium that now surrounds bone instead of cartilage is called the periosteum.

     g. Capillaries of the periosteum begin to grow into the calcified cartilage matrix. This leads to the development of the primary ossification center (still in the center of the diaphysis). The cartilage is replaced by spongy bone.

     h. Spongy bone is formed through the entire thickness of the diaphysis, but then osteoclasts break down the bone in the center, forming the marrow cavity.

     i. Ossification spreads both directions from the center, up and down the shaft.

     j. At a later time (about the time of birth) separate secondary ossification centers appear at each epiphysis and begin to change more cartilage to bone by the same process, except that spongy bone fills the interior of the epiphyses, which have no central medullary cavity.

     k. The hyaline cartilage of the model remains in 2 areas:

 

         1) Ends of the epiphyses (articular cartilages)

        

         2) Between the diaphysis and epiphysis, where it forms the epiphyseal plate and is responsible for lengthwise growth

 

PHYSIOLOGY OF BONE GROWTH

Epiphyseal plate--area of hyaline cartilage that remains between the diaphysis and epiphyses    (Figure. 6.7 P. 182)                                             1. Zone of resting cartilage-- anchors  

                                                                                epiphyseal plate to epiphysis

                                                                              2. Zone of proliferating cartilage--stacks of  

                                                                                  young chonddrocytes that continuously                                                                                                                

                                                                                  divide

                                                                              3. Zone of hypertrophic cartilage--new

                                                                                   cartilage cells mature

                                                                              4. Zone of calcified cartilage--cartilage cells

                                                                                  die and matrix becomes calcified.

 

 

Osteoclasts remove calcified cartilage matrix and osteoblasts spread into the area and lay down bone. New chondrocytes are formed on the epiphyseal side of the plate and old chondrocytes are replaced by bone on the diaphyseal side. The bone of the diaphysis steadily increases in length. Spongy bone is formed first and later replaced by compact bone.

 

All lengthwise growth of bone must occur at the epiphyseal plate. This occurs throughout childhood until early adulthood. A fracture in the area of the epiphyseal plate before growth is complete often causes that bone not to reach normal length.

 

As growth ends, cartilage cells of the epiphyseal plate die and are no longer replaced by new ones. The epiphyseal plate becomes completely ossified (fusion of epiphyses) and is now called the epiphyseal line. All epiphyses are generally fused by age 25 or before.

 

Growth in diameter occurs as osteoblasts from the periosteum add new bone on the surface. This is known as appositional growth. As the bone thickens, osteoclasts enlarge the marrow cavity.

 

 

BONE REMODELING

 

Bone must continually renew itself throughout life. Remodeling is the replacement of old bone tissue with new bone tissue. Bone is never at rest. Matrix is redistributed according to stress. Compact bone is formed from spongy bone. Worn and injured bone is removed and replaced with new tissue. We hope to keep a fairly steady balance between breakdown and building.

 

Remodeling occurs at different rates in various body regions.

     Distal femur--completely replaced every 4 months

     Some bones may not be replaced or only over years

 

Osteoclasts are the cells of bone resorption. They remove both minerals and collagen fibers in balance with replacement by osteoblasts. An osteoclast attaches tightly to the bone surface, forming a leak-proof seal. The part of its plasma membrane next to the bone is arranged in deep folds, forming what is called the ruffled border. The osteoclast then secretes:

     Enzymes which break down collagen

     Acids which dissolve mineral salts

Materials released from bone are absorbed into the bloodstream

 

 

Adequate supplies of minerals and amino acids are necessary for the building of new bone. Hormones continue to play a role. Sex hormones and hGH encourage the maintenance and rebuilding of bone. Calcitonin and parathyroid hormone also influence the process. Exercise (stress on bone) plays a vital role in maintaining or increasing the strength of bone.

 

 

FACTORS AFFECTING BONE GROWTH & REMODELING

 

For normal growth and remodeling we need:

1. Minerals

     Calcium

     Phosphorus

     Fluoride

     Magnesium

     Iron

     Manganese

 

2. Vitamins

     Vit D--calcitriol allows us to absorb Ca from the GI tract

     Vit A

     Vit C

     Vit B12

         Vit K

 

3. Hormones

     a. Insulin-like growth factors (IGFs) produced in response to hGH (human growth hormone)--pituitary gland--general growth of all tissues--great effect on height. This hormone causes cells to produce insulinlike growth factors, which promote osteoblast production and protein synthesis. Even after we have achieved full growth, this hormone plays a major role in bone maintenance.

     b. Sex hormones (estrogens/testosterone)--appear in large amounts at puberty and promote activity in the epiphyseal plate--but after a period of rapid growth the cartilage cells "burn out" and all die--epiphyses then fuse. In mature individuals the sex hormones promote bone maintenance and replacement. In females, estrogen production tapers off beginning in the thirties, and this is one reason for the problems with osteoporosis.

     c. Calcitonin/Parathyroid hormone—discussed in their own section

     d. Insulin

     e. Thyroid hormones

     f.  Anabolic steroids—tend to cause premature fusion of epiphyses

 

 

         

FRACTURE REPAIR

 

Fracture--any break in a bone

 

See P. 186 for list of types of fractures & pictures of some in Figure 6.9 P. 185

 

Reduction--aligning the broken ends of the bone properly

 

Closed reduction--done by means of only a cast, splint, etc.--ends are placed in proper alignment and immobilized while healing takes place

 

Open reduction--surgery--using pins, plates, screws, and/or wires to align fragments--then also may have a cast or splint for support

 

Bone healing is slow--bone cells grow slowly and deposition of matrix is slow. Complete healing of a fracture takes about 1 year, although the bone is usually functional in 6-8 weeks.

 

Steps in fracture repair:

 

1. FORMATION OF THE FRACTURE HEMATOMA: Blood vessels crossing the fracture line are broken and blood forms a clot called the fracture hematoma (within 6-8 hours of the injury). Bone cells and periosteal cells in the immediate area of the fracture die. Swelling and inflammation occur and bring phagocytic white blood cells, which aid osteoclasts in removing dead tissue and debris. This continues for several weeks after the injury. No real healing occurs here---this is mainly a clean-up job.

 

2. a. FORMATION OF THE PROCALLUS: Increased numbers of capillaries grow into the area and the fracture hematoma becomes a procallus made up of granulation tissue.

 

     b. FORMATION OF THE FIBROCARTILAGE (SOFT) CALLUS: Fibroblasts and osteogenic cells from the periosteum, endosteum and marrow invade the procallus. The fibroblasts produce collagen fibers and osteogenic cells from the area right at the break develop into chondroblasts and form fibrocartilage, transforming the procallus into a fibrocartilaginous  (soft) callus. The callus is a mass of repair tissue that bridges the broken ends. The two parts of this stage require about 3 weeks.

 

3. FORMATION OF THE BONY (HARD) CALLUS: Osteogenic cells in healthy bone tissue (further away from the break) become osteoblasts and begin to produce spongy bone, which joins the original fragments. The fibrocartilage of the soft callus is converted to spongy bone and is then called a bony or hard callus. This stage lasts 3-4 months.

 

4. REMODELING OF THE CALLUS: Dead bone is reabsorbed by osteoclasts. Compact bone replaces spongy bone. The thickened callus becomes more normal in appearance, although a thickened area may remain. This stage lasts up to 6 months or more.

 

 

CALCIUM HOMEOSTASIS

Bone is the major calcium reservoir in the body. Calcium level in blood must be carefully regulated. In extreme cases disturbances can result in death:

   Too high--cardiac arrest

   Too low--respiratory arrest  

 

   Nerve cells require precise levels to function

   Calcium is involved in muscle contractions

   Many enzymes require Ca as the cofactor

   Blood clotting requires Ca

 

Regulated by hormones, bone releases or takes up calcium to keep the blood level within normal limits. These 2 hormones causing this are released with no regard to bone strength, although they have a great influence over it.

     1. Parathyroid hormone (PTH)--receptors in the parathyroid glands detect a drop in blood Ca and this causes a release of PTH. The effect is to increase the number and activity of osteoclasts, which break down bone matrix and release Ca into the blood. In addition, PTH decreases Ca loss in urine and enhances activation of Vitamin D. Osteoclasts are just as likely to break down healthy bone as not. The only concern is raising blood Ca.

     2. Calcitonin--secreted by special cells in the thyroid gland when blood Ca level rises above normal. It inhibits the activity of osteoclasts and speeds deposition of Ca from the blood into the bones by osteoblasts. Of course, this would strengthen bone, but that is not the main reason we produce calcitonin. We are putting the calcium into bone to givve a safe place to store in until it is needed.

 

EXERCISE AND BONE

Bone can alter its strength in response to mechanical stress (pull of skeletal muscles, pull of gravity, as well as lifting weights). Bone becomes stronger with increased stress, so exercise is essential for bone health. It strengthens bone by:

   1. Increasing deposition of mineral salts

   2. Increasing production of collagen fibers

   3. Increasing production of calcitonin

With no stress, bone remodeling gets out of balance, with more resorption than deposition of new bone. Bone loses both collagen and minerals--loss of up to 1% of bone mass per week.

       Bedridden

       Limb in cast

       Astronauts

 

AGING

2 main effects:

1. Loss of Ca and other minerals--begins around age 30 in women and accelerates at 40-45. Average loss of Ca 30% by age 70. Read about osteoporosis p. 189-190. Also occurs in males but begins later (around 60) so has less years to progress & male bones are often stronger to begin with.

 

2. Decrease in rate of protein synthesis--decrease in collagen fibers which also weakens bone--bones become brittle.