This unit discusses the basic characteristics, structure and functions of the bone tissue, as well as discuss in detail the metabolism of calcium and bone physiology.
The skeletal system includes bones of the skeleton and the cartilages, ligaments and other connective tissues that stabilize or connect the bones. Bones are therefore rigid organs that form part of the endoskeleton of vertebrates. There are 206 bones in the adult body and about 300 bones in the fetal body. Bones support the body, work with muscles to maintain body posture and produce controlled precise movements. Without the skeleton to pull against, contracting muscle fibers would not be able to make us sit, walk or run.
Bone Characteristics and Functions
Bone is a special type of connective tissue made up of a collagenous matrix that has been impregnated with minerals especially calcium and phosphorus.
The primary bone tissue – osseous tissue is a relatively lightweight composite material, formed mostly of calcium phosphate in the chemical arrangement called hydroxyapatite. (This is the osseous tissue that gives bones their rigidity).
Bones have relatively high compressive strength but poor tensile strength, meaning that it resists pushing forces well, but not pulling forces. Bone is essentially brittle but it does have a significant degree of elasticity, which is contributed by collagen.
The bone is a living tissue; constantly being resorted and new ones formed; permitting it to respond to the stresses and strains that are put upon it. It is well vascularized with a total blood flow of 200 – 400ml/min in adult humans.
All bones consist of living cells embedded in the mineralized organic matrix that makes up the osseous tissue.
Functions
Bones play several significant functions in the body some of which are:
Shape and Support
The entire skeletal system provides a frame to keep the body supported. Individual bones or groups of bones provide a framework for the attachment of soft tissues and organs.
Protection of Body Organs
Bones serve to protect many internal organs and soft tissues by surrounding them. For example; the skull protects the brain; the ribcage protects the heart and lungs; the vertebrae protect the spinal cord and the pelvis protects the delicate reproductive organs.
Storage of Minerals and Lipids
Bones serve as reserves of minerals most notably calcium and phosphorus. Calcium is the most abundant mineral in the body and 99% of calcium are in the skeleton. The calcium salts of bones are a valuable reserve that maintain the normal concentration of calcium ions and phosphates in body fluids.
Bones of the skeleton also store energy reserves as lipids in areas filled with yellow marrow.
Production of Blood Cells
Red blood cells, white blood cells and other blood elements are produced in the red marrow which fills the internal cavities of many bones in a process known as haematopoiesis.
Leverage and Movement
Many bones function as levers and can change the magnitude and direction of forces generated by muscles. Bones, skeletal muscles, tendons, ligaments and joints function together to generate and transfer forces so that individual parts of the whole body can be manipulated in three dimensional space.
Other functions include:
Acid-Base Balance
Bones buffer the blood against excessive pH changes by absorbing and releasing alkaline salts.
Detoxification
Bone tissues can also store heavy metals and other foreign elements, removing them from the blood and reducing their effects on other tissues. These can later be gradually released for excretion.
Sound Transduction
Bones are important in the mechanical transmission of sounds for hearing.
Bone Structure
Bone is not a uniformly solid material. Each bone contains two forms of tissue: Compact (dense) bone and spongy or trabecular bone.
Compact Bone is the hard outer layer of compact bone tissue, so called due to its minimal gaps and spaces. It is much denser and less metabolically active. This tissue is what gives bones their smooth, white and solid appearance. It accounts for 75 – 80% of the total bone mass though it can vary with the shape of the bone. Compact bone is thickest where stresses arrive from a limited range of directions. Nutrients are provided to the compact bone through Haversian canals which contain blood vessels. Collagen of compact bones is arranged in concentric layers forming cylinders called osseous or Haversian systems.
Trabecular Bone forms the inner layer of open cell porous network also called spongy or chancellor’s bone. It is composed of a network of rod and plate-like elements that make the overall organ lighter, allowing room for blood vessels and marrow. Spongy bone is located where bones are not heavily stressed or where stresses arrive from many different directions.
Trabecular bone accounts for the remaining 20 – 25% of total bone mass, but has nearly ten times the surface area of compact bone. Nutrients diffuse from bone ECF into the trabecular.
Bone is composed of tough organic matrix greatly strengthened by calcium salts. Average compact bone contains by weight, approximately 30% matrix and 70% salts. The organic matrix of bone is 90 – 95% collagen fibres. The rest is ground substance which is composed of extracellular fluid plus proteoglycans like chondroitin, glycosaminoglycan, hyaluronic acid etc. The collagen fibres are mostly type I in tendons and skin.
Macroscopically, a typical (long) bone consists of the following structures visible to the naked eye; diaphysis, epiphyses, articular cartilage, periosteum, medullary cavity (marrow) and endosteum.
The diaphysis is the main shaft like portion. It consists of a hollow cylindrical cavity of compact bone tissue with marrow (medullary cavity). This composition adapts the diaphysis well for its function of providing strong support without cumbersome weight. The Epiphysis located at the extremities of long bones, is roughly spherical (bulbous) in shape. It is composed of spongy or cancellous bone and only a thin outer layer of dense compact bone. Marrow fills the spaces of cancellous bone – which can be yellow marrow in most adults, but red marrow in the proximal epiphysis of the humorous and femur. Separating these two main sections at either end of the bone is the metaphysis. It is made up of the epiphyseal (growth) plate.
The growth plate is a thick plate of hyaline cartilage. The epiphyseal plates and metaphysis are the only places where long bones continue to grow in length after birth.
Articular cartilage is a thin layer of hyaline cartilage that covers articular or joint surfaces of epiphyses. This material cushions jars and blows by its resiliency.
Covering the outer surface of a bone (except at joint surfaces) is the periosteum, a fibrous dense white membrane that has the potential to form bone during growth periods and in fractures healing. The periosteum contains nerves, lymphatic vessels and many capillaries that provide nutrients to the bone and give the pink colour to living bones. Its blood vessels send branches into the bone, therefore the periosteum, is essential for the nutrition and therefore survival of the bone cells.
The medullary cavity is a hollow tube-like cavity that runs through the length of the diaphysis. It contains yellow marrow (fatty marrow). Lining the medullary cavity of compact bone tissue, and covering the trabecular of spongy bone tissue is the endosteum – the membrane that lines the internal cavity of bones.
Bone Cells
There are several types of cells that make up the bone and these are capable of changing their roles as the needs of the body change.
Estrogenic Cells
These are found mostly in deep layers of the periosteum and in bone marrow. These cells are capable of being transformed into borne-forming cells or bone destroying cells during times of stress and healing.
Osteoblasts
These are mononucleate bone-forming cells which descend from osteoprogenitor cells. They synthesize a protein (an un mineralized ground substance) called osteoids which mineralizes to become bone. Osteoid is composed of type I collagen. Osteoblasts act to move calcium and phosphates into and out of bone tissue thereby calcifying or decalcifying them. Osteoblasts also manufacture hormones like prostaglandins, to act on the bone itself. They also produce alkaline phosphates, an enzyme that plays a role in the mineralization of bones as well as many matrix. Osteoblasts are the immature bone cells.
Osteocytes
These are the main cells of the fully developed bones. They are surrounded by calcified matrix and take on the shape of their individual lacunae within the matrix Osteocytes originate from osteoblasts which have migrated into and become trapped and surrounded by bone matrix which they themselves produce. The spaces which they occupy are known as lacunae. Osteocytes have many processes which reach out to meet other osteoblasts and osteocytes. The function of osteocytes include the following, to varying degrees; formation of bone, matrix maintenance and calcium homeostasis. They help in the release of calcium from bone tissue into the blood thereby regulating the concentration of calcium in body fluids.
Osteoclasts
These are large, multinucleated cells located on bone surfaces in what are called resorption pits. These resorption pits are left behind after the breakdown of bone and often present as scalloped surfaces on the bone. Osteoclasts are derived for hematopoietic stem-cells via monocytes. Therefore they can phagocytose bone, digesting it in their cytoplasm just like circulating macrophages can engulf and phagocytose invading organisms.
Bone Lining Cells
These are essentially inactive osteoblasts i.e. those that cease their physiological activity and flatten out on the bone surface. Some of their functions include serving as barrier for movement of calcium and phosphates into and out of the bone matrix. They may also serve as osteogenic cells that can divide and differentiate into osteoblasts.
Types of Bones
The types of bones include: long, short, flat, irregular and sesamoid bones. Long Bones are characterized by a shaft, (the diaphysis) that is much greater in length than width. They are composed mostly of compact bone and lesser amounts of marrow, which is located within the medullary cavity and spongy bone. Most bones of the limbs, including those of the fingers and toes are long bones except those of the wrist, ankle and knee cap.
Short Bones are roughly cube-shaped and have only a thin layer of compact bone surrounding a spongy interior. The bones of the wrist and ankle are short bones, and the sesamoid bones.
Flat Bones are thin and generally curved, with two parallel layers of compact bones sandwiching a layer of spongy bone. Most of the bones of the skull are flat bones as well as the sternum.
Irregular Bones do not fit into any of the above categories. They consist of thin layers of compact bone surrounding a spongy interior. Their shapes are irregular and complicated. The bones of the spine and hips are irregular bones.
Diagram of a Long Bone
Sesamoid Bones are bones embedded in tendons. They act to hold the tendon further away from the joint. Examples of sesamoid bones are the patella and the pisiform.
Bone Development and Growth
The growth of the skeleton determines the size and proportion of the body. Bones begin to form in a mother’s womb about six weeks following fertilization and portions of the skeleton continue to grow till about the age of 25. Most bones originate as hyaline cartilage or some fibrous membrane structure shaped like bones. The cartilage or membrane is gradually converted to bone through a process of ossification or osteogenesis.
Bones develop in the embryo (during foetal development) by two processes: intramembranous ossification and endochondral ossification. In both cases bones are formed from pre-existing connective tissue skeleton. Note that bone is the same no matter how it develops.
Intramembranous Ossification
This occurs where bone tissue develops directly from mesenchymal tissue. For example the flat bones of the skull and face, including those lining the oral and nasal cavities and part of the clavicle are formed this way. It occurs in the following steps.
Development of ossification Centre
Calcification
Formation of trabeculae
Development of periosteum
From the time of initial bone development, intramembranous ossification spreads rapidly from its Centre until large areas of the skull are covered with protecting and supporting bone.
Bone tissue development begins when thin strands that will eventually become branching trabelucae appear in the matrix. At about the same time, the mesenchymal cells become larger and more numerous and their processes thicken and connect with other embryonic connective tissue cells forming a ring of cells around a blood vessel. The site of this ring formation is a Centre of ossification. It begins about the second month of prenatal life.
The messenchymal cells differentiate into osteoid secreting osteoblasts which begin to cause calcium salt deposits that form the spongy bone matrix. (From the spongy matrix the trabeculae of cancellous bone will later form).
As the process of calcification continues, some osteoblasts become trapped inside lacunae of the developing matrix and lose their ability to form bone tissue. These are now called osteocytes. As bone forming osteoblasts change into osteocytes, they are replaced by new osteoblasts which develop from the estrogenic cells in the surrounding connective tissue. This way bones continue to grow.
At the same time that osteoblasts are synthesizing and mineralizing the matrix, osteoclasts play a role in bone resorption by removing small areas of bone from the wall of the lacunae.
The trabeculae continue to thicken into the dense network that is typical of cancellous bone tissue. The collagenous fibrils deposited on the trabeculae crowd blood vessels which eventually condense into blood forming marrow.
The osteoblasts on the surface of the spongy bone tissue then form the Periosteum – the membrane covering the outer surface of the bone. The Periosteum is made up of an inner osteogenic layer (with osteoblasts) and a thick fibrous outer layer. The inner layer eventually creates a protective layer of compact bone tissue over the cancellous tissue interior. When this intramembranous ossification has stopped, the osteogenic layer becomes inactive at least temporarily. It becomes active again when necessary for example, to repair a bone fracture.
Endochondral Ossification
This is the kind of bone tissue development that occurs by the replacement of hyaline cartilage. Here the initial model is made of hyaline cartilage and it then becomes eroded. Endochodral ossification produces long bones and all other bones not formed by intramembranous ossification. It must be noted that cartilage is not converted into bone but rather the cartilage model is completely destroyed and replaced by newly formed bone.
Endochondral ossification is a slower process that begins with points in the cartilage called the “primary ossification Centre’s” which appear during fetal development. It continues after birth through the occurrence of the secondary ossification Centre still the period of skeletal maturity (18 – 25 years of age).
About 6 to 8 weeks after fertilization, mesenchymal cells multiply rapidly and bunch together in a dense central core of precartilage tissue that eventually forms the cartilage model. This is followed by the appearance of the primitive perichondrium that covers the surface of the cartilage. The cartilage model is then invaded by capillaries which trigger the Transformation of the perichondrium into (bone producing periosteum the fibrous membrane that covers bones).
An intramembranous ossification occurs in the periosteum forming a hollow cylinder of trabecular bone called bone collar around the cartilage of the diaphysis.
By the second to third month of prenatal life the primary Centre ofossification is formed around the middle of what will become the diaphysis Bone cells develop rapidly in the diaphyseal area and blood vessels develop in the periosteum and branch into the diaphysis. The diaphysis now has a layer of bone tissue just under the periosteum and an increasing amount of marrow in the Centre of the shaft. The ends still consist of cartilage.
After birth the chondrocytes (cartilage cells) in the epiphysis begin the process of dying as in the diaphysis. Blood vessels and estrogenic cells from the periosteum enter the epiphyses where they develop into osteoblasts. The Centre’s of this activity in the epiphyses are called the secondary Centre’s of ossification.
Some cartilage remains on the outer, joint edge of each epiphysis to form the articular cartilage for the smooth operation of the joint. Also a layer of cartilage known as the epiphyseal cartilage or epiphyseal plate remains between each epiphysis and the diaphysis until bone growth in length is complete. The growth of bone length occurs in small spaces in the epiphyseal plate. During growth cartilage cells proliferate and cause thickening of the layer. Osteoblasts then synthesize organic bone matrix and this undergoes calcification, as a result the bone grows longer. This continues till sometime between adolescence and early twenties depending on which bone.
As growth in length slows down, the distal epiphyseal plate disappears first leading to fusion or closure of the epiphysis. The proximal plate disappears a bit later. As growth in length ends the epiphyseal cartilage is completely replaced by osseous tissue.
Remodeling of Bones
No new growth in bone length continues after age 25, however the diameter of bones may continue to increase throughout most of our lives. Through intramembranous ossification, estrogenic cells in the periosteum deposit new bone tissue beneath the periosteum while most of the old bone tissue erodes away. The combination of cell deposition and erosion widens the bone without thickening its walls. The width of the marrow cavity may increase too.
Bones can thicken or become denser to keep up with any physical changes in the body that may increase stress or load on the bones. For example, in athletes who greatly increase their muscles, the bones can also be strengthened at the same time. If not, the increased pull of the stronger muscles may have to fracture them.
The same thing can happen in people who are overweight with resultant increase in the load on their skeleton. On the other hand, inactivity will lead to decalcification – loss of minerals and resultant weakening in a bone. For example a leg that is put in a cast for a month thins out. This is because the muscles of the leg have atrophied and the bones have decalcified by about 30%.
Remodeling of bones (that process of resorption followed by replacement of bone with little or no change in shape) is a local process that is carried out in small areas sometimes called remodeling units. The cycle takes about 100 days and up to 20% of the adult skeleton is remodeled each year.
There are about 2 million remodeling units that are active at any one time in the human skeleton. The remodeling is related in part to the stresses and strains imposed on the skeleton by gravity (as already discussed). This is regulated by hormones in the systemic circulation and by growth factors, most of which act locally. Prostaglandins seem to play a part. Infact steoblasts and osteoclasts coupled together via paracrine cell signaling is what is called remodeling units.
The overall purpose of remodeling is to regulate calcium metabolism, repair micro-damaged bone (from daily stress) and also to shape and sculpture the skeleton during growth.
Homeostasis and the Physiological Functions of Bones
The bone performs many physiological functions which though may not be apparent but they help in maintenance of homeostasis in the body. Some of these functions which are not obvious include the production of blood cells, maintenance of calcium, phosphate and magnesium salts balance in the body and so for the highlight.
Calcium Storage and Release
The functions of calcium are numerous in the body. In the first place bones consist mainly of calcium, so without calcium, there would be no bones. Calcium also plays important roles in many chemical and electrical activities in the body. Without calcium, some enzymes could not function, cells would come apart, the permeability of cell membranes would be affected, muscles (including the heart) could not contract, nerve functions would be hampered and blood would not cloth and so forth.
When the diet does not provide enough calcium the bones release it and if there is too much calcium, in the body, the bones store it. In order to maintain homeostasis bones help regulate the amount and consistency of extracellular fluid by either adding calcium to it or by taking calcium out of it. Small decreases of calcium in extracellular fluid and plasma can cause the nervous system to become more excitable because of increased neuronal membrane permeability with resultant muscular spasms (tetany). On the other hand, too much calcium (hypocalcaemia) in body fluids depress the nervous system.
Phosphate Storage and Release
Bones also help to regulate the amount of phosphates in the body. Under hormonal control bones can release phosphate salts when needed by the body. Though changing the level of phosphate in the extracellular fluid or blood does not have immediate significant effects on the body, the proper amount, of phosphate is vital to the body’s acid-base balance.
Production of Blood cells
The marrow within bones contribute to homeostasis by manufacturing some blood cells. The adult red bone marrow is the main blood-making tissue of the body. It produces all the red blood cells, platelets, and some white blood cells (e.g. granular leukocytes and immature lymphocytes and monocytes).
All the bone marrow at birth is red marrow. By adolescence, most of it is replaced by yellow fat cells which form the yellow marrow. In the adult, red marrow is found only in the proximal epiphyses of bones such as the femur and humerus, in some short bones and in the vertebrae, sternum, ribs and cranium.
The continued production of red blood cells is very important because the cells live only for about 120 days and need to be replaced as they die. About 2.5 million red cells are produced per second and 200 billion daily.
In addition, some of the macrophages and white blood cells from the red marrow help to protect the body from disease.
Hormonal Control of Calcium and Bone Physiology
Several hormones have a direct effect on bones, and bones also have an effect on hormone secretion. (See relevant sections of the endocrine system).
Several hormones and vitamins are important in bone maturation and in the regulation of calcium in the body.
Parathyroid hormone (PTH) acts directly on bones to increase bone
Reabsorption and mobilize Ca++ leading to increase in plasma
calcium levels. It also depresses plasma phosphate and increases the excretion of phosphate in the urine. The latter is as a result of a decrease in reabsorption of phosphates in the proximal tubules. PTH also increases the reabsorption of calcium in the distal tubules.
PTH increases Ca++ reabsorption from the intestine but this action is due to the fact that it stimulates the formation of 1, 25 – dihydroxy-cholecalciferol, the active metabolite of vitamin D.
The secretion of PTH appears to be stimulated by low calcium levels in the blood. Its secretion raises blood calcium levels by the actions enumerated above. When levels of calcium rise sufficiently to normal, in the ECF and plasma, the secretion of PTH is inhibited by a negative feedback loop.
1, 25 – dihydroxycholecalciferol the physiologically active form of vitamin D3 dictates the formation of a calcium – binding protein. It also increases the pumping of Ca++ out of the bsolateral membranes of intestinal epithelial cells. It facilitates the reabsorption of Ca++ in the kidney.
It also acts on bone where it mobilizes Ca++ and Po43- probably by an initial action to release osteoblast factors that activate osteoclasts and subsequently by increasing the number of osteoclasts. All these are aimed towards increasing the level of Ca++ in plasma, and ECF.
Calcitonin is a hormone secreted by the thyroid gland whose action balances the action of parathyroid hormone. Calcitonin receptors are found in bones and the kidney. Calcitonin lowers the circulating calcium and phosphorus levels. It exerts its calcium lowering effect by directly inhibiting bone resorption. It inhibits the activity of osteoclasts. It also increase Ca++ excretion in the urine.
Other hormones include growth hormone, thyroxin adrenal cortical hormones, plus vitamins A and D. These are important in bone maturation. Growth hormones and thyroxine stimulate the endochondral ossification process. Growth hormone increases intestinal absorption of calcium, thyroxine causes hypocalcaemia.
Both male and female sex hormones (from the gonads) regulate growth rates by controlling the appearance of Centre’s of ossification and the rate of bone maturation. Oestrogens prevent osteoporosis probably by direct effect on osteoblasts. Insulin increases bone formation and there is significant bone loss in untreated diabetes. Glucocorticoids lower plasma Ca2+ levels by inhibiting osteoclast formation and activity. Over long periods, they cause osteopeorosis by decreasing bone formation and increasing bone resorption. They decrease bone formation by inhibiting cellular replication and protein synthesis in bone and they inhibit the function of osteoblasts. They also decrease the absorption of Ca2+ and Po43_ from the intestine by an anti – vitamin D action.
Bone Diseases
The diseases that affect the bone occur as a result of the interplay of factors that maintain normal bone function.
Osteogenesis Imperfecta (brittle bone disease) is an inherited condition in which the bones are abnormally brittle and subject to fractures. The basic cause of this disorder is a decrease in the activity of osteoblasts during bone formation (osteogenesis). In some cases the fractures occur during prenatal life and so the child is born with deformities. In order cases the fractures occur as the child begins to walk.
Osteomalacia and Rickets are skeletal defects caused by a deficiency of vitamin D which leads to a widening of the epiphyseal growth plates, an increased number of cartilage cells, a decrease in linear growth etc.
Rickets is the childhood form of the disease. Skeletal deformities manifest as bowed legs; knock knees and bulging forehead. Leg deformities occur if the child is old enough to attempt to walk, resulting in excessive pressure being put upon the soft legs.
Osteomalacia (adult rickets) leads to demineralization and an excessive loss of calcium and phosphorus. Although the skeletal deformities of rickets may be permanent, the similar skeletal abnormalities of osteomalacia may disappear with proper treatment with large doses of vitamin D.
In Osteoporosis, both matrix and mineral are cost from the bone, and there is a loss of bone mass and strength, with an increased incidence of fractures. This disease is almost an opposite of osteopetrosis in that it is characterized over time by a net excess of bone resorption over bone formation. It has multiple causes but is associated mostly with advancing age and the menopause. The WHO defines osteoporosis in women as a bone mineral density (BMD) 2.5 standard deviations in below peak bone mass (20 year – old sex – matched healthy person average).
Osteopetrosis is a rare and severe disease in which the osteoclasts are defective and are unable to resorb bone in their usual fashion. The result is a steady increase in bone density. Neurologic defects occur due to narrowing and distortion of foramina through which nerves normally pass Haematologic defects occur due to crowding out of the marrow cavities.
SKELETAL AND MUSCULAR SYSTEM
BONES AND OSSEOUS TISSUE
The skeletal system includes bones of the skeleton and the cartilages, ligaments and other connective tissues that stabilize or connect the bones. Bones are therefore rigid organs that form part of the endoskeleton of vertebrates. There are 206 bones in the adult body and about 300 bones in the fetal body. Bones support the body, work with muscles to maintain body posture and produce controlled precise movements. Without the skeleton to pull against, contracting muscle fibers would not be able to make us sit, walk or run.
Bone Characteristics and Functions
Bone is a special type of connective tissue made up of a collagenous matrix that has been impregnated with minerals especially calcium and phosphorus.
The primary bone tissue – osseous tissue is a relatively lightweight composite material, formed mostly of calcium phosphate in the chemical arrangement called hydroxyapatite. (This is the osseous tissue that gives bones their rigidity).
Bones have relatively high compressive strength but poor tensile strength, meaning that it resists pushing forces well, but not pulling forces. Bone is essentially brittle but it does have a significant degree of elasticity, which is contributed by collagen.
The bone is a living tissue; constantly being resorted and new ones formed; permitting it to respond to the stresses and strains that are put upon it. It is well vascularized with a total blood flow of 200 – 400ml/min in adult humans.
All bones consist of living cells embedded in the mineralized organic matrix that makes up the osseous tissue.
Functions
Bones play several significant functions in the body some of which are:
Shape and Support
The entire skeletal system provides a frame to keep the body supported. Individual bones or groups of bones provide a framework for the attachment of soft tissues and organs.
Protection of Body Organs
Bones serve to protect many internal organs and soft tissues by surrounding them. For example; the skull protects the brain; the ribcage protects the heart and lungs; the vertebrae protect the spinal cord and the pelvis protects the delicate reproductive organs.
Storage of Minerals and Lipids
Bones serve as reserves of minerals most notably calcium and phosphorus. Calcium is the most abundant mineral in the body and 99% of calcium are in the skeleton. The calcium salts of bones are a valuable reserve that maintain the normal concentration of calcium ions and phosphates in body fluids.
Bones of the skeleton also store energy reserves as lipids in areas filled with yellow marrow.
Production of Blood Cells
Red blood cells, white blood cells and other blood elements are produced in the red marrow which fills the internal cavities of many bones in a process known as haematopoiesis.
Leverage and Movement
Many bones function as levers and can change the magnitude and direction of forces generated by muscles. Bones, skeletal muscles, tendons, ligaments and joints function together to generate and transfer forces so that individual parts of the whole body can be manipulated in three dimensional space.
Other functions include:
Acid-Base Balance
Bones buffer the blood against excessive pH changes by absorbing and releasing alkaline salts.
Detoxification
Bone tissues can also store heavy metals and other foreign elements, removing them from the blood and reducing their effects on other tissues. These can later be gradually released for excretion.
Sound Transduction
Bones are important in the mechanical transmission of sounds for hearing.
Bone Structure
Bone is not a uniformly solid material. Each bone contains two forms of tissue: Compact (dense) bone and spongy or trabecular bone.
Compact Bone is the hard outer layer of compact bone tissue, so called due to its minimal gaps and spaces. It is much denser and less metabolically active. This tissue is what gives bones their smooth, white and solid appearance. It accounts for 75 – 80% of the total bone mass though it can vary with the shape of the bone. Compact bone is thickest where stresses arrive from a limited range of directions. Nutrients are provided to the compact bone through Haversian canals which contain blood vessels. Collagen of compact bones is arranged in concentric layers forming cylinders called osseous or Haversian systems.
Trabecular Bone forms the inner layer of open cell porous network also called spongy or chancellor’s bone. It is composed of a network of rod and plate-like elements that make the overall organ lighter, allowing room for blood vessels and marrow. Spongy bone is located where bones are not heavily stressed or where stresses arrive from many different directions.
Trabecular bone accounts for the remaining 20 – 25% of total bone mass, but has nearly ten times the surface area of compact bone. Nutrients diffuse from bone ECF into the trabecular.
Bone is composed of tough organic matrix greatly strengthened by calcium salts. Average compact bone contains by weight, approximately 30% matrix and 70% salts. The organic matrix of bone is 90 – 95% collagen fibres. The rest is ground substance which is composed of extracellular fluid plus proteoglycans like chondroitin, glycosaminoglycan, hyaluronic acid etc. The collagen fibres are mostly type I in tendons and skin.
Macroscopically, a typical (long) bone consists of the following structures visible to the naked eye; diaphysis, epiphyses, articular cartilage, periosteum, medullary cavity (marrow) and endosteum.
The diaphysis is the main shaft like portion. It consists of a hollow cylindrical cavity of compact bone tissue with marrow (medullary cavity). This composition adapts the diaphysis well for its function of providing strong support without cumbersome weight. The Epiphysis located at the extremities of long bones, is roughly spherical (bulbous) in shape. It is composed of spongy or cancellous bone and only a thin outer layer of dense compact bone. Marrow fills the spaces of cancellous bone – which can be yellow marrow in most adults, but red marrow in the proximal epiphysis of the humorous and femur. Separating these two main sections at either end of the bone is the metaphysis. It is made up of the epiphyseal (growth) plate.
The growth plate is a thick plate of hyaline cartilage. The epiphyseal plates and metaphysis are the only places where long bones continue to grow in length after birth.
Articular cartilage is a thin layer of hyaline cartilage that covers articular or joint surfaces of epiphyses. This material cushions jars and blows by its resiliency.
Covering the outer surface of a bone (except at joint surfaces) is the periosteum, a fibrous dense white membrane that has the potential to form bone during growth periods and in fractures healing. The periosteum contains nerves, lymphatic vessels and many capillaries that provide nutrients to the bone and give the pink colour to living bones. Its blood vessels send branches into the bone, therefore the periosteum, is essential for the nutrition and therefore survival of the bone cells.
The medullary cavity is a hollow tube-like cavity that runs through the length of the diaphysis. It contains yellow marrow (fatty marrow). Lining the medullary cavity of compact bone tissue, and covering the trabecular of spongy bone tissue is the endosteum – the membrane that lines the internal cavity of bones.
Bone Cells
There are several types of cells that make up the bone and these are capable of changing their roles as the needs of the body change.
Estrogenic Cells
These are found mostly in deep layers of the periosteum and in bone marrow. These cells are capable of being transformed into borne-forming cells or bone destroying cells during times of stress and healing.
Osteoblasts
These are mononucleate bone-forming cells which descend from osteoprogenitor cells. They synthesize a protein (an un mineralized ground substance) called osteoids which mineralizes to become bone. Osteoid is composed of type I collagen. Osteoblasts act to move calcium and phosphates into and out of bone tissue thereby calcifying or decalcifying them. Osteoblasts also manufacture hormones like prostaglandins, to act on the bone itself. They also produce alkaline phosphates, an enzyme that plays a role in the mineralization of bones as well as many matrix. Osteoblasts are the immature bone cells.
Osteocytes
These are the main cells of the fully developed bones. They are surrounded by calcified matrix and take on the shape of their individual lacunae within the matrix Osteocytes originate from osteoblasts which have migrated into and become trapped and surrounded by bone matrix which they themselves produce. The spaces which they occupy are known as lacunae. Osteocytes have many processes which reach out to meet other osteoblasts and osteocytes. The function of osteocytes include the following, to varying degrees; formation of bone, matrix maintenance and calcium homeostasis. They help in the release of calcium from bone tissue into the blood thereby regulating the concentration of calcium in body fluids.
Osteoclasts
These are large, multinucleated cells located on bone surfaces in what are called resorption pits. These resorption pits are left behind after the breakdown of bone and often present as scalloped surfaces on the bone. Osteoclasts are derived for hematopoietic stem-cells via monocytes. Therefore they can phagocytose bone, digesting it in their cytoplasm just like circulating macrophages can engulf and phagocytose invading organisms.
Bone Lining Cells
These are essentially inactive osteoblasts i.e. those that cease their physiological activity and flatten out on the bone surface. Some of their functions include serving as barrier for movement of calcium and phosphates into and out of the bone matrix. They may also serve as osteogenic cells that can divide and differentiate into osteoblasts.
Types of Bones
The types of bones include: long, short, flat, irregular and sesamoid bones. Long Bones are characterized by a shaft, (the diaphysis) that is much greater in length than width. They are composed mostly of compact bone and lesser amounts of marrow, which is located within the medullary cavity and spongy bone. Most bones of the limbs, including those of the fingers and toes are long bones except those of the wrist, ankle and knee cap.
Short Bones are roughly cube-shaped and have only a thin layer of compact bone surrounding a spongy interior. The bones of the wrist and ankle are short bones, and the sesamoid bones.
Flat Bones are thin and generally curved, with two parallel layers of compact bones sandwiching a layer of spongy bone. Most of the bones of the skull are flat bones as well as the sternum.
Irregular Bones do not fit into any of the above categories. They consist of thin layers of compact bone surrounding a spongy interior. Their shapes are irregular and complicated. The bones of the spine and hips are irregular bones.
Diagram of a Long Bone
Sesamoid Bones are bones embedded in tendons. They act to hold the tendon further away from the joint. Examples of sesamoid bones are the patella and the pisiform.
Bone Development and Growth
The growth of the skeleton determines the size and proportion of the body. Bones begin to form in a mother’s womb about six weeks following fertilization and portions of the skeleton continue to grow till about the age of 25. Most bones originate as hyaline cartilage or some fibrous membrane structure shaped like bones. The cartilage or membrane is gradually converted to bone through a process of ossification or osteogenesis.
Bones develop in the embryo (during foetal development) by two processes: intramembranous ossification and endochondral ossification. In both cases bones are formed from pre-existing connective tissue skeleton. Note that bone is the same no matter how it develops.
Intramembranous Ossification
This occurs where bone tissue develops directly from mesenchymal tissue. For example the flat bones of the skull and face, including those lining the oral and nasal cavities and part of the clavicle are formed this way. It occurs in the following steps.
Development of ossification Centre
Calcification
Formation of trabeculae
Development of periosteum
From the time of initial bone development, intramembranous ossification spreads rapidly from its Centre until large areas of the skull are covered with protecting and supporting bone.
Bone tissue development begins when thin strands that will eventually become branching trabelucae appear in the matrix. At about the same time, the mesenchymal cells become larger and more numerous and their processes thicken and connect with other embryonic connective tissue cells forming a ring of cells around a blood vessel. The site of this ring formation is a Centre of ossification. It begins about the second month of prenatal life.
The messenchymal cells differentiate into osteoid secreting osteoblasts which begin to cause calcium salt deposits that form the spongy bone matrix. (From the spongy matrix the trabeculae of cancellous bone will later form).
As the process of calcification continues, some osteoblasts become trapped inside lacunae of the developing matrix and lose their ability to form bone tissue. These are now called osteocytes. As bone forming osteoblasts change into osteocytes, they are replaced by new osteoblasts which develop from the estrogenic cells in the surrounding connective tissue. This way bones continue to grow.
At the same time that osteoblasts are synthesizing and mineralizing the matrix, osteoclasts play a role in bone resorption by removing small areas of bone from the wall of the lacunae.
The trabeculae continue to thicken into the dense network that is typical of cancellous bone tissue. The collagenous fibrils deposited on the trabeculae crowd blood vessels which eventually condense into blood forming marrow.
The osteoblasts on the surface of the spongy bone tissue then form the Periosteum – the membrane covering the outer surface of the bone. The Periosteum is made up of an inner osteogenic layer (with osteoblasts) and a thick fibrous outer layer. The inner layer eventually creates a protective layer of compact bone tissue over the cancellous tissue interior. When this intramembranous ossification has stopped, the osteogenic layer becomes inactive at least temporarily. It becomes active again when necessary for example, to repair a bone fracture.
Endochondral Ossification
This is the kind of bone tissue development that occurs by the replacement of hyaline cartilage. Here the initial model is made of hyaline cartilage and it then becomes eroded. Endochodral ossification produces long bones and all other bones not formed by intramembranous ossification. It must be noted that cartilage is not converted into bone but rather the cartilage model is completely destroyed and replaced by newly formed bone.
Endochondral ossification is a slower process that begins with points in the cartilage called the “primary ossification Centre’s” which appear during fetal development. It continues after birth through the occurrence of the secondary ossification Centre still the period of skeletal maturity (18 – 25 years of age).
About 6 to 8 weeks after fertilization, mesenchymal cells multiply rapidly and bunch together in a dense central core of precartilage tissue that eventually forms the cartilage model. This is followed by the appearance of the primitive perichondrium that covers the surface of the cartilage. The cartilage model is then invaded by capillaries which trigger the Transformation of the perichondrium into (bone producing periosteum the fibrous membrane that covers bones).
An intramembranous ossification occurs in the periosteum forming a hollow cylinder of trabecular bone called bone collar around the cartilage of the diaphysis.
By the second to third month of prenatal life the primary Centre of ossification is formed around the middle of what will become the diaphysis Bone cells develop rapidly in the diaphyseal area and blood vessels develop in the periosteum and branch into the diaphysis. The diaphysis now has a layer of bone tissue just under the periosteum and an increasing amount of marrow in the Centre of the shaft. The ends still consist of cartilage.
After birth the chondrocytes (cartilage cells) in the epiphysis begin the process of dying as in the diaphysis. Blood vessels and estrogenic cells from the periosteum enter the epiphyses where they develop into osteoblasts. The Centre’s of this activity in the epiphyses are called the secondary Centre’s of ossification.
Some cartilage remains on the outer, joint edge of each epiphysis to form the articular cartilage for the smooth operation of the joint. Also a layer of cartilage known as the epiphyseal cartilage or epiphyseal plate remains between each epiphysis and the diaphysis until bone growth in length is complete. The growth of bone length occurs in small spaces in the epiphyseal plate. During growth cartilage cells proliferate and cause thickening of the layer. Osteoblasts then synthesize organic bone matrix and this undergoes calcification, as a result the bone grows longer. This continues till sometime between adolescence and early twenties depending on which bone.
As growth in length slows down, the distal epiphyseal plate disappears first leading to fusion or closure of the epiphysis. The proximal plate disappears a bit later. As growth in length ends the epiphyseal cartilage is completely replaced by osseous tissue.
Remodeling of Bones
No new growth in bone length continues after age 25, however the diameter of bones may continue to increase throughout most of our lives. Through intramembranous ossification, estrogenic cells in the periosteum deposit new bone tissue beneath the periosteum while most of the old bone tissue erodes away. The combination of cell deposition and erosion widens the bone without thickening its walls. The width of the marrow cavity may increase too.
Bones can thicken or become denser to keep up with any physical changes in the body that may increase stress or load on the bones. For example, in athletes who greatly increase their muscles, the bones can also be strengthened at the same time. If not, the increased pull of the stronger muscles may have to fracture them.
The same thing can happen in people who are overweight with resultant increase in the load on their skeleton. On the other hand, inactivity will lead to decalcification – loss of minerals and resultant weakening in a bone. For example a leg that is put in a cast for a month thins out. This is because the muscles of the leg have atrophied and the bones have decalcified by about 30%.
Remodeling of bones (that process of resorption followed by replacement of bone with little or no change in shape) is a local process that is carried out in small areas sometimes called remodeling units. The cycle takes about 100 days and up to 20% of the adult skeleton is remodeled each year.
There are about 2 million remodeling units that are active at any one time in the human skeleton. The remodeling is related in part to the stresses and strains imposed on the skeleton by gravity (as already discussed). This is regulated by hormones in the systemic circulation and by growth factors, most of which act locally. Prostaglandins seem to play a part. Infact steoblasts and osteoclasts coupled together via paracrine cell signaling is what is called remodeling units.
The overall purpose of remodeling is to regulate calcium metabolism, repair micro-damaged bone (from daily stress) and also to shape and sculpture the skeleton during growth.
Homeostasis and the Physiological Functions of Bones
The bone performs many physiological functions which though may not be apparent but they help in maintenance of homeostasis in the body. Some of these functions which are not obvious include the production of blood cells, maintenance of calcium, phosphate and magnesium salts balance in the body and so for the highlight.
Calcium Storage and Release
The functions of calcium are numerous in the body. In the first place bones consist mainly of calcium, so without calcium, there would be no bones. Calcium also plays important roles in many chemical and electrical activities in the body. Without calcium, some enzymes could not function, cells would come apart, the permeability of cell membranes would be affected, muscles (including the heart) could not contract, nerve functions would be hampered and blood would not cloth and so forth.
When the diet does not provide enough calcium the bones release it and if there is too much calcium, in the body, the bones store it. In order to maintain homeostasis bones help regulate the amount and consistency of extracellular fluid by either adding calcium to it or by taking calcium out of it. Small decreases of calcium in extracellular fluid and plasma can cause the nervous system to become more excitable because of increased neuronal membrane permeability with resultant muscular spasms (tetany). On the other hand, too much calcium (hypocalcaemia) in body fluids depress the nervous system.
Phosphate Storage and Release
Bones also help to regulate the amount of phosphates in the body. Under hormonal control bones can release phosphate salts when needed by the body. Though changing the level of phosphate in the extracellular fluid or blood does not have immediate significant effects on the body, the proper amount, of phosphate is vital to the body’s acid-base balance.
Production of Blood cells
The marrow within bones contribute to homeostasis by manufacturing some blood cells. The adult red bone marrow is the main blood-making tissue of the body. It produces all the red blood cells, platelets, and some white blood cells (e.g. granular leukocytes and immature lymphocytes and monocytes).
All the bone marrow at birth is red marrow. By adolescence, most of it is replaced by yellow fat cells which form the yellow marrow. In the adult, red marrow is found only in the proximal epiphyses of bones such as the femur and humerus, in some short bones and in the vertebrae, sternum, ribs and cranium.
The continued production of red blood cells is very important because the cells live only for about 120 days and need to be replaced as they die. About 2.5 million red cells are produced per second and 200 billion daily.
In addition, some of the macrophages and white blood cells from the red marrow help to protect the body from disease.
Hormonal Control of Calcium and Bone Physiology
Several hormones have a direct effect on bones, and bones also have an effect on hormone secretion. (See relevant sections of the endocrine system).
Several hormones and vitamins are important in bone maturation and in the regulation of calcium in the body.
Parathyroid hormone (PTH) acts directly on bones to increase bone
Reabsorption and mobilize Ca++ leading to increase in plasma
calcium levels. It also depresses plasma phosphate and increases the excretion of phosphate in the urine. The latter is as a result of a decrease in reabsorption of phosphates in the proximal tubules. PTH also increases the reabsorption of calcium in the distal tubules.
PTH increases Ca++ reabsorption from the intestine but this action is due to the fact that it stimulates the formation of 1, 25 – dihydroxy-cholecalciferol, the active metabolite of vitamin D.
The secretion of PTH appears to be stimulated by low calcium levels in the blood. Its secretion raises blood calcium levels by the actions enumerated above. When levels of calcium rise sufficiently to normal, in the ECF and plasma, the secretion of PTH is inhibited by a negative feedback loop.
1, 25 – dihydroxycholecalciferol the physiologically active form of vitamin D3 dictates the formation of a calcium – binding protein. It also increases the pumping of Ca++ out of the bsolateral membranes of intestinal epithelial cells. It facilitates the reabsorption of Ca++ in the kidney.
It also acts on bone where it mobilizes Ca++ and Po43- probably by an initial action to release osteoblast factors that activate osteoclasts and subsequently by increasing the number of osteoclasts. All these are aimed towards increasing the level of Ca++ in plasma, and ECF.
Calcitonin is a hormone secreted by the thyroid gland whose action balances the action of parathyroid hormone. Calcitonin receptors are found in bones and the kidney. Calcitonin lowers the circulating calcium and phosphorus levels. It exerts its calcium lowering effect by directly inhibiting bone resorption. It inhibits the activity of osteoclasts. It also increase Ca++ excretion in the urine.
Other hormones include growth hormone, thyroxin adrenal cortical hormones, plus vitamins A and D. These are important in bone maturation. Growth hormones and thyroxine stimulate the endochondral ossification process. Growth hormone increases intestinal absorption of calcium, thyroxine causes hypocalcaemia.
Both male and female sex hormones (from the gonads) regulate growth rates by controlling the appearance of Centre’s of ossification and the rate of bone maturation. Oestrogens prevent osteoporosis probably by direct effect on osteoblasts. Insulin increases bone formation and there is significant bone loss in untreated diabetes. Glucocorticoids lower plasma Ca2+ levels by inhibiting osteoclast formation and activity. Over long periods, they cause osteopeorosis by decreasing bone formation and increasing bone resorption. They decrease bone formation by inhibiting cellular replication and protein synthesis in bone and they inhibit the function of osteoblasts. They also decrease the absorption of Ca2+ and Po43_ from the intestine by an anti – vitamin D action.
Bone Diseases
The diseases that affect the bone occur as a result of the interplay of factors that maintain normal bone function.
Osteogenesis Imperfecta (brittle bone disease) is an inherited condition in which the bones are abnormally brittle and subject to fractures. The basic cause of this disorder is a decrease in the activity of osteoblasts during bone formation (osteogenesis). In some cases the fractures occur during prenatal life and so the child is born with deformities. In order cases the fractures occur as the child begins to walk.
Osteomalacia and Rickets are skeletal defects caused by a deficiency of vitamin D which leads to a widening of the epiphyseal growth plates, an increased number of cartilage cells, a decrease in linear growth etc.
Rickets is the childhood form of the disease. Skeletal deformities manifest as bowed legs; knock knees and bulging forehead. Leg deformities occur if the child is old enough to attempt to walk, resulting in excessive pressure being put upon the soft legs.
Osteomalacia (adult rickets) leads to demineralization and an excessive loss of calcium and phosphorus. Although the skeletal deformities of rickets may be permanent, the similar skeletal abnormalities of osteomalacia may disappear with proper treatment with large doses of vitamin D.
In Osteoporosis, both matrix and mineral are cost from the bone, and there is a loss of bone mass and strength, with an increased incidence of fractures. This disease is almost an opposite of osteopetrosis in that it is characterized over time by a net excess of bone resorption over bone formation. It has multiple causes but is associated mostly with advancing age and the menopause. The WHO defines osteoporosis in women as a bone mineral density (BMD) 2.5 standard deviations in below peak bone mass (20 year – old sex – matched healthy person average).
Osteopetrosis is a rare and severe disease in which the osteoclasts are defective and are unable to resorb bone in their usual fashion. The result is a steady increase in bone density. Neurologic defects occur due to narrowing and distortion of foramina through which nerves normally pass Haematologic defects occur due to crowding out of the marrow cavities.
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