Lecture 03. Bone Introduction

Question 1

Functions of the Skeleton

Answer 1

• **Support: **Bones of the legs, pelvis, and vertebral column hold up the body; the jaw bones support the teeth; and nearly all bones provide support for muscles.
• Movement: Skeletal muscles would serve little purpose if not for their attachment to the bones and ability to move them.
• Protection: Bones enclose and protect such delicate organs and tissues as the brain, spinal cord, lungs, heart, pelvic viscera, and bone marrow.
• **Blood Formation: **Red bone marrow is the major producer of blood cells, including most cells of the immune system.
• Electrolyte Balance: The skeleton is the body’s main reser- voir of calcium and phosphate. It stores these minerals and releases them when needed for other purposes.
• Acid–base Balance: Bone buffers the blood against excessive pH changes by absorbing or releasing alkaline salts such as calcium phosphate.
• Detoxification: Bone tissue absorbs heavy metals and other foreign elements from the blood and thus mitigates their toxic effects on other tissues. It can later release these contaminants more slowly for excretion. The tendency of bone to absorb foreign elements can, however, have terrible consequences.

Question 2

What is Stiffness?

Answer 2

Stiffness: The slope of a stress straining curve

Stress: Force per unit area

Strain: Change in length divided by initial length

Elastic Region: Certain period bone can bend and snap back (within this region you can measure stiffness).

Plastic Region (Yield Point): anything past a certain point will NOT snap back

Fracture Point: Apply more forece, eventually you will reach the fracture point

Cannot continue past fracture point - LINE CANNOT GO PAST FRACTURE POINT

Question 3

Bone Structure

(Macroscopic Level)

Answer 3

Shape of Bones:

• Long bones: Longer than they are wide.
  Include most the bones in the appendicular skeleleton (radius, ulna, tibia, fibia)
  Epiphysis: Expanded head at each end. Enlarged to strengthen the joint and provide added surface area for the attachment of tendons and ligaments. (In adolescents an epiphyseal plate of hyaline cartilage separates the marrow cavities of the epiphysis and diaphysis. On X-rays, it appears as a transparent line at the end of a long bone).
  Diaphysis: Shaft. Provides leverage.
  Metaphysis: In between the epiphysis and diaphysis (where bone growth and lengthening occur).
• Short Bones: cube shaped bones.
  Include small bones of the wrist (carpals), ankle (talas)
• Flat Bones:“Spongy bone sandwich” - Compat on outside/Spongy in the middle/ Compact on inside. Provides for strength, spongy bone absorbs force.
  (Scapula, sternum, most of the bones of the cranium frontal bone parietieal bones, occipital bone).
• Irregular Bone: Everything else that does not fit into these categories
  (Sphenoid, ethmoid, vertebrae)
• Periosteum: Sheath that covers bone externally. Has a tough, outer fibrous layer of collagen and an inner osteogenic layer of bone-forming cells. Some collagen fibers of the outer layer are continuous with the tendons that bind muscle to bone, and some penetrate into the bone matrix as perforating fibers. The periosteum thus provides strong attachment and continuity from muscle to tendon to bone. The osteogenic layer is important to the growth of bone and healing of fractures. Blood vessels of the periosteum penetrate into the bone through minute holes called nutrient foramina.
• Endosteum: A thin layer of reticular connective tissue that covers the internal surface of a bone. Lined with with cells that deposit osseous tissue and others that dissolve it.
• Articular Cartilage: A thin layer of hyaline cartilage found at most joints that lack periosteum. Together with a lubricating fluid secreted between the bones, this cartilage enables a joint to move far more easily than it would if one bone rubbed directly against the other.

Question 4

Bone Structure

(Microscopic Level)

Answer 4

Cells of osseous tissue:

• Osteogenic cells: Stem cells found in the endosteum, the inner layer of the periosteum, and within the central canals. They arise from embryonic mesenchyme. Osteogenic cells multiply continually and give rise to osteoblasts.
• Osteoblasts: Bone-forming cells that synthesize the organic matter of the matrix and help to mineralize the bone. They line up in rows in the endosteum and inner layer of periosteum and resemble a cuboidal epithelium on the bone surface. Osteoblasts are nonmitotic, so the only source of new osteoblasts is the osteogenic cells. Stress and fractures stimulate accelerated mitosis of those cells and therefore a rapid rise in the number of osteoblasts, which then reinforce or rebuild the bone.
• Osteocytes: Former osteoblasts that have become trapped in lacunae of the matrix, which are connected to each other by slender channels called canaliculi. Each osteocyte has delicate cytoplasmic processes that reach into the canaliculi to meet the processes of neighboring osteocytes. Adjacent osteocytes are joined by gap junctions at the tip of these processes. These junctions allow osteocytes to pass nutrients and chemical signals to each other and to transfer wastes to the nearest blood vessels for disposal. Osteocytes also communicate by gap junctions with the osteoblasts on the bone surface. Osteocytes have multiple functions. Some resorb bone matrix and others deposit it, so they contribute to the homeostatic maintenance of both bone density and blood concentrations of calcium and phosphate ions. Also are strain sensors. When a load is applied to a bone, it produces a flow in the extracellular fluid of the lacunae and canaliculi. Osteocytes have a little antenna—a solitary cilium—that senses this fluid flow. This stimulates the osteocytes to secrete biochemical signals that may regulate bone remodeling—adjustments in bone shape and density to adapt to stress.
• Osteoclasts: Bone-dissolving macrophages found on bone surfaces. They develop from the same bone marrow stem cells that give rise to blood cells. Several stem cells fuse with each other to form an osteoclast; thus, osteoclasts are unusually large (up to 150 μm in diameter) and typically have 3 or 4 nuclei, but sometimes up to 50. The side of the osteoclast facing the bone has a ruffled border with many deep infoldings of the plasma membrane, increasing its surface area. Hydrogen pumps in the ruffled border secrete hydrogen ions (H+) into the extracellular fluid, and chloride ions (Cl–) follow by electrical attraction; thus, the space between the osteoclast and the bone becomes filled with hydrochloric acid (HCl). The HCl, with a pH of about 4, dissolves the minerals of the adjacent bone. Lysosomes of the osteoclast then release enzymes that digest the organic component. Osteoclasts often reside in little pits called resorption bays (Howship lacunae) that they have etched into the bone surface.

Question 5

Matrix

Answer 5

Bone is a two phase substance made of two major types of matter:** **

• 1/3 Organic material:
  23% organic collagen
  10% water
  2% noncollagenous protein
• 2/3 Inorganic material:
  65% calcium hydroxyapetite crystals
• Combination provides for strength and resilience

(Fossils = remaining inorganic matter)

Question 6

Calcium Storage

Answer 6

Calcium storage

Under hormonal control - get calcium out of bone (negative feedback)

• A decrease in plasmic calcium stimulates glands in the thyroid (the parathyroid glands) to creat PCH (parathyroid hormones)
• Acts on bones to incease reabsorption - the breakdown of bone releases calcium into the plasma
• Stimulates kidneys to increase reabsorption and create vitamin D derrivitate, which wil act on the intenstine to increase calcium absorption, bringing plasmic calcium levels back towards normal

If calcium levels get too low: muscle spasms, affects skeletel muscle then heart.

(Discovered parathyroid glands after removing the thyroid from cancer patients, was causing calcium deficiencies).

Question 7

Blood Cells

Answer 7

All red/white blood cells made in bone.

Created from hematopoietic stem cells:

• Band neutrophil
• Basophil
• Eosinophil
• Erythrocyte (Red blood cell)
• Lymphocyte (White blood cell)
• Monocyte
• Platelets
• Segmented neutrophil
• Also makes platelets

Issue with bone marrow = issue with making blood cells.
If you do not make enough red blood cells = anemia.
Problem making white blood cells = leukemia.

Question 8

collagen

Answer 8

• triple helix of polypeptides
• bundled into ropes - resist tension
• provides sites for mineralization
• Tough - takes high level of energy to fracture

Calcium phosphate mineral

HYDROXYAPATITE

Ca10(PO4)6(OH)2

Key point: fibers open arranged in plywood-­‐like organization - helps give bones strength

do not resist twisting (contortion)

Question 9

Histology

(Compact Bone)

Answer 9

Outter layer of bone.

organized by osteons layers of bone surrounding central canal (contains nerve and blood vesels) connected to each other and outter layers by perforating canals volcman

• Circumfrencial Lumelae go around the entire bone.
• Trabacular: Layers in small struts
• Osteonal: tube-­like layers around a vascular channel

NB: cortical bone is well vascularized!

As you age, more and more bone is filled with osteons young bone looks differnet than older bone. not as many osteons.

becuase bone is a mineralized stiff rigis and har tissue changes in shape and repair of damaged tissue can only occue by means of surface or appositional remodeling. Lamellar bone deposition or resorption (removal)​

Question 10

Bone Marrow

Answer 10

• In medullary cavity (long bone) and among trabeculae (spongy bone)
• Red marrow in young (like thick blood)
• Yellow marrow in older (red marrow replaced by fat yellow marrow)

Question 11

Other Connectice tissue

Answer 11

Cartilage (hyaline): Poorly organized complex of Hydrophillic proteoglycan complexes (GAGs) Cartilage in joints acts like a water bed. Water is non-­compressible. Highly negative electrochemical charges hold apart GAG complexes under load.

Ligaments (bone to bone): Collagen bundles with limited elasticity. Limited joint movement.

Tendons (muscle to bone): Achilles tendon (calcaneal tendon) It serves to attach the plantaris, gastrocnemius (calf) and soleus muscles to the calcaneus (heel) bone (dense regular connecive tissue). Springlike function, apply forece, stretch, elasctic energy.

Question 12

Bone Formation

Answer 12

Several major types of cells respond to many stimuli:

Depository cells

• Bone: Osteoblasts (become osteocytes or lining cells)
• Cartilage: Chondrocytes
• Tendons: Fibroblasts
• Ligaments: Fibroblasts

​Resorptive Cells

• Chondroclasts
• Osteoclasts

Bon gets dissolved and released into the bloodstream by osteoclasts.
Bone can be formed in two step process:

1. Osteoblasts lay down a collagen matrix (osteoid)
2. It creates supersaturated solution of calcium phosphate which will then mineralize.

Question 13

Intramembranous Ossification

Answer 13

Intramembranous Ossification: Produces the flat bones of the skull and most of the clavicle.

1. Mesenchyme first condenses into a soft sheet of tissue permeated with blood vessels—the membrane to which intramembranous refers. Mesenchymal cells line up along the blood vessels, become osteoblasts, and secrete a soft collagenous osteoid tissue in the direction away from the vessel. Osteoid tissue resembles bone but is not yet hardened by minerals.
2. Calcium phosphate and other minerals crystallize on the collagen fibers of the osteoid tissue and harden the matrix into a network of spongy bone trabeculae. Continued osteoid deposition and mineralization squeeze the blood vessels and future bone marrow into narrower and narrower spaces. As osteoblasts become trapped in their own hardening matrix, they become osteocytes.
3. While the foregoing processes are going on, more of the mesenchyme adjacent to the developing bone condenses and forms a fibrous periosteum on each surface. The spongy bone becomes a honeycomb of slender calcified trabeculae.
4. At the surfaces, osteoblasts beneath the periosteum deposit layers of bone, fill in the spaces between trabeculae, and create a zone of compact bone on each side, as well as thickening the bone overall. This process gives rise to the sandwichlike structure typical of a flat cranial bone—a layer of spongy bone between two surface layers of compact bone.

Intramembranous ossification also plays an important role in the lifelong thickening, strengthening, and remodeling of the long bones discussed next. Throughout the skeleton, it is the method of depositing new tissue on the bone surface even past the age where our bones can no longer grow in length.

Question 14

Endochondral Ossification

Answer 14

Endochondral Ossification: A process in which a bone develops from a preexisting model composed of hyaline cartilage. It begins around the sixth week of fetal development and continues into a person’s 20s. Most bones of the body, including the vertebrae, ribs, sternum, scapula, pelvis, and bones of the limbs, develop in this way. In the metacarpal bones, this occurs in only one epiphysis. In longer bones of the arms, forearms, legs, and thighs, it occurs at both ends and is relatively complex. The epiphyses of those bones are formed from several pieces of childhood bone with multiple ossification centers. Bones such as the metacarpals, metatarsals, and phalanges afford simpler illustrations of the ossification process.

1. Mesenchyme develops into a body of hyaline cartilage, covered with a fibrous perichondrium, in the location of a future bone. For a time, the perichondrium produces chondrocytes and the cartilage model grows in thickness.
2. In a primary ossification center near the middle of this cartilage, chondrocytes begin to inflate and die, while the thin walls between them calcify. The perichondrium stops producing chondrocytes and begins producing osteoblasts. These deposit a thin collar of bone around the middle of the cartilage model, encircling it like a napkin ring and providing physical reinforcement. The former perichondrium is now considered to be a periosteum.
3. Blood vessels grow inward from the periosteum and invade the ossification center. Osteoclasts arrive in the blood and digest calcified tissue in the shaft, hollowing it out and creating the primary marrow cavity. Osteoblasts also arrive and deposit layers of bone lining the cavity, thickening the shaft. As the bony collar under the periosteum thickens and elongates, a wave of cartilage death progresses toward the ends of the bone. Osteoclasts in the marrow cavity follow this wave, dissolving calcified cartilage remnants and enlarging the marrow cavity of the diaphysis. The region of transition from cartilage to bone at each end of the primary marrow cavity is called a metaphysis. Soon, chondrocyte enlargement and death occur in the epiphysis of the model as well, creating a secondary ossification center.
4. The secondary ossification center hollows out by the same process as the diaphysis, generating a secondary marrow cavity at the end of the bone. This cavity expands outward from the center, in all directions. In bones with two secondary ossification centers, one center lags behind the other in development, so at birth there is a secondary marrow cavity at one end, but chondrocyte growth has just begun at the other. The joints of the limbs are still cartilaginous at birth.
5. During infancy and childhood, the epiphyses fill with spongy bone. Cartilage is then limited to the articular cartilage covering each joint surface, and to the epiphyseal plate of cartilage separating the primary and secondary marrow cavities at one or both ends of the bone. The plate persists through childhood and adolescence and serves as a growth zone for bone elongation. This growth process is described in the next section.
6. By the late teens to early twenties, all remaining cartilage in the epiphyseal plate is generally consumed, and the gap between the epiphysis and diaphysis closes. The primary and secondary marrow cavities then unite into a single cavity. The bones can grow no longer, and one attains his or her maximum adult height. The only remnants of the original cartilage model are the articular cartilages that cover the joint surfaces of the bone.

Question 15

Bone Elongation

Answer 15

Epiphyseal Plates: On an X-ray, the plate can appear as a translucent line across the end of a bone if it has not yet ossified. It consists of a band of typical hyaline cartilage in the middle and a metaphysis on each side. Even if one end of a bone lacks an epiphyseal plate, it has a metaphysis— the transitional zone between the epiphyseal cartilage and diaphy- seal osseous tissue.

At the metaphysis, the cartilage thickens by cell division and enlargement and then undergoes replacement by bone.

Structure of Metaphysis

1. Zone of reserve cartilage: This region, farthest from the marrow cavity, consists of typical resting hyaline cartilage.
2. Zone of cell Proliferation: A little closer to the marrow cavity, chondrocytes multiply and arrange themselves into longitudinal columns of flattened lacunae.
3. Zone of cell Hypertrophy: Next, the chondrocytes cease to multiply and begin to hypertrophy (enlarge), much like they do in the primary ossification center of the fetus. The walls of matrix between lacunae become very thin.
4. Zone of Calcification: Minerals are deposited in the matrix between the columns of lacunae and calcify the cartilage. These are not the permanent mineral deposits of bone,
5. but only a temporary support for the cartilage that would otherwise soon be weakened by the breakdown of the enlarged lacunae.
6. Zone of bone deposition: Within each column, the walls between the lacunae break down and the chondrocytes die. This converts each column into a longitudinal channel (white spaces in the figure), which is immediately invaded by blood vessels and marrow from the marrow cavity. Osteoblasts line up along the walls of these channels and begin depositing concentric lamellae of matrix, while osteoclasts dissolve the temporarily calcified cartilage.

Height: Chondrocyte multiplication in zone 2 and hypertrophy in zone 3 continually push the zone of reserve cartilage toward the ends of the bone, so the bone elongates. In the lower limbs, this process causes a person to grow in height, while bones of the upper limbs grow proportionately.

Question 16

Bone Widening and Thickening

(Appositional Growth)

Answer 16

Appositional Growth: Occurs by intramembranous ossification at the bone surface. Osteoblasts in the inner layer of periosteum deposit osteoid tissue on the bone surface, calcify it, and become trapped in it as osteocytes.
They lay down matrix in layers parallel to the surface, not in cylindrical osteons like those deeper in the bone. This process produces the surface layers of bone called circumferential lamellae.
As a bone increases in diameter, its marrow cavity also widens. This is achieved by osteoclasts of the endosteum dissolving tissue on the inner bone surface. Therefore, we see that flat bones develop by intramembranous ossification alone, whereas long bones develop by a combination of endochondral and intramembranous ossification.

Question 17

Bone Remodeling

Answer 17

Bones are continually remodeled throughout life by the absorption of old bone and deposition of new.
This process replaces about 10% of the skeletal tissue per year. It repairs microfractures, releases minerals into the blood, and reshapes bones in response to use and disuse.

Bone remodeling comes about through the collaborative action of osteoblasts and osteoclasts. If a bone is little used, osteoclasts remove matrix and get rid of unnecessary mass. If a bone is heavily used or a stress is consistently applied to a particular region of a bone, osteoblasts deposit new osseous tissue and thicken the bone. Consequently, the comparatively smooth bones of an infant or toddler develop a variety of surface bumps, ridges, and spines as the child begins to walk.

On average, bones have greater density and mass in athletes and people engaged in heavy manual labor than they do in sedentary people. Anthropologists who study ancient skeletal remains use evidence of this sort to help distinguish between members of different social classes, such as distinguishing aristocrats from laborers. Even in studying modern skeletal remains, as in investigating a suspicious death, Wolff’s law comes into play as the bones give evidence of a person’s sex, race, height, weight, work or exercise habits, nutritional status, and medical history.

Question 18

Wolff’s Law

Answer 18

States that the architecture of a bone is determined by the mechanical stresses placed upon it, and the bone thereby adapts to withstand those stresses.

Form and function, showing that the form of a bone is shaped by its functional experience.

Example: Tennis players whom the bones of the racket arm and the clavicle on that side are more robust than those of the other side.

Question 19

Nutritional and Hormonal Factors

Answer 19

The balance between bone deposition and resorption is influenced by nearly two dozen nutrients, hormones, and growth factors.

Most important factors that promote bone deposition:

• Calcium and Phosphate: Needed as raw materials for the calcified ground substance of bone.
• Vitamin A: Promotes synthesis of the glycosaminoglycans (GAGs) of the bone matrix.
• Vitamin C (ascorbic acid): Promotes the cross-linking of collagen molecules in bone and other connective tissues.
• Vitamin D (calcitriol): Necessary for calcium absorption by the small intestine, and it reduces the urinary loss of calcium and phosphate. Vitamin D is synthesized by one’s own body. The process begins when the ultraviolet radiation in sunlight acts on a cholesterol derivative (7-dehydrocholesterol) in the keratinocytes of the epidermis. The product is picked up by the bloodstream, and the liver and kidneys complete its conversion to vitamin D.
• **Calcitonin: **A hormone secreted by the thyroid gland, stimulates osteoblast activity. It functions chiefly in children and pregnant women; it seems to be of little significance in non- pregnant adults.
• Growth Hormone: Promotes intestinal absorption of calcium, the proliferation of cartilage at the epiphyseal plates, and the elongation of bones.
• Sex Steroids (estrogen and testosterone): Stimulate osteoblasts and promote the growth of long bones, especially in adolescence.

Bone deposition is also promoted by thyroid hormone, insulin, and local growth factors produced within the bone itself.

Bone resorption is stimulated mainly by one hormone:

• Parathyroid Hormone (PTH): Produced by four small parathyroid glands, which adhere to the back of the thyroid gland in the neck. The parathyroid glands secrete PTH in response to a drop in blood calcium level. PTH stimulates osteoblasts, which then secrete an osteoclast-stimulating factor that promotes bone resorption by the osteoclasts. The principal purpose of this response is not to maintain bone composition but to maintain an appropriate level of blood calcium, without which a person can suffer fatal muscle spasms. PTH also reduces urinary calcium losses and promotes calcitriol synthesis.

Question 20

Fractures

Answer 20

1. Stress fracture: caused by trama
2. pathological fractures: bones that have already been weakened by disease.

classified by characteristics

• Open Fracture: Bone goes through skin
• **Closed Fracture: **Bone does not go through skin
• Nondisplaced Fracture: Bone is broken, ends are still in allignment
• Displaced Fracture: Bone broken, ends are out of allignment
• Communuted Fracture: Bone is broken into multiple pieces
• Greenstick Frature: Bone is not broken all the way through

Question 21

Healing

Answer 21

Normally 8 -­‐ 12 weeks (longer in elderly) Can be affected by what you eat and drink.

Stages of healing

1. Fracture Hematoma
2. Soft Callus
3. Hard Callus
4. Remodeling in 3 to 4 months

Treatement of fractures

• Closed Reduction: Set, cast
• Open Reduction: Pins, plates, screws
• Electrical Stimulation: Serious breaks, supports bone regrowth

Question 22

Calcium and Phosphate

Answer 22

Phosphate is component of DNA, RNA, ATP, phospholipids, and pH buffer

Calcium needed in neurons, muscle contrac.on, blood clotting and exocytosis

Question 23

Ion Imbalances

Answer 23

Changes in phosphate levels can have little affect on physiology
Changes in calcium can be serious!

• Hypocalcemia: Deficiency of blood calcium (causes spasms/random twitches - not muscle cramps) causes excitability of nervous system if too low.
• Hypercalcemia: Excess of blood calcium.
• Binding to cell surface makes sodium channels less likely to open, depressing nervous system
• Calcium phosphate homeostasis depends on calcitriol, calcitonin and PTH hormone regulation

Question 24

Hormonal Control of Calcium Balance

Answer 24

Calcitriol, PTH and calcitonin maintain normal blood calcium concentration.

Calcitriol: (Activated Vitamin D)

• Calcitriol behaves as a hormone that raises blood calcium concentration
• Abnormal softness in children and in adults without vitamin D

Question 25

Calcitriol Synthesis and Action

Answer 25

brings calcium up

Question 26

Correction for Hypercalcimia

(Hormonal Negative Feedback Loop)

Answer 26

Bodies response to too much calcium.

(First compex hormonal feedback loop - know calcitonin and calcitriol)

• Calcitonin: a 32-amino acid linear polypeptidehormone that is produced in humans primarily by the parafollicular cells (also known as C-cells) of the thyroid, and in many other animals in the ultimobranchial body.[2] It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone(PTH).
• Calcitriol: Increases the level of calcium (Ca2+) in the blood by increasing the uptake of calcium from the gut into the blood, and possibly increasing the release of calcium into the blood from bone.

Question 27

Other Factors Affecting Bone

Answer 27

Hormones, vitamins and growth factors

• Growth rapid at puberty
• Growth stops (epiphyseal plate “closes”)

Question 28

Osteoporosis

Answer 28

Bones lose mass and become brittle (loss of organic matrix and minerals)

Postmenopausal white women at greatest risk – by age 70, average loss is 30% of bone mass

Osteoporosis: when bone resorption is greater than bone deposition. (Affects mostly trabecular bone).

Question 29

Estrogen’s role in Osteoporosis

Answer 29

Effects on parathyroid hormone (PTH)

When Ca++ levels are low, parathyroid gland PTH, which stimulates bone resorption by osteoclasts

(Originally treated by estrogren replacement therapy - caused CANCER).

Question 30

Treatment/Prevention of Osteoporosis

Answer 30

(with/without hormone replacement therapy)

women stop growing earlier, ajain lower peak bone mass than men

Effects of lower estrogen following menopause