C H A P T E R 6

BonesBones and Skeletal and Skeletal Tissues: Part BTissues: Part B

Bone Development

• Osteogenesis (ossification) bone tissue formation

• 3 Stages

• Bone formation begins in the 2nd month of development

• Postnatal bone growth until early adulthood

• Bone remodeling and repair lifelong

Two Types of Ossification

1. Intramembranous ossification

• At about 8 weeks of development, ossification begins on fibrous connective tissue.

• Forms clavicles and cranial bones (What bone shape are these?)

2. Endochondral ossification

• Beginning the 2nd month of development, this process uses hyaline cartilage “bones” formed earlier as models for bone construction.

• Forms most of the rest of the skeleton below skull except clavicles

Figure 6.8, (1 of 4)

Mesenchymalcell

CollagenfiberOssificationcenter

Osteoid

Osteoblast

Ossification centers appear in the fibrousconnective tissue membrane.• Selected centrally located mesenchymal cells cluster

and differentiate into osteoblasts, forming anossification center.

1

Intramembranous ossification

Figure 6.8, (2 of 4)

Osteoid

Osteocyte

Newly calcifiedbone matrix

Osteoblast

Bone matrix (osteoid) is secreted within thefibrous membrane and calcifies.• Osteoblasts begin to secrete osteoid, which is calcified

within a few days.• Trapped osteoblasts become osteocytes.

2

Figure 6.8, (3 of 4)

Mesenchymecondensingto form theperiosteum

Blood vessel

Trabeculae ofwoven bone

Woven bone and periosteum form.• Accumulating osteoid is laid down between embryonic

blood vessels in a random manner. The result is a network(instead of lamellae) of trabeculae called woven bone.

• Vascularized mesenchyme condenses on the external faceof the woven bone and becomes the periosteum.

3

Figure 6.8, (4 of 4)

FibrousperiosteumOsteoblast

Plate ofcompact bone

Diploë (spongybone) cavitiescontain redmarrow

Lamellar bone replaces woven bone, just deep tothe periosteum. Red marrow appears.• Trabeculae just deep to the periosteum thicken, and are later

replaced with mature lamellar bone, forming compact boneplates.

• Spongy bone (diploë), consisting of distinct trabeculae, per-sists internally and its vascular tissue becomes red marrow.

4

Endochondral Ossification

• Uses hyaline cartilage models

• Requires breakdown of hyaline cartilage prior to ossification

Figure 6.9, step 1

Bone collar forms aroundhyaline cartilage model.1

Hyaline cartilage

Week 9

Bone collar

Primaryossificationcenter

Figure 6.9, step 2

Cartilage in the centerof the diaphysis calcifiesand then develops cavities.

2

Area of deterioratingcartilage matrix

Figure 6.9, step 3

The periosteal bud inavadesthe internal cavities andspongy bone begins to form.

3

Spongyboneformation

Bloodvessel ofperiostealbud

Month 3

Figure 6.9, step 4

The diaphysis elongates and a medullary cavity formsas ossification continues. Secondary ossification centersappear in the epiphyses in preparation for stage 5.

4

Epiphysealblood vessel Secondary

ossificationcenter

Medullarycavity

Birth

Figure 6.9, step 5

The epiphyses ossify. When completed, hyaline cartilageremains only in the epiphyseal plates and articular cartilages.5

Epiphyseal platecartilage

Articular cartilage

Childhood to adolescence

Spongy bone

Figure 6.9

Bone collarforms aroundhyaline cartilagemodel.

Cartilage in thecenter of thediaphysis calcifiesand then developscavities.

The periostealbud inavades theinternal cavitiesand spongy bonebegins to form.

The diaphysis elongatesand a medullary cavityforms as ossificationcontinues. Secondaryossification centers appearin the epiphyses inpreparation for stage 5.

The epiphysesossify. Whencompleted, hyalinecartilage remains onlyin the epiphysealplates and articularcartilages.

Hyalinecartilage

Area ofdeterioratingcartilage matrix

Epiphysealblood vessel

Spongyboneformation

Epiphysealplatecartilage

Secondaryossificationcenter

Bloodvessel ofperiostealbud

Medullarycavity

Articularcartilage

Childhood toadolescence

BirthWeek 9 Month 3

Spongybone

BonecollarPrimaryossificationcenter

1 2 3 4 5

Postnatal Bone Growth

Infancy Adolescence bones grow by:

• Interstitial growth:

• length of long bones

• Appositional growth:

• thickness and remodeling of all bones by osteoblasts and osteoclasts on bone surfaces

Growth in Length of Long Bones

• Epiphyseal plate cartilage organizes into four important functional zones:

• Proliferation (growth)

• Hypertrophic

• Calcification

• Ossification (osteogenic)

Figure 6.10

Calcified cartilagespicule

Osseous tissue(bone) coveringcartilage spicules

Resting zone

Osteoblast depositingbone matrix

Proliferation zoneCartilage cells undergo rapid Mitosis and push the epiphysis away from the diaphysis causing the bone to lengthen. Hypertrophic zoneOlder cartilage cells enlarge.

Ossification zoneNew bone formation is occurring.

Calcification zoneMatrix becomes calcified; cartilage cells die; matrix begins deteriorating.

1

2

3

4

Growth in Width (Thickness)

• Growing bones widen as they lengthen

•Bone thickening occurs through appositional growth

•Osteoblasts beneath the periosteum secrete bone matrix on the external surface of the bone

•Meanwhile, osteoclasts remove bone on the endosteal surface of the diaphysis to prevent the bone from becoming too heavy

Bones don’t begin as bones. What do they begin as?

Answer:

Cartilage

Check Point!!!

What membrane lines the internal canals and covers the trabeculae of a bone?

Answer:

Endosteum

Check Point!!!

Which component of bone – organic or inorganic – makes it hard?

Answer:

Inorganic

Check Point!!!

What name is given to a cell that acts to break down bone matrix?

Answer:

Osteoclasts

Check Point!!!

What name is given to a cell that acts to build up bone (secretes bone matrix)?

Answer:

Osteoblasts

Check Point!!!

Hormonal Regulation of Bone Growth

• Growth hormone (pituitary gland) stimulates epiphyseal plate activity

• Thyroid hormone modulates activity of growth hormones

• ensures that the skeleton has proper proportions as it grows

• Excesses or deficits can cause abnormal skeletal growth such as gigantism or dwarfism

• Testosterone and estrogens (at puberty)

• Promote adolescent growth spurts

• End growth by inducing epiphyseal plate closure ending longitudinal bone growth

Bone Deposit• Occurs where bone is injured or added

strength is needed

• Requires a diet rich in protein; vitamins C, D, and A; calcium; phosphorus; magnesium; and manganese

Bone Remodeling & Repair

Bone Deposit

• Sites of new matrix deposits by osteoblasts are apparent due to the presence of the

• Osteoid seam

• Unmineralized band of gauzy looking bone matrix

• Calcification front

• The abrupt transition zone between the osteoid seam and the older mineralized bone

Bone Resorption

• Osteoclasts move along a bone surface, digging grooves as they break down bone matrix

• Osteoclasts secrete

• Lysosomal enzymes (digest organic matrix)

• Acids (convert calcium salts into soluble forms)

• Dissolved matrix enters interstitial fluid and then blood

Control of Remodeling

• What controls continual remodeling of bone?

• Hormonal mechanisms that maintain calcium homeostasis in the blood

Primarily involve parathyroid hormone (PTH)

• Mechanical and gravitational forces acting on the skeleton

Hormonal Control of Blood Ca2+

• Calcium is necessary for

• Transmission of nerve impulses

• Muscle contraction

• Blood coagulation

• Secretion by glands and nerve cells

• Cell division

• Human body contains 1200-1400g of calcium more than 99% present in bone minerals

Hormonal Control of Blood Calcium

• Parathyroid Hormone (PTH) is released when blood levels of Calcium decline

• Increased levels of PTH trigger osteoclasts to resorb bone which releases calcium into the blood

• As blood concentrations of Calcium rise, the stimulus for PTH stops

Remember homeostasis?

What feedback mechanism is this?

Response to Mechanical Stress

• Wolff’s law: A bone grows or remodels in response to forces or demands placed upon it

• Observations supporting Wolff’s law:

• Handedness (right or left handed) results in bone of one upper limb being thicker and stronger

• Curved bones are thickest where they are most likely to buckle

• Trabeculae form along lines of stress

• Large, bony projections occur where heavy, active muscles attach

Classification of Bone Fractures • Bone fractures may be

classified by four “either/or” classifications:

1. Position of bone ends after fracture:

• Nondisplaced—ends retain normal position

• Displaced—ends out of normal alignment

2. Completeness of the break

• Complete—broken all the way through

• Incomplete—not broken all the way through

Classification of Bone Fractures

3. Orientation of the break to the long axis of the bone:

• Linear—parallel to long axis of the bone

• Transverse—perpendicular to long axis of the bone

4. Whether or not the bone ends penetrate the skin:

• Compound (open)—bone ends penetrate the skin

• Simple (closed)—bone ends do not penetrate the skin

Common Types of Fractures

• All fractures can be described in terms of

• Location

• External appearance

• Nature of the break

Table 6.2

Table 6.2

Table 6.2

Stages in the Healing of a Bone Fracture

1. Hematoma forms

• Torn blood vessels hemorrhage

• Clot (hematoma) forms

• Site becomes swollen, painful, and inflamed

Stages in the Healing of a Bone Fracture

2. Fibrocartilaginous callus forms

• Phagocytic cells clear debris

• Osteoblasts begin forming spongy bone within 1 week

• Fibroblasts secrete collagen fibers to connect bone ends

• Mass of repair tissue now called fibrocartilaginous callus

Stages in the Healing of a Bone Fracture

3. Bony callus formation

• New trabeculae form a bony (hard) callus

• Bony callus formation continues until firm union is formed in ~2 months

(how long do you wear a cast for?)

Stages in the Healing of a Bone Fracture

4. Bone remodeling

• In response to mechanical stressors over several months

• Final structure resembles original

Figure 6.15

Homeostatic Imbalances

• Osteomalacia and rickets

• Osteomalacia includes a number of disorders where bones are inadequately mineralized

• Osteoid is produced but calcium salts are not deposited bones soften and weaken

• Rickets (childhood disease) causes bowed legs and other bone deformities

• Because the ephyseal plates cannot be calcified, they continue to widen and the ends of long bones become enlarged and abnormally long

• Cause: vitamin D deficiency or insufficient dietary calcium

Homeostatic Imbalances• Osteoporosis

• Loss of bone mass—bone resorption outpaces deposit

• Bones become so fragile that something like a sneeze or stepping off a curb can cause them to break

• Spongy bone of spine and neck of femur become most susceptible to fracture

• Risk factors

• Lack of estrogen (smoking reduces estrogen levels), calcium or vitamin D; petite body form; immobility; low levels of TSH (thyroid); diabetes mellitus

Figure 6.16

Osteoporosis: Treatment and Prevention

• Calcium, vitamin D, and fluoride supplements

• Weight-bearing exercise throughout life

• Hormone (estrogen) replacement therapy (HRT) slows bone loss

• Some drugs (Fosamax, SERMs, statins) increase bone mineral density

Paget’s Disease

• Excessive and haphazard bone formation and breakdown, usually in spine, pelvis, femur, or skull

• Pagetic bone has very high ratio of spongy to compact bone and reduced mineralization

• Unknown cause (possibly viral)

• Treatment includes calcitonin and biphosphonates

Developmental Aspects of Bones

• Embryonic skeleton ossifies predictably so fetal age easily determined from X rays or sonograms

• At birth, most long bones are well ossified (except epiphyses)

Developmental Aspects of Bones• Nearly all bones completely ossified by age 25

• Bone mass decreases with age beginning in 4th decade

• Rate of loss determined by genetics and environmental factors

• In old age, bone resorption predominates

Let’s Practice!!!