Lecture 6: Osseous Tissue and Bone Structure

Topics:

Skeletal cartilage Structure and function of bone tissues Types of bone cells Structures of the two main bone tissues Bone membranes Bone formation Minerals, recycling, and remodeling Hormones and nutrition Fracture repair The effects of aging

The Skeletal System

Skeletal system includes:bones of the skeletoncartilages, ligaments, and connective tissues

Skeletal Cartilage

Contains no blood vessels or nerves Surrounded by the perichondrium (dense

irregular connective tissue) that resists outward expansion

Three types – hyaline, elastic, and fibrocartilage

Hyaline Cartilage

Provides support, flexibility, and resilience Is the most abundant skeletal cartilage Is present in these cartilages:

Articular – covers the ends of long bonesCostal – connects the ribs to the sternumRespiratory – makes up larynx, reinforces air

passagesNasal – supports the nose

Elastic Cartilage

Similar to hyaline cartilage, but contains elastic fibers

Found in the external ear and the epiglottis

Fibrocartilage

Highly compressed with great tensile strength

Contains collagen fibers Found in menisci of the knee and in

intervertebral discs

Growth of Cartilage

Appositional – cells in the perichondrium secrete matrix against the external face of existing cartilage

Interstitial – lacunae-bound chondrocytes inside the cartilage divide and secrete new matrix, expanding the cartilage from within

Calcification of cartilage occursDuring normal bone growthDuring old age

Bones and Cartilages of the Human Body

Figure 6.1

Functions of the Skeletal System1. Support

2. Storage of minerals (calcium)

3. Storage of lipids (yellow marrow)

4. Blood cell production (red marrow)

5. Protection

6. Leverage (force of motion)

Bone (Osseous) Tissue

Supportive connective tissue Very dense Contains specialized cells Produces solid matrix of calcium salt

deposits and collagen fibers

Characteristics of Bone Tissue

Dense matrix, containing:deposits of calcium saltsosteocytes within lacunae organized around

blood vessels Canaliculi:

form pathways for blood vesselsexchange nutrients and wastes

Osteocyte and canaliculi

Characteristics of Bone Tissue

Periosteum: covers outer surfaces of bones consist of outer fibrous and inner cellular

layersContains osteblasts responsible for bone

growth in thickness Endosteum

Covers inner surfaces of bones

Bone Matrix

Solid ground is made of mineral crystals 2/3 of bone matrix is calcium phosphate,

Ca3(PO4)2:reacts with calcium hydroxide, Ca(OH)2 to

form crystals of hydroxyapatite, Ca10(PO4)6(OH)2 which incorporates other calcium salts and ions

Bone Matrix

Matrix Proteins:1/3 of bone matrix is protein fibers (collagen)

Question: why aren’t bones made of ALL collagen if it’s so strong?

Bone Matrix

Mineral salts make bone rigid and compression resistant but would be prone to shattering

Collagen fibers add extra tensile strength but mostly add tortional flexibility to resist shattering

Chemical Composition of Bone: Organic Cells:

Osteoblasts – bone-forming cellsOsteocytes – mature bone cellsOsteoprogenitor cells – grandfather cellsOsteoclasts – large cells that resorb or break

down bone matrix Osteoid – unmineralized bone matrix

composed of proteoglycans, glycoproteins, and collagen; becomes calcified later

There are four major types of cells

in matrix only

endosteum only

periosteum + endo

1. Osteoblasts

Immature bone cells that secrete matrix compounds (osteogenesis)

Eventually become surrounded by calcified bone and then they become osteocytes

Figure 6–3 (2 of 4)

2.Osteocytes

Mature bone cells that maintain the bone matrix

Figure 6–3 (1 of 4)

Osteocytes

Live in lacunae Found between layers (lamellae) of matrix Connected by cytoplasmic extensions through

canaliculi in lamellae (gap junctions) Do not divide (remember G0?) Maintain protein and mineral content of matrix Help repair damaged bone

3. Osteoprogenitor Cells Mesenchyme

stem cells that divide to produce osteoblasts

Are located in inner, cellular layer of periosteum

Assist in fracture repair

4. Osteoclasts

Secrete acids and protein-digesting enzymes

Figure 6–3 (4 of 4)

Osteoclasts

Giant, mutlinucleate cells Dissolve bone matrix and release stored

minerals (osteolysis) Often found lining in endosteum lining the

marrow cavity Are derived from stem cells that produce

macrophages

Homeostasis

Bone building (by osteocytes and -blasts) and bone recycling (by osteoclasts) must balance:more breakdown than building, bones become

weakexercise causes osteocytes to build bone

Bone cell lineage summary

Osteoprogenitor cells

osteoblasts

osteocytes

Osteoclasts are related to macrophages (blood cell derived)

Gross Anatomy of Bones: Bone Textures Compact bone – dense outer layer Spongy bone – honeycomb of trabeculae

filled with yellow bone marrow

Compact Bone

Figure 6–5

Osteon

The basic structural unit of mature compact bone

Osteon = Osteocytes arranged in concentric lamellae around a central canal containing blood vesselsLamella – weight-bearing, column-like matrix

tubes composed mainly of collagen

Three Lamellae Types

Concentric Lamellae Circumferential Lamellae

Lamellae wrapped around the long bone line tree rings

Binds inner osteons together Interstitial Lamellae

Found between the osteons made up of concentric lamella

They are remnants of old osteons that have been partially digested and remodeled by osteoclast/osteoblast activity

Compact Bone

Figure 6–5

Microscopic Structure of Bone: Compact Bone

Figure 6.6a, b

Microscopic Structure of Bone: Compact Bone

Figure 6.6a

Microscopic Structure of Bone: Compact Bone

Figure 6.6b

Microscopic Structure of Bone: Compact Bone

Figure 6.6c

Spongy Bone

Figure 6–6

Spongy Bone Tissue

Makes up most of the bone tissue in short, flat, and irregularly shaped bones, and the head (epiphysis) of long bones; also found in the narrow rim around the marrow cavity of the diaphysis of long bone

Spongy Bone

Does not have osteons The matrix forms an open network of

trabeculae Trabeculae have no blood vessels

Bone Marrow

The space between trabeculae is filled with marrow which is highly vascular Red bone marrow

supplies nutrients to osteocytes in trabeculae forms red and white blood cells

Yellow bone marrow yellow because it stores fat

Question: Newborns have only red marrow. Red changes into yellow marrow in some bones as we age. Why?

Location of Hematopoietic Tissue (Red Marrow)

In infantsFound in the medullary cavity and all areas of

spongy bone In adults

Found in the diploë of flat bones, and the head of the femur and humerus

Bone Membranes Periosteum – double-layered protective

membrane Covers all bones, except parts enclosed in joint

capsules (continuois w/ synovium) Made up of:

outer, fibrous layer (tissue?) inner, cellular layer (osteogenic layer) is composed of

osteoblasts and osteoclasts

Secured to underlying bone by Sharpey’s fibers

Endosteum – delicate membrane covering internal surfaces of bone

Sharpy’s (Perforating) Fibers

Collagen fibers of the outer fibrous layer of periosteum, connect with collagen fibers in bone

Also connect with fibers of joint capsules, attached tendons, and ligaments

Tendons are “sewn” into bone via periosteum

Periosteum

Figure 6–8a

Functions of Periosteum

1. Isolate bone from surrounding tissues

2. Provide a route for circulatory and nervous supply

3. Participate in bone growth and repair

Endosteum

Figure 6–8b

Endosteum

An incomplete cellular layer: lines the marrow cavitycovers trabeculae of spongy bone lines central canals

Contains osteoblasts, osteoprogenitor cells, and osteoclasts

Is active in bone growth and repair

Bone Development

Human bones grow until about age 25 Osteogenesis:

bone formation

Ossification: the process of replacing other tissues with bone

Osteogenesis and ossification lead to: The formation of the bony skeleton in embryos Bone growth until early adulthood Bone thickness, remodeling, and repair through life

Calcification

The process of depositing calcium salts Occurs during bone ossification and in

other tissues

Formation of the Bony Skeleton

Begins at week 8 of embryo development Ossification

Intramembranous ossification – bone develops from a fibrous membrane

Endochondral ossification – bone forms by replacing hyaline cartilage

Intramembranous OssificationNote: you don’t have to know the steps of this process in detail Also called dermal ossification (because it

occurs in the dermis)produces dermal bones such as mandible and

clavicle Formation of most of the flat bones of the

skull and the clavicles Fibrous connective tissue membranes are

formed by mesenchymal cells

The Birth of Bone

When new bone is born, either during development or regeneration, it often starts out as spongy bone (even if it will later be remodeled into compact bone)

Endochondral OssificationNote: you DO have to know this one Begins in the second month of development Uses hyaline cartilage “bones” as models for

bone construction then ossifies cartilage into bone

Common, as most bones originate as hyaline cartilage

This is like a “trick” the body uses to allow long bones to grow in length when bones can only grow by appositional growth

Bone formation in a chick embryo

Stained to represent hardened bone (red) and cartilage (blue)

: This image is the cover illustration from The Atlas of Chick Development by Ruth Bellairs and Mark Osmond, published by Academic Press (New York) in 1998

Fetal Primary Ossification Centers

Figure 6.15

Stages of Endochondral Ossification Bone models form out of hyaline cartilage Formation of bone collar Cavitation of the hyaline cartilage Invasion of internal cavities by the periosteal

bud, and spongy bone formation Formation of the medullary cavity; appearance

of secondary ossification centers in the epiphyses

Ossification of the epiphyses, with hyaline cartilage remaining only in the epiphyseal plates

Stages of Endochondral Ossification

Figure 6.8

Formation ofbone collararound hyalinecartilage model.

Hyalinecartilage

Cavitation ofthe hyaline carti-lage within thecartilage model.

Invasion ofinternal cavitiesby the periostealbud and spongybone formation.

Formation of themedullary cavity asossification continues;appearance of sec-ondary ossificationcenters in the epiphy-ses in preparationfor stage 5.

Ossification of theepiphyses; whencompleted, hyalinecartilage remains onlyin the epiphyseal platesand articular cartilages.

Deterioratingcartilagematrix

Epiphysealblood vessel

Spongyboneformation

Epiphysealplatecartilage

Secondaryossificatoncenter

Bloodvessel ofperiostealbud

Medullarycavity

Articularcartilage

Spongybone

Primaryossificationcenter

Bone collar

1

2

34

5

Endochondral Ossification: Step 1 (Bone Collar) Blood vessels grow

around the edges of the cartilage

Cells in the perichondrium change to osteoblasts: producing a layer of

superficial bone (bone collar) around the shaft which will continue to grow and become compact bone (appositional growth) Figure 6–9 (Step 2)

Endochondral Ossification: Step 2 (Cavitation)

Chondrocytes in the center of the hyaline cartilage of each bone model:enlarge form struts and calcifydie, leaving cavities in cartilage

Figure 6–9 (Step 1)

Endochondral Ossification: Step 3 (Invasion)

Periosteal bud brings blood vessels into the cartilage:bringing osteoblasts and

osteoclastsspongy bone develops at the

primary ossification center

Figure 6–9 (Step 3)

Endochondral Ossification: Step 4a (Remodelling)

Figure 6–9 (Step 4)

Remodeling creates a marrow (medullary) cavity:bone replaces cartilage at the

metaphysesDiaphysis elongates

Endochondral Ossification: Step 4b (2° Ossification)

Capillaries and osteoblasts enter the epiphyses:creating secondary

ossification centers (perinatal)

Figure 6–9 (Step 5)

Endochondral Ossification: Step 5 (Elongation)

Epiphyses fill with spongy bone but cartilage remains at two sites: ends of bones within the

joint cavity = articular cartilage

cartilage at the metaphysis = epiphyseal cartilage (plate)

Figure 6–9 (Step 6)

Postnatal Bone Growth

Growth in length of long bonesCartilage on the side of the epiphyseal plate

closest to the epiphysis is relatively inactiveCartilage abutting the shaft of the bone organizes

into a pattern that allows fast, efficient growth Cells of the epiphyseal plate proximal to the

resting cartilage form three functionally different zones: growth, transformation, and osteogenic

Functional Zones in Long Bone Growth Growth zone – cartilage cells undergo mitosis,

pushing the epiphysis away from the diaphysis Transformation zone – older cells enlarge, the

matrix becomes calcified, cartilage cells die, and the matrix begins to deteriorate

Osteogenic zone – new bone formation occurs

Growth in Length of Long Bone

Figure 6.9

Postnatal bone growth

Remember that bone growth can only occur from the outside (appositional growth). So this type of endochondral growth is a way for bones to grow from the inside and lengthen because it is the cartilage that is growing, not the bone

Key Concept

As epiphyseal cartilage grows through the division of chondrocytes it pushes the ends of the bone outward in length.

At the “inner” (shaft) side of the epiphyseal plate, recently born cartilage gets turned into bone, but as long as the cartilage divides and extends as fast or faster than it gets turned into bone, the bone will grow longer

Long Bone Growth and Remodeling Growth in length – cartilage continually

grows and is replaced by bone as shown Remodeling – bone is resorbed and added

by appositional growth as shown compact bone thickens and strengthens

long bones with layers of circumferential lamellae

Long Bone Growth and Remodeling

Figure 6.10

Appositional Growth

Epiphyseal Lines

When long bone stops growing, between the ages of 18 – 25: epiphyseal cartilage disappears epiphyseal plate closes visible on X-rays as an epiphyseal line

At this point, bone has replaced all the cartilage and the bone can no longer grow in length

Epiphyseal Lines

Figure 6–10

During infancy and childhood, epiphyseal plate activity is stimulated by growth hormone

During puberty, testosterone and estrogens: Initially promote adolescent growth spurtsCause masculinization and feminization of

specific parts of the skeletonLater induce epiphyseal plate closure, ending

long bone growth

Hormonal Regulation of Bone Growth During Youth

Remodeling

Remodeling continually recycles and renews bone matrix

Turnover rate varies within and between bones If deposition is greater than removal, bones get

stronger If removal is faster than replacement, bones get

weaker Remodeling units – adjacent osteoblasts and

osteoclasts deposit and resorb bone at periosteal and endosteal surfaces

Bone Deposition 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

Alkaline phosphatase is essential for mineralization of bone

Sites of new matrix deposition are revealed by the: Osteoid seam – unmineralized band of bone matrix Calcification front – abrupt transition zone between

the osteoid seam and the older mineralized bone

Effects of Exercise on Bone

Mineral recycling allows bones to adapt to stress

Heavily stressed bones become thicker and stronger

Response to Mechanical Stress

Wolff’s law – a bone grows or remodels in response to the forces or demands placed upon it

Observations supporting Wolff’s law include Long bones are thickest midway along the shaft

(where bending stress is greatest) 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

Response to Mechanical Stress

Figure 6.12

Bone Resorption

Accomplished by osteoclasts Resorption bays – grooves formed by

osteoclasts as they break down bone matrix Resorption involves osteoclast secretion of:

Lysosomal enzymes that digest organic matrix Acids that convert calcium salts into soluble forms

Dissolved matrix is transcytosed across the osteoclast cell where it is secreted into the interstitial fluid and then into the blood

Bone Degeneration

Bone degenerates quickly Up to 1/3 of bone mass can be lost in a

few weeks of inactivity

Minerals, vitamins, and nutrients

Rewired for bone growth A dietary source of calcium and phosphate

salts: plus small amounts of magnesium, fluoride,

iron, and manganese Protein, vitamins C, D, and A

Hormones for Bone Growth and Maintenance

Table 6–2

Calcitriol

The hormone calcitriol:synthesis requires vitamin D3 (cholecalciferol)

made in the kidneys (with help from the liver)helps absorb calcium and phosphorus from

digestive tract

The Skeleton as Calcium Reserve Bones store calcium and other minerals Calcium is the most abundant mineral in the

body Calcium ions in body fluids must be closely

regulated because: Calcium ions are vital to:

membranes neurons muscle cells, especially heart cells blood clotting

Calcium Regulation: Hormonal Control Homeostasis is maintained by calcitonin and

parathyroid hormone which control storage, absorption, and excretion

Rising blood Ca2+ levels trigger the thyroid to release calcitonin

Calcitonin stimulates calcium salt deposit in bone

Falling blood Ca2+ levels signal the parathyroid glands to release PTH

PTH signals osteoclasts to degrade bone matrix and release Ca2+ into the blood

Hormonal Control of Blood Ca

Figure 6.11

PTH;calcitoninsecreted

Calcitoninstimulatescalcium saltdepositin bone

Parathyroidglands releaseparathyroidhormone (PTH)

Thyroidgland

Thyroidgland

Parathyroidglands

Osteoclastsdegrade bonematrix and releaseCa2+ into blood

Falling bloodCa2+ levels

Rising bloodCa2+ levels

Calcium homeostasis of blood: 9–11 mg/100 ml

PTH

Imbalance

Imbalance

Calcitonin and Parathyroid Hormone Control Bones:

where calcium is stored Digestive tract:

where calcium is absorbed Kidneys:

where calcium is excreted

Parathyroid Hormone (PTH)

Produced by parathyroid glands in neck

Increases calcium ion levels by: stimulating osteoclasts increasing intestinal

absorption of calcium decreases calcium

excretion at kidneys

Secreted by cells in the thyroid gland

Decreases calcium ion levels by: inhibiting osteoclast

activity increasing calcium

excretion at kidneys Actually plays very

small role in adults

Calcitonin

Fractures

Fractures:cracks or breaks in bonescaused by physical stress

Fractures are repaired in 4 steps

Fracture Repair Step 1: Hematoma Hematoma formation

Torn blood vessels hemorrhage

A mass of clotted blood (hematoma) forms at the fracture site

Site becomes swollen, painful, and inflamed

Bone cells in the area die

Figure 6.13.1

Fracture Repair Step 2: Soft Callus Cells of the endosteum and

periosteum divide and migrate into fracture zone

Granulation tissue (soft callus) forms a few days after the fracture from fibroblasts and endothelium

Fibrocartilaginous callus forms to stabilize fracture external callus of hyaline

cartilage surrounds break internal callus of cartilage and

collagen develops in marrow cavity

Capillaries grow into the tissue and phagocytic cells begin cleaning debris

Figure 6.13.2

Stages in the Healing of a Bone Fracture The fibrocartilaginous callus forms when:

Osteoblasts and fibroblasts migrate to the fracture and begin reconstructing the bone

Fibroblasts secrete collagen fibers that connect broken bone ends

Osteoblasts begin forming spongy boneOsteoblasts furthest from capillaries secrete an

externally bulging cartilaginous matrix that later calcifies

Fracture Repair Step 3: Bony Callus Bony callus formation

New spongy bone trabeculae appear in the fibrocartilaginous callus

Fibrocartilaginous callus converts into a bony (hard) callus

Bone callus begins 3-4 weeks after injury, and continues until firm union is formed 2-3 months later

Figure 6.13.3

Fracture Repair Step 4: Remodeling Bone remodeling

Excess material on the bone shaft exterior and in the medullary canal is removed

Compact bone is laid down to reconstruct shaft walls

Remodeling for up to a year reduces bone callus may never go away completely

Usually heals stronger than surrounding bone

Figure 6.13.4

Clinical advances in bone repair Electrical stimulation of fracture site.

results in increased rapidity and completeness of bone healing electrical field may prevent  parathyroid hormone from activating

osteoclasts at the  fracture site thereby increasing formation of bone and minimizing breakdown of bone,

Ultrasound.  Daily treatment results in decreased healing time of  fracture by

about 25% to 35% in broken arms and shinbones. Stimulates cartilage cells to make bony callus.

Free vascular fibular graft technique. Uses pieces of fibula to replace bone or splint two broken ends

of a bone.  Fibula is a non-essential bone, meaning it does not play a role in bearing weight; however, it does help stabilize the ankle.

Bone substitutes. synthetic material or crushed bones from cadavers serve as

bone fillers (Can also use sea coral).  

Aging and Bones

Bones become thinner and weaker with age

Osteopenia begins between ages 30 and 40

Women lose 8% of bone mass per decade, men 3%

Osteoporosis

Severe bone loss which affects normal function Group of diseases in which bone reabsorption

outpaces bone deposit The epiphyses, vertebrae, and jaws are most

affected, resulting in fragile limbs, reduction in height, tooth loss

Occurs most often in postmenopausal women Bones become so fragile that sneezing or

stepping off a curb can cause fractures Over age 45, occurs in:

29% of women 18% of men

Notice what happens in osteoporosis

Osteoporosis: Treatment

Calcium and vitamin D supplements Increased weight-bearing exercise Hormone (estrogen) replacement therapy (HRT)

slows bone loss Natural progesterone cream prompts new bone

growth Statins increase bone mineral density PPIs may decrease density

Hormones and Bone Loss

Estrogens and androgens help maintain bone mass

Bone loss in women accelerates after menopause

Cancer and Bone Loss

Cancerous tissues release osteoclast-activating factor:stimulates osteoclastsproduces severe osteoporosis

Paget’s Disease

Characterized by excessive bone formation and breakdown

An excessively high ratio of spongy to compact bone is formed

Reduced mineralization causes spotty weakening of bone

Osteoclast activity wanes, but osteoblast activity continues to work

Developmental Aspects of Bones Mesoderm gives rise to embryonic

mesenchymal cells, which produce membranes and cartilages that form the embryonic skeleton

The embryonic skeleton ossifies in a predictable timetable that allows fetal age to be easily determined from sonograms

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

Developmental Aspects of Bones By age 25, nearly all bones are completely

ossified In old age, bone resorption predominates A single gene that codes for vitamin D

docking determines both the tendency to accumulate bone mass early in life, and the risk for osteoporosis later in life

SUMMARY

Skeletal cartilage Structure and function of bone tissues Types of bone cells Structures of compact bone and spongy bone Bone membranes, peri- and endosteum Ossification: intramembranous and endochondral Bone minerals, recycling, and remodeling Hormones and nutrition Fracture repair The effects of aging

Figure 6–16 (1 of 9)

The Major Types of Fractures

Simple (closed): bone end does not break the skin Compound (open): bone end breaks through the skin Nondisplaced – bone ends retain their normal position Displaced – bone ends are out of normal alignment Complete – bone is broken all the way through Incomplete – bone is not broken all the way through Linear – the fracture is parallel to the long axis of the

bone Transverse – the fracture is perpendicular to the long

axis of the bone Comminuted – bone fragments into three or more

pieces; common in the elderly

Types of fractures (just FYI)

More fractures