Lecture 6 - Bone.pdf

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 skeleton  cartilages, 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 bones  Costal – connects the ribs to the sternum  Respiratory – makes up larynx, reinforces air passages  Nasal – 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 occurs 

 During

normal bone growth  During old age

Bones and Cartilages of the Human Body

Figure 6.1

Functions of the Skeletal System 1. 2. 3. 4. 5. 6.

Support Storage of minerals (calcium) Storage of lipids (yellow marrow) Blood cell production (red marrow) Protection 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 salts  osteocytes within lacunae organized around blood vessels 

Canaliculi:  form

pathways for blood vessels  exchange nutrients and wastes

Osteocyte and canaliculi

Characteristics of Bone Tissue 

Periosteum:  covers

outer surfaces of bones  consist of outer fibrous and inner cellular layers  Contains 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 cells  Osteocytes – mature bone cells  Osteoprogenitor cells – grandfather cells  Osteoclasts – 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

periosteum + endo

endosteum only

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 weak  exercise 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 vessels 

 Lamella

– 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 infants  Found

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. 2.

3.

Isolate bone from surrounding tissues Provide a route for circulatory and nervous supply Participate in bone growth and repair

Endosteum

Figure 6–8b

Endosteum 

An incomplete cellular layer:  lines

the marrow cavity  covers 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 Ossification Note: 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 Ossification Note: 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 Secondary ossificaton center

Deteriorating cartilage matrix

Hyaline cartilage Primary ossification center

Spongy bone formation

Epiphyseal blood vessel

Medullary cavity

Articular cartilage Spongy bone

Epiphyseal plate cartilage

Bone collar

1 Formation of bone collar around hyaline cartilage model.

Blood vessel of periosteal bud 2 Cavitation of the hyaline cartilage within the cartilage model.

3 Invasion of internal cavities by the periosteal bud and spongy bone formation.

4 Formation of the medullary cavity as ossification continues; appearance of secondary ossification centers in the epiphyses in preparation for stage 5.

5 Ossification of the epiphyses; when completed, hyaline cartilage remains only in the epiphyseal plates and articular cartilages.

Figure 6.8

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 calcify  die, 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 osteoclasts  spongy bone develops at the primary ossification center

Figure 6–9 (Step 3)

Endochondral Ossification: Step 4a (Remodelling) 

Remodeling creates a marrow (medullary) cavity:  bone

replaces cartilage at the metaphyses  Diaphysis elongates

Figure 6–9 (Step 4)

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 bones  Cartilage

on the side of the epiphyseal plate closest to the epiphysis is relatively inactive  Cartilage 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

Hormonal Regulation of Bone Growth During Youth During infancy and childhood, epiphyseal plate activity is stimulated by growth hormone  During puberty, testosterone and estrogens: 

 Initially

promote adolescent growth spurts  Cause masculinization and feminization of specific parts of the skeleton  Later induce epiphyseal plate closure, ending long bone growth

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,  blood

clotting

especially heart cells

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

PTH; calcitonin secreted

Calcitonin stimulates calcium salt deposit in bone

Thyroid gland

Rising blood Ca2+ levels Calcium homeostasis of blood: 9–11 mg/100 ml Falling blood Ca2+ levels

Thyroid gland Osteoclasts degrade bone matrix and release Ca2+ into blood

Parathyroid glands

PTH

Parathyroid glands release parathyroid hormone (PTH)

Figure 6.11

Calcitonin and Parathyroid Hormone Control 

Bones:  where



Digestive tract:  where



calcium is stored 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 

Calcitonin  

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

Fractures 

Fractures:  cracks

or breaks in bones  caused 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 bone  Osteoblasts 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.  



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. 



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,

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 osteoclastactivating factor:  stimulates  produces

osteoclasts

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

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 Figure 6–16 (1 of 9)

Types of fractures (just FYI)

More fractures