肌肉骨骼系统 骨 骼. Content 骨骼大体解剖 骨组织学 骨组织新陈代谢 骨组织生物力学 骨折愈合.

肌肉骨骼系统

骨 骼

Content

骨骼大体解剖

骨组织学

骨组织新陈代谢

骨组织生物力学

骨折愈合

骨骼疾病

骨折愈合（不愈合）

骨坏死

骨折疏松

器械、生物材料，药物，细胞，因子

4

By age 25 the skeleton is completely hardened

206 bones make up the adult

skeleton (20% of body mass) 80 bones of the axial skeleton

126 bones of the appendicular skeleton

The actual number of bones in the human

skeleton varies from person to person

骨骼的大体解剖

Functions of Skeletal System

Provides support and framework for body

Protects delicate internal organs

Also provides attachment sites for organs such as skeletal muscles

Bones serve as mineral storage for Calcium and phosphorus

Bones are also the site of red blood cell formation in their marrow

Bone as a signalling centre

314 | NATURE | VOL 481 | 19 JANUARY 2012

Osteocalcin, a bone-derived multifunctional hormone

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should be familiar with

all major bones( 脊柱、

骨盆、四肢长骨）

SKELETON

Bone Shapes

• Long– Upper and lower limbs

• Short– Carpals （腕骨） and

tarsals （跗骨）• Flat

– Ribs, sternum （胸骨） , skull, scapulae （肩胛骨）

• Irregular– Vertebrae, facial

10

Divisions of the Skeleton

• Axial Skeleton• Skull • Spine • Rib cage

• Appendicular Skeleton• Upper limbs• Lower limbs• Shoulder girdle• Pelvic girdle

Hyoid

Cranium

Face

Clavicle

Scapula

Sternum

Ribs

Humerus

Ulna

Hipbone

Radius

Femur

Patella

Tibia

Fibula

Tarsals

Metatarsals

Phalanges

Phalanges

Skull

Vertebralcolumn

Vertebralcolumn

Sacrum

Coccyx

Carpals

Metacarpals

(a) (b)

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Coronal suture

Frontal bone

Sphenoid bone

Ethmoid boneLacrimal boneNasal bone

Zygomatic bone

Maxilla

Mental foramen

MandibleCoronoid process

Styloid process

Mandibular condyleMastoid process

External acoustic meatus Temporal processof zygomatic bone

Zygomatic processof temporal bone

Occipital boneTemporal bone

Parietal bone

Lambdoid suture

Squamous suture

Skull•cranium (brain case) and the facial bones

Infantile Skull

• Fontanels – fibrous membranes

Anterior fontanel

Posterior fontanel

Frontal bone

Frontal suture(metopic suture)

Sagittal suture

13

Vertebral Column

The vertebral column, or spinal column,

consists of many vertebrae separated

by cartilaginous intervertebral discs.

14

Vertebral Column

Cervical vertebrae (7)

Thoracic vertebrae (12)

Lumbar vertebrae (5)

Sacral (4-5 fused segments)

• Sacrum is fused bone

Coccygeal (3-4 fused segments)

• Coccyx is fused bone

(b)(a)

Cervicalcurvature

Thoraciccurvature

Lumbarcurvature

Lumbarvertebrae

Thoracicvertebrae

Cervicalvertebrae

Sacralcurvature

Vertebraprominens

Rib facet

Intervertebral

Intervertebralforamina

Sacrum

Coccyx

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Typical Vertebrae

Includes the following parts:• Vertebral body （椎体）• Pedicles （椎弓根）• Lamina （椎板）• Transverse processes （横突）•Spinous process （棘突）• Vertebral foramen （椎孔）• Facets （关节突）

Cervical Vertebrae Atlas – 1st; supports

head( 寰椎） Axis – 2nd; dens pivots

to turn head （枢椎） Transverse foramina

Bifid spinous

processes

Vertebral prominens

– useful landmark(b) (c)

(a)

Anterior

Posterior

Atlas

Axis

Body

Dens (odontoidprocess)

Spinous processDens

Inferior articularprocess

Facet that articulateswith dens (odontoid process)of axis

Facet that articulateswith occipital condyle

Spinousprocess

Anterior articularfacet for atlas

Transverseforamen

Transverseprocess

Superiorarticular facet

Vertebralforamen

Transverseprocess

Transverseforamen

Thoracic Vertebrae

BodySuperiorarticularprocess

Spinousprocess

Transverseprocess

Inferior articularprocess

Intervertebraldisc

Anterior

Posterior

Body

PedicleVertebral foramen

Superior articular process

Facet for tubercle of rib

Transverse processLamina

Spinous process

Inferior articularprocess

Intervertebral notchBody

Pedicle

SuperiorarticularprocessTransverseprocessFacet fortubercle of rib

Spinousprocess

(a)

(c)

(b)

• Long spinous processes• Rib facets

18

Lumbar Vertebrae

• Large bodies• Thick, short spinous processes

(c) Lumbar vertebra

Lamina

Pedicle

Body

Vertebral foramen

Spinous process

Superior articularprocess

Transverse process

Sacral canal

Tubercleof mediansacral crest

Auricularsurface

Posterior sacralforamenSacral hiatus

Coccyx

Sacrum

Superior articular process

Sacral promontory

Anterior sacralforamen

(a) (b)

Sacrum

• 4-5 fused segments• Median sacral crest• Posterior sacral foramina• Posterior wall of pelvic cavity• Sacral promontory aka base• Area toward coccyx is the apex

Coccyx• Aka tailbone

• 3-4 fused segments

Sacral canal

Tubercleof mediansacral crest

Auricularsurface

Posterior sacralforamenSacral hiatus

Coccyx

Sacrum

Superior articular processSacral promontory

Anterior sacralforamen

(a) (b)

21

Thoracic Cage

• The thoracic cage includes the ribs, the

thoracic vertebrae, the sternum, and the

costal cartilages that attach the ribs to the

sternum.

22

Thoracic Cage• Ribs (12)• Sternum• Thoracic vertebrae (12)• Costal cartilages• Supports shoulder girdleand upper limbs• Protects viscera• Role in breathing

1

2

3

4

5

6

7

8

9

1011

12

True ribs(vertebrosternalribs)

VertebrochondralribsFalse

ribs

(a)

Floating ribs(vertebral ribs)

SternumBody

Manubrium

Ribs

Costalcartilage

Xiphoid process

Thoracic vertebra

Clavicular notch

Sternal angle

Jugular notch(suprasternal notch)

(b)b: © Victor B. Eichler, PhD

Pectoral Girdle

• Also known as the shoulder girdle • Clavicles• Scapulae• Supports upper limbs• True shoulder joint is simply the articulation of the humerus and scapula

Sternum

CostalcartilageRibScapula

Humerus

Ulna

Radius

Clavicle

(a)

Coracoidprocess

Head ofhumerus

Acromionprocess

Acromial endSternal end

Upper Limb

Olecranonprocess

Head of radius

Neck of radiusUlna

Olecranonfossa

Carpals

Metacarpals

Phalanges

Humerus

Humerus

Ulna

Ulna

Radius

(c)

(d)(a) Hand (palm anterior) (b) Hand (palm posterior)

• Humerus• Radius• Ulna(Interosseous membrane)• Carpals• Metacarpals• Phalanges

Humerus

• Head• Greater tubercle• Lesser tubercle• Anatomical neck• Surgical neck• Deltoid tuberosity• Capitulum• Trochlea• Coronoid fossa• Olecranon fossa

CapitulumTrochlea

Deltoid tuberosity

Head

Lesser tubercle

Greater tubercle Greater tubercle

(a) (b)

Lateralepicondyle

Coronoidfossa

Intertuberculargroove

Medialepicondyle

Olecranonfossa

Anatomicalneck

Surgicalneck

Lateralepicondyle

26

Radius

• Lateral forearm bone• Head• Radial tuberosity• Styloid process

Styloid process Ulnar notch of radius

Styloid process

Head of ulna

Ulna

Radius

Radial tuberosity

Head of radius

Coronoid process

Trochlear notch Olecranonprocess

(b)

(a)

OlecranonprocessTrochlearnotch

CoronoidprocessRadialnotch

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27

Ulna

• Medial forearm bone• Trochlear notch• Olecranon process• Coronoid process• Styloid process

Styloid process Ulnar notch of radius

Styloid process

Head of ulna

Ulna

Radius

Radial tuberosity

Head of radius

Coronoid process

Trochlear notch Olecranonprocess

(b)

(a)

Olecranonprocess

Trochlearnotch

CoronoidprocessRadialnotch

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28

Pelvic Girdle

• Coxal Bones (2)• Supports trunk of body• Protects viscera• Forms pelvic cavity

Sacrum

Sacral promontory

Sacroiliac joint

Acetabulum

Pubis

Symphysispubis

(a)

Pubic arch

IschiumPubic tubercle

Ilium

Obturator foramen

Ischium

Coccyx

Sacral hiatus

Sacrum

(b)

Ilium

Sacral canal

Pubis

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(c)c: © Martin Rotker

Hip Bones• Also known as the coxae:

• Acetabulum • There are three (3) bones:

1. Ilium• Iliac crest• Iliac spines• Greater sciatic notch

2. Ischium• Ischial spines• Lesser sciatic notch• Ischial tuberosity

3. Pubis• Obturator foramen• Symphysis pubis• Pubic arch

Iliac crest

Iliac crestIliac fossa

IliumIlium

Ischium

IschiumPubis

Pubis

Ischial spineObturator foramen

Acetabulum

Pubic crest

Pubic tubercle

(b)(a)

Anteriorsuperioriliac spine

Anteriorinferioriliac spine

Posteriorsuperioriliac spine

Posteriorinferioriliac spine

Greatersciatic notch

Lessersciatic notch

Ischialtuberosity

Obturatorforamen

30

Greater and Lesser Pelves• Greater Pelvis

• Lumbar vertebrae posteriorly• Iliac bones laterally• Abdominal wall anteriorly

• Lesser Pelvis• Sacrum and coccyx posteriorly• Lower ilium, ischium, and pubic bones laterally and anteriorly

Sacral promontory

Flared ilium

Pelvic brim

Symphysis pubis

Pubic arch

Pubic arch

(a) Female pelvis

(b) Male pelvis

Sacral promontory

Sacral curvature

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31

Differences Between Male Female Pelves

• Female pelvis• Iliac bones more flared• Broader hips• Pubic arch angle greater• More distance between ischial spines and ischial tuberosities• Sacral curvature shorter and flatter• Lighter bones

Sacral promontory

Flared ilium

Pelvic brim

Symphysis pubis

Pubic arch

Pubic arch

(a) Female pelvis

(b) Male pelvis

Sacral promontory

Sacral curvature

32

Lower Limb

• Femur

• Patella

• Tibia

• Fibula

• Tarsals

• Metatarsals

• Phalanges Metatarsals

Fibula

Tibia

Tibia

Patella

Femur

Fibula

(c) Lateral view

Fibula

Tibia

Lateralcondyle

(d) Posterior view

(b)

Medialcondyle

Femur

Tarsals

Phalanges

Femur

Patella

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Femur

• Longest bone of body• Head• Fovea capitis• Neck• Greater trochanter• Lesser trochanter• Linea aspera• Condyles• Epicondyles

Neck Head

Fovea capitis

(a) (b)

Lateralcondyle

Medialcondyle

Intercondylarfossa

Medialepicondyle

Patellarsurface

Lateralepicondyle

Greatertrochanter Gluteal

tuberosityLessertrochanter

Lineaaspera

34

Patella

• Aka kneecap• Anterior surface of the knee joint• Flat sesamoid bone located in the quadriceps tendon

Metatarsals

Fibula

Tibia

Tibia

Patella

Femur

Fibula

(c) Lateral view

Fibula

Tibia

Lateralcondyle

(d) Posterior view

(b)

Medialcondyle

Femur

T arsals

Phalanges

Femur

Patella

Tibia

• Aka shin bone• Medial to fibula• Condyles• Tibial tuberosity• Anterior crest• Makes the medial malleolus

Tibia

Fibula

Medialmalleolus

Tibialtuberosity

Anteriorcrest

Medialcondyle

Intercondylareminence

Lateralmalleolus

Lateralcondyle

Head offibula

Fibula

• Lateral to tibia• Long, slender• Head• Makes the lateral malleolus• Non-weight bearing

Tibia

Fibula

Medialmalleolus

Tibialtuberosity

Anteriorcrest

Medialcondyle

Intercondylareminence

Lateralmalleolus

Lateralcondyle

Head offibula

37

Foot• Tarsal Bones (14)

• Calcaneus• Talus• Navicular• Cuboid• Lateral (3rd) cuneiform• Intermediate (2nd) cuneiform• Medial (1st) cuneiform

• Metatarsal Bones (10)

• Phalanges (28)• Proximal• Middle• Distal

(b)

Tibia

Fibula

Talus

Navicular

Phalanges

Calcaneus

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Medialcuneiform

Metatarsals(metatarsus)

Tarsals(tarsus)

Calcanealtuberosity

骨骼的组织学

Long boneDiaphysis: long shaft of boneEpiphysis: ends of boneEpiphyseal plate: growth plateMetaphysis: b/w epiphysis and diaphysisArticular cartilage: covers epiphysisPeriosteum: bone covering (pain sensitive)Sharpey’s fibers: periosteum attaches to underlying

boneMedullary cavity: Hollow chamber in bone

- red marrow produces blood cells- yellow marrow is adipose.

Endosteum: thin layer lining the medullary cavity

Periosteum(review)

Periosteum: double-layered membrane on external surface of bones

Inner layer:osteogenic stem cells that differentiate (specialize) into bone cells like osteoblasts (bone

forming) or osteoclasts (bone

dissolving) cells.

Outer layer: protective, fibrous dense irregular connective tissue

Histology of bone tissueCells are surrounded by matrix.

- 25% water- 25% protein- 50% mineral salts

Abundant inorganic mineral salts:

- Tricalcium phosphate in crystalline form -- hydroxyapatite Ca3(PO4)2(OH)2

-Calcium Carbonate: CaCO3

-Magnesium Hydroxide: Mg(OH)2

-Fluoride and Sulfate

These salts are deposited on the collagen fiber framework (tensile strength)

and crystallization occurs.- calcification or mineralization

Bone cellsOsteoclasts4 cell types make up osseous tissue

Osteoprogenitor cells

Osteoblasts

Osteocytes

The different stages of osteoblast lineage cell differentiation

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Developmental signals regulating key steps of osteoblast differentiation

28 | JANUARY 2012 | VOLUME 13 nature

The different stages of osteoclast lineage cell differentiation

NATURE | VOL 423 | 15 MAY 2003

6-47

Bone Matrix

Structure of Bone Tissue• Compact bone

– Hard, densely calcified “typical bone”– Living tissue with blood supply, nerves– Organized of osteons

Structure of Bone Tissue

• Compact bone– Osteon（骨单元）

• Central (Haversian) canal at center

• Osteocytes in lacunae surrounding Haversian canal

• Lamellae of bone matrix between rings of osteocytes

6-51

Cancellous Bone

• Consists of trabeculae– Oriented along lines of

stress

Structure of Spongy Bone

• Spongy bone– Trabeculae （小

梁）• Irregular thin plates

& struts of hydroxyapatite with osteocytes

– Spaces between filled with marrow (yellow or red)

Compact vs. spongy bone

Compact bone– External layer– Arranged in osteons– Lamellae are found

around periphery and between osteons

– Central canals connected to each other by perforating canals

Spongy bone– No osteons– Arranged in trabeculae– Major type of tisse in

short, flat, irregular bones

– Much lighter than compact bone

– Supports red bone marrow

骨骼的发育

Formation of Bone: Ossification

Two mechanisms– Intramembranous

ossification– Endochondral

ossificationNo difference in

final result.

55

Endochondral ossificationPerichondrium becomes periosteumMesenchyme cells become osteoblasts

Form primary ossification centerCartilage under bone collar calcifies & dies

57

Endochondral ossificationInvasion of nutrient blood vessel,Continued deterioration of cartilage,Formation of spongy bone

58

Endochondral ossificationPrimary ossification

center grows, elongates,

Formation of marrow cavity,

Formation of secondary ossification centers at ends,

Ossification of epiphyses.

Growth in Bone Length

• Appositional growth– New bone on old bone

or cartilage surface

• Epiphyseal plate zones– Resting cartilage– Proliferation– Hypertrophy– Calcification

Physiology of bone growth:- epiphyseal plate (bone length)

- 4 zones of bone growth under hGH.1- Zone of resting cartilage:

- no bone growth- located near the epiphyseal plate- scattered chondrocytes- anchors plate to bone

2- Zone of proliferating cartilage- chondrocytes stacked like coins- chondrocytes divide

3- Zone of hypertrophic (maturing) cartilage- large chondrocytes arranged in columns- lengthwise expansion of epiphyseal plate

4- Zone of calcified cartilage- few cell layers thick- occupied by osteoblasts and osteoclasts and capillaries from the diaphysis- cells lay down bone- dead chondrocytes surrounded by a calcified matrix.

Extracellular signals regulating growth plate development

on August 28, 2013 - Published by Cold Spring Harbor Laboratory

Age 18-21: Longitudinal bone growth ends when epiphysis fuses with the diaphysis.

- epiphyseal plate closure- epiphyseal line is remnant of this- last bone to stop growing: clavicle

65

Intramembranous ossification

Begins in embryonic mesenchyme membranes

Mesenchyme cells become osteoblasts

Begin laying down matrix (osteoid)

66

Intramembranous ossification

Layer of “woven bone” and periosteum

Remodeling to form compact bone on surfaces

Cranial & facial bones, mandible, clavicles.

Growth in Bone Width

Osteoclast and osteoblast lineage cells

28 | JANUARY 2012 | VOLUME 13 nature

骨骼的维持

Bone Remodeling

Wolff’s Law

bone is laid down where needed and resorbed where not needed

shape of bone reflects its function tennis arm of pro tennis players have cortical

thicknesses 35% greater than contralateral arm (Keller & Spengler, 1989)

osteoclasts resorb or take-up boneosteoblasts lay down new bone

Bone is Dynamic!Bone is constantly remodeling and recycling

Coupled process between:Bone deposition (by osteoblasts)Bone destruction/resorption (by osteoclasts)

5-7% of bone mass recycled weekly All spongy bone replaced every 3-4 years. All compact bone replaced every 10 years.

Prevents mineral salts from crystallizing; protecting against brittle bones and fractures

Bone Resorption

Osteoclasts are related to macrophages:

secrete lysosomal enzymes and HCl acid

Move along surface of bone, dissolving grooves into

bone with acid and enzymes

Dissolved material passed through osteoclasts and

into bloodstream for reuse by the body

Bone Remodeling Sequence

Activation

Resorption

Reversal

Quiescence

Formation & Mineralization

Osteocytes

Age, Bone Mass and Gender

From: Biomechanics of Musculoskeletal Injury, Whiting and Zernicke

Bon

e M

ass

(g o

f C

a)

1000 5025 75

500

1000

Age (yr)

Effects of Aging on Skeletal System

• Bone Matrix decreases • Bone Mass decreases• Increased bone fractures• Bone loss causes deformity, loss of height,

pain, stiffness– Stooped posture– Loss of teeth

Changes in Bone Over TimeOlder Adults

• 30 yrs males and 40 yrs females– BMD peaks (Frost, 1985; Oyster et al., 1984)

– decrease BMD, diameter and mineralization after this

• activity slows aging process

Osteoporosis

HormonalFactors

NutritionalFactors

PhysicalActivity

OsteopeniaReduced BMDslightly elevated risk of fracture

Severe BMD reductionvery high risk offracture(hip, wrist, spine, ribs)

28 million Americans affected – 80% of these are women10 million suffer from osteoporosis18 million have low bone mass

Osteoporosis

• age– women lose 0.5-1% of their bone mass

each year until age 50 or menopause– after menopause rate of bone loss

increases (as high as 6.5%)

Hormonal control of bone resorption

Hormonal control of bone resorption

NATURE | VOL 423 | 15 MAY 2003

Hormonal control of bone resorption

NATURE | VOL 423 | 15 MAY 2003

骨骼的生物力学

Organic Components(e.g. collagen)

Inorganic Components(e.g., calcium and phosphate)

65-70%(dry wt) H2O

(25-30%)

one of the body’s hardest structures

Viscoelastic 粘弹性

Ductile 延展性

Brittle 易脆性

Biomechanical Characteristics of Bone - Bone Tissue

25-30%(dry wt)

Compression Tension Shear Torsion Bending

Mechanical Loading of Bone

Tensile Loading

Main source of tensile load is muscle

tension can stimulate tissue growth

fracture due to tensile loading is usually an avulsion 撕裂other injuries include sprains, strains, inflammation, bony deposits

when the tibial tuberosity experiences excessive loads from quadriceps muscle group develop condition known as Osgood-Schlatter’s disease

Vertebral fracturescervical fracturesspine loaded through heade.g., football, diving, gymnastics

once “spearing” was outlawed in football the number of cervical injuries declined dramatically

lumbar fracturesweight lifters, linemen, or gymnastsspine is loaded in hyperlordotic(aka swayback) position

Compressive Loading

Shear Forces

created by the application of compressive, tensile or a combination of these loads

Usually a 3- or 4-pointforce application

Bending Forces

Torsional ForcesCaused by a twistingtwisting forceproduces shear, tensile, and compressive loads

tensile and compressive loads areat an angle

often see a spiral fracture developfrom this load

Bone geometry

d= 2.0

d = 2.5

I II

III

Exam I Exam II Exam IIIPeriostial 2 2 2.5Endosteal 0.5 0 2Bone area 2.95 3.14 1.77Area I 0.78 0.79 1.13Force 20 20 20Stress 256 253 221

Increase in stiffness without adding mass

Why not solid bones?

Material Properties Comparison

MaterialMaterial Compressive Compressive Strength (MPa)Strength (MPa)

Modulus Modulus (GPa)(GPa)

Cortical Cortical 10-16010-160 4-274-27

TrabelcularTrabelcular 7-1807-180 1-111-11

ConcreteConcrete ~ 4~ 4 3030

SteelSteel 400-1500400-1500 200200

WoodWood 100100 1313

elasticregion

plastic region

fracture/failure

Str

ess

(Loa

d)

Strain (Deformation)

stress

strain

Elastic & Plastic responses

•elastic thru 3%deformation

•plastic response leads to fracturing

•Strength defined by failure point

•Stiffness defined as the slope of the elastic portion of the curve

Elastic Biomaterials (Bone)

•Elastic/Plastic characteristics

Brittle material fails before permanent deformation

Ductile material deforms greatly before failure

Bone exhibits both properties

Load/deformation curves

deformation (length)

load ductile material

elasticlimit

bone

brittle material

Fatigue of BoneMicrostructural damage due to repeated loads

below the bone’s ultimate strength – Occurs when muscles become fatigued and less able to

counter-act loads during continuous strenuous physical activity

– Results in Progressive loss of strength and stiffness

Cracks begin at discontinuities within the bone (e.g. haversian canals, lacunae) – Affected by the magnitude of the load, number of cycles,

and frequency of loading

Fatigue of Bone (Cont’)• 3 Stages of fatigue fracture

– Crack Initiation• Discontinuities result in points of increased local stress where

micro cracks form – Often bone remodeling repairs these cracks

– Crack Growth (Propagation)• If micro cracks are not repaired they grow until they encounter a

weaker material surface and change direction– Often transverse growth is stopped when the crack turns from

perpendicular to parallel to the load

– Final Fracture• Occurs only when the fatigue process progresses faster than

the rate of remodeling

http://www.orthoteers.co.uk/Nrujp~ij33lm/Orthbonemech.htm Simon, SR. Simon, SR. Orthopaedic Basic ScienceOrthopaedic Basic Science. Ohio: American Academy of Orthopaedic Surgeons; 1994.. Ohio: American Academy of Orthopaedic Surgeons; 1994.

Fatigue Fracture

A fatigue fracture may be caused by:– Abnormal muscle stress

• Loss of shock absorption• Strenuous or repeated activity

– Associated with new or different activity• Abnormal loading• Abnormal stress distribution

Fatigue Theory– During repeated efforts (as in running)

• Muscles become unable to support during impact

• Muscles do not absorb the shock

• Load is transferred to the bone

• As the loading surpasses the capacity of the bone to adapt

• A fracture develops

骨折愈合

• Fractures: Any bone break.- blood clot will form around break

- fracture hematoma- inflammatory process begins- blood capillaries grow into clot- phagocytes and osteoclasts remove damaged tissue- procallus forms and is invaded by osteoprogenitor cells and fibroblasts- collagen and fibrocartilage turns procallus to fibrocartilagenous (soft) callus

- broken ends of bone are bridged by callus- Osteoprogenitor cells are replaced by osteoblasts and spongy

bone is formed- bony (hard) callus is formed- callus is resorbed by osteoclasts and compact bone replaces

spongy bone.Remodeling : the shaft is reconstructed to resemble original unbroken bone.

6-101

Bone Repair

Fractures MUST have ablood supply to heal

Bone blood supply

• Endosteal– Inner 2/3rds

• Periosteal– Outer 1/3rd

• Disrupted by a fracture• Further damaged by

surgery

Bone blood supply Plates

• Damage periosteal blood supply

• Causes underlying necrosis

Bone blood supply - plates

• Can be reduced by– LCDCP– Locking plate

Augmentation of fracture healing

Bone GraftsBone Graft SubstitutesOsteo-inductive agentsMechanical methodsUltrasoundElectromagnetic fields

Bone Graft PropertiesOsteoconduction

3D scaffoldOsteo-induction

Biological stimulusOsteogenic

Contains living cells that can differentiate to from bone

Mesenchymal cells Osteoprogenitor cells

Structural

Osteo-inductive agents

• Transforming growth factor Superfamily– BMPs– GDFs (growth differentiation factors)– Possibly TGF-β 1, 2, and 3.

Demineralized bone matrix

• Acid extraction of allograft– type-1 collagen– non-collagenous proteins– osteoinductive growth factors: BMP, GDFs, TGF1,2 + 3

Different companies , processing differentALLOGRAFT, no reported infection transmission

BMP 7 (OP-1)

• Tibial non-unions– RCT OP1 v autogenous graft– No difference in union rate– Less infections – Friedlaender et al J Bone Joint Surg Am. 2001;83 Suppl

1(Pt 2):S151-8.

• Open Tibia– OP1 v control– Less secondary interventions– McKee et al Proceedings of the 18th Annual Meeting of

the Orthopaedic Trauma Association; 2002 Oct 11-13

• OP 1• 653 cases, overall

success rate 82%

Injury, Int. J. Care Injured (2005) 36S, S47—S50

• BMP £ 3000 per vial• Mean number of operations

• Pre BMP 4.16• Post BMP 1.2

• Hospital stay and cost• Pre BMP 26.84 days and £ 13,844.68• Post BMP 7.8 days and £ 7338.40

• Overall cost using BMP-7 - 47.0% less.

Injury, Int. J. Care Injured (2007) 38, 371—377

BMP 2

• BESTT• Open tibial fractures

– Control v 6mg v 12mg– Higher dose

• Fewer secondary procedures• accelerated time to union• improved wound-healing• Reduced infection rateGovender et al Recombinant human bone morphogenetic protein-2 for

treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am. 2002;84:2123-34.

Osteoconductive

Making the break. Karin Hing's fellowship has brought independence to pursue her work on bone graft substitutes.

Osteoconductive RCT’s osteoconductive materials Vs autograft

encouraging.– Calcium sulfate

• Predictable resorption• Resorbs a little too fast

– Calcium phosphates • Tricalcium phosphate TCP• Hydroxyapatite• TCP is more rapidly absorbed than hydroxyapatite, TCP

inadequate when structural support is desired

– Injectable osteoconductive cements• Several variations

Concentrated bone marrow aspirate

• Non union – 75-95% success• Aseptic non-unions

– Only works if adequate cell concentration

– Hernigou Pet al Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am. 2005;87:1430 -7

• Concentrated BM aspirate– Ongoing multicentre RCT in France– Open tibial fractures

Composite synthetic graft

• Prospective multicenter RCT• 249 long-bone #, min two years FU• Bone graft v biphasic calcium phosphate mixed with bovine

collagen + autogenous bone marrow

• No sig. diff.– More infections with bone graft (22 v 9 p=0.008)

• Chapman MW et al. Treatment of acute fractures with a collagen-calcium phosphate graft material. A randomized clinical trial. J Bone Joint Surg Am. 1997;79:495-502.

Mechanical

Controlled axial micromotionCompressionDistractionLIPUSElectromagnetic

Controlled axial micromotion

• Prospective RCT 102 tibial fractures– 1.0 mm at 0.5 Hz /30 minutes per day

• Sig. reduction– Time to union– Secondary surgery

• Kenwright J, Goodship AE. Controlled mechanical stimulation in the treatment of tibial fractures. Clin Orthop 1988;241:36-47.

Low Intensity Ultrasound

• Several RCTs• Reduced time to union

– Non-op tibia (No benefit in nailed #)

– Scaphoids– Impacted distal radius– Jones

• May reduce time to healing• JW Busse et al. The effect of low-intensity pulsed ultrasound therapy on time

to fracture healing: a meta-analysis. Canadian Medical Association Journal 2002 166: 437-441

Sonic Accelerated Fracture Healing

System (SAFHS®) -Exogen 2000®

• Acute fractures with ultrasound• Inconsistency in evidence ? Type II failure• Available evidence supports the use of ultrasound in the

treatment of acute fractures of tibia and radius treated with plaster immobilization. (non op)

• No benefit of LIPUS in the treatment of fractures of the tibia managed with intramedullary fixation.

J Trauma. 2008 Dec;65(6):1446-52

• Current evidence on the efficacy of low-intensity pulsed ultrasound to promote fracture healing is adequate to show that this procedure can reduce fracture healing time and gives clinical benefit, particularly in circumstances of delayed healing and fracture non-union.

• There are no major safety concerns. • Therefore this procedure may be used with normal

arrangements for clinical governance, consent and audit

Electromagnetic devices

• In vivo– Osteoblasts BMP,TGFs, IGF

• Small RCT– 66% vs 0 healing of tibial non-unionScott G, King JB. A prospective double blind trial of electrical capacitive coupling in

the treatment of nonunion of long bones. J Bone Joint Surg [Am] 1994;76-A:820-6.

• Several series– 64-87% union of tibial non-union

术后 3 周术前

自体自体 PRPPRP 浓集治疗骨折不愈合临床研究浓集治疗骨折不愈合临床研究

浙江省男排主力（二传）戴 ** ， 男， 20 岁 骨折不愈合 11 月余

浙大案例浙大案例

骨髓干细胞治疗骨髓干细胞治疗

治疗前治疗前 治疗两年后治疗两年后

两年后股骨头坏死区体积比较。骨髓干细胞移植治疗组（实线），对照组（虚线）

骨髓干细胞治疗骨髓干细胞治疗

PRP 联合生物材料治疗• Wei 等进行了一项长达 7 年的 PRP 联合异体骨移植治疗跟骨关节内骨折移位

临床试验。

• 将 254 例患者随机分成自体骨移植组、 PRP 联合异体骨移植组和异体骨移植组，通过影像学、三维立体扫描断层技术和足踝功能评分评估治疗结果，发现在 12 个月， 24 个月和 72 个月时 PRP 联合异体骨移植组和自体骨移植组明显优于单纯异体骨移植组，显示 PRP 对跟骨关节内骨折移位治疗有促进作用。

术前 术后 12 月

国际现状国际现状 ------ 《《 20092009 年 世界再生医学调查报年 世界再生医学调查报告告》》

2008-2009 年 已进入临床实验期的组织工程和再生医学产品

国际上 2008-2009 已市场化的组织工程和再生医学产品

产业化产业化较成熟较成熟

更新活跃更新活跃

目标组织

关节软骨 皮肤 骨 牙科 眼科 美容 其他 总

计产品

数 15 28 34 11 4 1 4 97

目标组织

关节软骨 骨

皮肤伤口愈合

心血管

糖尿病

肝脏

中枢神经系统

总计

产品数 12

17

27 41 4 3 1105

我国组织工程和再生医学技术的开发和临床转化我国组织工程和再生医学技术的开发和临床转化明显严重滞后！！！明显严重滞后！！！

我国组织工程和再生医学技术的开发和临床转化我国组织工程和再生医学技术的开发和临床转化明显严重滞后！！！明显严重滞后！！！

知识要点 能够描述脊柱组成，胸廓组成，骨盆组成

能够绘画肱骨，尺骨，桡骨，股骨，胫骨大体结构

能够描述骨的细胞和组织成分

能够绘画骨单位结构

能够描述骨组织发育主要阶段

能够描述 osteoblast 和 osteoclast 的分化阶段

能够描述骨组织的主要生物力学特性

能够描述骨愈合主要过程

能够描述骨质疏松疾病中相应“骨的宏观 / 微观结构 - 力学性能 -

osteoblast/osteoclast- 主要信号通路”每一层面的改变和相互联系，并能思考针对每一个层面改变可能采取的干预措施。

谢 谢！