1-20 final bone quality & induction of osteoporotic fractures

8/14/2019 1-20 Final Bone Quality & Induction of Osteoporotic Fractures

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Bone QualityInduction of Osteoporotic

Fractures

Prof. Dr. Hazem Abd El-Azeem

Professor of Orthopaedic

Surgery


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g y

Traditional (Old) Definition ofOsteoporosis

1.1. Pathological :Pathological : A disease characterized by low

bone mass leading to bonefragility and increased risk offractures.

1. Denstiometry

T-score -1= normal , -1:-2.5 =

osteopenia )


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SStaging of osteoporosis based on BMDtaging of osteoporosis based on BMD(DEXA) and vertebral fracture(DEXA) and vertebral fracture

Clinical StageClinical Stage

00 osteopeniaosteopenia

(preclinical osteoporosis)(preclinical osteoporosis)

11 Osteoporosis withoutOsteoporosis withoutfracturesfractures

22 Established osteoporosisEstablished osteoporosis

(with fractures)(with fractures)

3 Advanced osteoporosis3 Advanced osteoporosis

CriteriaCriteria

-- loweredlowered BMDBMD(T score: 1 to 2.5 SD)(T score: 1 to 2.5 SD)

reducedreduced BMDBMD, no fractures, no fractures

(T score: 22.5 ).5 )

- reducedreduced BMD,BMD, multiplemultiplevertebral fractures, oftenvertebral fractures, often


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Fluoride

s sodium fluoride, BMD at thelumbar spine increased by

35%. but there was nodecrease in fracture incidence.


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Quality:Evolution of the Paradox

Positive bone former/antiresorptive agent

Increase in %vertebral BMD

Decrease in vertebralfracture risk

Fluoride1 35 0

Calcltonin-salmon2 1-1.5 36

Raioxifene3 2-3 30

Risedronate4 3-5 41

Alendronate5 6-8 47

1. Riggs BL et al. N Engi J Med 1990;322:802-9.

2. Chesnut C III et al. Am J Med. 2000;109:267-76.

3. Ettinger B et al. JAMA. 1999;282:637-45.

4. Harris ST et al. JAMA. 1999;282:1344-52


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BMD increase is not proportional to reduction

relative risk of vertebral fracture

Risedronate

Alendronate

Raloxifen

Calcitonin

Tested

Product

495.9

VERT-MN

(Reginsteret al. ,

OsteoporosisInt 2000)

446.8FIT2(Cumm ings et al., JAMA

1998)

302.6MORE

(Ettingeret al., JAMA 1999)

360.5

PROOF

(Chesnutet al.,

Am.J.Med.2000)

% reduction of verte

fracture risk over 3 y

Change inBMD versus

control (%)Studies


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Bone Mechanics

s Bone mechanics can beused to define the

material properties ofbone such as strength,resilience andtoughness.

sThe mechanics of bone canbe illustrated using

a stress-strain curve.


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Bone QuantityBone QuantityMassMass

Bone MineralBone MineralDensityDensity

SizeSize

Bone Strength is the

Function

of Multiple Factors!

Bone Quality-Micro-

Architecture

Connectivity

Mineralization

Micro-damage

Collagen cross-linking

Chesnut et al. JBMR 2001; 16: 2163-72.Chesnut et al. JBMR 2001; 16: 2163-72.


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The Basic Bone QualityConcept

s Because osteoporosis is associatedwith low bone mass, BM D

measurements are used to assess theefficacy of treatment for the disease.However, there is growing evidencethat bone mass is just one of many

factors that contribute to bonestrength. The concept of bone qualityhas been introduced to incorporatethese other factors.


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What is Bone Quality?

s ArchitectureArchitecture

s MineralizationMineralization

s Organic matrixOrganic matrix

s Damage stateDamage state


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Baseline 1 Year

Borah, et al. OI 2002 World Congress on OsteoporosisDufresne, et al. OI 2002 World Congress on Osteoporosis

Amount of BoneBone volume

Trabecular Status

Trabecularnumber

Trabecular

separation

Porosity

Marrow Star

VolumeControl Patients

Rapid Deterioration of Microarchitecture

parameters


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Osteoporotic Changes in theOsteoporotic Changes in the

Trabecular Architecture ofTrabecular Architecture of

VertebraeVertebraeNormal Female, 54 yr Osteoporotic Female (with vert. Fx), 82yr.

Loss of bone mass and horizontal trabeculae connectivity

Borah et al. Anat. Rec. 2001-D computertomography, human cadaver vertebral bone


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NormalNormal

ModerateModerate

OsteoporosisOsteoporosis

SevereSevere

OsteoporosisOsteoporosis

Decrease in trabecular thickness is

more pronounced for non load-

bearing horizontal trabeculae.

Decrease in connections between

horizontal trabeculae

Decrease in trabecular strength

and increased susceptibility to

fracture from gravity and physical

activity.

Why Is It Important to ExamineWhy Is It Important to Examine

Trabecular Connectivity ?Trabecular Connectivity ?

Mosekilde L. Calcified Tissue Inter. 53(Suppl 1): S121-S126. 1993


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Architecture

s Similarly inosteoporosis a smallincrease in the mass of

structurally importanttrabeculae would havelittle effect on totalBUD, but wouldimprove bone strength

greatly.


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Architecture

s The supportivestrength of a series

of columns canbe enhancedgreatly, but withminimal effect on

mass, by adding afew, relatively smallcrossstruts.


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Mineralization

s Changes in the mineral densityor organic matrix of bone may

effect bone strength..


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Organic Matrix

s The organic matrix is composed mostlyof type l collagen and provides theplasticity of bone.

s Collagen-deficient bone are less toughthan bone with normal collagen,although the difference in BMD wasminor .(shown in animal studies onmice )


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Damage State

s The extent of fatigue or micro-damage affects the mechanics of any

material, and particularly itsstrength

s The number of micro-cracksincreases exponentially with age and

cannot be assessed by BMDmeasurements.


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Osteoporosis Normal

Preservation of horizontal Trabecular

struts


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Bone remodeling


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B R d lli


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Bone RemodellingCycle

Initiated by:

Unknown signal:? Hormonal

? Stress

? ? ?


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s First : - Erosion phase(resorption)

- Cell: Osteoclast

-- Span: From 2-4 weeks

- Loss: Erosion of 40-60hm


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Bone remodellingBone remodelling

cyclecycle

s Second :- LagSecond :- Lag

phase..phase..s 7 to 10 days7 to 10 days


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s Third : reversal phase:

- Cell : Osteoblast

- Span :Variable

- Gain : Variable - dependingon several factors: Up to 22 yearsof age

22 years to menopause

After menopause


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Is it Reparative orDamaging ?

s The main functions of bone remodellingare mineral homeostasis and themaintenance of strength,

s A high resorption rate is 'coupled with asignificantly increased fracture risk.

s Resorption affects bone strength bymechanisms that are independent of

bone density.


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Excessive repairs weaken structures


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Bone Remodelling

s Possible theoretical explanations:

1. increased resorption results. in a

greater number of boneremodelling. cavities, which mayseverely weaken, or possiblybreach, crucial trabeculae. Bone

quality would be impaired, but withonly a minimal change in BMD.


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Bone Remodelling

s Possible theoreticalexplanations:

2. Excessive remodelling atmicro-damaged sties mayoccur, weakening the bone

even further and possiblyleading to increased micro-damage.


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Bone Remodelling

s Possible theoretical explanations:

3. A high resorption rate may

prevent complete mineralization ofnew bone before the remodellingprocess begins again. This willimpact on bone trength, but also

affects BMD.


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Bone Quality Concept

s That is why some newly addedwords to the definition of

osteoporosis emphasize theimportance of the bone micro-architecture.


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Bone Quality Concept

s High resorption rateassociated with osteoporosis

reduces bone strength withoutnecessarily reducing bonemass.

s Bone strength can beimproved without increasingbone mass.

New defintionNew defintion


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New defintionNew defintion Bone Strength replacing BMD as theBone Strength replacing BMD as thekeykey

endpoint for proof of efficacyendpoint for proof of efficacyBeforeBefore NowNow

De fini t ion of O steopo rosisDe fini t ion of O steopo rosis

N orm al Osteop o ro s is

Oste oporosis is a skeletal disorder character ized by co mp romised

bonestrengthpred isp osing a pe rson to an increas ed r isk of fracture.1

1. ConsensesDevelopment Conference, JAMA2001;285: 785-95.

consensus conference

eoporosis is aemic skeletal disease

racterized by

bone mass and micro

hitectural deteriorationone tissue with a resultant

ease in fragility and

of fracture


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Bone QuantityBone QuantityMassMass

Bone MineralBone MineralDensityDensity

SizeSize

Bone Strength is the

Function

of Multiple Factors!

Bone Quality-Micro-

Architecture

Connectivity

Mineralization

Micro-damage

Collagen cross-linking

Chesnut et al. JBMR 2001; 16: 2163-72.Chesnut et al. JBMR 2001; 16: 2163-72.


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How to Assess BoneQuality?

s Bone quality could not be assessedBone quality could not be assessed

clinically.clinically.

s New imaging techniques (e.g. scanningNew imaging techniques (e.g. scanning

electron microscopy) assessing boneelectron microscopy) assessing bone

architecture and micro-damage.architecture and micro-damage.

s Bone remodelling markers e.g.Bone remodelling markers e.g.

dexoxypyridinoline ( bone resorption )dexoxypyridinoline ( bone resorption )

and alkaline phosphates ( boneand alkaline phosphates ( bone

formationformation


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Micro-Computed Tomography

Proposed Hypothesis:


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Proposed Hypothesis:Actions of Antiresorptive Therapies in

Reducing Osteoporotic Fracture Risk1-4

1. Riggs BL and Melton LJ. J Bone Miner Res. 2002;17:11-4

2. Chesnut CH III et al AMJ Med. 2000; 109:267-76.

3. Chesnut CH III and Rosen CJ. J Bone Miner Res. 20001;16:2163-72.


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Conclusion

s Fracture incidence can be reducedsignificantly with only a smallincrease in bone mass, and that

improvements in bone quality mayexplain the increase in bonestrength,

s Risk of osteoporotic fractures is

minimised by combined effect of :1. Increase of BMD2. Improvement of micro-architecture by

induction of slow remodelling


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1-20 final bone quality & induction of osteoporotic fractures

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