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 )
- reduced- reduced 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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Bone RemodellingCycle
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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Bone RemodellingCycle
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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