Download - Bladder Cancer and Osteoporosis (2)
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Supported by National Institute for Disability and Rehabilitation Research, Grant # H133B031114
Secondary Conditions After SCI:
Recognizing and Treating
Cardiovascular Disease,Osteoporosis and Bladder Cancer
Suzanne L. Groah, MD, MSPHSuzanne L. Groah, MD, MSPH
www.SCI-Health.Orgwww.SCI-Health.Org
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Objectives
s List 3 major secondary conditions that occurList 3 major secondary conditions that occur
after SCIafter SCI
s Discuss risk factors for each of these secondaryDiscuss risk factors for each of these secondaryconditionsconditions
s
Describe when and how to monitor for theseDescribe when and how to monitor for thesesecondary conditionssecondary conditions
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Part 1: Bladder Cancer Risk and
Prevention
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Bladder Cancer Epidemiology
s 5th most common cancer5th most common cancer
s 12th leading cause of cancer mortality12th leading cause of cancer mortality
s Adjusted yearly incidenceAdjusted yearly incidence 17.0 per 100,00017.0 per 100,000
s 54,400 new cases per year54,400 new cases per year
s MalesMales at greater riskat greater risk
s Majority areMajority are transitional cell carcinomatransitional cell carcinoma
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Risk Factors for Bladder
Cancer
s SmokingSmoking
s Male genderMale gender
s Aromatic aminesAromatic amines
s SchistosomiasisSchistosomiasis
s UTIUTI
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Hypotheses
1 Incidence of bladder cancer is higher in SCIIncidence of bladder cancer is higher in SCIthan in the general populationthan in the general population
2
Indwelling catheter use is associated withIndwelling catheter use is associated withbladder cancer in SCIbladder cancer in SCI
3 There is an increasing risk of bladder cancer3 There is an increasing risk of bladder cancer
with longer duration of IDC usewith longer duration of IDC use
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Part 1 Design: Retrospective
Cohort
N o n - R a n d o m i z e d
I n d w e l l i n g
C a t h e t e r U s e
( I D C )
M u l t i p l e
M e t h o d s ( M u l t i )
N o n - I n d w e l l i n g
C a t h e t e r U s e
( N I D C )
B l a d d e r C a n c e r
N oB l a d d e r
C a n c e r
B l a d d e r C a n c e r
N oB l a d d e r
C a n c e r
B l a d d e r C a n c e r
N oB l a d d e r
C a n c e r
R e t r o s p e c t i v e
1 9 5 0
1 9 9 8
1 9 5 1 - 1 9 9 7
S C I d u r a t i o n
> 1 y e a r
S c r e e n i n g
c y s t o s c o p y
A s c e r t a i n m e n t o f B l a d d e r C a n c e r S t a t u s v i a C y s t o s c o p y
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Results
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Demographics
IDC Multi NIDC p Value
Number 1,728 314 1,628 ---
P-Y 20,092 4,411 15,226 ---
Cases 15 3 4 .05
Age at SCI* 29 29 30 .06
Duration ofSCI*
14.0 11.8 9.9 .003
Duration ofIDC*
11.8 6.9 N/A
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Demographics
Bladder Management GroupFactor NIDC Multi IDC
Level of SCI
Cervical 35% 40% 68%Thoracic 54% 56% 30%
Lumbosacral 11% 4% 2%ASIA
Classification
A 47% 60% 65%B 14% 18% 20%
C 13% 9% 11%D 25% 13% 4%E 1% 0% 0%
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Comparison to General
Population (SMRMales )
Bladder
management
method
Observed ExpectedObserved/
Expected
95%
confidence
interval
NIDC 3 0.57 5.26 1.20 15.36
Multi 3 0.19 16.18 3.70 47.27
IDC 15 .60 25.4 14.0-41.9
All 21 1.4 15.50 9.12 24.12
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Risk of Bladder Cancer
s Age-adjusted rate of bladder cancerAge-adjusted rate of bladder cancer(per 100,000)(per 100,000)
x Indwelling catheter -Indwelling catheter - 77.077.0
x Multi methods- 56.1Multi methods- 56.1
x
No indwelling catheter - 25.1No indwelling catheter - 25.1s Age-adjusted RR Age-adjusted RR 4.94.9**
s Attributable risk percent due to catheter 64.8%Attributable risk percent due to catheter 64.8%
s
Attributable risk percent due to SCI 55.8%Attributable risk percent due to SCI 55.8%
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Factors Contributing to
Bladder Cancer
54%
33%
13%
CatheterMale gender
Bladder calculi
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Cumulative Incidence of
Bladder Cancer
0.000%
0.001%
0.002%
0.003%
0.004%
0.005%
0.006%
0.007%
0.008%
0.009%
0.010%
0 5 10 15 20 25 30 35 40 45 50 55 60
Years Post-SC
CumulativeIncidence
IDC
NIDC
Wilcoxan < 0.05
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Cumulative Incidence of
Bladder Cancer
0.000%
0.001%
0.002%
0.003%
0.004%0.005%
0.006%
0.007%
0.008%
0.009%
0.010%
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80
Age
Cumulative
Incidence
IDC
NIDC
Wilcoxan < 0.05
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Part 1: Conclusions
Incidence of bladder cancer is higher in SCIIncidence of bladder cancer is higher in SCI
than in the general populationthan in the general population
Indwelling catheter use is associated withIndwelling catheter use is associated with
bladder cancer in SCIbladder cancer in SCI The risk of bladder cancer increases withThe risk of bladder cancer increases with
increasing duration of indwelling catheter useincreasing duration of indwelling catheter use
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Part 2: Bladder Cancer Mortality
id i l f l dd
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Epidemiology of Bladder
Cancer Mortality
s Adjusted riskAdjusted risk3.23.2 per 100,000per 100,000
s Associated with ageAssociated with age
x >50% deaths occur in 70+ year olds>50% deaths occur in 70+ year olds
s Mortality related to stage at diagnosisMortality related to stage at diagnosisx Superficial 5-yr survival: 90%Superficial 5-yr survival: 90%
x Invasive 5-yr survival:
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Hypotheses
1 Bladder cancer mortality is heightened in SCI comparedBladder cancer mortality is heightened in SCI comparedwith the general populationwith the general population
2 Compared with other bladder management methods,2 Compared with other bladder management methods,
indwelling catheter use is associated with heightened BCindwelling catheter use is associated with heightened BCmortalitymortality
3 The risk of BC mortality increases with increasing3 The risk of BC mortality increases with increasing
duration of indwelling catheter useduration of indwelling catheter use
P 2 D i R i
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Part 2 Design: Retrospective
Cohort
Indwelling
Catheter Use
(IDC)
Multiple
Methods (Multi)
Non-Indwelling
Catheter Use
(NIDC)
Bladder
cancer
No
Bladder
Cancer
Bladder
cancer
No
Bladder
Cancer
Bladder
cancer
No
Bladder
Cancer
SCI > 1 year
Mortality Survival Mortality Survival Mortality Survival
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Bladder Cancer Mortality
IndwellingCatheter
MultipleMethods
NoIndwellingCatheter
Bladdercancer cases 15 3 3
# deceased 10 3 0
# deceaseddue to BC
10 2 0
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Risks
s Indwelling catheter age-adjusted BC mortality:Indwelling catheter age-adjusted BC mortality:
51.2/100,000 p-y51.2/100,000 p-y
s Multi age-adjusted BC mortality:Multi age-adjusted BC mortality:
31.5/100,000 p-y31.5/100,000 p-y
s SMR SCI vs. SEER: 70.9*SMR SCI vs. SEER: 70.9*
s SMR IDC vs. SEER: 127.9*SMR IDC vs. SEER: 127.9*
Bl dd C M t lit b
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Bladder Cancer Mortality by
Age
0
20
40
6080
100
120
140
160
180
0-9 10-19 20-29 30-39 40-49 50-59 60+
Age (years)
Mortalityin100,000P-Y
Indwelling Cathete
SEER
P ti l M t lit D t
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Proportional Mortality Due to
Bladder Cancer
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1 3 5 7 9 1 1 1 3 1 5 1 7 1 9 2 1 2 3 2 5 2 7 2 9 3 1 3 3 3 5 3 7 3 9
Years post-S
ProportionSurvivingwithBC Indwelling Cathet
S i l Aft Bl dd
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Survival After Bladder
Cancer Diagnosis
s Of those dying due to BC, majority of deathOf those dying due to BC, majority of death
occurred inoccurred in
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Part 2: Conclusions
Bladder cancer mortality is heightened in SCIBladder cancer mortality is heightened in SCIcompared with the general populationcompared with the general population
Compared with other bladder managementCompared with other bladder managementmethods, IDC use is associated with heightenedmethods, IDC use is associated with heightened
BC mortalityBC mortality
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Part 3: Risk Factors, Diagnosis, and
Surveillance
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Purpose
s To evaluate factors influencing survival afterTo evaluate factors influencing survival afterbladder cancer in individuals with SCIbladder cancer in individuals with SCI
s To examine bladder cancer surveillanceTo examine bladder cancer surveillance
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Hypotheses
1 Bladder cancer survivors have fewerBladder cancer survivors have fewergenitourinary risk factors than those dying duegenitourinary risk factors than those dying due
to bladder cancerto bladder cancer
2 Bladder cancer survivors have undergone more2 Bladder cancer survivors have undergone more
intense genitourinary surveillanceintense genitourinary surveillance
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Part 3 Design: Case-control
B l a d d e r
c a n c e r
s u r v i v o r s
C o n t r o l s
d e c e a s e d
d u e t o
b l a d d e r
c a n c e r
A g e a t S C I
D u r a t i o n o f S C I
A g e a t B C
L e v e l o f S C I
A S I A
M e t h o d o f b l a d d e r m a n a g e m e n t
H i s t o l o g y
P r e s e n t a t i o n
D i a g n o s i s
S u r v e i l l a n c e
B i o p s y r e s u l t s
R i s k F a c t o r s
M e d i c a l r e c o r d
r e v i e w
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Methods
s Design: case-controlDesign: case-controlx 8 BC survivors8 BC survivors
x 12 BC controls who died12 BC controls who died
s Outcome measures:Outcome measures:x
DemographicsDemographicsx Frequency of surveillanceFrequency of surveillance
x Risk factorsRisk factors
s Analyses:Analyses:x Students t testStudents t test
x Fishers exact testFishers exact test
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Demographics
Survivor(%) Control (%) p Value
Cervical SCI 50 56 .6
Thoracic SCI 50 44 .1
ASIA A 100 78 .3
ASIA B 0 11 .07
ASIA C 0 11 .07
ASIA D 0 0
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Demographics
Survivor* Control* p ValueMean age at SCI 29 23 > .05
Mean duration ofSCI
20 22 > .05
Mean age at BC 48.6 45.1 > .05
Mean time ofsurvival after BC
6.5 1 < .001
Survival range 3 10 .4 3.3
*data presented in years
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Presentation
0%
10%
20%
30%
40%
50%
60%
70%
S/Sx H/O gross
hematuria
Gross hematuria Renal failure
Survivor Control
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Diagnosis
0%
10%
20%
30%
40%
50%
60%
70%
80%
Cystoscopy Screen-cysto Screen-other
Survivor Control
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Bladder Cancer Histology
0%
25%
50%
75%
TCC SCC Adeno
S ur vivo r C on tr ol
Potential Associated Risk
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Potential Associated Risk
Factors
*
*
0%
25%
50%
75%
100%
IDC use Tobacco use Calculi Pyelonephritis Prophylactic
antibiotic
Survivor Control
Ri k F
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Risk Factors
*
*
*
0%
25%
50%
0 RF 1 RF 2 RF 3 RF 4 RF
Survivor
Control
RF: IDC use, tobacco use, calculi, or pyelonephritis
H h i 2
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Hypothesis 2
2 Bladder cancer survivors have undergone more2 Bladder cancer survivors have undergone more
intense genitourinary surveillanceintense genitourinary surveillance
Bl dd C S ill
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Bladder Cancer Surveillance
Survivor Control p value
Mean numbercystoscopies
7.8 16.8 .06
Mean numberbiopsies
1.6 3.6 > .1
C l i
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Conclusions
Bladder cancer survivors have fewer genitourinary riskBladder cancer survivors have fewer genitourinary riskfactors than those dying due to bladder cancerfactors than those dying due to bladder cancer
?
While IDC use is related to BC incidence, concurrentWhile IDC use is related to BC incidence, concurrentmultiple risk factor status may be related to mortalitymultiple risk factor status may be related to mortality
Bladder cancer survivors have undergone more intenseBladder cancer survivors have undergone more intense
genitourinary surveillancegenitourinary surveillance
Cli i l C l t
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Clinical Correlates
s Encourage methods of bladder managementEncourage methods of bladder managementother than indwelling catheters when appropriateother than indwelling catheters when appropriate
s Foley and suprapubic catheters DO have a roleFoley and suprapubic catheters DO have a role
after SCIafter SCI
s In people at risk, encourage periodic screeningIn people at risk, encourage periodic screening
by a urologistby a urologist
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Cardiovascular Disease
Epidemiology of
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American Heart Association, 1997
p gy
Cardiovascular Disease
s CVD is #1 cause of death in USCVD is #1 cause of death in USs 1993 CVD mortality rate 163 per 100,0001993 CVD mortality rate 163 per 100,000
s 1993 CHD mortality rate 95 per 100,0001993 CHD mortality rate 95 per 100,000
s 28.6% decline in mortality due to MI28.6% decline in mortality due to MIs 84.6% of mortality due to MI in 65yo+84.6% of mortality due to MI in 65yo+
Reversible Risk Factors for
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Source: American Journal of Epidemiology 1978;108:3-8
CVD
s HypertensionHypertensions Low HDL cholesterolLow HDL cholesterol
s HypercholesterolemiaHypercholesterolemia
s HypertriglyceridemiaHypertriglyceridemia
s High lipoprotein AHigh lipoprotein A
s Tobacco useTobacco uses Sedentary lifestyleSedentary lifestyle
s Abdominal obesityAbdominal obesity
s Diabetes mellitusDiabetes mellitus
s HyperinsulinemiaHyperinsulinemia
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Data from the Craig Collaborative Aging
Study
Cholesterol Level by
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Craig Collaborative Aging Study, 1997
Neurologic Group
*
* *
195
200
205
210
215
220
225
230
235
240
245
Tetra ABC Para ABC All D's
Study Period 1
Study Period 2
Serum Lipids
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Craig Collaborative Aging Study, 1997
Serum Lipids
s Cholesterol significantly higher in ParaABCsCholesterol significantly higher in ParaABCsand All Ds than TetraABCsand All Ds than TetraABCs
s HDL significantly lower in TetraABCs than AllHDL significantly lower in TetraABCs than All
DsDs
s HDL decreased significantly in ParaABCs andHDL decreased significantly in ParaABCs and
TetraABCs over timeTetraABCs over time
CVD and CHD Mortality
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Craig Collaborative Aging Study, 1997
CVD and CHD Mortality
s 33 total deaths33 total deathss CVD mortality rate 42%CVD mortality rate 42%
s CHD mortality rate 33%CHD mortality rate 33%
s CVD case fatality rate 22%CVD case fatality rate 22%s CHD case fatality rate 17%CHD case fatality rate 17%
Epidemiology of CHD and
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American Heart Association, 1997
CVD
s General populationGeneral populationx CVD #1 CODCVD #1 COD
x CHD prevalence 12.7-CHD prevalence 12.7-
22%22%
x
CHD accounts for 51.2%CHD accounts for 51.2%of CVD mortalityof CVD mortality
x 17% CVD mortality in17% CVD mortality in
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Data from Cardiovascular Disease AfterData from Cardiovascular Disease After
Spinal Cord Injury:Spinal Cord Injury: SuspectedSuspected Causes,Causes,
Available Treatments, and InvestigationalAvailable Treatments, and Investigational
ImperativesImperatives
National Cholesterol
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Education Panel Guidelines
s HDL < 40 is abnormalHDL < 40 is abnormals LDL 130 159 is borderline highLDL 130 159 is borderline high
s LDL > 160 is highLDL > 160 is high
s
LDL target is 100LDL target is 100s Triglyceride 150-199 is borderline highTriglyceride 150-199 is borderline high
s Triglyceride < 150 is normalTriglyceride < 150 is normal
Observed Lipid Levels After
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Chronic Paraplegia
sNormal total cholesterolNormal total cholesterolsNormal or elevated LDLNormal or elevated LDL
sNormal or elevated triglyceridesNormal or elevated triglycerides
s
Consistently low HDLConsistently low HDLs Significantly elevated TC:HDL ratioSignificantly elevated TC:HDL ratio
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Data from the University of Miami:
Risk Stratification of Young,
Healthy, Tobacco Non-Users withParaplegia at T6 and Lower
Using NCEP Guidelines
Lipid Abnormalities
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Lipid Abnormalities
ATPATP XX s.d.s.d. MinMin MaxMax RiskRisk At RiskAt Risk
TC (mg/dl)TC (mg/dl) IIII 172172 3434 9797 225225 < 200< 200 10/4610/46
IIIIII < 200< 200 10/4610/46TG (mg/dl)TG (mg/dl) IIII 189189 4545 100100 300300 < 200< 200 14/4614/46
IIIIII < 150< 150 32/4632/46
TC/HDL-CTC/HDL-C 4.24.2 1.11.1 2.42.4 6.56.5 < 4.5< 4.5 21/4621/46
*data from M. Nash, University of Miami, Miami Project to Cure Paralysis
Lipid Abnormalities
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Lipid Abnormalities
ATPATP MeanMean s.d.s.d. Min / MaxMin / Max RiskRisk At RiskAt Risk
HDL-C (mg/dl)HDL-C (mg/dl)IIII4444 1212 23 / 6823 / 68 > 35> 35 14/4614/46
IIIIII > 40> 40 25/4625/46
LDL-C (mg/dl)LDL-C (mg/dl) IIII9090 2626 40 /40 /139139 < 130/160< 130/160 16/4616/46 11
IIIIII < 100/130< 100/130 32/4632/46
22
22 = (1) 70.453, p < 0.001= (1) 70.453, p < 0.001
11 ATP II: Lipid-Lowering intervention indicated in 16/46 (34.7%) casesATP II: Lipid-Lowering intervention indicated in 16/46 (34.7%) cases22 ATP III: Lipid-Lowering intervention indicated in 20/26 (69.6%) casesATP III: Lipid-Lowering intervention indicated in 20/26 (69.6%) cases
Etiology of Lipid AbnormalitiesEtiology of Lipid Abnormalities
Af P l iAft P l i
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After ParaplegiaAfter Paraplegia
o Sedentary Lifestyle / Physical DeconditioningSedentary Lifestyle / Physical Deconditioning
(L)(L)
o Insulin Resistance / Metabolic Syndrome (X)Insulin Resistance / Metabolic Syndrome (X)
(L,P)(L,P)
o Imprudent DietImprudent Diet (P?)(P?)
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Abnormal Calcium and Bone Metabolism
After SCI: Osteoporosis, Stones and
More
Osteoporosis
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p
s SCI results in immediate and often permanentSCI results in immediate and often permanentgravitational unloadinggravitational unloading
x Similar to space flightSimilar to space flight
s Bone loss isBone loss is universal after SCIafter SCI
s Most persons with SCI will have a pathologicMost persons with SCI will have a pathologic
fracture at some pointfracture at some point
s Osteoporosis occurs rapidlyOsteoporosis occurs rapidly
Bone Metabolism
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s
Normally there is a balance betweenNormally there is a balance betweenx Osteoclast (bone resorption/breakdown) activtyOsteoclast (bone resorption/breakdown) activty
x Osteoblast (bone rebuilding) activityOsteoblast (bone rebuilding) activity
s Pathology after SCIPathology after SCI
x Imbalance between bone breakdown and bone formationImbalance between bone breakdown and bone formationx After SCI osteoblastic AND osteoclastic activity increaseAfter SCI osteoblastic AND osteoclastic activity increase
x Osteoblasts increase only slightlyOsteoblasts increase only slightly
x Osteoclast activity increases 10-fold, peaking at 10 weeksOsteoclast activity increases 10-fold, peaking at 10 weeks
Etiology of Osteoporosis
Aft SCI
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After SCI
s Gravitational unloadingGravitational unloading
s Lack of muscle traction on boneLack of muscle traction on bone
s
Acutely, absorption of CaAcutely, absorption of Ca++++
decreases after SCIdecreases after SCIs Other neural factorsOther neural factors
Pathology of Abnormal Bone
d C l i M t b li
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and Calcium Metabolism
s
Increase in osteoclast activity within days/weeksIncrease in osteoclast activity within days/weeksx urine calciumurine calcium
3 Observed within 10d, peaks 1-6mObserved within 10d, peaks 1-6m
3 2-4x that seen in people after prolonged bedrest2-4x that seen in people after prolonged bedrest
x blood calciumblood calciumx markers of bone resorptionmarkers of bone resorption
Osteoporosis
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p
s
Definition - Bone density less than 2.5 SD below meanDefinition - Bone density less than 2.5 SD below means Bone density lossBone density loss
x Trabecular bone affected mostTrabecular bone affected most
x Distal femurDistal femur
x
Proximal tibiaProximal tibiax Os calcisOs calcis
s Bone loss greater withBone loss greater with
x Paraplegics have > arm BMD than tetraplegicsParaplegics have > arm BMD than tetraplegics
x Complete injuryComplete injury
Bone Loss or Gain Post-SCI
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6 months 1 year 10 years
Femoral neck 27% >50%
Mid-shaftfemur 25% >50%
Proximaltibia
43% >50%
Arms
Trunk
Osteoporosis
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p
s
MorbidityMorbidityx Pathologic fracture in 6%Pathologic fracture in 6%
x Outpatient Model System Center reviewOutpatient Model System Center review3 14% at 5 years14% at 5 years
3
28% at 10 years28% at 10 years3 39% at 15 years39% at 15 years
x SitesSites3 Supracondylar region and tibiaSupracondylar region and tibia
x ? Fracture threshold of 50% loss for the knee? Fracture threshold of 50% loss for the knee
x Inciting event minimal/no trauma, ROMInciting event minimal/no trauma, ROM
Osteoporosis
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s
PreventionPreventionx ExerciseExercise
x MedicationsMedications
s Restoration of bone loss difficultRestoration of bone loss difficult
s Monitor at risk individualsMonitor at risk individuals
Osteoporosis/Abnormal Bone
Metabolism
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Metabolism
s
ExerciseExercisex Animal model Early mobilization of paralyzedAnimal model Early mobilization of paralyzed
limbs with FES slowed bone losslimbs with FES slowed bone loss
x Acute (1-4 week) standing program slowed boneAcute (1-4 week) standing program slowed boneloss at the tibialoss at the tibia
x Acute (1-5 weeks) standing/treadmill program inAcute (1-5 weeks) standing/treadmill program inincompletes halted bone lossincompletes halted bone loss
x FES ambulation in completes with chronic SCI didFES ambulation in completes with chronic SCI didnotnot restorerestore BMD lossBMD loss
x FES cycling does notFES cycling does not restorerestore BMD chronicallyBMD chronically
Osteoporosis/Abnormal BoneMetabolism
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Metabolism
s
ExerciseExercisex FES to quads 1 hr/d, 5 d/wk x 24 weeks restores LEFES to quads 1 hr/d, 5 d/wk x 24 weeks restores LE
bone loss (Belanger)bone loss (Belanger)
x FES-cycle 30min/d, 3d/wk x 12 mos restores 10%FES-cycle 30min/d, 3d/wk x 12 mos restores 10%
proximal tibia bone loss (Mohr)proximal tibia bone loss (Mohr)x FES-cycle 30min/d, 1d/wk x 12 mos did not changeFES-cycle 30min/d, 1d/wk x 12 mos did not change
proximal tibia bone lossproximal tibia bone loss
x RRTC Project R2 effect of FES 1hr/d, 5d/wk x 6RRTC Project R2 effect of FES 1hr/d, 5d/wk x 6
weeks acutelyweeks acutely
Osteoporosis/Abnormal BoneMetabolism
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Metabolism
s
PharmacologicPharmacologicx BisphosphonatesBisphosphonates
3 Etidronate shown to prevent BMD loss acutely, but mayEtidronate shown to prevent BMD loss acutely, but may
inhibit formationinhibit formation
3
Pamidronate IV inhibited bone resorption and reversedPamidronate IV inhibited bone resorption and reversedPTH inhibitionPTH inhibition
3 Alendronate increase BMD in ASIA DAlendronate increase BMD in ASIA D
3 ZoledronateZoledronate
Clinical Correlates
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s
Osteoporosis is universal after SCIOsteoporosis is universal after SCIs Osteoporosis likely can be prevented, but toOsteoporosis likely can be prevented, but to
what degree and for how long?what degree and for how long?
s Consider assessing BMD before initiatingConsider assessing BMD before initiating
standing or especially ambulation programstanding or especially ambulation program
s Consider assessment of BMD in those withConsider assessment of BMD in those with
chronic SCIchronic SCI
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Thank you