Secondary Conditions After SCI:

Recognizing and Treating

Cardiovascular Disease,
Osteoporosis and Bladder Cancer
Suzanne L. Groah, MD, MSPH
www.SCI-Health.Org
Supported by National Institute for Disability and Rehabilitation Research, Grant # H133B031114
 Objectives
 List 3 major secondary conditions that occur
after SCI

 Discuss risk factors for each of these secondary

conditions

 Describe when and how to monitor for these

secondary conditions
Part 1: Bladder Cancer Risk and
Prevention
 Bladder Cancer Epidemiology
 5th most common cancer
 12th leading cause of cancer mortality
 Adjusted yearly incidence 17.0 per 100,000
 54,400 new cases per year
 Males at greater risk
 Majority are transitional cell carcinoma
 Risk Factors for Bladder
Cancer
 Smoking
 Male gender
 Aromatic amines
 Schistosomiasis
 UTI
 Hypotheses
1 Incidence of bladder cancer is higher in SCI
than in the general population

2 Indwelling catheter use is associated with

bladder cancer in SCI

3 There is an increasing risk of bladder cancer

with longer duration of IDC use
 Part 1 Design: Retrospective
Cohort
SCI duration
> 1year
Retrospective
Screening
cystoscopy 1950

Non-Randomized

Indwelling Non-Indwelling
Multiple 1951 - 1997
Catheter Use Catheter Use
Methods (Multi)
(IDC) (NIDC)

Ascertainment of Bladder Cancer Status via Cystoscopy

No No No
Bladder Bladder Bladder 1998
Bladder Bladder Bladder
Cancer Cancer Cancer
Cancer Cancer Cancer
Results
 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

% Male 79% 84% 80% >.05

Age at SCI* 29 29 30 .06

Duration of
14.0 11.8 9.9 .003
SCI*
Duration of
11.8 6.9 N/A <.0001
IDC*
*data presented in years
 Demographics
Bladder Management Group
Factor 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%
 Comparison to General
Population (SMRMales)
Bladder 95%
Observed/
management Observed Expected confidence
Expected
method 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

 Risk of Bladder Cancer
 Age-adjusted rate of bladder cancer (per 100,000)
 Indwelling catheter - 77.0
 Multi methods- 56.1
 No indwelling catheter - 25.1
 Age-adjusted RR – 4.9*
 Attributable risk percent due to catheter – 64.8%
 Attributable risk percent due to SCI – 55.8%
Factors Contributing to
Bladder Cancer

13%

Catheter
Male gender
54% Bladder calculi
33%
 Cumulative Incidence of
Bladder Cancer
0.010%
0.009%
IDC
0.008%
Cumulative Incidence

NIDC
0.007%
0.006%
0.005%
0.004%
0.003%
0.002%
0.001%
0.000%
0 5 10 15 20 25 30 35 40 45 50 55 60

Years Post-SCI
Wilcoxan < 0.05
 Cumulative Incidence of
Bladder Cancer
0.010%
0.009%
IDC
0.008%
Cumulative Incidence

NIDC
0.007%
0.006%
0.005%
0.004%
0.003%
0.002%
0.001%
0.000%
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80
Age
Wilcoxan < 0.05
 Part 1: Conclusions
 Incidence of bladder cancer is higher in SCI
than in the general population
 Indwelling catheter use is associated with
bladder cancer in SCI
 The risk of bladder cancer increases with
increasing duration of indwelling catheter use
Part 2: Bladder Cancer Mortality
 Epidemiology of Bladder
Cancer Mortality
 Adjusted risk 3.2 per 100,000
 Associated with age
 >50% deaths occur in 70+ year olds
 Mortality related to stage at diagnosis
 Superficial 5-yr survival: 90%
 Invasive 5-yr survival: <50%
 Hypotheses
1 Bladder cancer mortality is heightened in SCI
compared with the general population

2 Compared with other bladder management methods,

indwelling catheter use is associated with heightened
BC mortality

3 The risk of BC mortality increases with increasing

duration of indwelling catheter use
 Part 2 Design: Retrospective
Cohort

SCI > 1 year

Indwelling Non-Indwelling
Multiple
Catheter Use Catheter Use
Methods (Multi)
(IDC) (NIDC)

No No No
Bladder Bladder Bladder
Bladder Bladder Bladder
cancer cancer cancer
Cancer Cancer Cancer

Mortality Survival Mortality Survival Mortality Survival

 Bladder Cancer Mortality

Indwelling Multiple No
Catheter Methods Indwelling
Catheter
Bladder
cancer cases 15 3 3

# deceased
10 3 0

# deceased
due to BC 10 2 0
 Risks

 Indwelling catheter age-adjusted BC mortality:

51.2/100,000 p-y
 Multi age-adjusted BC mortality:
31.5/100,000 p-y
 SMR SCI vs. SEER: 70.9*
 SMR IDC vs. SEER: 127.9*
 Bladder Cancer Mortality by
Age

180
160 Indwelling Catheter
Mortality in 100,000 P-Y

140 SEER
120
100
80
60
40
20
0
0-9 10-19 20-29 30-39 40-49 50-59 60+
Age (years)
 Proportional Mortality Due to
Bladder Cancer
100%
90% Indwelling Catheter
Proportion Surviving with BC

80%
70%
60%
50%
40%
30%
20%
10%
0%
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39
Years post-SCI
 Survival After Bladder
Cancer Diagnosis

 Of those dying due to BC, majority of death

occurred in <1 year
 Survival range .4 – 3.3 years
 Part 2: Conclusions
 Bladder cancer mortality is heightened in SCI
compared with the general population

 Compared with other bladder management

methods, IDC use is associated with heightened
BC mortality
Part 3: Risk Factors, Diagnosis, and
Surveillance
 Purpose
 To evaluate factors influencing survival after
bladder cancer in individuals with SCI

 To examine bladder cancer surveillance

 Hypotheses
1 Bladder cancer survivors have fewer
genitourinary risk factors than those dying due
to bladder cancer

2 Bladder cancer survivors have undergone more

intense genitourinary surveillance
 Part 3 Design: Case-control

Bladder Age at SCI

cancer Duration of SCI
survivors Age at BC
Level of SCI
ASIA
Method of bladder
Medical record
management
review Histology
Presentation
Controls Diagnosis
deceased Surveillance
due to Biopsy results
bladder Risk Factors
cancer
 Methods
 Design: case-control
 8 BC survivors
 12 BC controls who died
 Outcome measures:
 Demographics
 Frequency of surveillance
 Risk factors
 Analyses:
 Student’s t test
 Fisher’s exact test
 Demographics

Survivor (%) Control (%) p Value

Cervical SCI
50 56 .6

Thoracic
50 44 .1
SCI
ASIA A 100 78 .3
ASIA B 0 11 .07
ASIA C 0 11 .07
ASIA D 0 0
 Demographics

Survivor* Control* p Value

Mean age at SCI 29 23 > .05
Mean duration of
SCI 20 22 > .05

Mean age at BC 48.6 45.1 > .05

Mean time of
survival after BC 6.5 1 < .001

Survival range 3 – 10 .4 – 3.3

*data presented in years
 Presentation
70%
Survivor Control
60%

50%

40%

30%

20%

10%

0%
S/Sx H/O gross Gross hematuria Renal failure
hematuria
 Diagnosis

80%
70% Survivor Control
60%
50%
40%
30%
20%
10%
0%
Cystoscopy Screen-cysto Screen-other
 Bladder Cancer Histology

75%
Survivor Control

50%

25%

0%
TCC SCC Adeno
 Potential Associated Risk
Factors
100%
Survivor Control
*
75%

*
50%

25%

0%
IDC use Tobacco use Calculi Pyelonephritis Prophylactic
antibiotic
 Risk Factors
50%
Survivor
*
Control

*
25%
*

0%
0 RF 1 RF 2 RF 3 RF 4 RF

RF: IDC use, tobacco use, calculi, or pyelonephritis

 Hypothesis 2

2 Bladder cancer survivors have undergone more

intense genitourinary surveillance
 Bladder Cancer Surveillance

Survivor Control p value

Mean
number 7.8 16.8 .06
cystoscopies
Mean
number 1.6 3.6 > .1
biopsies
 Conclusions

 Bladder cancer survivors have fewer genitourinary risk

factors than those dying due to bladder cancer

 While IDC use is related to BC incidence, concurrent

multiple risk factor status may be related to mortality

 Bladder cancer survivors have undergone more intense

genitourinary surveillance
 Clinical Correlates
 Encourage methods of bladder management
other than indwelling catheters when appropriate
 Foley and suprapubic catheters DO have a role
after SCI
 In people at risk, encourage periodic screening
by a urologist
Cardiovascular Disease
 Epidemiology of
Cardiovascular Disease
 CVD is #1 cause of death in US
 1993 CVD mortality rate 163 per 100,000
 1993 CHD mortality rate 95 per 100,000
 28.6% decline in mortality due to MI
 84.6% of mortality due to MI in 65yo+

American Heart Association, 1997

 Reversible Risk Factors for
CVD
 Hypertension  Tobacco use
 Low HDL cholesterol  Sedentary lifestyle
 Hypercholesterolemia  Abdominal obesity
 Hypertriglyceridemia  Diabetes mellitus
 High lipoprotein A  Hyperinsulinemia

Source: American Journal of Epidemiolog

y 1978;108:3-8
Data from the Craig Collaborative Aging
Study
 Cholesterol Level by
Neurologic Group
245 * * Study Period 1
240 Study Period 2
235
230
225
220 *
215
210
205
200
195
Tetra ABC Para ABC All D's

Craig Collaborative Aging Study, 1997

 Serum Lipids
 Cholesterol significantly higher in ParaABC’s
and All D’s than TetraABC’s
 HDL significantly lower in TetraABC’s than All
D’s
 HDL decreased significantly in ParaABC’s and
TetraABC’s over time

Craig Collaborative Aging Study, 1997

 CVD and CHD Mortality
 33 total deaths
 CVD mortality rate 42%
 CHD mortality rate 33%
 CVD case fatality rate 22%
 CHD case fatality rate 17%

Craig Collaborative Aging Study, 1997

 Epidemiology of CHD and
CVD
 General population
 CVD #1 COD
 CHD prevalence 12.7-
22%
 CHD accounts for 51.2%
of CVD mortality
 17% CVD mortality in
<65 yo
American Heart Association, 1997
 Long-term SCI
 CVD #1 COD (30 yrs
post-SCI)
 CHD prevalence 15%
 CHD accounts for 79% of
CVD mortality
 64% CVD mortality in
<65 yo
 35% deaths in those >60
years
Data from Cardiovascular Disease After
Spinal Cord Injury: Suspected Causes,
Available Treatments, and Investigational
Imperatives
 National Cholesterol
Education Panel Guidelines
 HDL < 40 is abnormal
 LDL 130 – 159 is borderline high
 LDL > 160 is high
 LDL “target” is 100
 Triglyceride 150-199 is borderline high
 Triglyceride < 150 is normal
 Observed Lipid Levels After
Chronic Paraplegia
 Normal total cholesterol
 Normal or elevated LDL
 Normal or elevated triglycerides
 Consistently low HDL
 Significantly elevated TC:HDL ratio
Data from the University of Miami:
Risk Stratification of Young,
Healthy, Tobacco Non-Users with
Paraplegia at T6 and Lower
Using NCEP Guidelines
 Lipid Abnormalities

ATP X s.d. Min Max Risk At Risk

TC (mg/dl) II 172 34 97 225 < 200 10/46
III < 200 10/46
TG (mg/dl) II 189 45 100 300 < 200 14/46
III < 150 32/46
TC/HDL-C 4.2 1.1 2.4 6.5 < 4.5 21/46

*data from M. Nash, University of Miami, Miami Project to Cure Paralysis

 Lipid Abnormalities

ATP Mean s.d. Min / Max Risk At Risk

HDL-C (mg/dl) II44 12 23 / 68 > 35 14/46

III > 40 25/46

LDL-C (mg/dl) II90 26 40 / 139 < 130/160 16/46 1

III < 100/130 32/46 2

Χ2 = (1) 70.453, p < 0.001

1 ATP II: Lipid-Lowering intervention indicated in 16/46 (34.7%) cases

2 ATP III: Lipid-Lowering intervention indicated in 20/26 (69.6%) cases
 Etiology of Lipid Abnormalities
After Paraplegia

o
Sedentary Lifestyle / Physical Deconditioning
(L)
o
Insulin Resistance / Metabolic Syndrome (X)
(L,P)
o
Imprudent Diet (P?)
 Clinical Correlates
 Role of nutrition and exercise
 Exercise may not be enough to correct the lipid
abnormalities associated with SCI
 Monitor cholesterol and lipid levels
 Screen with exercise stress test
Abnormal Calcium and Bone Metabolism
After SCI: Osteoporosis, Stones and
More
 Osteoporosis
 SCI results in immediate and often permanent
gravitational unloading
 Similar to space flight
 Bone loss is universal after SCI
 Most persons with SCI will have a pathologic
fracture at some point
 Osteoporosis occurs rapidly
 Bone Metabolism
 Normally there is a balance between
 Osteoclast (bone resorption/breakdown) activty
 Osteoblast (bone rebuilding) activity
 Pathology after SCI
 Imbalance between bone breakdown and bone formation
 After SCI osteoblastic AND osteoclastic activity increase
 Osteoblasts increase only slightly
 Osteoclast activity increases 10-fold, peaking at 10 weeks
 Etiology of Osteoporosis
After SCI

 Gravitational unloading
 Lack of muscle traction on bone
 Acutely, absorption of Ca++ decreases after SCI
 Other neural factors
 Pathology of Abnormal Bone
and Calcium Metabolism
 Increase in osteoclast activity within days/weeks
 ↑ urine calcium
 Observed within 10d, peaks 1-6m
 2-4x that seen in people after prolonged bedrest
 ↑ blood calcium
 ↑ markers of bone resorption
 Osteoporosis
 Definition - Bone density less than 2.5 SD below mean
 Bone density loss
 Trabecular bone affected most
 Distal femur
 Proximal tibia
 Os calcis
 Bone loss greater with
 Paraplegics have > arm BMD than tetraplegics
 Complete injury
 Bone Loss or Gain Post-SCI

6 months 1 year 10 years

Femoral 27% >50%
neck
Mid-shaft 25% >50%
femur
Proximal 43% >50%
tibia
Arms ↑
Trunk ↑ ↑
 Osteoporosis
 Morbidity
 Pathologic fracture in 6%
 Outpatient Model System Center review
 14% at 5 years
 28% at 10 years
 39% at 15 years
 Sites
 Supracondylar region and tibia
 ? Fracture threshold of 50% loss for the knee
 Inciting event – minimal/no trauma, ROM
 Osteoporosis
 Prevention
 Exercise
 Medications
 Restoration of bone loss difficult
 Monitor at risk individuals
 Osteoporosis/Abnormal Bone
Metabolism
 Exercise
 Animal model – Early mobilization of paralyzed
limbs with FES slowed bone loss
 Acute (1-4 week) standing program slowed bone
loss at the tibia
 Acute (1-5 weeks) standing/treadmill program in
incompletes halted bone loss
 FES ambulation in completes with chronic SCI did
not restore BMD loss
 FES cycling does not restore BMD chronically
 Osteoporosis/Abnormal Bone
Metabolism
 Exercise
 FES to quads 1 hr/d, 5 d/wk x 24 weeks restores LE
bone loss (Belanger)
 FES-cycle 30min/d, 3d/wk x 12 mos restores 10%
proximal tibia bone loss (Mohr)
 FES-cycle 30min/d, 1d/wk x 12 mos did not change
proximal tibia bone loss
 RRTC Project R2 – effect of FES 1hr/d, 5d/wk x 6
weeks acutely
 Osteoporosis/Abnormal Bone
Metabolism
 Pharmacologic
 Bisphosphonates
 Etidronate – shown to prevent BMD loss acutely, but may
inhibit formation
 Pamidronate – IV inhibited bone resorption and reversed
PTH inhibition
 Alendronate – increase BMD in ASIA D
 Zoledronate
 Clinical Correlates
 Osteoporosis is universal after SCI
 Osteoporosis likely can be prevented, but to
what degree and for how long?
 Consider assessing BMD before initiating
standing or especially ambulation program
 Consider assessment of BMD in those with
chronic SCI
Thank you