Prolotherapy as a treatment for
knee osteoarthritic pain
David Rabago, MD
Rosa DeLucia
UW Department of Family Medicine
NIH-NCCAM, DFM, Hackett-Hemwall Foundation
Jeff Patterson, Jessica Grettie
Learning Objectives
►To
briefly review significance of knee
osteoarthritis
►To
review the preliminary results of an
NIH/UW clinical trial assessing
prolotherapy for knee OA pain
The efficacy of prolotherapy for knee
osteoarthritic pain
►Knee
OA: Bad
 leading cause of disability/pain in the world
 present and symptomatic in up to 6% of the
population over 30 in the US
 Multiple risk factors and presumed etiologies
 incidence increases up to 10 fold from
30 to 65 years of age
 no definitive non-surgical, pain-control and
disease-modifying treatment
What is Prolotherapy?
Technique for treating chronic MSK pain
► Multiple injections of bioactive solution
► Proliferant injected and at tender ligament and
tendon insertion points and within joints
► Stimulates the body’s native healing
 ?Inflammatory process
 ?Growth factor recruitment
 ?Sclerose neovascularity associated with chronic
tendon disease
► Growing
in popularity nationwide
Prolotherapy Clinical Reports
Number of Prolotherapy Research Papers over Time
16
14
12
10
8
6
4
2
16
14
Randomized
Controlled Trials
12
10
Non-Randomized
Controlled Trials
8
6
Case Reports
4
2
0
1930s 1940s 1950s 1960s 1970s 1980s 1990s 2000s
0
1930s 1940s 1950s 1960s 1970s 1980s 1990s 2000s
Decade
Decade
OA Knee Pain Trial: Hypotheses
Rabago et al. In progress
►1.
Prolotherapy can
improve chronic pain,
stiffness, function and…
►2.
Subjects will adhere
to therapy, be satisfied
and use less pain
medication
Knee OA trial: Subject Recruitment
ICD-9 Billing codes/Media/Direct
Clinic
Phone Screen (Secondary
Inclusion/Exclusion criteria)
Prospective Case Series
Meeting (Info, Consent,
Questionnaires)
Dextrose (n=36)
3-5 monthly sessions
Randomized Controlled Trial
Follow up Questionnaires at weeks
5, 9, 12, 24, 52
Patient Eligibility Criteria
► Adults
35-75 y.o.
► Osteoarthritic pain
> 3 months
► Crepitus
► Radiographic criteria
► Quality-of-life impact
score
► Prolotherapist
approval
► BMI
>42
► Chronic pain greater
than knee pain
► Chronic pain
requiring narcotic
► Prolo patient
► Surgical
Intervention
►“Standard”
knee protocol
 Intra-articular: 25% Dex.
 Extra-articular: 15% Dex.
►3
prolo injection series monthly
►2 optional prolo sessions monthly
Outcome Measures
►Western
Ontario and McMaster
University osteoarthritis index (WOMAC)
 pain, stiffness, function
►Knee
Pain Scale (KPS)
 pain severity, frequency per knee
►Quality
of life, side effects, patient
satisfaction and medication use
Baseline Subject Demographics
► Female,
n (%) 21 (58.3%)
► Age, mean (SD) 60.5 ± 8.7
► BMI, mean (SD) 30.7 ± 6.9
► WOMAC
 Pain
57.9 ± 2.9
 Stiffness 51.7 ± 3.8
 Function 57.3 ± 2.8
► KPS
(Left)
 Pain Freq 35.1 ± 4.9
 Pain Sev 59.2 ± 3.9
► KPS
(Right)
 Pain Freq 33.6 ± 3.3
 Pain Sev 57.8 ± 2.9
Change in WOMAC Scores over
Change in WOMAC Score over Time
12
Months (p<0.05) (93% of data)
Score
90
85
9080
75
70
8065
60
55
50
Score
Relative
Effect Size
Pain
28.3%
Stiffness 28.9%
Function 35.6%
52
W
k
24
W
k
W
k
12
9
W
k
5
k
W
Ba
se
l
in
e
70
Time
60
Pain
Stiffness
Function
50
Baseline
Wk 5
Wk 9
Wk 12
Time
Wk 24
Wk 52
Change in KPS Score on Injected Left Knee
(93% of data) (p<0.05)
Score
80
Relative
Effect Size
W
k
50
Pain Frequency
84.6%
24
60
(n
=3
W
2)
k
52
(n
=
15
)
(n
=3
1)
70
Pain Severity
27.9%
40
Pain Frequency
Time
30
Baseline
Wk 5
Wk 9
Wk 12
Time
Pain Severity
Wk 24
Wk 52
Change in KPS Score on Injected Right Knee
(93% of data) (p<0.05)
Score
80
Relative
Effect Size
Pain Frequency
96.4%
24
2
60
(n
=3
W
2)
k
52
(n
=
15
)
(n
=3
1)
70
W
k
50
Pain Severity
29.9%
40
Pain Frequency
Time
30
Baseline
Wk 5
Wk 9
Wk 12
Time
Pain Severity
Wk 24
Wk 52
Correlations
► Do
any of the following demographic criteria
predict outcomes?
► No








Tobacco
BMI
Hx Arthroscopic Surgery
Diabetes
Duration of Knee Pain
Weight
History of ACL surgery
X-ray severity grade
Correlations
► Do
any other demographic criteria predict
better outcomes?
► Yes
 Gender (F)
►Pain
36% (p=0.03)
►Stiffness 59.7% (p=0.003)
►Function 39.9% (p=0.02)
► Maybe
 Age (56-65)
►Pain
52% (p=0.08)
►Stiffness 36% NS
►Function 39% NS
Further Analyses
► Demographic




Data Correlations
Duration of Knee Pain
Weight
History of ACL surgery
X-ray severity grade
► Patient
Satisfaction, Qualitative Interview
► Patient Adherence
► Medication Use
Safety
► Routine
injection side effects
 Injection pain
 Mild bleeding, bruising
 One case of superficial neuropathy, slowly
resolving
 No significant adverse effects
► Prolotherapy
appears to be no more
dangerous than other injection therapies
►
Dagenais S, Ogunseitan O, Haldeman S, Wooley JR, Newcomb RL. Side effects
and adverse events related to intraligamentous injection of sclerosing solutions
(prolotherapy) for back and neck pain: a survey of practitioners. Arch Phys
Med Rehabil 2006;87:909-913.
Context
► Percentage
improvement meets or exceeds
minimal clinical important difference for
WOMAC (12% improvement from baseline)
and chronic pain (15-20%)
► Comparison to standard of care therapies in
progress
► Further analyses in progress
► More to come!
 Study complete in early 2009
 Data Analysis in Progress
►Patient
Satisfaction
►Knee x-ray severity correlations
Strengths and Limitations
► Strengths
 Pragmatic: generalizable patients
 Tests a usual prolotherapy protocol for a
common condition
 1 year follow-up
 Standard, validated patient-oriented outcome
measure
 Substantial, consistent results
► Weaknesses
 Non-randomized design
 Small sample size
Conclusions/Future Directions
► Consistent
moderate-large effect sizes in
this pragmatic sample
► Prolotherapy may be of clinical use for knee
OA; further studies are warranted
 Larger, randomized studies
 Other injectants
►Platelet-Rich Plasma
►Sodium Morrhuate/Dextrose solution
►Autologous Stem Cells?!
Thanks!
Strength of Evidence: 2,500 treatments
BMJ Clinical Evidence; How much do we know?;
http://clinicalevidence.bmj.com/ceweb/about/knowledge.jsp; 2007
► Where
does prolotherapy fit?
► What is required to change practice?
Knee OA trial: Subject Recruitment
ICD-9 Billing code screen/Media/Direct
Clinic
Phone Screen (Secondary
incl/excl criteria)
Case Series
Meeting (Info, Consent,
Randomization, Q’naires)
Meeting (Info, Consent,
Q’naires)
Dextrose
N=37
Saline
N=37
MRI: T0, 6 m & 12 m
Exercise
M=37
Dextrose
N=37
MRI: T0 & 12 m
Follow up questionnaires at wks 5, 9, 12,
24 and 52
What really happened?
► Screened:
1198
► Interviewed: 193
► Total Injected: 134
► Knees Injected: 201
 4.5 sessions/pt
 20 skin
punctures/knee
 4 skin
slides/puncture
► 72,360
solution
“deliveries”