Prolotherapy%20as%20a%20treatment%20for%20knee%20osteoarthritic%20pain

1
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

2
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

3
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

4
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 bodys native healing
• ?Inflammatory process
• ?Growth factor recruitment
• ?Sclerose neovascularity associated with chronic
  tendon disease
• Growing in popularity nationwide

5
Prolotherapy Clinical Reports
Decade
6
(No Transcript)
7
OA Knee Pain Trial HypothesesRabago 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

8
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 (n36) 3-5
monthly sessions
Follow up Questionnaires at weeks 5, 9, 12, 24, 52
Randomized Controlled Trial
9
Patient Eligibility Criteria

• Adults 35-75 y.o.
• Osteoarthritic pain
• gt 3 months
• Crepitus
• Radiographic criteria
• Quality-of-life impact score
• Prolotherapist approval

• BMI gt42
• Chronic pain greater than knee pain
• Chronic pain requiring narcotic
• Prolo patient
• Surgical

10
Intervention

• Standard knee protocol
• Intra-articular 25 Dex.
• Extra-articular 15 Dex.
• 3 prolo injection series monthly
• 2 optional prolo sessions monthly

11
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

12
Baseline Subject Demographics

• Female, n () 21 (58.3)
• Age, mean (SD) 60.5 8.7
• BMI, mean (SD) 30.7 6.9

• 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

• WOMAC
• Pain 57.9 2.9
• Stiffness 51.7 3.8
• Function 57.3 2.8

13
Change in WOMAC Scores over 12 Months (plt0.05)
(93 of data)
Score
Relative Effect Size
90 80 70 60 50
Pain 28.3 Stiffness 28.9 Function 35.6
Baseline Wk 5 Wk 9 Wk 12
Wk 24 Wk 52
Time
14
Change in KPS Score on Injected Left Knee (93 of
data) (plt0.05)
Score
80 70 60 50 40 30
Relative Effect Size Pain Frequency 84.6 Pain
Severity 27.9
Baseline Wk 5 Wk 9 Wk 12
Wk 24 Wk 52
Time
15
Change in KPS Score on Injected Right Knee (93
of data) (plt0.05)
Score
80 70 60 50 40 30
Relative Effect Size Pain Frequency 96.4 Pain
Severity 29.9
Baseline Wk 5 Wk 9 Wk 12
Wk 24 Wk 52
Time
16
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

17
Correlations

• Do any other demographic criteria predict better
  outcomes?
• Yes
• Gender (F)
• Pain 36 (p0.03)
• Stiffness 59.7 (p0.003)
• Function 39.9 (p0.02)
• Maybe
• Age (56-65)
• Pain 52 (p0.08)
• Stiffness 36 NS
• Function 39 NS

18
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

19
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 200687909-913.

20
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

21
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

22
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?!

23
Thanks!
24
Strength of Evidence 2,500 treatments BMJ
Clinical Evidence How much do we know?
http//clinicalevidence.bmj.com/ceweb/about/knowle
dge.jsp 2007

• Where does prolotherapy fit?
• What is required to change practice?

25
Knee OA trial Subject Recruitment
ICD-9 Billing code screen/Media/Direct Clinic
Case Series
Phone Screen (Secondary incl/excl criteria)
Meeting (Info, Consent, Qnaires)
Meeting (Info, Consent, Randomization, Qnaires)
Dextrose N37
Saline N37
Exercise M37
Dextrose N37
MRI T0, 6 m 12 m
MRI T0 12 m
Follow up questionnaires at wks 5, 9, 12, 24 and
52
26
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