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 body’s native healing  ?Inflammatory process  ?Growth factor recruitment  ?Sclerose neovascularity associated with chronic tendon disease ► Growing in popularity nationwide

5. Prolotherapy Clinical Reports Decade

7. 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

8. 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 Follow up Questionnaires at weeks 5, 9, 12, 24, 52 Randomized Controlled Trial Knee OA trial: Subject Recruitment

9. 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

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 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 (p<0.05) (93% of data) Relative Effect Size Pain 28.3% Stiffness 28.9% Function 35.6% Score Time Baseline Wk 5 Wk 9 Wk 12 Wk 24 Wk 52 9080706050

14. 8070 60504030 Relative Effect Size Pain Frequency 84.6% Pain Severity 27.9% Score Time Change in KPS Score on Injected Left Knee (93% of data) (p<0.05)

15. Score 8070 60504030 Time Baseline Wk 5 Wk 9 Wk 12 Wk 24 Wk 52 Relative Effect Size Pain Frequency 96.4% Pain Severity 29.9% Change in KPS Score on Injected Right Knee (93% of data) (p<0.05)

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% (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

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 2006;87:909-913.

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/knowledge.jsp; 2007 http://clinicalevidence.bmj.com/ceweb/about/knowledge.jsp ► Where does prolotherapy fit? ► What is required to change practice?

25. Meeting (Info, Consent, Q’naires) Case Series Follow up questionnaires at wks 5, 9, 12, 24 and 52 ICD-9 Billing code screen/Media/Direct Clinic Phone Screen (Secondary incl/excl criteria) Dextrose N=37 Saline N=37 Exercise M=37 MRI: T0, 6 m & 12 mMRI: T0 & 12 m Meeting (Info, Consent, Randomization, Q’naires) Knee OA trial: Subject Recruitment Dextrose N=37

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”