Prolotherapy as a treatment Prolotherapy as a treatment for knee osteoarthritic painfor knee osteoarthritic pain

David Rabago, MDDavid Rabago, MDRosa DeLucia Rosa DeLucia

UW Department of Family MedicineUW Department of Family MedicineNIH-NCCAM, DFM, Hackett-Hemwall FoundationNIH-NCCAM, DFM, Hackett-Hemwall Foundation

Jeff Patterson, Jessica GrettieJeff Patterson, Jessica Grettie

Learning ObjectivesLearning Objectives►To briefly review significance of To briefly review significance of

knee osteoarthritisknee osteoarthritis

►To review the preliminary results of To review the preliminary results of an NIH/UW clinical trial assessing an NIH/UW clinical trial assessing prolotherapy for knee OA painprolotherapy for knee OA pain

The efficacy of prolotherapy for The efficacy of prolotherapy for knee osteoarthritic painknee osteoarthritic pain

►Knee OA: Bad Knee OA: Bad leading cause of disability/pain in the worldleading cause of disability/pain in the world present and symptomatic in up to 6% of the present and symptomatic in up to 6% of the

population over 30 in the USpopulation over 30 in the US Multiple risk factors and presumed etiologiesMultiple risk factors and presumed etiologies incidence increases up to 10 fold fromincidence increases up to 10 fold from

30 to 65 years of age30 to 65 years of age no definitive non-surgical, pain-control and no definitive non-surgical, pain-control and

disease-modifying treatment disease-modifying treatment

What is Prolotherapy?What is Prolotherapy?Technique for treating chronic MSK painTechnique for treating chronic MSK pain►Multiple injections of bioactive solutionMultiple injections of bioactive solution►Proliferant injected and at tender ligament Proliferant injected and at tender ligament

and tendon insertion points and within joints and tendon insertion points and within joints ►Stimulates the body’s native healingStimulates the body’s native healing

?Inflammatory process?Inflammatory process ?Growth factor recruitment?Growth factor recruitment ?Sclerose neovascularity associated with chronic ?Sclerose neovascularity associated with chronic

tendon diseasetendon disease►Growing in popularity nationwideGrowing in popularity nationwide

Prolotherapy Clinical ReportsProlotherapy Clinical Reports

Decade

OA Knee Pain Trial: OA Knee Pain Trial: HypothesesHypothesesRabago et al. In progressRabago et al. In progress

►1. Prolotherapy can 1. Prolotherapy can improve chronic pain, improve chronic pain, stiffness, function stiffness, function and…and…

►2. Subjects will 2. Subjects will adhere to therapy, be adhere to therapy, be satisfied and use less satisfied and use less pain medicationpain medication

ICD-9 Billing codes/Media/Direct ICD-9 Billing codes/Media/Direct ClinicClinic

Phone Screen (Secondary Phone Screen (Secondary Inclusion/Exclusion criteria)Inclusion/Exclusion criteria)

Prospective Case SeriesProspective Case Series

Meeting (Info, Consent, Meeting (Info, Consent, Questionnaires)Questionnaires)

Dextrose (n=36) Dextrose (n=36) 3-5 monthly sessions3-5 monthly sessions

Follow up Questionnaires at weeks Follow up Questionnaires at weeks 5, 9, 12, 24, 525, 9, 12, 24, 52Randomized Controlled TrialRandomized Controlled Trial

Knee OA trial: Subject RecruitmentKnee OA trial: Subject Recruitment

Patient Eligibility CriteriaPatient Eligibility Criteria►Adults 35-75 y.o.Adults 35-75 y.o.► Osteoarthritic painOsteoarthritic pain

> 3 months> 3 months► CrepitusCrepitus► Radiographic Radiographic

criteriacriteria►Quality-of-life Quality-of-life

impact scoreimpact score►Prolotherapist Prolotherapist

approvalapproval

►BMI >42BMI >42►Chronic pain Chronic pain

greater than knee greater than knee painpain

►Chronic pain Chronic pain requiring narcotic requiring narcotic

►Prolo patientProlo patient►SurgicalSurgical

InterventionIntervention►““Standard” knee protocolStandard” knee protocol

Intra-articular: 25% Dex.Intra-articular: 25% Dex. Extra-articular: 15% Dex.Extra-articular: 15% Dex.

►3 prolo injection series monthly3 prolo injection series monthly►2 optional prolo sessions 2 optional prolo sessions

monthlymonthly

Outcome MeasuresOutcome Measures►Western Ontario and McMaster Western Ontario and McMaster

University osteoarthritis index University osteoarthritis index (WOMAC)(WOMAC) pain, stiffness, functionpain, stiffness, function

►Knee Pain Scale (KPS)Knee Pain Scale (KPS) pain severity, frequency per knee pain severity, frequency per knee

►Quality of life, side effects, patient Quality of life, side effects, patient satisfaction and medication usesatisfaction and medication use

Baseline Subject Baseline Subject DemographicsDemographics

► Female, n (%) Female, n (%) 21 (58.3%)21 (58.3%)► Age, mean (SD) Age, mean (SD) 60.5 ± 8.760.5 ± 8.7► BMI, mean (SD) BMI, mean (SD) 30.7 ± 6.930.7 ± 6.9

► KPS (Left) KPS (Left) Pain Freq 35.1 ± 4.9Pain Freq 35.1 ± 4.9 Pain Sev 59.2 ± 3.9Pain Sev 59.2 ± 3.9

► KPS (Right) KPS (Right) Pain Freq 33.6 ± 3.3Pain Freq 33.6 ± 3.3 Pain Sev 57.8 ± 2.9Pain Sev 57.8 ± 2.9

► WOMACWOMAC PainPain 57.9 ± 2.9 57.9 ± 2.9 Stiffness 51.7 ± Stiffness 51.7 ±

3.83.8 Function 57.3 ± Function 57.3 ±

2.82.8

Change in WOMAC Scores over Change in WOMAC Scores over 12 Months (p<0.05) (93% of 12 Months (p<0.05) (93% of

data)data)Relative Relative

Effect SizeEffect SizePain 28.3%Pain 28.3%

Stiffness 28.9%Stiffness 28.9%

Function 35.6%Function 35.6%

ScoreScore

TimeTimeBaseline Wk 5 Wk 9 Wk 12 Wk 24 Wk 52Baseline Wk 5 Wk 9 Wk 12 Wk 24 Wk 52

9090

8080

7070

6060

5050

Baseline Wk 5 Wk 9 Wk 12 Wk 24 Wk 52Baseline Wk 5 Wk 9 Wk 12 Wk 24 Wk 52

8080

7070

6060

5050

4040

3030

Relative Relative Effect SizeEffect Size

Pain Frequency Pain Frequency 84.6%84.6%

Pain Severity Pain Severity 27.9%27.9%

ScoreScore

TimeTime

Change in KPS Score on Injected Left Change in KPS Score on Injected Left Knee (93% of data) (p<0.05) Knee (93% of data) (p<0.05)

ScoreScore8080

7070

6060

5050

4040

3030

TimeTimeBaseline Wk 5 Wk 9 Wk 12 Wk 24 Wk 52Baseline Wk 5 Wk 9 Wk 12 Wk 24 Wk 52

Relative Relative Effect SizeEffect Size

Pain Frequency Pain Frequency 96.4%96.4%

Pain Severity Pain Severity 29.9%29.9%

Change in KPS Score Change in KPS Score onon Injected Right Injected Right Knee (93% of data) (p<0.05) Knee (93% of data) (p<0.05)

CorrelationsCorrelations►Do any of the following demographic Do any of the following demographic

criteria predict outcomes?criteria predict outcomes?►NoNo

TobaccoTobacco BMIBMI Hx Arthroscopic SurgeryHx Arthroscopic Surgery DiabetesDiabetes Duration of Knee PainDuration of Knee Pain WeightWeight History of ACL surgeryHistory of ACL surgery X-ray severity gradeX-ray severity grade

CorrelationsCorrelations►Do any other demographic criteria Do any other demographic criteria

predict better outcomes?predict better outcomes?►YesYes

Gender (F) Gender (F) ►Pain 36% (p=0.03)Pain 36% (p=0.03)►Stiffness 59.7% (p=0.003)Stiffness 59.7% (p=0.003)►Function 39.9% (p=0.02)Function 39.9% (p=0.02)

►MaybeMaybe Age (56-65) Age (56-65)

►Pain 52% (p=0.08)Pain 52% (p=0.08)►Stiffness 36% NSStiffness 36% NS►Function 39% NSFunction 39% NS

Further AnalysesFurther Analyses►Demographic Data CorrelationsDemographic Data Correlations

Duration of Knee PainDuration of Knee Pain WeightWeight History of ACL surgeryHistory of ACL surgery X-ray severity gradeX-ray severity grade

►Patient Satisfaction, Qualitative InterviewPatient Satisfaction, Qualitative Interview►Patient AdherencePatient Adherence►Medication UseMedication Use

SafetySafety►Routine injection side effectsRoutine injection side effects

Injection painInjection pain Mild bleeding, bruisingMild bleeding, bruising One case of superficial neuropathy, slowly One case of superficial neuropathy, slowly

resolvingresolving No significant adverse effectsNo significant adverse effects

►Prolotherapy appears to be no more Prolotherapy appears to be no more dangerous than other injection therapiesdangerous than other injection therapies

► Dagenais S, Ogunseitan O, Haldeman S, Wooley JR, Newcomb RL. Side Dagenais S, Ogunseitan O, Haldeman S, Wooley JR, Newcomb RL. Side effects and adverse events related to intraligamentous injection of effects and adverse events related to intraligamentous injection of sclerosing solutions (prolotherapy) for back and neck pain: a survey of sclerosing solutions (prolotherapy) for back and neck pain: a survey of practitioners. practitioners. Arch Phys Med RehabilArch Phys Med Rehabil 2006;87:909-913. 2006;87:909-913.

ContextContext►Percentage improvement meets or Percentage improvement meets or

exceeds minimal clinical important exceeds minimal clinical important difference for WOMAC (12% improvement difference for WOMAC (12% improvement from baseline) and chronic pain (15-20%)from baseline) and chronic pain (15-20%)

►Comparison to standard of care therapies Comparison to standard of care therapies in progressin progress

►Further analyses in progressFurther analyses in progress►More to come! More to come!

Study complete in early 2009Study complete in early 2009 Data Analysis in ProgressData Analysis in Progress

►Patient SatisfactionPatient Satisfaction►Knee x-ray severity correlationsKnee x-ray severity correlations

Strengths and LimitationsStrengths and Limitations►StrengthsStrengths

Pragmatic: generalizable patientsPragmatic: generalizable patients Tests a usual prolotherapy protocol for a Tests a usual prolotherapy protocol for a

common conditioncommon condition 1 year follow-up1 year follow-up Standard, validated patient-oriented Standard, validated patient-oriented

outcome measureoutcome measure Substantial, consistent resultsSubstantial, consistent results

►WeaknessesWeaknesses Non-randomized designNon-randomized design Small sample sizeSmall sample size

Conclusions/FutureConclusions/Future DirectionsDirections

►Consistent moderate-large effect sizes Consistent moderate-large effect sizes in this pragmatic samplein this pragmatic sample

►Prolotherapy may be of clinical use for Prolotherapy may be of clinical use for knee OA; further studies are warrantedknee OA; further studies are warranted Larger, randomized studiesLarger, randomized studies Other injectantsOther injectants

►Platelet-Rich PlasmaPlatelet-Rich Plasma►Sodium Morrhuate/Dextrose solutionSodium Morrhuate/Dextrose solution►Autologous Stem Cells?!Autologous Stem Cells?!

Thanks!Thanks!

Strength of Evidence: 2,500 Strength of Evidence: 2,500 treatmentstreatments

BMJ Clinical Evidence; BMJ Clinical Evidence; How much do we know?How much do we know?; ; http://clinicalevidence.bmj.com/ceweb/about/knowledge.jsp; 2007; 2007

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

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)

DextroseN=37

SalineN=37

ExerciseM=37

MRI: T0, 6 m & 12 m MRI: T0 & 12 m

Meeting (Info, Consent, Randomization, Q’naires)

Knee OA trial: Subject RecruitmentKnee OA trial: Subject Recruitment

DextroseN=37

What What reallyreally happened? happened?► Screened: 1198Screened: 1198► Interviewed: 193Interviewed: 193► Total Injected: 134Total Injected: 134► Knees Injected: Knees Injected:

201201 4.5 sessions/pt4.5 sessions/pt 20 skin 20 skin

punctures/kneepunctures/knee 4 skin 4 skin

slides/punctureslides/puncture► 72,360 solution 72,360 solution

“deliveries”“deliveries”