The document summarizes research on prolotherapy, which involves injections to repair soft tissues like ligaments and tendons. It discusses definitions of prolotherapy and focuses on dextrose prolotherapy. It provides evidence that prolotherapy is not experimental, as it is taught in postgraduate medical programs and supported by published studies. Several studies on specific conditions like Achilles tendinosis, knee osteoarthritis, and low back pain are summarized, demonstrating safety and efficacy of prolotherapy though some need further research.

1. Prolotherapy
Research:
Summary and
Status
AAOM 29th Annual Conference April 18-21 2012
K. Dean Reeves, M.D.
Clinical Associate Professor
University of Kansas

2. Sections of Talk
• Definitions and Focus
• Is Prolotherapy Experimental?
• Studies by Topic.

3. Definition of Prolotherapy:
Option One
• Injection to repair or restore function of
soft tissue which includes cartilage,
ligament, tendon, nerve, and supportive
matrix.
• PRP, stem cell, and ozone injection are all
methods of reparative injection and can
reasonably be called prolotherapy.
• For billing purposes connective tissue or
joint prolo should be distinct from Neural
prolo.

4. Definition of Prolotherapy:
Option Two
• Injection to repair soft tissue which
includes cartilage, ligament, tendon,
nerve, and supportive matrix.
• Injection to restore nerve function neural
prolotherapy is best termed Lyftogt
technique.
• For billing purposes connective tissue or
joint prolo should be distinct from Neural
prolo.

5. Focus of This Talk
• Dextrose prolotherapy as data on other
types of injectants is much more limited.
• However, we will consider how other
injectants can be evaluated in similar
ways.

6. Dextrose Prolotherapy Is Not
Experimental Because
• It is taught as an acceptable method
procedure by one or more approved post
graduate programs for the healing arts?
(Univ Wisconsin, specialty college in
AOA), and
• It is based upon sufficient learned
publications supporting the safety and
efficacy? (Level B or higher in multiple
areas)

7. Taught in Department of Family
Medicine at University of Wisconsin
• “Prolotherapy is performed and taught to Family
Medicine residents on a regular basis at the
University of Wisconsin School of Medicine and
Public Health. Residents in this program also
participate in a 2 week hands on CME training
program in prolotherapy in Honduras. This counts
as part of their orthopedic elective time in the
residency.”
Jeffrey J. Patterson, Professor of F.P. at U.W Wisconsin

8. Taught in Continuing Education
Programming By University of
Wisconsin
• “In addition the The University of Wisconsin School
of Medicine and Public health sponsors post
graduate CME programs in prolotherapy through
the UW Department of Continuing Medical
Education. These are held annually on the UW
campus. “
Jeffrey J. Patterson, Professor of Family Practice at U.W Wisconsin

9. Prolotherapy is An Official Specialty
College Listing Within the American
Osteopathic Association.
• The official listing of Specialty Colleges within
the American Osteopathic Association on the
AAOM website includes 23 specialties: addiction
medicine, allergy and immunology, anesthesiology, dermatology,
emergency medicine, family medicine, internal medicine, medical
informatics, neurology and psychiatry, obstetrics and gynecology,
occupational and preventative medicine, ophthalmology and otolaryngology,
orthopedics, osteopathy, pathology, pediatrics, physical medicine and
prolotherapy and integrative
rehabilitation, proctology,
pain management, radiology, rheumatology, sports medicine,
and surgery.
• http://www.osteopathic.org/inside-aoa/about/affiliates/Pages/osteopathic-specialty-colleges.aspx

10. U.S. Preventative Service Task Force
Classification of Evidence
• Level I: Well designed RCT (s) with clinical and
statistically significant evidence.
• Level II: Well designed:
II-1 Controlled trials without randomization
II-2 Cohort or case control studies from more
than one center.
II-3 Dramatic result from uncontrolled trial,
Blinded Machine Measure case control
Level III. Substantially flawed RCTs or other controlled
studies. Single well designed cohort or case control
study

11. When SHOULD You Discuss
Prolotherapy With Patients
• A: Good evidence Benefit > Risk
• B: Fair evidence Benefit > Risk
• C. Fair evidence Benefit = Risk
• D. Fair evidence Benefit < Risk
• I. Insufficient , poor quality or conflicting
evidence.

12. References for Levels of Evidence
Rabago D, Slattengren A, Zgierska A.
Prolotherapy in Primary Care Practice. Prim
Care. 2010;37(1):65-80.
Reeves KD. Lyftogt J Prolotherapy:
Regenerative injection therapy. In: Waldman
SD (ed): Pain Management. Philadelphia;
Saunders (Elsevier), 2nd ed; 2011:1027-1044.

13. Low Risk Level With Prolotherapy
Therefore Quality Level ≈ Recommendation
Good RCT I=A Osgood Schlatter
Good NRCT II-1=B Achilles Tendinosis , Finger OA,
Fair RCT Knee OA (2000), Lat Epicond (2008),
Low Back Pain, S-I Pain (2010)
>1 Cohort II-2= B
Dramatic CC, II-3= B Adductor tendinopathy
BMM CC, >1 CC,
Many CP
1 Cohort, Small III=C Coccygodynia , Plantar fasciosis,
BMM CC, Med # ACL laxity.
CP
NRCT = Nonrandomized Controlled Study, CC = Case Controlled, CP =
Consecutive Patient , BMM = Blinded Machine Measure

14. Referrals for Prolotherapy Are
Not Just Based on Evidence
• Competition
• Literature ignorance
• Invasiveness
• Artfulness

15. Insurance Coverage Is Not Just Based
on Evidence
• Standardized method. This will
require introduction into medical
schools or repeated RCTs.
• Simple method compatible with
single level payment.

16. Benefit of Insurance Coverage Is Not
Just Based on Evidence
• Option to bill above single level
payment for more complex cases?
(Time based or condition based
approach is too advanced to expect in
a socialist system)
• Insurance company abuse.

17. Achilles Tendinosis (Chronic)
• RCT Nonblinded: #40 (15/14/15), Yelland 2009, 20%
Dextrose + .1 Lido/Ropiv, subcu, weekly, mean 9.5 Rx, 1 Yr
fup, 5 dropouts (3 intolerant of ELE). Neural prolo = Best
Usual Care (ELE),
• Case series: #35, Maxwell 2007. 25% Dextrose + 1% Lido,
intratendon, 6 week interval, 4(2-11) Rx, 1 Yr fup, 90% data,
VAS sport 78%, HRUS injection guidance but no fup image
• Case series #108, Ryan 2010, 25% Dextrose + .5% Lido,
intratendon, 6 wk interval, 5(1-13) Rx, 28 wk(5-73) HRUS
fup, 1-4 Yr symptom fup, 70% data, VAS sport 74%
improvement, HRUS correlation.
• CONCLUSION = Fair evidence of benefit and objective
ultrasound findings but methods needing improvement
in efficacy to exceed therapy standard of care. = B

18. ACL Ligament Laxity
• Case series #18: Reeves 2003, KT-1000 ADD >1, single intraartic
10% Dextrose + .1 Lido + .9 BA in water VS same without 10%
Dextrose. 9 ml Q 2 mo X 3 and then PRN for 3 years. (25%
dextrose given in some injections after year one) 2 dropout (1
disseminated cancer and 1 w/c bound with travel issues), 10/16 no
laxity and sustained at 3 months, pain with walking improved 43%,
subjective swelling improved 63%, ROM by 10.5 degrees total
flexion.

19. ACL Ligament Laxity
• Summary: Single case series but with objective end
point. (KT-1000 measure)  Level B/C Safety plus fair
evidence of effectiveness but small study needing
confirmation.
• Option: Repeat with delayed treatment cohort and
blinded machine measure.
• Reeves KD, Hassanein K. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern
Ther Health Med (United States), May-Jun 2003, 9(3) p58-62

20. Adductor Tendinosis
• Case Series #72 Topol 2008,12.5%
dextrose + 0.5% lido, enthesis, 1 month
interval, μ (1-6) Rx, μ 26(6-72) month fup,
100% data capture, 82% improvement in
groin pain, 92% return to full sport.

21. Adductor Tendinosis
• Summary: Moderate size study with failure of usual
treatment and clear endpoint of unrestricted sport. 
Level B Evidence. Safety and good evidence of efficacy.
• Options: Repeat study for stronger B level evidence as
blinding not feasible/ethical. Consider neural therapy
approaches as they are clarified.
Topol GA, Reeves KD: Regenerative injection of elite athletes with career-altering chronic groin pain who fail
conservative treatment: a consecutive case series. Am J Phys Med Rehabil. 2008;87(11):890-902

22. Coccygodynia Pain
• Case Series #37: Khan 2008, 20%
dextrose + .4% lido 10 ml over most
tender area, 2 week interval, 2-3 Rx, fup
time not mentioned, marked improvement
in VAS for pain in 30/37.

23. Coccygodynia Pain
• Summary: Level B/C Evidence. Attractive surgery
alternative but small size and fup time not specified.
May have neural effect via large volume.
• Option: Repeat with neural prolo and potentially
enthesis injection as well and more defined followup
timing.
• Khan SA, Kumar A, Varshney MK, Trikha V, Yadav CS. Dextrose prolotherapy for recalcitrant coccygodynia. J
Orthop Surg 2008;16:27–29.

24. Finger Osteoarthritis
• RCT #27 (13 Dextrose/ 14 Lido): Reeves 2000, medial
and lateral injection of ½ ml of either 10% Dextrose + .1
Lido + .9 BA in water VS same without 10% Dextrose.
Q 1 mo X 3. 6 mo fup blinded. Then all received
dextrose through 1 year. 100% data capture to 1 year. 6
month data showed pain with movement significantly
better with dextrose (42% vs 15% p = .027) and flexion
range improved more (+8 vs -8.7 degrees, p =.003)

25. Finger Osteoarthritis
• Summary: Small single RCT.  Level A Safety plus fair
evidence of effectiveness. However other classification
is 1B evidence with small high quality RCT with fewer
than 2 consistent RCTs. Discomfort with injection is
drawback to this method.
• Option: Vitamin D study due to pain with injection as an
alternative.
Reeves KD, Hassanein K: Randomized prospective placebo-controlled double-blind study of dextrose prolotherapy
for osteoarthritic thumbs and fingers (DIP, PIP and trapeziometacarpal Joints) : Evidence of clinical efficacy. Jnl
Alt Compl Med 2000;6(4):311-320.

26. Knee Osteoarthritis
• RCT #120: Reeves 2000, single intraartic 10% Dextrose
+ .1 Lido + .9 BA in water VS same without 10%
Dextrose. 9 ml Q 2 mo X 3. 6 mo fup blinded. 6 Month
additional fup for 1 yr. 9 dropouts (5 medial, 4 efficacy[3
lido]). 100% data capture for remaining 111. Pain
improvements not different but ROM and subjective
swelling and buckling episodes were better in the
dextrose group. (Overall Dextrose better with P = .015)
• RCT # ___ UW Study with final results pending.
• Pre and Post Arthroscopy study Argentina in bone on
bone (medial compartment) knees with results pending.

27. Knee Osteoarthritis
• Summary: Level B Evidence. Risks minimal (dextrose
alone). Good clinical response but not level A because
control improved pain enough that lidocaine or benzyl
alcohol or hypotonic solution injection may not be a
control intervention. Needs further confirmation for that
reason.
• Option: Await UW Study and arthroscopy study results.
May repeat without lidocaine vs Saline. (Dextrose has
been found to be analgesic). OR may combine neural
therapy, or alternatively treat with neural prolotherapy
without intraarticular prolo.
Reeves KD, Hassanein K: Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for
knee osteoarthritis with or without ACL laxity. Alt Ther Hlth Med 2000;6(2):68-80.

28. Lateral Epicondylosis (Chronic,
non PRP)
• RCT #24 (12,12), Scarpone 2008, .
7NaMorr + 10% Dex + .3 Lid + .03
Sensorcaine, bone contact 3 locations, 4
wk interval, 3 Rx, 1 Yr fup, 1 dropout
(control), 90% vs 27% VAS impr resting
elbow pain, impr grip and isometric
strength.

29. Lateral Epidondylosis (Chronic,
Non PRP)
• Summary: Small single RCT.  Level A Safety plus fair
evidence of effectiveness. However other classification
is 1B evidence with small high quality RCT with fewer
than 2 consistent RCTs.
• Option: Vit D cream or US guided dextrose blinded,
subcu dextrose vs usual care RCT, consec subcu +/-
bone contact in failure usual care.
• Note: Method refinements marked in subcu method.
• Scarpone M, Rabago DP, Zgierska A, Arbogast G, Snell E: The efficacy of prolotherapy for lateral
epicondylosis: a pilot study. Clin J Sport Med 2008;18(3):248-54

30. Low Back Pain: Non specific
• RCT: Ongley 87, Klein 93. Multiple simultaneous treatments but
strong sustained effects on pain and disability.
• RCT: Dechow 99. Incorrect injection areas with strong proliferant.
Non interpretable.
• RCT #110: Yelland 2003, 20% Dextrose + .2% Lido, enthesis, 2
week Rx interval, μ7.1 Rx, 96% data capture 1 year and 80% at 2
years, no signif differences with saline but 36%/33% improvement in
pain and 42%/31% improvement in disability scores at 1 year,
sustainable to 2 years.

31. Low Back Pain: Non specific
• Summary: Level B/C Evidence. Fair sized study with
safety and fair efficacy for dextrose but control appeared
as efficacious. (Could be level B if control shown not to
be control)
• Option: Cluneal nerve treatment, dextrose versus
steroid epidural.
Ongley MJ, Klein RG, Dorman TA, Eck B: A new approach to the treatment of chronic low back pain. Lancet
1987;2:143-146.
Klein RG, Bjorn CE, DeLong B, Mooney V: A randomized double-blind trial of dextrose-glycerine-phenol injections for
chronic low back pain. J Spinal Disord 1993;6(1):23-33.
Dechow E, Davies RK, Carr AJ, Thompson P: A randomized, double-blind, placebo-controlled trial of sclerosing
injections in patients with chronic low back pain. Rheumatology 1999;38(12):1255-1259.
Yelland MJ, Glasziou PP, Bogduk N, Schluter PJ, McKernon M: Prolotherapy injections, saline injections, and
exercises for chronic low-back pain: A randomized trial. Spine 2003;29(1):9-16.

32. Osgood-Schlatter Disease
• RCT #65: Topol Pending, Dextrose >
Lidocaine > Usual Care.

33. Plantar fasciosis (Chronic)
• Case series #20, Ryan 2009, 25%
Dextrose + 1% Lido, Intratendon, 6 week
internal, 3(1-12) Rx, 11 month (6-20 mo)
fup, 100% data capture, 75%
improvement in 80% of patients, no fup
HRUS.

34. Plantar Fasciosis (Chronic)
• Summary: Level B/C Evidence. Safety and fair evidence
of efficacy but consec patient and small without HRUS
fup.
• Option: Vit D cream, subcu dextrose, US driven
dextrose.
• Note: Nerve involvement has been clarified.
• Ryan MB, Wong AD, Gillies JH, Wong J, Traunton JE Sonographically guided intratendinous injections of
hyperosmolar dextrose/lidocaine: a pilot study for the treatment of chronic plantar fasciitis. Br J Sports Med
2009;43:303-306.

35. Sacroiliac Pain
• RCT #48 (23 dextrose, 25 steroid): Kim 2010, Dextrose
water conc? vs triamcinolone (INTRAARTICULAR) in
confirmed SI via anethetic injection with 50%
improvement for 3 months or longer, Q2 week Rx, 3 Rx.
59% vs 10% improvement at 15 month fup.
• Case series #25. Cusi 2010, 17% Dextrose + . 4%
bupivicaine + contrast. .8 in SI ligament via guidance.
(EXTRAARTICULAR) 3 Rx. 76% data capture at 1
year. Marked reduction in SI laxity measures by exam
and improvement in Quebec Back Pain Diabilitity and
Roland Morris Questionnaire measures.

36. Sacroiliac Pain
• Summary: Level A/B evidence for SI injection in
anesthetic confirmed SI pain. Need detail confirmation
and another study for confirmation of level A. Level B/
C evidence for small volume SI ligament only injeciton
with exam confirmed SI pain due to small size,
measurable but not blinded end points, significant
dropout.
• Option: Clarify details for confirmation via consecutive
patient data of Kim et al. For Cusi et al repeat with
delayed treatment and blinded testing between
immediate and delayed treatment groups.
• Kim WM; Lee HG; Won Jeong C; Kim CM; Yoon MH. ARTICLE TITLE: A randomized controlled trial of intra-
articular prolotherapy versus steroid injection for sacroiliac joint pain [In Process Citation] ARTICLE SOURCE: J
Altern Complement Med (United States), Dec 2010, 16(12) p1285-90
• Cusi M, Saunders J, Hungerford B, Wisbey-Roth T, Lucas P, Wilson S: The use of prolotherapy in the sacro-iliac
joint. Br J Sports Med 2010;44:100-110.