Letters to the Editor  |   February 2013
Prolotherapy: An Effective Adjunctive Therapy for Knee Osteoarthritis
Author Notes
  • Department of Family Medicine, University of Wisconsin School of Medicine and Public Health, Madison 
Article Information
Neuromusculoskeletal Disorders / Arthritis
Letters to the Editor   |   February 2013
Prolotherapy: An Effective Adjunctive Therapy for Knee Osteoarthritis
The Journal of the American Osteopathic Association, February 2013, Vol. 113, 122-123. doi:
The Journal of the American Osteopathic Association, February 2013, Vol. 113, 122-123. doi:
To the Editor: 
The November 2012 article by Van Manen and colleagues1 on the management of knee osteoarthritis (OA) provides a useful update of several therapies. However, numerous complementary and alternative therapies also exist that are supported by varying degrees of evidence-based data. Among these, prolotherapy is particularly well suited to the osteopathic community, appears to be effective for knee OA, and deserves mention. 
Prolotherapy is an injection therapy for chronic musculoskeletal injury, including knee OA.24 Small volumes of an irritant solution are injected during several treatment sessions at painful tendon and ligament insertions and in adjacent joint spaces.2 Although the mechanism of action is unclear, inflammatory and neural effects have been suggested.2 Because sources of pain in knee OA include intra-articular and supportive extra-articular structures,5,6 prolotherapy injections targeting multiple potential pain generators in and around the knee joint may be well suited to address the multifactorial etiologic process of knee OA pain. 
An early report documented the use of prolotherapy 75 years ago, when the technique was referred to as sclerotherapy because of the scar-forming properties of early injectants.7 Current injection protocols were formalized in the 1950s, when the more commonly used term prolotherapy (from proliferant therapy) was adopted on the basis of the observation that ligamentous tissue exhibited a larger cross-sectional area after prolotherapy injection in animal models.8 Early scientific literature of generally low methodologic rigor documented positive clinical outcomes from the 1930s to the early 2000s.9 
Our group has conducted an open-label trial10 and a blinded randomized controlled trial11,12 (Clinical Trial number NCT00085722) assessing prolotherapy for patients with knee OA. In the open-label trial, we compared pain and disability in participants receiving prolotherapy to their baseline levels;10 in the randomized controlled trial, we compared the effects of prolotherapy with blinded saline control or at-home exercise therapy.11,12 Outcomes in both studies were assessed by the validated Western Ontario McMaster University Osteoarthritis Index (WOMAC; 100-point scale) at 52 weeks. 
Participants in the open-label study10 reported improvement in overall WOMAC scores at as early as 4 weeks progressing through 52 weeks (mean [standard deviation (SD)] point improvement, 15.9 [2.5]; P<.001). Interestingly, while participants reported less severe baseline knee OA in uninjected contralateral knees compared with injected knees, they reported small but statistically significant improvements in pain severity and frequency (P<.001) and severity alone (43%; P=.001) at 52 weeks as well, suggesting a compensatory mechanism associated with prolotherapy.10 
In the randomized controlled trial,11,12 WOMAC scores among prolotherapy recipients improved more at 52 weeks than did scores among saline control and at-home exercise participants (mean [SD] score change, 15.3 [3.5] vs 7.6 [3.4] and 8.2 [3.3], respectively; P<.05). In both studies,10-12 the improvement in WOMAC scores exceeded the minimal clinically important difference for the WOMAC of 12 points, satisfaction with prolotherapy was high, and no adverse events occurred. 
Definitive determination of the clinical utility of prolotherapy for knee OA will require confirmation in a larger effectiveness trial that includes biomechanical and imaging outcome measures to assess potential disease modification. Additional reports now in preparation or review will address long-term (3-year) qualitative and magnetic resonance imaging findings. However, our findings suggest that prolotherapy is clinically appropriate before total knee arthroplasty for carefully selected patients with knee OA in whom conservative therapy has been unsuccessful. 
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Hackett GS, Hemwall GA, Montgomery GA. Ligament and Tendon Relaxation Treated by Prolotherapy. 5th ed. Oak Park, IL: Gustav A. Hemwall; 1993.
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Rabago D, Zgierska A, Fortney Let al. Hypertonic dextrose injections (prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. J Altern Complement Med. 2012;18(4):408-414. [CrossRef] [PubMed]
Rabago D, Patterson JJ, Mundt Met al. A randomized controlled trial of dextrose prolotherapy for knee osteoarthritis. Ann Fam Med. In press.
Rabago D, Miller DJ, Zgierska Aet al. Dextrose prolotherapy for knee osteoarthritis: results of a randomized controlled trial [abstract 308]. Osteoarthritis Cartilage. 2011;19(suppl 1):S142-S143. [CrossRef]