Clinicians at the Universities of Wisconsin and Iowa identified previous studies of Prolotherapy as lacking in quality design methodology. They collaborated to design a rigorous clinical trial Prolotherapy for Knee Painevaluating the effect of dextrose prolotherapy on quality of life for persons with osteoarthritis of the knee.

The Study Method

  • Ninety adults ages 40 -76 years with moderate to severe osteoarthritis of the knee for at least 3 months duration participated. Patients were either overweight or obese (74%), reported more than 5 years of knee pain and had failed at least one conservative therapy.
  • Subjects were randomly assigned to one of 3 groups: a 25% dextrose injection group, a saline injection group, or a home exercise group.
  • Injections were given at one, five and nine weeks with optional injections at 13 and 17 weeks. Subjects were given Tylenol and Oxycodone but were discouraged from using NSAIDs. The home exercise group was instructed to complete knee exercises daily and to gradually increase therapy over 20 weeks.


  • At 52 weeks the dextrose group reported a 24% improvement over baseline on pain, stiffness, and function. Near-maximal improvement was noted at 26 weeks and remained stable through 52 weeks. The most dramatic improvement was in knee function.
  • All groups showed some improvement, however the improvement of the dextrose group was statistically significant over the saline and home exercise program group. There were no adverse effects reported.

Why Does Prolo Work?

It’s not clear how Prolotherapy works, although it has been hypothesized that it stimulates healing of chondrocytes (cartilage cells), as well as affected tissues surrounding the joint.

  • It has also been suggested that Prolotherapy stimulates release of growth factors that favor soft tissue healing.
  • Clinical experience suggests that tune-up sessions after 52 weeks improve outcomes and do not carry additional risks. The results of this study were generally consistent with findings from other studies.



Rabago, D., Patterson, J., Mundt, M., Kijowski, R., Grettie, J., Segal, N. & Zgierska, A. (2013). Dextrose prolotherapy for knee osteoarthritis: A randomized controlled trial. Annals of Family Medicine, 11(3): 229-237.