University of Wisconsin–Madison

Magnetic Resonance Imaging in a Study of Prolotherapy for Knee Osteoarthritis

March 2007 to December 2009


Knee osteoarthritis (OA) is a common, painful, debilitating, age-related condition with enormous clinical importance to patients in Wisconsin and worldwide. Magnetic resonance (MR) imaging is recognized as the optimal imaging modality of the osteoarthritic knee in Phase 2 clinical trials investigating potentially disease-modifying therapy for the knee. However, MR assessment of the entire knee can take up to 1 hour, limiting its application. Prolotherapy (PrT) is an injection-based therapy for knee OA that is reported to decrease pain and modify disease by promoting improved strength and biomechanical integrity of ligament and tendon attachments and intra-articular collagenous structures. One randomized controlled trial (RCT) has reported significantly improved patellofemoral joint space width on knee radiographs after PrT treatment for knee OA.


The goal of this Medical Education Research Committee (MERC) grant is to assess changes in anatomic structures associated with knee OA using two MR protocols for whole organ knee evaluation – a standard MR protocol and a much faster “vastly undersampled isotropic projection reconstruction” (VIPR) protocol.

Preliminary Studies

MR assessment will be performed by Co-PI Richard Kijowski MD, a fellowship-trained musculoskeletal radiologist. Preliminary studies by Dr. Kijowski et al. of the VIPR MR sequence for NIH-mandated whole-organ assessment of knee OA suggest that assessment time can be reduced from 1 hour to 5 minutes. The VIPR method shows great promise for use in clinical trials investigating new disease-modifying OA therapies.

The applicant is the PI of an ongoing Phase 2 RCT comparing treatment outcomes of subjects with knee OA who receive either dextrose PrT or sham injections with physiologic saline (blinded intervention group), or at-home physical therapy. Subjects in the blinded intervention group are significantly outperforming their physical therapy counterparts on primary clinical outcome measures (pain, function and stiffness scores). These preliminary data suggest that PrT has a positive clinical effect. MR imaging is needed to determine whether PrT also has a disease-modifying effect on structures involved in knee OA.


Pre- and post-treatment MR evaluation will be added to the outcome assessment strategy of 42 subjects to be enrolled in the parent RCT. Dr. Kijowski will supervise MR evaluation using a protocol consistent with recent guidelines calling for evaluation of the knee as 1) a “whole organ” and 2) as individual tissue structures. The primary outcome will be a blinded score on the Whole Organ Magnetic Resonance (WORM) scale; WORM scores obtained using the 5-minute VIPR sequence will be compared to WORM scores obtained using a one-hour MR protocol to determine whether both methods can provide similar assessment of the osteoarthritic knee. Secondary outcomes will include blinded quantitative assessment of individual structures related to knee OA severity including knee synovium, synovial fluid, bone marrow edema, and cartilage volume.

Potential Benefits

The propsed study will add value by leveraging an existing IRB-approved study that is generating promising results. The proposed interdisciplinary, translational study is consistent with the mission of the MERC: 1) Positive outcomes would suggest that PrT has pain-control and disease-modifying effects, providing strong preliminary evidence for PrT as a primary treatment of knee OA improving the quality of life of Wisconsin knee OA patients. 2) Positive MR outcomes would enhance the study’s methodological rigor, encouaging funding for a larger, more definitive clinical trial. 3) The ability of the VIPR sequence to provide similar “whole-organ” knee assessment compared to currently used MR protocols would provide faster, less expensive MR evaluation, decreasing the burden of OA assessment and treatment on Wisconsin patients and the Wisconsin health care system.

This project led by: Richard Kijowski, MD