Discussion
A series of Prolotherapy treatments improved the X-ray findings in these five degenerated knees. Specifically, the joint space width (JSW) in these X-rays increased with Prolotherapy, signifying the regeneration of articular cartilage. The three patients also reported improvements in their pain and function with the Prolotherapy treatments.
Articular cartilage degeneration is the hallmark of the osteoarthritis that affects 46 million Americans. It has a major impact on functioning and independence and is the leading cause of disability in the general population of the United States according to the Center for Disease Control (CDC).[24] As the U.S. population ages, these numbers are likely to increase sharply. Among adults of working age (18 to 64 years), work limitations attributable to arthritis affects about one in 20 adults in the general population and one-third of those with arthritis.[25] For example, the annual cost of OA per person living with OA is approximately $5,700, but the economic burden of disabling knee and hip osteoarthritis has an annual cost per person of almost $10,000.[26,27] Needless to say efforts or treatments that could potentially reverse or stop the progression of OA would have a huge quality of life, as well as economic impact not only on individual patients but on health care costs overall.
Radiography is currently the most widely used method to assess damage in osteoarthritis, and regulatory requirements for the development of disease-modifying drugs in osteoarthritis still consider the measurement of joint space narrowing on plain X-rays to be the appropriate primary endpoint for demonstration of efficacy.[28,29,30] The radiographic grade of osteoarthritis has been shown to correlate with the amount of actual articular cartilage degeneration in the knee with chronic pain.[31] Standardized techniques for measuring joint space width (JSW) in the tibiofemoral compartments, taken from carefully acquired radiographs, have become accepted for quantifying changes in tibiofemoral hyaline articular cartilage thickness in knee osteoarthritis.[32,33] JSW measurement is used in the diagnosis of OA.[34] (See Figure 4.)

Absolute values for what is normal JSW is impossible because cartilage thickness varies so much from person to person.[35] Its use though is invaluable when monitoring the normal progression of OA and would be following the regression of OA with Prolotherapy.[36]
According to the American Association of Orthopedic Surgeons from a clinical perspective, the most compelling definition of knee OA is one that combines the pathology of osteoarthritis through confirming radiographs with patient reported symptoms of pain that occurs with joint use.[37] When evaluating patients with osteoarthritis of the knee, anterior/posterior, and lateral radiographs allow an adequate evaluation of the medial and lateral joint spaces.[38] To adequately assess the joint space, the anterior/ posterior view should be obtained with the patient in a standing position.[39] The lateral view also allows evaluation of the patellofemoral joint; however, an additional view, known as the sunrise view, can offer, even more information about this joint space (this is also called the merchant or sunrise view).[40] To ensure that the pre and post-Prolotherapy X-rays could be compared in regard to angle of the X-ray, a board certified radiologist reviewed all the films.[41]
X-rays were obtained in these five knees upon the request of the patients. It is not routine to order X-rays on patients with positive or curative results. These five knees suggest that standard clinical radiographs of the knee may prove beneficial in confirming the reason for the patients’ improvement with Prolotherapy.
Cases one and two represent the most common form of knee OA, degeneration of the medial femorotibial joint. The improvement of the JSW in case one was 0.5mm. In case two, the right knee JSW increased by 0.4mm and the left by 0.3mm. Case three involved the regeneration of the patellofemoral joint. This person had chondromalacia patellae. Not only was there evidence of increase in the JSW laterally of 0.6mm bilaterally, but the tracking of the patella improved. All of this improvement came while the patients’ functions improved. All met their pretreatment goals except case three, JL, who did not get back to unlimited competitive tennis. One item not in her favor is her 5’4”, 200+ pound muscular frame.
Previous attempts at cartilage regeneration have been numerous and mostly futile.[42,43,44,45] While a number of very complex surgical techniques exist, they require extensive rehabilitation periods and tremendous expense. Prolotherapy, on the other hand, is a simple, cost effective, time-efficient alternative. Prolotherapy injections are an outpatient procedure, taking the clinician just minutes to perform. Patient activities are virtually unlimited during the course of Prolotherapy treatments with a gradual return to pre-injury exercise levels. While the potential is there for Prolotherapy to improve the quality of life of patients with degenerative knee arthritis and be a cost savings, future long-term controlled studies will be needed to assess this.
To the age old question “Can adult articular cartilage cells be regenerated?” these five knees suggest the answer is “yes.” Each of the five post-Prolotherapy radiographs revealed an increase in joint space width which coincided with symptom relief and return of most function. This suggests in these five degenerated knees that Prolotherapy has the potential to reverse degenerative knee arthritis. Further research with a larger patient population and under a more controlled setting is needed to provide further evidence of cartilage regeneration and Prolotherapy.