Chondrogenic Effect of Intra-articular Hypertonic-Dextrose (Prolotherapy) in Severe Knee Osteoarthritis

Background Dextrose injection is reported to improve knee osteoarthritis (KOA)−related clinical outcomes, but its effect on articular cartilage is unknown. A chondrogenic effect of dextrose injection has been proposed. Objective To assess biological and clinical effects of intra-articular hypertonic dextrose injections (prolotherapy) in painful KOA. Design Case series with blinded arthroscopic evaluation before and after treatment. Setting Physical medicine and day surgery practice. Participants Symptomatic KOA for at least 6 months, arthroscopy-confirmed medial compartment exposed subchondral bone, and temporary pain relief with intra-articular lidocaine injection. Intervention Four to 6 monthly 10-mL intra-articular injections with 12.5% dextrose. Main Outcome Measures Visual cartilage growth assessment of 9 standardized medial condyle zones in each of 6 participants by 3 arthroscopy readers masked to pre-/postinjection status (total 54 zones evaluated per reader); biopsy of a cartilage growth area posttreatment, evaluated using hematoxylin and eosin and Safranin-O stains, quantitative polarized light microscopy, and immunohistologic cartilage typing; self-reported knee specific quality of life using the Western Ontario McMaster University Osteoarthritis Index (WOMAC, 0-100 points). Results Six participants (1 female and 5 male) with median age of 71 years, WOMAC composite score of 57.5 points, and a 9-year pain duration received a median of 6 dextrose injections and follow-up arthroscopy at 7.75 months (range 4.5-9.5 months). In 19 of 54 zone comparisons, all 3 readers agreed that the posttreatment zone showed cartilage growth compared with the pretreatment zone. Biopsy specimens showed metabolically active cartilage with variable cellular organization, fiber parallelism, and cartilage typing patterns consistent with fibro- and hyaline-like cartilage. Compared with baseline status, the median WOMAC score improved 13 points (P =.013). Self-limited soreness after methylene blue instillation was noted. Conclusions Positive clinical and chondrogenic effects were seen after prolotherapy with hypertonic dextrose injection in participants with symptomatic grade IV KOA, suggesting disease-modifying effects and the need for confirmation in controlled studies. Minimally invasive arthroscopy (single-compartment, single-portal) enabled collection of robust intra-articular data.