Prolotherapy (Dextrose Injection Therapy) — Regenerative Therapies
Injection of hypertonic dextrose solution to stimulate healing of damaged ligaments and tendons. Moderate evidence for chronic pain.
Overview
Prolotherapy (proliferation therapy or regenerative injection therapy) involves the injection of a concentrated dextrose solution (typically 12.5-25% dextrose in water) into damaged or degenerated ligament and tendon attachments (entheses). The hyperosmolar dextrose solution creates a local inflammatory response that stimulates the body's natural healing cascade, promoting fibroblast proliferation, collagen synthesis, and tissue remodeling at the injection site. Originally developed by George Hackett, MD in the 1950s, prolotherapy has been used for decades for chronic musculoskeletal pain conditions. A systematic review and meta-analysis by Sit et al. (2016) found moderate-quality evidence supporting prolotherapy for knee osteoarthritis, with significant improvements in pain and function at 12-52 weeks compared to exercise alone. Evidence for chronic low back pain (ligamentous origin), lateral epicondylitis, and Achilles tendinopathy shows mixed but generally positive results. The proposed mechanism involves the hypertonic dextrose creating an osmotic and cellular stress that activates local growth factor release (PDGF, TGF-beta, FGF, IGF-1), attracting inflammatory cells and fibroblasts to the injection site. This inflammatory initiation is followed by proliferative and remodeling phases that strengthen the collagenous tissue. Prolotherapy is typically performed as a series of 3-6 injection sessions spaced 2-6 weeks apart, with progressive improvement occurring over months.
Indications
- Evidence-supported: Knee osteoarthritis (pain and function improvement)
- Evidence-supported: Chronic low back pain (ligamentous origin)
- Moderate evidence: Lateral epicondylitis (tennis elbow)
- Moderate evidence: Achilles tendinopathy
- Emerging evidence: Temporomandibular joint (TMJ) dysfunction
- Emerging evidence: Sacroiliac joint instability
Mechanism of Action
Hypertonic dextrose (12.5-25%) creates osmotic cellular stress at the injection site, triggering a local inflammatory response
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Dextrose 15-25% | 0.5-3 mL per site | Every 2-6 weeks x 3-6 sessions | Standard prolotherapy protocol; multiple injection sites per session |
| Dextrose 12.5-25% | 3-5 mL | Every 4-6 weeks x 3-5 sessions | Knee osteoarthritis protocol |
Evidence Grade
GRADE C
Safety & Contraindications
- Generally safe — dextrose is a natural sugar with minimal systemic toxicity
- Injection site pain and temporary flare (24-72 hours) is expected and common
- Bruising and swelling at injection sites
- Infection risk (standard sterile injection precautions)
- Avoid NSAIDs 48 hours before and 1-2 weeks after injection
- Not recommended for inflammatory arthritis (RA)
- Multiple sessions required — not a single-treatment solution