Table 1.
Summary of trial design and protocol characteristics for included studies.
| # | Study | Design | Participant characteristics | Injection characteristics | Injectate characteristics |
|---|---|---|---|---|---|
| 1 | Eroğlu 2016 | Three-armed RCT; Dextrose prolotherapy vs PRP vs saline control; Follow-up at 3 and 6 months after first injection | Total 58 (Kellgren-Lawrence 1–3); Dextrose: 20, PRP: 18, Saline: 20 | Dextrose: Up to 15 EA injections using peppering technique based on major tender points followed by 1 IA injection from infero-medial approach; 3 procedures at 3-weekly intervals. PRP: Up to 15 EA injections using peppering tehcnique based on major tender points followed by 1 IA injection from infero-medial approach; 3 procedures at 3-weekly intervals. Saline: Up to 15 EA injections using peppering tehcnique based on major tender points followed by 1 IA injection from infero-medial approach; 3 procedures at 3-weekly intervals | Dextrose: 22.5 mLs of solution (concentration not disclosed) injected EA followed by 6 mLs of IA solution. PRP: 22.5 mLs of solution (2 centrifugations of 1500 rpm × 6 mins then 3500 rpm × 6 mins, activated with 10% calcium chloride) injected EA followed by 6 mLs of IA solution. Saline: 22.5 mLs of solution (reported concentration 0.09%) injected EA followed by 6 mLs of IA solution |
| 2 | Hashemi 2015 | RCT; Hypertonic dextrose prolotherapy vs ozone prolotherapy (prolozone); Follow-up at 3 months after last injection | Total 80 (Kellgren-Lawrence 1–2); Hypertonic dextrose: 40, Prolozone: 40 | Hypertonic dextrose: 1 IA injection from inferomedial approach; 3 procedures at intervals of 7–10 days. Prolozone: 1 IA injection from inferomedial approach; 3 procedures at intervals of 7–10 days | Hypertonic dextrose: 7 cm3 of 12.5% dextrose. Prolozone: 5–7 cm3 of 15 g/mL ozone-oxygen mixture |
| 3 | Hosseini 2019 | RCT; Hypertonic dextrose-saline vs hyaluronic acid prolotherapy; Follow-up at 3 months | Total 104 (Kellgren-Lawrence ≥2); Hypertonic dextrose-saline: 52, Hyaluronic acid: 52 | Hypertonic dextrose-saline: 4 peri-articular injections using fan-wise technique (2 injections at superolateral patella, 1 at medial knee joint line, 1 at anterior fibular head); 3 procedures at days 0, 7, and 14. Hyaluronic acid: 1 IA injection from inferomedial approach; 3 procedures at days 0, 7, and 14 | Hypertonic dextrose-saline: 10 mLs of 12.5% dextrose (2.5 cc at each point). Hyaluronic acid: 2.5 mLs of hyaluronic acid |
| 4 | Pishgahi 2020 | Three-arm RCT; Dextrose prolotherapy vs PRP vs autologous conditioned serum (ACS); Follow-up at 1 and 6 months | Total 92 (Radiologic grade 2–4); Dextrose: 30, PRP: 30, ACS: 32 | Dextrose: 1 IA injection from supra-lateral approach; 3 procedures at weekly intervals. PRP: 1 IA injection from supra-lateral approach; 2 procedures at weekly intervals. ACS: 1 IA injection from supra-lateral approach; 2 procedures at weekly intervals | Dextrose: 2 mLs of 50% dextrose mixed with 2 mLs water and 1 mL of 2% lidocaine. PRP: 4X concentration of platelets from 20 mLs of venous blood. ACS: 2 mLs of conditioned supernatant from 20 mLs of venous blood |
| 5 | Rabago 2013 | Three-arm partially-blinded RCT; Dextrose prolotherapy vs saline control vs home exercise; Follow-up at 5, 9, and 12 weeks in person, 26 and 52 weeks by telephone | Total 98 (Moderate-severe pain); Dextrose: 30, Saline: 29. Exercise: 31 | Dextrose: Up to 15 EA injections using peppering tehcnique at ligament-bone insertions followed by 1 IA injection from infero-medial approach; 3–5 procedures at 1,5, and 9 weeks (optional sessions at 13 and 17 weeks). Saline: Up to 15 EA injections using peppering tehcnique at ligament-bone insertions followed by 1 IA injection from infero-medial approach; 3–5 procedures at 1,5, and 9 weeks (optional sessions at 13 and 17 weeks) | Dextrose: 22.5 mLs containing 6.75 mLs of 50% dextrose, 4.5 mLs of 1% lidocaine, and 11.25 mLs of 0.9% saline (EA); 6 mLs from a 10 mL solution containing 5 mLs of 50% dextrose and 5 mLs of 1% lidocaine/saline (IA). Saline: 22.5 mLs containing 18 mLs of 0.9% sodium chloride and 4.5 mLs of 1% lidocaine (EA); 6 mLs from a 10 mL solution containing 5 mLs of 0.9% sodium chloride and 5 mLs of 1% lidocaine (IA) |
| 6 | Rahimzadeh 2014 | Three-arm double-blind RCT; Erythropoietin prolotherapy (EPO) vs dextrose prolotherapy vs pulsed radiofrequency; Follow-up at 2, 4, and 12 weeks | Total 70 (Kellgren-Lawrence 1–3 or clinical class I-III); EPO: 20, Dextrose: 24, Pulsed radiofrequency: 26 | EPO: 1 IA injection from anteroposterior approach at superolateral patella, fluoroscopic guidance; single procedure. Dextrose: 1 IA injection from anteroposterior approach at superolateral patella, fluoroscopic guidance; single procedure. Pulsed radiofrequency: 1 IA injection from anteroposterior approach at superolateral patella, fluoroscopic guidance; single procedure | EPO: 4000 international units. Dextrose: 5 cc 25% dextrose with 5 cc of 0.5% ropivacaine. Pulsed radiofrequency: 20 ms, 2 Hz, 45 V, 15 min s, 42 °C, 2 cycles |
| 7 | Rahimzadeh 2018 | Double-blind RCT; Platelet-rich plasma (PRP) vs dextrose prolotherapy; Follow-up at 1, 2, and 6 months | Total 42 (Kellgren-Lawrence 1–2); PRP: 21, Dextrose: 21 | PRP: 1 IA injection from upper outer quadrant approach; 2 procedures at monthly intervals. Dextrose: 1 IA injection from upper outer quadrant approach; 2 procedures at monthly intervals | PRP: 7 mLs of separated plasma from 20 mLs of venous blood centrifuged for 20 min s at 3200 rpm and then 5 min s at 1500 rpm. Dextrose: 7 mLs of 25% dextrose |
| 8 | Reeves 2000 | Double-blind RCT; Dextrose prolotherapy vs placebo injection; Follow-up at 12 months | Total 31 (Radiologic grade ≥2); Group numbers undisclosed | Dextrose: 1 IA injection from inferomedial approach; 3 procedures at 2-monthly intervals (optional open-label fontinuation at 6, 8, and 10 months). Placebo: 1 IA injection from inferomedial approach; 3 procedures at 2-monthly intervals | Dextrose: 9 cc of 10% dextrose and lidocaine solution (0.075%) in bacteriostatic water. Placebo: 9 cc of lidocaine solution (0.075%) in bacteriostatic water |
| 9 | Rezasoltani 2020 | Four-arm RCT; Physiotherapy modalities vs botulinum neurotoxin A vs hyaluronic acid vs dextrose prolotherapy; Follow-up at 1 and 4 weeks, and 3 months | Total 120 (Kellgren-Lawrence 3–4); Modalities: 30, Botulinum neurotoxin: 30, Hyaluronic acid: 30, Dextrose: 30 | Botulinum neurotoxin: 1 IA injection, ultrasound-guided; single procedure. Hyaluronic acid: 1 IA injection, ultrasound-guided; 3 procedures at weekly intervals. Dextrose: 1 IA injection, ultrasound-guided; 3 procedures at monthly intervals | Botulinum neurotoxin: 250 units of Dysport diluted with 5 mLs of normal saline. Hyaluronic acid: 2 mLs of hyaluronic acid. Dextrose: 8 mLs of 20% dextrose and 2 mLs of 2% lidocaine |
| 10 | Sit 2020 | Double-blind RCT; Hypertonic dextrose prolotherapy vs normal saline; Follow-up at 16, 26, and 52 weeks | Total 76 (Pain score ≥ 3/6); Dextrose: 38, Normal saline: 38 | Dextrose: 1 IA injection from suprapatellar approach, ultrasound-guided; single procedure. Normal saline: 1 IA injection from suprapatellar approach, ultrasound-guided; single procedure | Dextrose: 5 mLs of 25% dextrose/water. Normal saline: 5 mLs of normal saline |
| 11 | Sert 2020 | Three-arm RCT; Hypertonic dextrose prolotherapy vs normal saline control vs exercise control; Follow-up at 6 and 18 weeks | Total 66 (Kellgren-Lawrence 2–3); Dextrose: 21, Normal saline: 22, Exercise: 19 | Dextrose: 1 IA injection from superolateral approach followed by multiple EA peppering injections to multiple pre-marked sites; 3 procedures at 3-weekly intervals. Normal saline: 1 IA injection from superolateral approach followed by multiple EA peppering injections to multiple pre-marked sites; 3 procedures at 3-weekly intervals | Dextrose: 5 mLs of 25% dextrose/saline solution for IA injection, followed by total 10 mLs of 15% dextrose/saline solution for EA injection. Normal saline: 2.5 mLs of normal saline with 2.5 mLs of 1% lidocaine for IA injection, followed by total 10 mLs (5 mLs of normal saline with 5 mLs of 1% lidocaine) for EA injection |
Abbreviations: EA: Extra-articular, IA: Intra-articular, PRP: Platelet-rich plasma; RCT: randomised control trial.