Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis

Regina Ws Sit, Vincent Ch Chung, Kenneth D Reeves, David Rabago, Keith Kw Chan, Dicken Cc Chan, Xinyin Wu, Robin St Ho, Samuel Ys Wong, Regina Ws Sit, Vincent Ch Chung, Kenneth D Reeves, David Rabago, Keith Kw Chan, Dicken Cc Chan, Xinyin Wu, Robin St Ho, Samuel Ys Wong

Abstract

Hypertonic dextrose injections (prolotherapy) is an emerging treatment for symptomatic knee osteoarthritis (OA) but its efficacy is uncertain. We conducted a systematic review with meta-analysis to synthesize clinical evidence on the effect of prolotherapy for knee OA. Fifteen electronic databases were searched from their inception to September 2015. The primary outcome of interest was score change on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Three randomized controlled trials (RCTs) of moderate risk of bias and one quasi-randomized trial were included, with data from a total of 258 patients. In the meta-analysis of two eligible studies, prolotherapy is superior to exercise alone by a standardized mean difference (SMD) of 0.81 (95% CI: 0.18 to 1.45, p = 0.012), 0.78 (95% CI: 0.25 to 1.30, p = 0.001) and 0.62 (95% CI: 0.04 to 1.20, p = 0.035) on the WOMAC composite scale; and WOMAC function and pain subscale scores respectively. Moderate heterogeneity exists in all cases. Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy.

Figures

Figure 1. Flow of literature search.
Figure 1. Flow of literature search.
Figure 2. Dextose vs Exercise on WOMAC…
Figure 2. Dextose vs Exercise on WOMAC Composite 12–16 week (SMD).
Figure 3. Dextrose vs Exercise on WOMAC…
Figure 3. Dextrose vs Exercise on WOMAC Function at 12–16 week (SMD).
Figure 4. Dextrose vs Exercise on WOMAC…
Figure 4. Dextrose vs Exercise on WOMAC Pain at 12–16 week (SMD).

References

    1. Brooks P. M. The burden of musculoskeletal disease–a global perspective. Clin. Rheumatol. 25(6), 778–781(2006).
    1. Fransen M. et al. The epidemiology of osteoarthritis in asia. Int. J. Rheum. Dis. 14(2), 113–121 (2011).
    1. Litwic A., Edwards M. H., Dennison E. M. & Cooper C. Epidemiology and burden of osteoarthritis. Br. Med. Bull. 105, 185–199 (2013).
    1. Gupta S., Hawker G. A., Laporte A., Croxford R. & Coyte P. C. The economic burden of disabling hip and knee osteoarthritis (OA) from the perspective of individuals living with this condition. Rheumatology (Oxford). 44(12), 1531–1537 (2005).
    1. Cross M. et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann. Rheum. Dis. 73(7), 1323–1330 (2014).
    1. Hochberg M. C. et al. American college of rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthrit. Care Res. (Hoboken). 64(4), 465–474 (2012).
    1. Bruyere O. et al. An algorithm recommendation for the management of knee osteoarthritis in europe and internationally: a report from a task force of the european society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO). Semin. Arthritis. Rheu. 44(3), 253–263 (2014).
    1. McAlindon T. E. et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr. Cartil. 22(3), 363–388 (2014).
    1. The national academies of sciences, engineering, medicine. Initial national priorities for comparative effectiveness research. (2009) Available at: . (Date of access: April 2014).
    1. Samson D. J. et al. Treatment of primary and secondary osteoarthritis of the knee. Evid. Rep. Technol. Assess (Full Rep.). 157, 1–157 (2007).
    1. Rabago D., Best T. M., Beamsley M. & Patterson J. A systematic review of prolotherapy for chronic musculoskeletal pain. Clin. J. Sport Med. 15(5), 376–380 (2005).
    1. Oh S. et al. Dextrose-induced subsynovial connective tissue fibrosis in the rabbit carpal tunnel: a potential model to study carpal tunnel syndrome? Hand (N. Y.). 3(1), 34–40 (2008).
    1. Yoshii Y. et al. The effects of hypertonic dextrose injection on connective tissue and nerve conduction through the rabbit carpal tunnel. Arch. Phys. Med. Rehab. 90(2), 333–339 (2009).
    1. Yoshii Y. et al. Effects of hypertonic dextrose injections in the rabbit carpal tunnel. J. Orthop. Res. 29(7), 1022–1027 (2011).
    1. Yoshii Y. et al. Effects of multiple injections of hypertonic dextrose in the rabbit carpal tunnel: a potential model of carpal tunnel syndrome development. Hand (N.Y.). 9(1), 52–57 (2014).
    1. Park Y. S. et al. Intra-articular injection of a nutritive mixture solution protects articular cartilage from osteoarthritic progression induced by anterior cruciate ligament transection in mature rabbits: a randomized controlled trial. Arthritis Res. Ther. 9(1), R8 (2007).
    1. Vora A., Borg-Stein J. & Nguyen R. T. Regenerative injection therapy for osteoarthritis: fundamental concepts and evidence-based review. P.M. & R. 4(5, Supplement), S104–S109 (2012).
    1. Rabago D., Slattengren A. & Zgierska A. Prolotherapy in primary care practice. Prim. Care. 37(1), 65–80 (2010).
    1. Distel L. M. & Best T. M. Prolotherapy: A clinical review of its role in treating chronic musculoskeletal pain. P.M. & R. 3(6, Supplement), S78–S81 (2011).
    1. Jahangiri A., Moghaddam F. R. & Najafi S. Hypertonic dextrose versus corticosteroid local injection for the treatment of osteoarthritis in the first carpometacarpal joint: a double-blind randomized clinical trial. J. Orthop. Sci. 19(5), 737–743 (2014).
    1. Reeves K. D. & Hassanein K. Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and trapeziometacarpal) joints: evidence of clinical efficacy. J. Altern. Complement. Med. 6(4), 311–320 (2000).
    1. Rabago D. et al. Hypertonic dextrose and morrhuate sodium injections (prolotherapy) for lateral epicondylosis (tennis elbow): results of a single-blind, pilot-level, randomized controlled trial. Am. J. Phys. Med. Rehabil. 92(7), 587–596 (2013).
    1. Topol G. A. & Reeves K. D. Regenerative injection of elite athletes with career-altering chronic groin pain who fail conservative treatment: a consecutive case series. Am. J. Phys. Med. Rehabil. 87(11), 890–902 (2008).
    1. Kim W. M., Lee H. G., Jeong C. W., Kim C. M. & Yoon M. H. A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain. J. Altern. Complement Med. 16(12), 1285–1290 (2010).
    1. Dagenais S., Yelland M. J., Del Mar C. & Schoene M. L. Prolotherapy injections for chronic low-back pain. Cochrane Database Syst. Rev. 2(2), CD004059 (2007).
    1. Rabago D. et al. A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet-rich plasma. Br. J. Sports Med. 43(7), 471–481 (2009).
    1. Rabago D., Mundt M., Zgierska A. & Grettie J. Hypertonic dextrose injection (prolotherapy) for knee osteoarthritis: long term outcomes. Complement Ther. Med. 23(3), 388–395 (2015).
    1. Dumais R. et al. Effect of regenerative injection therapy on function and pain in patients with knee osteoarthritis: a randomized crossover study. Pain Med. 13(8), 990–999 (2012).
    1. Reeves K. D. & Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern. Ther. Health Med. 6(2), 68–74 (2000).
    1. Rabago D. et al. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann. Fam. Med. 11(3), 229–237 (2013).
    1. Rabago D. et al. Association between disease-specific quality of life and magnetic resonance imaging outcomes in a clinical trial of prolotherapy for knee osteoarthritis. Arch. Phys. Med. Rehabil. 94(11), 2075–2082 (2013).
    1. Moher D., Liberati A., Tetzlaff J. & Altman D. G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int. J. Surg. 8(5), 336–341(2010).
    1. Altman R. D. Criteria for classification of clinical osteoarthritis. J. Rheumatol. Suppl. 27, 10–12 (1991).
    1. Roos E. M., Klassbo M. & Lohmander L. S. WOMAC osteoarthritis index. reliability, validity, and responsiveness in patients with arthroscopically assessed osteoarthritis. western ontario and MacMaster universities. Scand. J. Rheumatol. 28(4), 210–215 (1999).
    1. Tubach F. et al. Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement. Ann. Rheum. Dis. 64(1), 29–33 (2005).
    1. Bellamy N. et al. Recommendations for a core set of outcome measures for future phase III clinical trials in knee, hip, and hand osteoarthritis. consensus development at OMERACT III. J. Rheumatol. 24(4), 799–802 (1997).
    1. Bellamy N., Buchanan W. W., Goldsmith C. H., Campbell J. & Stitt L. W. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J. Rheumatol. 15(12), 1833–1840 (1988).
    1. Rejeski W. J. et al. The evaluation of pain in patients with knee osteoarthritis: the knee pain scale. J. Rheumatol. 22(6), 1124–1129 (1995).
    1. Wong-Baker Faces. Available at: . (Date of access: April 2014 (2009)).
    1. Higgins J. P. et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. B.M.J. 343, 5928 (2011).
    1. Wallace B. C., Schmid C. H., Lau. J. & Trikalinos T. A. Meta-analyst: software for meta-analysis of binary, continuous and diagnostic data. B.M.C. Med. Res. Methodol. 9(1), 80 (2009).
    1. Borenstein M., Hedges L. V., Higgins J. P. T. & Rothstein H. R. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 1(2), 97–111 (2010).
    1. Deeks J. J., Higgins J. P. T. & Altman D. G. Heterogeneity in Cochrane handbook for systematic reviews of interventions. (eds Higgins J. P. T. & Green S.) Ch.9.5, 276–282 (Wiley-Blackwell, 2008).
    1. Tubach F., Wells G. A., Ravaud P. & Dougados M. Minimal clinically important difference, low disease activity state, and patient acceptable symptom state: methodological issues. J. Rheumatol. 32(10), 2025–2029 (2005).
    1. Ehrich E. W. et al. Minimal perceptible clinical improvement with the western ontario and McMaster universities osteoarthritis index questionnaire and global assessments in patients with osteoarthritis. J. Rheumatol. 27(11), 2635–2641 (2000).
    1. Brandt K. D., Fife R. S., Braunstein E. M. & Katz B. Radiographic grading of the severity of knee osteoarthritis: relation of the kellgren and lawrence grade to a grade based on joint space narrowing, and correlation with arthroscopic evidence of articular cartilage degeneration. Arthritis Rheum. 34(11), 1381–1386 (1991).
    1. Rabago D. et al. Hypertonic dextrose injections (prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. J Altern. Complement Med. 18(4), 408–414 (2012).
    1. Faraone S. V. Interpreting estimates of treatment effects: implications for managed care. P. & T. 33(12), 700 (2008).
    1. Borenstein M., Hedges L. V., Higgins J. P. T. & Rothstein H. R. Identifying and quantifying heterogeneity in Introduction to meta-analysis. Ch. 16, 107–125. (John Wiley & Sons, Ltd, 2009).
    1. Noordzij M. et al. Sample size calculations: basic principles and common pitfalls. Nephrol. Dial. Transplant. 25(5), 1388–1393 (2010).
    1. Banks A. A rationale for prolotherpay. J. Orthop. Med. 13(3), 54–59 (1991).
    1. Vora A., Borg-Stein J. & Nguyen. R. T. Regenerative injection therapy for osteoarthritis: fundamental concepts and evidence-based review. P.M. & R. 4(5, Supplement), S104–S109 (2012).
    1. Dobson F. et al. OARSI recommended performance-based tests to assess physical function in people diagnosed with hip or knee osteoarthritis. Osteoarthr. Cartil. 21(8), 1042–1052 (2013).
    1. Hoogeboom T. J. et al. Joint-pain comorbidity, health status, and medication use in hip and knee osteoarthritis: a cross-sectional study. Arthrit. Care Res. 64(1), 54–58 (2012).
    1. Hosnijeh F. S., Runhaar J., van Meurs J. B. & Bierma-Zeinstra S. M. Biomarkers for osteoarthritis: can they be used for risk assessment? a systematic review. Maturitas. 82(1), 36–49 (2015).
    1. Xie F. et al. Use of a disease-specific instrument in economic evaluations: mapping WOMAC onto the EQ-5D utility index. Value Health. 13(8), 873–878 (2010).
    1. Jancso G. Neurogenic mechanisms in arthritis in Neurogenic inflammation in health and disease (eds Donaldson L. F.) Ch.4, 211–241 (Elsevier, 2009).
    1. Lyftogt J. Subcutaneous prolotherapy treatment of refractory knee, shoulder and lateral elbow pain. Australas Musculoskelet. Med. 12(2), 110–112 (2007).
    1. Qvistgaard E. et al. Guidance by ultrasound of intra-articular injections in the knee and hip joints. Osteoarthr. Cartil. 9(6), 512–517 (2001).
    1. Guyatt G. H. et al. GRADE guidelines 6. rating the quality of evidence–imprecision. J. Clin. Epidemiol. 64(12), 1283–1293 (2011).
    1. Deeks J. J., Higgins J. P. T. & Altman D. G. Analysing data and undertaking meta-analyses in Cochrane handbook for systematic reviews of interventions. (eds Higgins J. P. T. & Green S.) Ch.9, 243–296 (Wiley-Blackwell, 2008).
    1. Ioannidis J. P., Patsopoulos N. A. & Rothstein H. R. Reasons or excuses for avoiding meta-analysis in forest plots. B.M.J. 336(7658), 1413–1415 (2008).
    1. Borenstein M., Hedges L. V., Higgins P. T. & Rothstein H. R. Vote Counting–A new name for an old problem in Introduction to meta-analysis. 251–255 (John Wiley & Sons, 2009).
    1. Borenstein M., Hedges L. V., Higgins P. T. & Rothstein H. R. Criticisms of meta-analysis in Introduction to meta-analysis.377–387 (John Wiley & Sons, 2009).
    1. Deeks J. J., Higgins J. P. T. & Altman D. G. Identifying and measuring heterogeneity in Cochrane handbook for systematic reviews of interventions. (eds Higgins J. P. T. & Green S.) Ch. 9.5.2, 277–278 (Wiley-Blackwell, 2008).

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться