Regenerative Injection Therapy for Osteoarthritis: Fundamental Concepts and Evidence‐Based Review

Abstract

Regenerative therapy involves the injection of a small volume of solution into multiple sites of painful ligament and tendon insertions (entheses) and adjacent joint spaces, with the goal of reducing pain and ostensibly promoting tissue repair and growth. Dextrose and platelet-rich plasma solutions have been shown to increase expression of growth factors in vivo and have shown promising clinical results in the treatment of tendinosus. In the treatment of osteoarthritis, small clinical trials and case series to date suggest safety, symptomatic improvement, and functional improvement at up to a year of follow-up; however, most of these studies are uncontrolled. Given the methodological limitations of clinical research on regenerative injections for osteoarthritis to date, this treatment should be considered only after execution of a comprehensive assessment and treatment plan, including optimization of biomechanics, weight loss, cardiovascular exercise, resistance training, and judicious use of more established topical, oral, and injectable medications.

Structural Basis of Joint Instability as Cause for Chronic Musculoskeletal Pain and Its Successful Treatment with Regenerative Injection Therapy (Prolotherapy)

“…Thirty of the 37 patients had improved visual analog scores [127]. Numerous other studies including case reports have documented success in utilizing prolotherapy in the treatment of chronic musculoskeletal pain [107,115,116,[128][129][130][131][132][133][134][135][136]. These studies offer promise for prolotherapy for a host of conditions and support the need for further RCTs aimed at more precise indications with this approach.…”

“…transforming growth factor-, epidermal growth factor, basic fibroblast growth factor, insulin-like growth factor, and connective tissue growth factor-having been found in vitro to promote the expression of type 1 and 3 collagen in tenocytes, and are pertinent to the formation and growth of ligament, tendon and cartilage [104][105][106][107]. Prolotherapy solutions that contain concentrations less than 10% dextrose are known to be non-inflammatory, while those greater than 10% are inflammatory [19,100].…”

“…This leads to local tissue trauma, which, in turn, attracts granulocytes and macrophages. The most common prolotherapy agents used in clinical practice are dextrose solutions ranging from 12.5%-25% [107]. Dextrose proliferant has been approved for injection by FDA, but not for prolotherapy; thus, it is currently used in prolotherapy as an off-label substance [11].…”

Prolotherapy Treatment in Musculoskeletal System Pain

“…4 Literatür gözden geçirildiğinde, proloterapi çeşitli tendinopatilerin tedavisinde kullanılmasının yanısıra lateral epikondilitli, aşil tendinopatili, adduktor tendinopatili ve planter fasiitli hastalarda yapılan çalışmalarda da etkinliği konusunda kanıt saptanmıştır. En güçlü kanıt ise lateral epikondilitte bulunmuştur.…”

“…[1][2][3] Amerika Birleşik Devletleri'nde yaklaşık 100 yıldır kullanılmasına ve olumlu sonuçlar alınmasına karşın, 1980'lerin ortalarından itibaren çalışmaların kalitesi ve kantitesinde artma ve son yıllarda kronik bel ağrısı, osteoartrit ve tendinopatilerde yapılan çalışmalarda proloterapinin etkinliği konusunda güçlü veri sağlanması ilgiyi artırmıştır. 4 Literatür gözden geçirildiğinde, proloterapi çeşitli tendinopatilerin tedavisinde kullanılmasının yanısıra lateral epikondilitli, aşil tendinopatili, adduktor tendinopatili ve planter fasiitli hastalarda yapılan çalışmalarda da etkinliği konusunda kanıt saptanmıştır. En güçlü kanıt ise lateral epikondilitte bulunmuştur.…”