title: Proliferative injection therapy for osteoarthritis: a systematic review.
abstract: To systematically analyse randomised controlled trials (RCTs) about efficacy and safety of proliferative injection therapy (prolotherapy) for treatment of osteoarthritis (OA).
  
  
  
  CENTRAL, Embase and MEDLINE were searched. Two reviewers independently conducted screening and data extraction. RCTs were assessed with the Cochrane risk of bias tool. Type of treatment, study design, dosing, efficacy outcomes and safety outcomes were analysed. The protocol was registered in PROSPERO (CRD42016035258).
  
  
  
  Seven RCTs were included, with 393 participants aged 40-75 years and mean OA pain duration from three months to eight years. Follow-up was 12 weeks to 12 months. Studies analysed OA of the knee joint (n = 5), first carpometacarpal joint (n = 1) and finger joints (n = 1). Various types of prolotherapy were used; dextrose was the most commonly used irritant agent. All studies concluded that prolotherapy was effective treatment for OA. No serious adverse events were reported. The studies had considerable methodological limitations.
  
  
  
  Limited evidence from low-quality studies indicates a beneficial effect of prolotherapy for OA management. The number of participants in these studies was too small to provide reliable evidence.
  
  
  
  Current data from trials about prolotherapy for OA should be considered preliminary, and future high-quality trials on this topic are warranted.
authors.affiliation: Department of Orthopedics, University Hospital Split, Split, Croatia.
authors.forename: Mišo
authors.initials: M
authors.lastname: Krstičević
authors.affiliation: Department of Dermatovenerology, General Hospital Zadar, Zadar, Croatia.
authors.forename: Milka
authors.initials: M
authors.lastname: Jerić
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Split, Split, Croatia.|Laboratory for Pain Research, University of Split School of Medicine, Šoltanska 2, 21000, Split, Croatia.
authors.forename: Svjetlana
authors.initials: S
authors.lastname: Došenović
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Šoltanska 2, 21000, Split, Croatia.|Department of Pediatrics, University Hospital Split, Split, Croatia.
authors.forename: Antonia
authors.initials: A
authors.lastname: Jeličić Kadić
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Šoltanska 2, 21000, Split, Croatia. livia@mefst.hr.
authors.forename: Livia
authors.initials: L
authors.lastname: Puljak
mesh_terms: D000328:Adult; D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D059408:Pain Management / Q000009:adverse effects / Q000379:methods; D000075527:Prolotherapy / Q000009:adverse effects / Q000379:methods*
keywords: Dextrose; Osteoarthritis; Pain; Proliferative injection therapy; Prolotherapy