Research Article The Efficacy of Ozone Prolotherapy Compared to Intra-Articular Hypertonic Saline Injection in Reducing Pain and Improving the Function of Patients with Knee Osteoarthritis: A Randomized Clinical Trial Hamid reza Farpour , 1,2 Alireza Ashraf , 1 and Seyed Saeed Hosseini 3 1 Shiraz Geriatric Research Center, Department of Physical Medicine and Rehabilitation, Shiraz University of Medical Sciences, Shiraz, Iran 2 Bone and Joint Diseases Research Center, Department of Physical Medicine and Rehabilitation, Shiraz University of Medical Sciences, Shiraz, Iran 3 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran Correspondence should be addressed to Seyed Saeed Hosseini; hsni.saeeid@gmail.com Received 15 February 2021; Accepted 27 July 2021; Published 3 August 2021 Academic Editor: Antonella Fioravanti Copyright © 2021 Hamid reza Farpour et al. is is an open access article distributed under the Creative Commons Attribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Background.Kneeosteoarthritisisacommondiseasethatisassociatedwithchronicpainanddisabilityinpatients.Prolotherapyis acomplementarytherapeuticapproachforimprovingpainandfunctioninpatientswithosteoarthritis.Weaimedtocomparethe effectofhypertonicsalinewithozoneplushypertonicsalineinimprovingthesymptomsofosteoarthritisinthepatients. Materials and Method. In this clinical trial, thirty-four adults with painful primary knee osteoarthritis for at least three months were randomized to two groups: ozone plus hypertonic saline 5% and hypertonic saline 5% alone. Prolotherapy and thrice follow-up with two-week intervals were done. e outcome measures included Oxford Knee Scale (OKS), Western Ontario McMaster University Osteoarthritis Index (WOMAC), and Visual Analog Scale (VAS), which were obtained from the patients before the injectionandafterthe2 nd and4 th weeksafterthestartofthestudy. Results.emeanageoftheparticipantswas60.12 ± 7.54years. erewerenostatisticallysignificantdifferencesbetweendemographiccharacteristicsbeforetheinjectionbetweenthetwogroups (p > 0.05).eresultsshowedthatVASandOKSvaluesdecreasedovertime(p < 0.001)ineachgroup,buttherewasnosignificant differenceinthereductionofthosebetweenthetwotreatmentgroups(p � 0.734and p � 0.734,respectively).Bothinterventions improved the mean values of WOMAC pain, WOMAC stiffness, WOMAC act, and WOMAC total. However, there was no significant difference in WOMAC pain reduction rate (p � 0.465), WOMAC stiffness rate (p � 0.656), WOMAC act rate (p � 0.376), and WOMAC total rate between the two methods (p � 0.528). Conclusion. e results showed that intra-articular prolozone therapy and hypertonic saline injection can lead to improvement of pain and function in patients with knee oste- oarthritis at the same status without any significant difference. 1. Introduction Osteoarthritis, the most common form of arthritis, is the leading cause of musculoskeletal pain and disability worldwide [1]. Osteoarthritis (OA) is an age-related de- generative disease resulting from articular cartilage failure induced by a complex interplay of genetic, metabolic, bio- chemical, and biomechanical factors with secondary components of inflammation leading to degradation of the cartilage,bone,andsynovium[2,3].Itsprevalencehasbeen increasinggiventheincreasingproportionofolderpeoplein the society [4]. In industrialized societies, OA is the leading cause of physical disability, increases in healthcare usage, and im- pairedqualityoflife[5].esocietalandpersonalburdenof disease is high due to utilization of healthcare resources, Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2021, Article ID 5579944, 7 pages https://doi.org/10.1155/2021/5579944