The clinical efficacy of intraarticular administration of bone marrow aspirate concentrate, platelet rich plasma and hyaluronic acid in the treatment of the knee osteoarthritis

Osteoartritis kolena predstavlja progresivno degenerativno oboljenje svih struktura kolena koji je u porastu kako u svetu tako i u našoj zemlji i predstavlja veliko opterećenje za pacijenta i njegovu porodicu ali i za zdravstveni sistem zemlje. Pored ranije definisanih etioloških faktora poput genetske predispozicije, gojaznosti, posledice traume i poremećene osovine donjeg ekstremiteta, u poslednje vreme se kao uzroci povećanja incidence ove bolesti kod mladih navode i posledice netretiranih povreda hrskavice, meniskusa i ligamenata kolena kao i sportske i radne aktivnosti sa repetitivnim mikrotaumama kolena. Lečenje ove bolesti podrazumeva kako više načina konzervativnog lečenja lekovima, modifikacijama aktivnosti, fizikalnom terapijom i intraartikularnim injekcijama tako i različitim hirurškim procedurama. U najvećem broju slučajeva, bolest progredira do faze kada je neophodna ugradnja totalne proteze kolena sa svim svojim benefitima i komplikacijama i velikom cenom koštanja i opterećenja za zdravstveni sistem. Unazad oko jednu deceniju, u svetskoj i domaćoj literaturi se kao opcije lečenja osteoartritisa kolena navode i regenerativne ili ortobiološke procedure koje podrazumevaju ubrizgavanje ili implantaciju autologih tkiva, pre svega ćelijskih koncentrata ili određenih autologih proteina, koji imaju antiinflamatorno i analgetsko dejstvo i sposobnost pokretanja anaboličkih i regenerativnih procesa u zglobu kolena. METOD: Prospektivna klinička studija koja je rađena na Klinici za ortopedsku hirurgiju i traumatologiju Kliničkog centra Vojvodine i uključila je 176 pacijenata koji su raspoređeni u tri grupe i tretirani intraartikularnom injekcijom koncentrata aspirata koštane srži (Angel Arthrex BMAC set), plazmom obogaćenom trombocitima (LR-PRP Tr 7-8 x baseline, Le 2-3 x Baseline) i preparatima HA - hijaluronske kiseline (inj. Cartinorm 20ml/2mg po jedna injekcija na 7 dana 3 nedelje) i koji su potom praćeni preinterventno i nakon 3, 7, 14, 21 dan i 1, 3, 6, 9 i 12 meseci. Injekcije su davane u koleno kod BMAC grupe kroz tri injekciona portala: suprapatelarno lateralno, infrapatelarno lateralno i medijalno dok su kod druge dve grupe inekcije aplikovane kroz identičan, lateralni suprapatelarni portal. Praćenje je podrazumevalo fizikalni pregled i popunjavanje upitnika VAS skale preinterventno i u prvom mesecu kao i KOOS, IKDC, WOMAC i SF 36 skale preinterventno i nakon 1,3,6,9 i 12 meseci, te davanjem informacija o komforu same procedure, uzimanju lekova nakon procedure i odlasku na fizikalnu terapiju. Statistička obrada je vršena standardnim metodama ( Hi-kvadrat test, analiza varijanse) uz upotrebu SPSS 20.0 softvera. REZULTATI: Ispitivane grupe nisu se razlikovale u pogledu pola, starosti, indeksu telesne mase i težine artroze kolena. Bol je kod svih grupa statistički značajno opao već nakon tri dana i to stanje se održalo do 21 dan ali je izraženiji pad bola zabeležen kod BMAC grupe. Na merenjima od mesec dana do 12 meseci, došlo je do statistički značajnog poboljšanja u svim skalama sve do dvanaestog meseca sa tim što je poboljšanje bilo izraženije u grupi BMAC u odnosu na druge dve grupe sa statističkom značajnošću između BMAC i HA grupe ali bez značajnosti između BMAC i PRP grupe kao i izmeću PRP i HA grupe, iako su svi parametri bili bolji kod grupe PRP u odnosu na grupu HA. Nije bilo statistički značajne razlike u parametrima kliničkog poboljšanja kod pacijenata tretiranih sa BMAC u odnosu na izbor portala za davanje injekcije. Nije zabeležen ni jedan ozbiljan neželjeni događaj tokom praćenja od 12 meseci a da je povezan sa intervencijom na kolenu. ZAKLJUČAK: Sve tri intervencije postižu dobre kliničke rezultate u smislu smanjenja bola i povećanja fukcije obolelog kolena u odnosu na preinterventni period koji traju i preko godinu dana. BMAC je terapija koja je klinički efikasnija u odnosu na PRP i HA terapiju. Sve tri metode su bezbedne i efikasne bez obzira na mesto davanja injekcije u koleno.Osteoarthritis is a progressive degenerative disease which include changes in all joint structures. The incidence of this disease is rising both in the world and in our country and represents a great burden for the patients and for their families as well as for overall health and socioeconomic system of the country. In addition to the well-known etiological factors such as genetic predisposition, obesity, consequences of trauma and malalignment of the lower extremity, the consequences of untreated injuries of cartilage, meniscus and knee ligaments as well as sports and work activities with repetitive knee microtaumas have recently been reported. Treatment of this disease includes several conservative treatment options such as non-steroid anti-inflammatory drugs, modifications of activities, physiotherapy and intra-articular injections, as well as various surgical procedures. In most cases, the disease progresses to the stage when total joint replacement is inevitable with all its benefits and complications and the high cost and burden on the health system. About a decade ago, in the world and national literature, regenerative or ortho-biological procedures comprising the injection or implantation of autologous tissues, primarily cellular concentrates or certain autologous proteins, whith anti-inflammatory and analgesic effects and the ability to move, have been introduced as a treatment options for osteoarthritis of the knee. METHOD: A prospective clinical study was conducted at the Departement for Orthopedic Surgery and Traumatology of the Clinical Center of Vojvodina and included 176 patients. The patients were divided into three groups, each of them treated with single intra-articular injection of Bone Marrow Aspirate Concentrate (Angel Arthrex BMAC set), Platelet rich Plasma single injection (Tr 7-8 x baseline, Le 2-3 x Baseline) or HA-hyaluronic acid injections (inj. Cartinorm 20ml / 2mg one injection every 7 days for 3 weeks). The patients were observed before the intervention and followedup after 3,7,14, 21 days and 1, 3, 6, 9 and 12 months. In the BMAC group, the maedication was admistrated through the three most popular injection portals (suprapatellar lateral, infrapatellar lateral and medial) , while in the other two groups were injected through the lateral suprapatelar portal. Monitoring included physical examination and completion of the VAS scale questionnaire preintervention and durintg the first month as well as KOOS, IKDC, WOMAC and SF 36 scales preintervention and after 1,3,6,9 and 12 months. We also provided information about the comfort of the procedure, usage of medication after the procedure and potential performance of physiotherapy. Statistical calculations were performed by standard methods (Chi-Square test, ANOVA) with SPSS 20.0 software. RESULTS: The study groups did not differ in terms of gender, age, body weight, and severity of knee osteoarthritis. Pain in all groups decreased significantly after three days, and this condition remained for 21 days. Pain decrease observed in the BMAC group was noteworthy. Concerning measurements from one month to 12 months, there were significant improvements in all scales up to the twelfth month, with the improvement being more pronounced in the BMAC group compared to the other two groups.There was statistically significance between BMAC and HA group but without significance between BMAC and PRP groups as well as between PRP and HA groups, although all parameters were better in the PRP group, compared to the HA group. There were no statistically significant differences in the parameters of clinical improvement in patients treated with BMAC concerning the injection portal location. There were no serious adverse events during the 12-month follow-up that were associated with knee intervention. CONCLUSION: All three interventions achieved good clinical results in terms of reducing pain and increasing the function of the affected knee, compared to the pre-intervention period. Positive results, , that were achieved persisted over 12 months. BMAC showed some advantages comparing to PRP, and proved to be significantly more effective than HA therapy. All three methods are safe and effective regardless of the injection site in the knee