A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis

Abstract

BackgroundPrior studies describing the treatment of symptomatic knee osteoarthritis with injections of bone marrow concentrate have provided encouraging results. The relationship between the cellular dose contained within the bone marrow concentrate and efficacy of the treatment, however, is unclear. In the present study we describe clinical outcomes for symptomatic knee osteoarthritis in relation to higher and lower cell concentrations contained within a bone marrow concentrate treatment protocol.MethodsData from an ongoing patient registry was culled to identify 373 patients that received bone marrow concentrate injections for the treatment of 424 osteoarthritic knee joints. The clinical scales for these patients were assessed at baseline and then tracked post-procedure at 1, 3, 6 and 12 months, and annually thereafter. Tracked outcomes included the numeric pain scale; a lower extremity functional questionnaire; an International Knee Documentation Committee scale; and a subjective improvement rating scale. Using pain and functional outcome measures, a receiver operating characteristic analysis was used to define an optimal clinical outcome threshold at which bone marrow nucleated cell count could be divided into either a lower or higher cell count group within a treatment protocol.ResultsThe lower and higher cell count groups were defined using a threshold of 4 × 108 cells. There were 224 and 185 knee joints treated in the lower (≤4 × 108) and higher (>4 × 108) cell count groups respectively. Most joints were diagnosed with early stage knee osteoarthritis. Both the lower and higher cell count groups demonstrated significant positive results with the treatment for all of the pain and functional metrics. The higher cell count group reported lower post treatment numeric pain scale values, in comparison with the lower cell count group (1.6 vs. 3.2; P < 0.001). No significant differences were detected for the other metrics, however.ConclusionsImproved function and reduced pain was observed in patients treated with a bone marrow concentrate protocol regardless of cellular dose; however, patients receiving a higher concentration of cells reported a better pain outcome in comparison with the lower dose group. These preliminary findings suggest that cell dose may be an important factor governing clinical outcomes in autologous bone marrow concentrate treatment of knee osteoarthritis. Further studies using a larger patient population may help elucidate these findings.

Avoidance of total knee arthroplasty in early osteoarthritis of the knee with intra-articular implantation of autologous activated peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial with differential effects of growth factor addition

“…The cellular doses administered in the present study were adequately high at all 3 occasions in both groups that received stem cells. Dose response analyses have failed to assign better outcomes with higher doses [3], and in this sense, repeated MSC cultures to ensure higher cell doses seem to be an unjustified risk at a great cost [31]. When autologous PB or BM is the source of the cellular therapy, synergistic action of all cellular components and their compatible and synchronous secretome seems to confer all the necessary endogenous advantages.…”

“…Trauma or osteoarthritis (OA) creates fullthickness chondral defects that cannot efficiently heal, thus leading to significant long-term disability [1]. Conventional treatments are unable to reverse or halt OA progression and are thus often restricted to activity modification, weight loss, and the management of symptoms (pain and inflammation) that, depending on disease severity, range from conservative treatment to surgical intervention, including total knee arthroplasty (TKA), with the numbers and costs of the latter having doubled between 2001 and 2012 [3]. Projections for 2030 estimate a 7-fold increase in TKA, while 67 million Americans will be afflicted by OA [4].…”

“…Projections for 2030 estimate a 7-fold increase in TKA, while 67 million Americans will be afflicted by OA [4]. Chronic conventional treatments with anti-inflammatory agents, especially in seniors, are marred by gastrointestinal and renal side effects while surgical interventions may be complicated by deep-vein thromboses, joint stiffness, and muscle atrophy and importantly by prosthesis failure due to infections, wear, and loosening especially in younger age groups [3,5,6]. Moreover, many senior patients may not be ideal candidates for surgery due to cardiovascular conditions [4] while in younger age groups, a higher risk of revision, especially for aseptic failure, is evident [6].…”

Biologic Augmented Microdrilling Surgery for Multiple and Large Full-Thickness Cartilage Lesions in the Knee: Early Clinical and Radiological Results

“…Saw and colleagues use the same number and timing of injections in their treatment protocol. Also, dose response studies have found that patients with osteoarthritis who received an IA injection with a higher concentration of MSCs experienced better clinical and histological results than patients who received a lower concentration of cells [30] [31].…”

Autologous Bone Marrow Concentrate in a Sheep Model of Osteoarthritis: New Perspectives for Cartilage and Meniscus Repair

“…[17][18][19][20][21] Some authors argue that the therapeutic potential of BMC is due to its constitutive mononuclear cell population that enables the tissue regeneration through the secretion of growth factors that would modulate the heterogeneous population in the niche. 22,23 Nevertheless, a full knowledge of the role of BMC for OA treatment is still scarce due to the complexity of this biological system.…”