Knee – Arthritis/Joint Disorders – BMAC

Introduction

We investigated the use of autologous bone marrow concentrate (BMC) with and without an adipose graft, for treatment of knee osteoarthritis (OA).

Methods

Treatment registry data for patients who underwent BMC procedures with and without an adipose graft were analyzed. Pre- and posttreatment outcomes of interest included the lower extremity functional scale (LEFS), the numerical pain scale (NPS), and a subjective percentage improvement rating. Multivariate analyses were performed to examine the effects of treatment type adjusting for potential confounding factors. The frequency and type of adverse events (AE) were also examined.

Results

840 procedures were performed, 616 without and 224 with adipose graft. The mean LEFS score
increased by 7.9 and 9.8 in the two groups (out of 80), respectively, and the mean NPS score decreased from 4 to 2.6 and from 4.3 to 3 in the two groups, respectively. AE rates were 6% and 8.9% in the two groups, respectively. Although pre- and posttreatment improvements were statistically significant, the differences between the groups were not.

Conclusion

BMC injections for knee OA showed encouraging outcomes and a low rate of AEs. Addition of an adipose graft to the BMC did not provide a detectible benefit over BMC alone.

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Background:

Bone marrow aspirate concentrate (BMAC) is increasingly used as a regenerative therapy for musculoskeletal pathological conditions despite limited evidence-based support.

Hypothesis:

BMAC will prove feasible, safe, and efficacious for the treatment of pain due to mild to moderate degenerative joint disease of the knee.

Methods:

In this prospective, single-blind, placebo-controlled trial, 25 patients with bilateral knee pain from bilateral osteoarthritis were randomized to receive BMAC into one knee and saline placebo into the other. Fifty-two milliliters of bone marrow was aspirated from the iliac crests and concentrated in an automated centrifuge. The resulting BMAC was combined with platelet-poor plasma for an injection into the arthritic knee and was compared with a saline injection into the contralateral knee, thereby utilizing each patient as his or her own control. Safety outcomes, pain relief, and function as measured by Osteoarthritis Research Society International (OARSI) measures and the visual analog scale (VAS) score were tracked initially at 1 week, 3 months, and 6 months after the procedure.

Results:

There were no serious adverse events from the BMAC procedure. OARSI Intermittent and Constant Osteoarthritis Pain and VAS pain scores in both knees decreased significantly from baseline at 1 week, 3 months, and 6 months (P .019 for all). Pain relief, although dramatic, did not differ significantly between treated knees (P . .09 for all).

Conclusion:

Early results show that BMAC is safe to use and is a reliable and viable cellular product. Study patients experienced a similar relief of pain in both BMAC- and saline-treated arthritic knees. Further study is required to determine the mechanisms of action, duration of efficacy, optimal frequency of treatments, and regenerative potential.

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Background:

Prior 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.

Methods:

Data 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.

Results:

The 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.

Conclusions:

Improved 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.

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Purpose

As a treatment method of degenerative arthritis of knee, this study evaluated the clinical efficacy of the intra-articular injection of autologous bone marrow aspirates concentrate (BMAC) with adipose tissue.

Materials and methods

Between April 2011 and May 2012, 41 patients (75 knees) who were diagnosed as a degenerative knee arthritis and underwent the BMAC injection with adipose tissue were included in this study. Mean age was 60.7 years old (ranged 53–80). Kellgren–Lawrence grade was used for assessing radiologic degree of osteoarthritis; there were each 12, 24, 33, and 6 cases of grade I, II, III, and IV. At preoperative and postoperative 3, 6, and 12 months, pain score using visual analogue scale (VAS) and functional scales were used for evaluation.

Results

After the procedure, mean VAS score was decreased from 7.0 preoperatively to 4.1, 3.5, and 3.3
postoperatively 3, 6, and 12 months. And functional scores were also improved; International Knee Documentation Committee score (from 37.7 preoperatively to 59.3, 66.3, 69.3 postoperatively), SF-36 health score (from 31.5 to 43.5, 45.6, 47.7), knee and osteoarthritis outcome score (from 43.1 to 64.9, 68.5, 70.6), Lysholm Knee Questionnaire (from 37.3 to 65.4, 68.6, 71.0) were all increased after the procedure. When classified according to K–L grade, the improvement of VAS score in grade IV group was 8.2 preoperatively to 5.5, 5.3, and 5.7 postoperatively, which was significantly poorer than those of grade I–III groups. In the knee functional scales, similar pattern was checked.

Conclusions

BMAC injection significantly improved both knee pain and functions in the patients with degenerative arthritis of knee. Also, the injection would be more effective in early to moderate phases.

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Aim:

Management of osteoarthritis (OA) is basically symptomatic. Recently, stem cells (SC) have been used in the search for an optimum treatment. We decided to conduct a controlled clinical trial to determine if a single intra-articular injection of in vivo stimulated bone marrow SC could lead to an improvement in pain management and quality of life in patients with knee OA.

Method:

This was a prospective, open-label, phase I/II clinical trial to assess the safety and efficacy of a single intra-articular injection of autologous stimulated bone marrow stem cells (BM-SC) in patients with knee OA. Individuals of both genders older than 30 years with confirmed diagnosis of OA who signed informed consent were included in two groups: SC group received in vivo BM stimulation with subcutaneous administration of granulocyte colony stimulating factor (G-CSF). SC were obtained by BM aspiration and administered in a single intra-articular injection. The control group received exclusively oral acetaminophen. Visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index scores were performed at 1 week, 1 month and 6 months in both groups. This trial was registered in ClinialTrials.gov NCT01485198.

Results:

A total of 61 patients were included. Socio-demographic characteristics, OA grades and initial scores were similar in both groups. The BM-SC group showed significant improvement in knee pain and quality of life during the 6-month follow-up.

Conclusion:

The study demonstrates feasibility and supports efficacy of a completely ambulatory procedure in treatment of knee OA.

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Background:

Microfracture is commonly performed for cartilage repair but usually results in fibrocartilage. Microfracture augmented by autologous bone marrow concentrate (BMC) was previously shown to yield structurally superior cartilage repairs in an equine model compared with microfracture alone. The current study was performed to test the hypothesis that autologous BMC without concomitant microfracture improves cartilage repair compared with microfracture alone.

Methods:

Autologous sternal bone marrow aspirate (BMA) was concentrated using a commercial system. Cells from BMC were evaluated for chondrogenic potential in vitro and in vivo. Bilateral full-thickness chondral defects (15-mm diameter) were created on the midlateral trochlear ridge in 8 horses. Paired defects were randomly assigned to treatment with BMC without concomitant microfracture, or to microfracture alone. The repairs were evaluated at 1 year by in vitro
assessment, arthroscopy, morphological magnetic resonance imaging (MRI), quantitative T2-weighted and ultrashort echo time enhanced T2* (UTE-T2*) MRI mapping, and histological assessment.

Results:

Culture-expanded but not freshly isolated cells from BMA and BMC underwent cartilage differentiation in vitro. In vivo, cartilage repairs in both groups were fibrous to fibrocartilaginous at 1 year of follow-up, with no differences observed between BMC and microfracture by arthroscopy, T2 and UTE-T2* MRI values, and histological assessment (p > 0.05). Morphological MRI showed subchondral bone changes not observed by arthroscopy and improved overall outcomes for the BMC repairs (p = 0.03). Differences in repair tissue UTE-T2* texture features were observed between the treatment groups (p < 0.05).

Conclusions:

When BMC was applied directly to critical-sized, full-thickness chondral defects in an equine model, the cartilage repair results were similar to those of microfracture. Our data suggest that, given the few mesenchymal stem cells in minimally manipulated BMC, other mechanisms such as paracrine, anti-inflammatory, or immunomodulatory effects may have been responsible for tissue regeneration in a previous study in which BMC was applied to microfracture repairs. While our conclusions are limited by small numbers, the better MRI outcomes for the BMC repairs may have been related to reduced surgical trauma to the subchondral bone.

Clinical Relevance:

MRI provides important information on chondral defect subsurface repair organization and subchondral bone structure that is not well assessed by arthroscopy.

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Regenerative therapeutic strategies for joint diseases usually employ either enriched concentrates of bone marrow-derived stem cells, chondrogenic preparations such as platelet-rich plasma, or irritant solutions such as hyperosmotic dextrose. In this case series, we describe our experience with a simple, cost-effective regenerative treatment using direct injection of unfractionated whole bone marrow (WBM) into osteoarthritic joints in combination with hyperosmotic dextrose. Seven patients with hip, knee or ankle osteoarthritis (OA) received two to seven treatments over a period of two to twelve months. Patient-reported assessments were collected in interviews and by questionnaire. All patients reported improvements with respect to pain, as well as gains in functionality and quality of life. Three patients, including two whose progress under other therapy had plateaued or reversed, achieved complete or near-complete symptomatic relief, and two additional patients achieved resumption of vigorous exercise. These preliminary findings suggest that OA treatment with WBM injection merits further investigation.

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