Use of autologous bone marrow stem cell implantation for osteonecrosis of the knee in sickle cell disease: a preliminary report

Abstract

Background: The purpose of our study was to evaluate safety, feasibility and clinical results of bone marrow mononuclear cell (BMC) implantation for early-stage osteonecrosis of the knee (OK) secondary to sickle cell disease.

Methods: Thirty-three SCD patients (45 knees) with OK treated with BMC implantation in the osteonecrotic lesion were clinically and functionally evaluated through the American Knee Society Clinical Score (KSS), Knee Functional Score (KFS) and Numeric Rating Scale (NRS) pain score. MRI and radiographic examinations of the knee were assessed during a period of five years after intervention.

Results: No complications or serious adverse event were associated with BMC implantation. From preoperative assessment to the latest follow-up, there was a significant (p < 0.001) improvement of clinical KSS (64.3 ± 9.7, range: 45-80 and 2.2 ± 4.1, range: 84-100, respectively), KFS (44.5 ± 8.0, range: 30-55 and 91.6 ± 5.8, range: 80-100, respectively) and reduction of NRS pain score (6.7 ± 1.2, range: 4-9 and 3.4 ± 1.0, range: 2-5, respectively). In total, 87% of patients (29/33) consistently experienced improvements in joint function and activity level as compared to preoperative score. No patient had additional surgery following BMC implantation. Radiographic assessment showed joint preservation and no progression to subchondral collapse at most recent follow-up.

Conclusions: The technique of BMC implantation is a promising, relatively simple and safe procedure for OK in SCD patients. Larger and long-term controlled trials are needed to support its clinical effectiveness.

Trial registration: ClinicalTrials.gov NCT02448121 . Retrospectively registered 19 May 2015.

Keywords: Avascular necrosis; Cell implantation; Joint preserving surgery; Knee; Osteonecrosis; Sickle cell disease.

Conflict of interest statement

Ethics approval and consent to participate

The Committee of Ethics in Research of the Climério de Oliveira Maternity and the National Committee of Ethics in Research (CONEP) approved the protocol of the present study under the authorization of the Ministry of Public Health of Brazil [registration number 11738, SIPAR/MS: 25000.039812/2005–99]. NIH trial registration: Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Osteonecrosis of the knees in a 33-year-old woman with SCD. (a - f) T1-weighted (a, d - sagittal) and proton density fat-suppressed (b, e - sagittal; c, f - axial) sequences demonstrates subchondral lesions (arrowheads) on the posterior portions of the right (a, b, c) and left (d, e, f) condyles. The osteonecrotic lesion is surrounded by border appearing hypo/hyperintense (double rim sign) (b, c, e, f) indicating granulation and sclerosis respectively (arrowheads). MRI scans before surgery shows subchondral lesions representing early osteonecrosis in Ficat II stage. Both knees were treated with BMC implantation

Fig. 2

Bilateral osteonecrosis of the knees in a symptomatic 39-year-old woman with SCD. (a - d) Proton density fat-suppressed (a, c – sagittal) and T2-weighted (b, d - axial) sequences demonstrate subchondral abnormalities (arrowheads) located in the medial femoral condyle (weight bearing zones). Subcortical high-intensity inner line (a – c) representing granulation tissue. MRI scans before surgery shows osteonecrotic lesion in Ficat I and II on left and right knees, respectively. Both knees were treated with BMC implantation

Fig. 3

BMC treatment significantly improved both clinical and functional outcome of early stage OK-SCD patients (a, b) Preoperative and postoperative changes of Knee and functional score for patients grouped over the entire postoperative period. Floating bar represent max and min range of variation, with line at mean score. c Pain level was evaluated using the Visual Analog Scale. Most of the patients with pain preoperative showed a significant decrease in Pain Scoring *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.001 versus preoperative score values (paired t-test)

Fig. 4

Functional and clinical improvement over time after BMC implantation. a, b Function score (a) and Knee score (b) evaluation preoperatively and at the time of follow-up showed increased and sustained clinical improvement over time. *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.001 versus preoperative score values (paired t-test)

Fig. 5

MR imaging after successfully treatment with BMC. a - c MR imaging of the 16-years-old boy before (a, b) and after surgery (c, d, 12 months postoperatively). PD-weighted (a, b) and T1-weighted (c, d) sequences demonstrate no subchondral bone erosion or fracture, normal contour of the epiphyseal head and preservation of the joint space. Proton density-weighted (a, b) sequences demonstrate mostly hematopoietic marrow without cystic or fibrotic lesion

Fig. 6

Radiographic imaging after successfully treatment with BMC. a, b Radiographs of the patient displayed on Fig. 1, 36 months postoperatively showing joint preservation and no subchondral bone fracture; (c, d) Radiographs of the patient displayed on Fig. 2, 60 months postoperatively. The joint space was preserved and the patient was asymptomatic ate final follow-up