Human bone marrow mesenchymal stem cell injection in subchondral lesions of knee osteoarthritis: a prospective randomized study versus contralateral arthroplasty at a mean fifteen year follow-up.

PURPOSE: Recently, mesenchymal stem cells (MSCs) have been proposed as potential treatment modalities for knee osteoarthritis. However, indications and long-term results have not been frequently reported. The purpose of this study was to determine whether bone marrow lesion on MRI are predictive of risk progression to total knee arthroplasty during the first ten years after subchondral cell therapy. METHODS: This study included 140 adults aged 65 to 90 years. These 140 patients (mean age 75.4 ± 14.2 years) planned to undergo staged-bilateral total knee arthroplasty (TKA) for medial osteoarthritis, had "comparable" pain in both knees, and accepted randomization of the knees for surgery. They received TKA on one side and a subchondral injection of MSCs (from iliac bone marrow concentrate) on the contralateral knee during the same anaesthetic. The bone marrow graft of 20 cm3 volume (10 cc in the tibia and 10 cc in the femur) contained average 7800 MSCs/mL (range 3120 to 11,560). The baseline volume of bone marrow lesions (BMLs) on the tibia and on the femoral condyle determined on MRI was average 3.4 cm3 (range 0.4 to 6.4 cm3). The risk of subsequent knee arthroplasty due to absence of bone marrow lesions regression as well as osteoarthritis (OA) grade was evaluated with Cox proportional-hazards ratio after control of baseline variables (number of cells injected, age, knee alignment). RESULTS: After treatment with MSCs injection in bone marrow lesions of the subchondral bone, medial femorotibial compartment BML volume experienced regression over 24 months (mean regression 1.5 cm3, range 0.8 to 3.2 cm3). At the most recent follow up (average of 15 years, range 10 to 20 years), a total of 25 (18%) of the 140 patients underwent total knee arthroplasty performed at a mean of ten years (range, 5 to 15 years) after the date of the cell therapy. The overall incidence of knee arthroplasty after cell therapy was 1.19% per person-year which was equivalent to the risk of a revision for a primary TKA in the contralateral knees of the same patient population (21 revisions, corresponding to 1.00% revision per person-year; p = 0.34). After adjusting for confounders, persistent BMLs larger than 3 cm3 after cell therapy was a strong independent risk factor for total knee arthroplasty (hazard ratio HR = 4.42 [95% CI = 2.34 to 7.21]; p < 0.001), regardless of OA grade, with higher risks demonstrated for larger BMLs. Incidence rates of arthroplasty were also higher for young patients and for knees presenting severe malalignment. CONCLUSIONS: This study showed that subchondral bone marrow concentrate (as compared with TKA) had a sufficient effect on pain to postpone or avoid the TKA in the contra lateral joint of patients with bilateral osteoarthritis. Bone marrow lesions were predictive factors for future knee arthroplasty in the knee with subchondral cell therapy at ten years follow-up.

Hip hemiarthroplasty: from Venable and Bohlman to Moore and Thompson.

In 1939, Frederick R. Thompson of New York and Austin T. Moore of South Carolina separately developed replacements for the entire ball of the hip. These were used to treat hip fractures and also certain arthritis cases. This type of hemiarthroplasty addressed the problem of the arthritic femoral head only. The diseased acetabulum (hip socket) was not replaced. This prosthesis consisted of a metal stem that was placed into the marrow cavity of the femur, connected in one piece with a metal ball fitted into the hip socket. Bohlman and Austin T. Moore (1939) collaborated for the fabrication and implantation of a custom made 12-inch-long vitallium (metal alloy invented by Venable) femoral head prosthesis for a patient with a recurrent giant cell tumour. This prosthesis functioned well and later on influenced the development of long stem femoral head prostheses.