Osteochondral lesions under 15mm2 of the Talus; is iliac crest Bone marrow Aspirate Concentrate the Key to success?

Osteochondral defects (OCDs) of the talus have a significant impact on the
quality of life of patients. When OCDs are of small nature (up to 15 mm in
diameter), and have failed conservative management, surgical intervention may
be necessary. For small cystic defects the current treatment is an arthroscopic
bone marrow stimulation (BMS) procedure, during which the damaged cartilage is
resected and the subchondral bone is microfractured (MF), in order to disrupt
intraosseous blood vessels and thereby introduce blood and bone marrow cells
into the debrided lesion, forming a microfracture fibrin clot, which contains a
dilute stem cell population from the underlying bone marrow. This procedure has
been reported to have a 75% successful long-term outcome. Recently, the
additional use of biological adjuncts has become popular, one of them being
bone marrow aspirate concentrate (BMAC) from the iliac crest. BMAC consists of
mesenchymal stem cells, hematopoietic stem cells and growth factors, which may
therefore theoretically improve the quality of subchondral plate and cartilage
repair. The current evidence for treating talar OCDs with BMS plus BMAC is
limited and heterogeneous. It is unclear to what extent the treatment of talar
OCDs with BMS plus BMAC is beneficial in comparison to BMS alone.

The main objective of the present study is to compare the clinical outcome of
bone marrow stimulation alone versus bone marrow stimulation and bone marrow
aspirate concentrate (BMAC) for small symptomatic osteochondral defects of the
talus.

This study concerns a physician and patient-blinded multicenter randomized
controlled trial with a 24-month follow-up period at the outpatient clinic. All
patients that visit the outpatient clinic (in any of the participating centers)
for small symptomatic talar OCDs up to 15 mm in depth and/or diameter -
anteroposterior or mediolateral-, eligible for BMS surgery will be asked if
they are willing to participate in the present study. If they are interested,
patients will be informed about this study and are given two weeks to decide
upon participation. In case patients provide their consent, they are screened
for meeting the inclusion criteria, and are assessed pre-operatively by
documenting a questionnaire containing the EQ5D, Numeric Rating Scale (NRS) of
pain, the American Orthopaedic Foot and Ankle Hindfoot Score (AOFAS) Foot and
Ankle Outcome Score (FAOS), Foot and Ankle Ability Measure (FAAM) and the
Short-Form 12 (SF-12). As part of the standard AMC pre-operative protocol
concerning talar OCDs, the patients will receive a preoperative dual energy
computed tomography (CT) scan. Additionally, the patients will receive an
Magnetic Resonance Imaging (MRI) scan pre-operatively. Subsequently after
surgery, patients will be followed-up at 2 weeks, six weeks, three months,
one-year and two years post-operatively. At two weeks post-operatively
complication assessment will be performed as well as on 6 weeks.
Pre-operatively, at three months and at one-year and two years post-operatively
outcome scores with the aforementioned scorews will be collected.
At these follow-up moments the patients will be requested to fill out
questionnaires and a physical examination will be performed. At one and two
-year of follow-up, a CT-scan and a MRI-scan will be made to guide prognosis
and judge the quality of the cartilage (the CT-scan is a standard follow-up
procedure, also in other surgical treatments for this indication). Apart from
the scores mentioned above in the pre-operative questionnaire, the
post-operative questionnaires will contain scores assessing the resumption to
sports, work, as well as maintenance of sport and work activities (Ankle
Activity Scale (AAS)).
As the use of biological adjuncts supplemental to bone marrow stimulation is
gaining popularity in the orthopaedic field, but has not yet been proven in
clinical trials that were controlled, it is of clinical importance to assess
the efficacy of the use of BMAC supplemental to BMS versus BMS alone. Bone
marrow stimulation alone will function as the control group in the present
study as this has been the conventional surgical method for small talar
osteochondral defects that are small of nature for the past decades. A control
group of untreated patients with persisting and disabling complaints of a talar
osteochondral defect cannot be justified as this impedes quality of life and
may have serious consequences.
The control group of the present study will receive arthroscopic bone marrow
stimulation. Additionally, from this group will receive a 2mm Jamashidi needle
puncture over the iliac crest. From this needle puncture, bone marrow aspirate
will be harvested. This will then be concentrated to check for the cell
characterization. The concentrated bone marrow will however not be implanted
into the osteochondral talar lesion. The reasoning behind this is that we can
check whether the cell characterization (average cell count and concentration)
of the control group is similar to the experimental arm of the present RCT.
This, as the BMAC cells will be sent for characterization for Colony Forming
Unit Cell counts in order to ensure that there are no discrepancies between the
experimental group and the control group with regards to BMAC quality. Also, by
these means, the control group will be blinded for BMAC harvesting by means of
the same 2mm puncture wound, in order to increase internal validity of the
study.
The experimental group will also receive arthroscopic treatment of the talar
OCD through bone marrow stimulation. Additionally this group will receive a
harvesting procedure of BMAC through a 2mm Jamashidi needle puncture wound over
the iliac crest, in the exact same manner as in the control group. 1mL of BMAC
obtained after spinning the bone marrow aspirate will be sent for CFU
characterization in order to compare with the control group. The BMAC that is
left after concentrating the aspirate will be implanted into the defect which
has undergone bone marrow stimulation by the orthopaedic surgeon. An interim
analysis will be conducted at 12 months postoperatively, in order to assess
short-term and mid-term results.

Both groups of patients are surgically treated with arthroscopic bone marrow
stimulation (BMS). The control group will receive BMS alone but with a
sham-treatment consisting of a Jamashidi (bone marrow aspiration) needle
puncture of the iliac crest. The aspirated bone marrow concentrate will be
collected and sent for cell characterisation but will not be inserted in the
talar OCD.
The intervention group will also receive arthroscopic BMS. From this group,
BMAC from the iliac crest will be taken by the same needle puncture. Part of
this concentrate will be sent for cell characterisation. Another part will be
implanted into the talar OCD.

Patient burden is mainly caused by the pre and postoperative questionnaires
that need to be filled out.Preoperatively and postoperatively patients will not
visit the outpatient clinical more frequently than standard care concerning
regular check-ups. The risk of the investigational treatment, that is BMS with
supplemental BMAC is equal to the standard risks associated with the control
group (BMS and sham stab incision) for this indication. Risks or complications
associated with ankle arthroscopy in general can be bleeding, infection, venous
thrombosis and damage to superficial nerves. Pre- and post-operative radiology
are not considered risks or extra burdens as these are part of standard care.