Content uploaded by Steven B Cohen
Author content
All content in this area was uploaded by Steven B Cohen on Dec 28, 2017
Content may be subject to copyright.
Subchondroplasty for Treating Bone Marrow
Lesions
Steven Brad Cohen, MD1Peter F. Sharkey, MD1
1Department of Orthopedic Surger y, Rothman Institute, Thomas
Jefferson University, Philadelphia, Pennsylvania
J Knee Surg 2016;29:555–563.
Address for correspondence Steven Brad Cohen, MD, Depar tment of
Orthopedic Surgery, Rothman Institute, Thomas Jefferson University,
925 Chestnut Street, Philadelphia, Pennsylvania 19107
(e-mail: steven.cohen@rothmaninstitute.com).
Bone marrow lesions (BMLs), also referred to as bone marrow
edemas (BMEs), are a commonly described magnetic reso-
nance imaging (MRI) finding associated with stress injuries,
trauma, or fractures. Osteoarthritis (OA)–related BMLs repre-
sent histologically and mechanically altered subchondral
bone, and have been shown to correlate with accelerated
joint deterioration.1Subchondral BMLs have been demon-
strated in the knee, hip, clavicle, foot, and ankle of patients
with OA.2–5These osseous defects are unrecognized by
standard radiographs, but in fat-suppressed MRI sequences
they appear as dif fuse water-consistent signals in the marrow
space.1,6,7 BMLs occur in association with OA when physio-
logic subchondral remodeling fails due to ongoing joint
forces, increased focalization of stress, and/or reduced
healing capacity of subchondral bone.8,9 BML development
is associated with localized inflammation, increased sub-
chondral vascularization, high bone turnover,1subchondral
bone attrition,8and progression of cartilage loss.10,11
Clinically, the presence of a BML closely correlates with
pain (presence and severity)12 and rapid joint deteriora-
tion.8,10,11 Bone retrieval analysis of a BML reveals altered
subchondral bone with loss of mechanical integrity in the
region of the BML an d a histologic appearance consistent with
a nonhealing chronic stress fracture.13
Arthroscopic debridement generally does not provide lasting
relief for patients with moderate to severe knee OA. In one
prospective trial of 180 patients randomized to receive
arthroscopic debridement, arthroscopic lavage, or placebo, and
followed over a 24-month period, “At no point did either of the
intervention groups report less pain or better function than the
placebo group.”14 In another prospective trial of 172 patients
randomized to receive either arthroscopic debridement/lavage
Keywords
►arthritis
►arthroscopy
►bone marrow edema
►bone marrow lesion
►subchondroplasty
Abstract The prognosis of osteoarthritis (OA) is worsened by persistent subchondral defects
known as bone marrow lesions (BMLs), which herald severe joint degeneration and the
need for joint replacement. Joint-preserving treatments that reverse the progression of
pain and immobility are limited. Subchondroplasty is a procedure developed to treat
BMLs by injecting a calcium phosphate bone substitute into compromised subchondral
bone, under fluoroscopic guidance. Here we evaluate the effectiveness of this approach
for relieving pain and improving function in patients with documented BMLs and
advanced knee OA, in a retrospective study. Data were collected from a consecutive
patient series (n¼66) who underwent subchondroplasty combined with arthroscopy,
performed at a single center by one surgeon. We observed significant improvements in
both pain and function following subchondroplasty with arthroscopic debridement, as
measured by the visual analog scale (VAS) and the International Knee Documentation
Committee (IKDC) Subjective Knee Evaluation Form, through 2 years postoperative
follow-up. Given that arthroscopic debridement alone has been previously shown to
yield insignificant pain relief beyond 6 months postoperatively, our results suggest that
subchondroplasty may be a promising approach for the treatment of OA with BMLs.
received
August 3, 2015
accepted after revision
October 10, 2015
published online
December 7, 2015
DOI http://dx.doi.org/
10.1055/s-0035-1568988.
ISSN 1538-8506.
Copyright © 2016 by Thieme Medical
Publishers, Inc., 333 Seventh Avenue,
New York, NY 10001, USA.
Tel: +1(212) 584-4662.
THIEME
Original Article 555
or medical/physical therapy alone, no differences in outcome
were seen between the groups at 24 months in any of the six
measures used to quantify pain and function.15 Finally, a recent
meta-analysis of nine studies identified a small improvement in
pain at 6 months after knee arthroscopy, but no improvement at
1or2years.
16
Natural history observations have shown that once a BML
defect forms in patients with knee OA, the need for imminent
total knee arthroplasty (TKA) is highly predictable.10,17,18
Additionally, BML development leads to rapid subchondral
bone attrition and progressive deformity due to subchondral
bone collapse.8An observational study of patients with OA
found that, compared with patients without a BML, patients
with an MRI-obser ved BML were nearly nine times as likely to
progress to TKA over a 3-year follow-up period.17
Although TKA has repeatedly been shown to be a durable
intervention, leading to reliable pain relief and improved
quality of life, it is a major surgical intervention and can be
associated with significant recovery time and complica-
tions.19 For these reasons, less invasive, joint-preserving
options are desirable, particularly for younger patients who
comprise a growing proportion of patients undergoing
TKA,20,21 and/or those seeking to delay TKA due to long
recovery times, associated costs, and/or lost productivity
during the rehabilitation process.22–25
The deficiencies of existing interventions for progressive
joint deterioration, and a need for therapies addressing
subchondral bone pathology, have been recognized.26 Others
who have investigated BMLs have theorized on the potential
for an approach specifically treating compromised subchon-
dral bone to modify symptoms.1Because of the substantial
pain and rapid bone and joint deterioration associated with a
BML, an intervention with the capacity to relieve symptoms,
repair subchondral bone, and alter the natural history of joint
deterioration is intriguing.27 Orthobiologic treatments that
mimic the strength of subchondral bone and promote bone
repair represent a novel treatment concept for appropriate
patients.28 Biologic solutions are also attractive due to their
capacity for joint preservation; however, the orthobiologic
must not alter subchondral bone properties in a way that
accelerates joint deterioration or complicates arthroplasty if
eventually required.6,9,29
Subchondroplasty (SCP), developed in 2007, is a procedure
that utilizes an orthobiologic to treat a chronic nonhealing
BML defect.30 It is performed under fluoroscopic guidance by
injecting a flowable, synthetic, calcium phosphate (CaP) bone
void filler6,9,30 into the region of a BML defect. SCP is often
performed in conjunction with arthroscopy to improve accu-
racy of the desired injection location and to correct associated
intra-articular pathologies (i.e., degenerative meniscus tears,
loose bodies, chondral flaps, synovitis), if present. The goal of
SCP is to improve the structural integrity of damaged
subchondral bone and create the potential for subchondral
bone remodeling.30,31 Previous reports have discussed the
theoretical basis, surgical technique, and preliminary results
of SCP.6,9,30 Farr and Cohen reported early findings and
preliminary results for patients undergoing SCP.9These
authors noted that SCP provided a viable approach to reduce
pain associated with BML, with minimal risk of significant
complications. The purpose of the current study was to assess
the potential of SCP combined with arthroscopy to achieve
pain relief and improve function in a population of patients
with BMLs associated with advanced knee OA and indications
for arthroplasty.
Methods
Inclusion and exclusion criteria are listed in ►Table 1.
Between May 2008 and May 2012, approximately 3,000
patients presented to the authors with indications for knee
arthroplasty (i.e., moderate to severe symptoms >2 months
and unsatisfactory response to nonoperative care) to consult
with a fellowship-trained arthroplasty surgeon to discuss
unicompartmental or TKA surgery. After clinical evaluation,
appropriate patients were informed about SCP, including a
description of the procedure and evidence limitations.
Patients were considered eligible for SCP if, after MRI evalua-
tion, they were determined to have BML in the tibia and/or
femur (►Fig. 1A,B); had pain generally localized to the same
compartment as the BML(s); and met the indications for
arthroplasty, including failure of weight loss, corticosteroid
injections, hyaluronic acid injections, nonsteroidal anti-
inflammatory drugs (NSAIDs), physical therapy, and/or
unloader bracing. Patients with a BML who were excluded
Table 1 Inclusion/exclusion criteria
Inclusion criterion Exclusion criterion
•Moderate to severe pain >2mo
•Failure of symptom relief with corticosteroid injections,
hyaluronic acid injections, NSAIDs, physical therapy, and/or
unloader bracing
•Presence of BML(s) on MRI in a weight-bearing region of the
knee (medial/lateral femoral condyle or tibial plateau)
•Patient pain confined to the same compartment as the BML
•Pain in compartment of BML at least 4/10
•Moderate to severe joint disease confined to the same
compartment as the BML
•Primary cause of patient pain and loss of function due to
pathology other than BML, by patient history and clinical
evaluation
•Presence of gross instability
•>8 degrees of varus or valgus
•Tricompartmental radiographic grade 4 OA
Abrreviations: BME, bone marrow edema; BML, bone marrow lesion; MRI, magnetic resonance imaging; NSAIDs, nonsteroidal anti-inflammatory
drugs; OA, osteoarthritis.
The Journal of Knee Surgery Vol. 29 No. 7/2016
Subchondroplasty for Treating Bone Marrow Lesions Cohen, Sharkey556
had greater than 8 degrees of varus or valgus alignment or
tricompartmental radiographic Kellgren-Lawrence (K-L)
grade 4 OA. Informed consent was obtained for all patients.
Patients meeting inclusi on/exclusion cr iteria for treatment
were given the option of arthroscopy combined with SCP as
an alternative to arthroplasty. Of the approximately 3,000
patients entering the clinic during the study period, 69 met
procedure criteria and chose SCP instead of arthroplasty.
At the outset of this retrospective study, Institutional
Review Board (IRB) approval was granted by a local IRB to
contact 66 of the 69 patients to review prospectively-
collected data and gather additional follow-up information.
Of the three patients excluded from analysis, one patient
received SCP from a surgeon not participating in the study,
one received SCP treatment to the patella, and one additional
patient passed away approximately 1 year following surgery
of causes unrelated to their knee surgery. Thus, this cohort
comprises 66 patients.
The SCP procedure was performed as described in prior
publications.6,9,30 Preoperative MRI was used to determine
the extent and location(s) of the BML. Intraoperative ante-
roposterior and lateral fluoroscopic views were used to guide
the injection of the bone substitute into the desired region of
the lesion (►Fig. 1C,D). Arthroscopy was performed to aid in
the accurate placement of the bone substitute, ensure that no
intra-articular extravasation of the injected material
occurred, evaluate intra-articular pathology, and address
correctable problems (e.g., chondral flaps, loose bodies,
degenerative meniscus tears, osteophytes, and synovitis).
Patients with gross knee instability, or whose primary
cause of pain and loss of function was due to pathology other
than a BML, were excluded from the study to limit
confounding factors.
Following SCP, patients were allowed to resume weight-
bearing activities as tolerated, with crutch assistance if needed
for up to 1 week. Physical therapy was initiated 10 to 14 days
after surgery, and a return to full unrestricted activities was
allowed 4 to 8 weeks postoperatively. Any patient who utilized a
preoperative unloader brace wasgiven the option of using it for 4
to 8 weeks postoperatively during recovery.
Following the initial postoperative period, patients were
encouraged to follow up regularly, as per standard clinical
practice. When possible, patients returning for follow-up
visits participated in formal clinical assessment via the visual
analog scale (VAC) for pain (VAS, 10.0 representing the “worst
pain ever”) and/or the International Knee Documentation
Committee (IKDC) Subjective Knee Evaluation Form.32 It was
also determined if and when a patient later “converted”to
knee arthroplasty. No VAS or IKDC scores were considered
after a patient underwent arthroplasty.
For each patient, all dates were indexed to the date of the
SCP. Baseline measures for both VAS and IKDC were
obtained prior to SCP. Because we are primarily interested
in long-term results, the “postoperative”measure used was
the final measurement available in the chart for each
instrument and patient. Because of variable patient partic-
ipation per visit, the final IKDC measure may have been
obtained at a different follow-up interval than the final VAS
measure. VAS and IKDC were analyzed independently. For
each, the null hypothesis was that scores were equally likely
to worsen as they were to improve. We tested this null
hypothesis using the binomial test (Minitab v16.1.1,
Minitab Inc., State College, PA). We applied this test to
the entire cohort, to patients with outcomes collected at
least 6 months posttreatment, and to those with outcomes
collected at least 2 years posttreatment.
Results
Characteristics of the Cohort
As summarized in ►Table 2, 52% of patients were female (34
of 66), the average age was 55.9 years (range 35.0–76.0), and
the average body mass index (BMI) was 30.1 kg/m
2
(range
20.3–53.2 kg/m
2
). Prior to surgery, patients had an average of
22.4 months duration of symptoms (range 2.0–180.0
months). The modified Outerbridge grade of the chondral
surface was determined during intraoperative diagnostic
arthroscopy.33 Ninety-six percent (96%) of subjects had grade
3 or 4 changes in the SCP-treated compartment, and 71% had
grade 2 or less in the contralateral tibial-femoral compart-
ment. Only two patients had less than grade 3 changes in the
SCP-treated compartment (one patient with grade 0 changes,
one with grade 2 changes). Sixty-two percent had grade 3 or 4
changes in the patellofemoral compartment. Patients
Fig. 1 Bone marrow lesions on MRI and intraoperative fluoroscopic
images. (A) Coronal T2 Fat Sat MRI showing bone marrow lesions
(arrows) in the medial femoral condyle and tibial plateaus. (B) Sagittal
PD Fat Sat MRI showing bone marrow lesion (arrow) in the medial
femoral condyle. (C) Intraoperative AP fluoroscopic image showing
placement of cannulas in the medial femoral condyle and tibial
plateau. (D) Intraoperative lateral fluoroscopic image after injection of
CaP bone substitute (diffuse gray-shaded regions within the
highlighted circles) into the medial femoral condyle and tibial plateau,
with cannula bores visible in the center (white circles).
The Journal of Knee Surgery Vol. 29 No. 7/2016
Subchondroplasty for Treating Bone Marrow Lesions Cohen, Sharkey 557
described mean preoperative pain as a 7.6 out of 10 (range 4–
10). Mean IKDC score at baseline was 30.5 (range 14.9–55.2).
Durable Improvement in Pain Scores after
Subchondroplasty with Arthroscopy
Preoperative (baseline) VAS scores were available for 59 out of
the66patients(89%),andatleastonepostoperativeVASscore
was available for 57 of these 59 (median postoperative time of
final follow-up VAS ¼27.2 months). As illustrated in ►Fig. 2A,
50 of these 57 patients exhibited pain improvement on final
follow-up, 3 had worse pain scores, and 4 were unchanged.
Notably, even those patients who ultimately elected to receive
arthroplasty (15 out of these 57 patients) typically showed
improved pain scores (see Discussion). ►Fig. 2B illustrates
that improvements in pain scores were observed at all durations
post-SCP.
The binomial test rejected the null hypothesis that pain
was not improved after SCP, both across all patients (<0.001),
or considering only those whose last follow-up VAS was
at least 6 months postoperative (n¼44, 38
improved, p<0.001), or at least 2 years postoperative fol-
low-up (n¼34, 29 improved, p<0.001). Thus, patients
experienced durable pain relief after SCP.
The magnitude of improvement in VAS pain scores was
clinically meaningful . Across the three groupings (all pat ients,
those with at least 6-month follow-up VAS and those with at
least 2-year follow-up VAS), the mean improvements in VAS
scores were 4.2, 4.3, and 4.5 points, respectively. For VAS pain
Table 2 Demographic characteristics of patients with bone marrow lesion treated with subchondroplasty (n¼66)
Mean age, y (range) 55.9 (35.0–76.0)
Sex (% female) 52%
Mean height, in (range)
a
67.0 (59.0–74.0)
Mean weight, lb (range)
a
195.0 (115.0–350.0)
Mean BMI, kg/m
2
(range)
b
30.1 (20.3–53.2)
Mean length of symptoms before subchondroplasty, mo (range)
a
22.4 (2.0–180.0)
Side of knee, n(%) Left ¼40 (61%)
Right ¼26 (39%)
Alignment, degrees varus, range
b
8to8
Treated area Outerbridge grade
b
Contralateral area Outerbridge grade
Patellofemoral Outerbridge grade
Grade 0: 1 (2%)
Grade 1: 0 (0%)
Grade 2: 1 (2%)
Grade 3: 17 (27%)
Grade 4: 43 (69%)
Grade 0: 16 (27%)
Grade 1: 4 (7%)
Grade 2: 22 (37%)
Grade 3: 13 (22%)
Grade 4: 4 (7%)
Grade 0: 7 (12%)
Grade 1: 1 (2%)
Grade 2: 15 (25%)
Grade 3: 28 (47%)
Grade 4: 9 (15%)
Preoperative ROM, range
a
Extension: 0–5 degrees
Flexion: 100–135 degrees
Prior treatments, n(%)
Arthroscopy
Bracing
Cortisone
Hyaluronic acid
NSAID
Partial medial meniscectomy
Physical therapy
19 (29%)
14 (21%)
41 (62%)
48 (73%)
30 (45%)
18 (27%)
8 (12%)
Baseline VAS scores, mean (SD, range)
c
7.6 (1.5, 4–10)
Baseline IKDC scores, mean (SD, range)
c
30.5 (10, 14.9–55.2)
Abbreviations: BMI, body mass index; IKDC, International Knee Documentation Committee; NSAID, nonsteroidal anti-inflammatory drug; OA,
osteoarthritis; ROM, range of motion; SD, standard deviation; VAS, visual analog scale.
a
<5% missing data points.
b
<10% missing data points.
c
<15% missing data points.
The Journal of Knee Surgery Vol. 29 No. 7/2016
Subchondroplasty for Treating Bone Marrow Lesions Cohen, Sharkey558
scores, an improvement of 2 points (20 mm on the 100-mm
scale) is considered clinically important (minimal clinically
important differences [MCID]).34
►Fig. 2C shows all three dimensions of the data
(baseline VAS, final VAS, and postoperative duration at final
follow-up) for all patients with at least 6 months of VAS
follow-up. ►Fig. 2D shows the distributions of scores in this
patient group.
Durable Improvement in IKDC (symptom/function)
Scores after Subchondroplasty with Arthroscopy
Preoperative (baseline) IKDC scores were available for 48
patients, all of whom also had at least one postoperative
score. As illustrated in ►Fig. 3A, 38 of these 48 patients
exhibited improvement (higher IKDC scores indicate
improved symptoms and function) on final follow-up, 9
had worse scores, and 1 was unchanged. ►Fig. 2B illustrates
that improvements in IKDC scores were observed at all
durations post-SCP.
The binomial test rejected the null hypothesis that
function was not improved after SCP, both across all patients
(p<0.001), or considering only those whose last follow-up
IKDC was at least 6 months postoperative (n¼35, 28
improved, p<0.001), or at least 2 years postoperative
(n¼26, 21 improved, p<0.002). Thus, patients experienced
durable functional/symptomatic improvement after SCP.
The magnitude of improvement in IKDC scores was
clinically meaningful . Across the three groupings (all pat ients,
those with at least 6 months follow-up IKDC, those with at
least 2-year follow-up IKDC), the mean improvements in
IKDC scores were 18.3, 17.2, and 17.8 points, respectively.
For IKDC pain scores, an improvement of 11.5 points is
considered clinically important (MCID).35
►Fig. 3C shows all three dimensions of the data
(baseline IKDC, final IKDC, and postoperative duration at final
follow-up) for all patients with at least 6 months of IKDC
follow-up. ►Fig. 3D shows the distributions of IKDC scores in
this patient group.
Fig. 2 Improvement of visual analog scale (VAS) pain scores after subchondroplasty. (A) Change in VAS scores (final minus baseline) for all 57
patients who had both a presurgical score and at least one follow-up score. (B) Change in VAS score, plotted versus the number of years after
subchondroplasty at which the final follow-up VAS score was obtained, for each patient. (C) Baseline and finalVASscores,forallpatientswhose
final follow-up VAS score was at least 6 months postsurger y (n¼44). (D) Box-and-whiskers plots of baseline and final VAS scores, showing median,
interquartiles, and range (whiskers). MCID, minimal clinically important differences.
The Journal of Knee Surgery Vol. 29 No. 7/2016
Subchondroplasty for Treating Bone Marrow Lesions Cohen, Sharkey 559
Conversion to Arthroplasty
Sixty of the 66 patients (91%) were available for 2-year follow-
up that allowed a determination of whether and when
patients elected to undergo arthroplasty. Of the six patients
not available, only one had 1-year follow-up data, and five
were lost to follow-up. Kaplan-Meier analysis (►Fig. 4),
demonstrated 2-year joint preservation survivorship of 70%
(42 out of 60) for study patients. Because patients in this study
initially presented for arthroplasty consultation, this survival
rate seems promising.
Variables potentially associated with conversion to ar thro-
plasty were assessed using logistic regression and included:
patient age, BMI, length of symptoms, joint alignment, pre-
operative VAS scores, treated area grade, previous partial
meniscectomy, and the presence of kissing lesions (adjacent
BMLs of the tibia and femur). Older age and a history of prior
meniscectomy were both positively associated with subse-
quent conversion to arthroplasty, with or without controlling
Fig. 3 Improvement of International Knee Documentation Committee (IKDC) function/pain scores after subchondroplasty. (A) Change in IKDC
scores (final minus baseline) for all 57 patients who had both a presurgical score andat least one follow-up score. (B) Change in IKDC score, plotted
versus the number of years after subchondroplasty at which the final follow-up IKDC score was obtained, for each patient. (C) Baseline and final
IKDC scores, for all patients whose final follow-up IKDC score was at least 6 months postsurger y (n¼44). (D) Box-and-whiskers plots of baseline
and final IKDC scores, showing median, interquartiles, and range (whiskers).
Fig. 4 Kaplan-Meier plot of conversion to total knee arthroplasty
(TKA). At 2 years after subchondroplasty, 70% of patients (42/60) did
not still elect to receive arthroplasty on the affected knee.
The Journal of Knee Surgery Vol. 29 No. 7/2016
Subchondroplasty for Treating Bone Marrow Lesions Cohen, Sharkey560
for length of symptoms and BMI (p<0.05). The mean age of
patients who converted to arthroplasty was 58.2 years (range
47.0–76.0), compared with a mean of 55.1 years (range 35.0–
73.0) among patients who did not. Thirty-nine percent (39%)
of patients who had subsequent arthroplasty also had a
previous partial meniscectomy, compared with 23% of
patients who did not. Other variables analyzed showed no
significant association with the probability of conversion.
Adverse Events. The observed number of adverse events
following the SCP procedure included one patient who
experienced postoperative drainage at the CaP injection
site, which resolved with surgica l irrigation and debridement,
and one patient diagnosed postoperatively with a deep
vein thrombosis, which required treatment with oral
anticoagulation.
Discussion
The natural history of OA is slow but progressive joint
degeneration. Knee OA patients with BMLs have a poor
prognosis, with accelerated progression to the need for total
knee replacement.8,10,11 Considering these facts, the magni-
tude and durability of the pain relief and functional improve-
ment observed in this retrospective study is noteworthy. For
patients with at least 2 years of follow-up, mean pain
improvement was 4.5 points on the VAS scale (corresponding
to “good to excellent”pain relief36), and mean functional/
symptomatic improvement was 17.8 points on the IKDC scale
(relative to the MCID of 11.5). Our results suggest that SCP
may be a promising treatment for BMLs associated with OA.
Several limitations of this study warrant discussion. First,
with any nonrandomized study, selection bias is possible. For
example, qualifying patients were allowed to select between
arthroplast y and the alternative treatment under study (SCP).
It is possible that an unidentified personal trait could predis-
pose someone to both (1) choose SCP over arthroplasty and
(2) exhibit sustained improvement in knee pain for reasons
unrelated to SCP. Mitigating this concern is the poor prog nosis
of patients entering this study, who were all originally
indicated for arthroplasty. A second limitation is a lack of
standardization in the collection of follow-up data. Not all
subjects completed the patient reported outcomes measures
at all time points, and the final follow-up data were collected
at varying time points. This makes it difficult to evaluate the
progression of pain and function outcomes for patients
treated with SCP from this dataset. A third limitation is a
lack of postoperative imaging to assess changes in the BML.
Future studies that include a series of MR images postopera-
tively may provide valuable insight into the remodeling of the
CaP material and potential relationships between the status
of the BML and patient outcome. A fourth limitation is the
absence of control cohorts: there was no placebo cohort, and
because SCP was always performed along with arthroscopy,
the relative contributions of these two procedures were not
empirically separated. Future study with an arthroscopy-
matched control group may be useful in further evaluating
efficacy. However, several studies of subjects with pathology
and symptoms similar to the present patient population
indicate that arthroscopic debridement alone provides no
durable relief of OA symptoms (►Table 3). The lack of durable
pain relief in these studies may have been due to the presence
of BMLs. BMLs are commonly present in this patient popula-
tion and are not treated by traditional arthroscopy.
Another recent study evaluated the effect of SCP on
outcomes in patients with knee BMLs,37 in a nonmatched
cohort of 22 patients with knee OA. They reported that both
the Knee Injury and Osteoarthr itis Outcome Score (KOOS) and
the Tegner-Lysholm Knee Scoring Scale scores significantly
improved (p<0.001) at greater than 6 months posttreat-
ment. Surprisingly, despite these improvements, the authors
Table 3 Review of studies quantifying the effects of knee arthroscopy on pain and function outcomes at 24 months
Study Patients Design Outcome
Moseley et al, New Engl J Med,
2002
•n¼180 patients
•VAS pain 4
•No severe joint deformity
•Prospective, randomized to
1. Arthroscopic debride-
ment
2. Arthroscopic lavage
3. Placebo
•Follow-up through 24 mo
Nodifferencesinpainor
function (6 different score
metrics) in any groups at any
time point
Kirkley et al, New Engl J Med,
2008
•n¼172 patients
•Kellgren-Lawrence grade 2,
3, or 4
•Prospective, randomized to
1. Arthroscopic debride-
ment and lavage to-
gether with optimized
physical and medical
therapy
2. Physical and medical
therapy alone
•Follow-up through 24 mo
No differences in WOMAC or
SF-36 scores between groups
Thorlund et al, BMJ, 2015 •n¼1,270 patients across 9
studies
•Meta-analysis
•Follow up through 24 mo
Small improvements at 3 and
6moinpain
Noimprovementinpainor
function at 12 and 24 mo
The Journal of Knee Surgery Vol. 29 No. 7/2016
Subchondroplasty for Treating Bone Marrow Lesions Cohen, Sharkey 561
concluded that the treatment was “ineffective.”However, the
authors defined “clinical failure”based on a categorization of
postoperative Tegner-Lysholm scores historically used to
evaluate success of anterior cruciate ligament (ACL)
reconstruction, a scoring method likely inappropriate for
evaluating the success rate of this treatment.38,39
The present study is the largest series to date evaluating
the effectiveness of SCP. Interestingly, although most patients
(70%) did not convert to arthroplasty, a majority of the
patients who did progress to ar throplasty actually had shown
improvements in both VAS and IKDC scores prior to their
decision to undergo a total knee replacement. Factors such as
patient expectations (both with SCP and total knee
replacement) and patient satisfaction were not evaluated in
this study. This highlights the complexity of the personal
decision to undergo surgery and thus the difficulty of using
revision to an elective surgery for assessing efficacy.
It is important to consider biologic options for subchondral
bone lesion treatment, such as calcium-phosphate SCP, in the
context of other treatment options. TKA provides
predictable pain relief; however, functionality is typically
reduced.22,23,25,30 Additionally, TKA is costly, invasive, and
requires substantial recovery time (typically, 6–12
months).24,40 SCP, on the other hand, represents a minimally
invasive approach that provides fairly reliable pain relief
while preserving the native joint, and enables patients to
resume some normal activities as soon as 1 week postpro-
cedure.30 These factors may be particularly important for
younger, active patients who wish to reduce pain and avoid
arthroplasty, but retain function and delay the productivity
losses associated with major surgery.
Conclusion
Patients with severe knee OA have limited options, usually
requiring arthroplasty to regain mobility and relieve pain. For
patients who also have BMLs, the prognosis is poor and joint
deterioration usually progresses rapidly. In this study we evalu-
ated the efficacy of using SCP—a technique for applying a CaP
bone substitute to the BML defect—with arthroscopy, as a less
invasive, joint-preserving option in patients with BMLs associat-
ed with advanced OA. We observed clinically significant and
durable improvements in pain and function in most patients in
our investigation. Understanding the limitations of retrospective
case studies, this first patient series shows potential for treating
patients with pain due to presence of BMLs.
References
1Eriksen EF, Ringe JD. Bone marrow lesions: a universal bone
response to injury? Rheumatol Int 2012;32(3):575–584
2Radke S, Kirschner S, Seipel V, Rader C, Eulert J. Treatment of
transient bone marrow oedema of the hip—a comparative study.
Int Orthop 2003;27(3):149–152
3Hofmann S, Engel A, Neuhold A, Le der K, Kramer J, Plenk H Jr. Bone-
marrow oedema syndrome and transient osteoporosis of the hip.
an MRI-controlled study of treatment by core decompression.
J Bone Joint Surg Br 1993;75(2):210–216
4Shubin Stein BE, Ahmad CS, Pfaff CH, Bigliani LU, Levine WN. A
comparison of magnetic resonance imaging findings of the acro-
mioclavicular joint in symptomatic versus asymptomatic patients.
J Shoulder Elbow Surg 2006;15(1):56–59
5Orr JD, Sabesan V, Major N, Nunley J. Painful bone marrow edema
syndrome of the foot and ankle. Foot Ankle Int 2010;31(11):949–953
6Cohen SB, Sharkey PF. Surgical treatment of osteoarthritis pain
related to subchondral bone defects or bone marrow lesions:
subchondroplasty. Tech Knee Surg 2012;11(4):170–175
7Jimenez-Boj E, Nöbauer-Huhmann I, Hanslik-Schnabel B, et al.
Bone erosions and bone marrow edema as defined by magnetic
resonance imaging reflect true bone marrow inflammation in
rheumatoid arthritis. Arthritis Rheum 2007;56(4):1118–1124
8Roemer FW, Neogi T, Nevitt MC, et al. Subchondral bone marrow
lesions are highly associated with, and predict subchondral bone
attrition longitudinally: the MOST study. Osteoarthritis Cartilage
2010;18(1):47–53
9Farr J II, Cohen SB. Expanding applications of the subchondro-
plasty procedure for the treatment of bone marrow lesions
observed on magnetic resonance imaging. Oper Tech Sports
Med 2013;21(2):138–143
10 Tanamas SK, Wluka AE, Pelletier JP, et al. Bone marrow lesions in
people with knee osteoar thritis predict progression of disease an d
joint replacement: a longitudinal study. Rheumatology (Oxford)
2010;49(12):2413–2419
11 Wluka AE, Wang Y, Davies-Tuck M, English DR, Giles GG, Cicuttini
FM. Bone marrow lesions predict progression of cartilage defects
and loss of cartilage volume in healthy middle-aged adults with-
out knee pain over 2 yrs. Rheumatology (Oxford) 2008;47(9):
1392–1396
12 Felson DT, Chaisson CE, Hill CL, et al. The association of bone
marrow lesions with pain in knee osteoarthritis. Ann Intern Med
2001;134(7):541–549
13 Taljanovic MS, Graham AR, Benjamin JB , et al. Bone mar row edema
pattern in advanced hip osteoarthritis: quantitative assessment
with magnetic resonance imaging and correlation with clinical
examination, radiographic findings, and histopathology. Skeletal
Radiol 2008;37(5):423–431
14 Moseley JB, O’Malley K, Petersen NJ, et al. A controlled trial of
arthroscopic surgery for osteoarthritis of the knee. N Engl J Med
2002;347(2):81–88
15 Kirkley A, Birmingham TB , Litchfield RB, et al. A randomized tr ial of
arthroscopic surgery for osteoarthritis of the knee. N Engl J Med
2008;359(11):1097–1107
16 Thorlund JB, Juhl CB, Roos EM, Lohmander LS. Arthroscopic
surgery for degenerative knee: systematic review and meta-
analysis of benefits and harms. BMJ 2015;350:h2747
17 Scher C, Craig J, Nelson F. Bone marrow edema in the knee in
osteoarthrosis and association with total knee ar throplasty within
a three-year follow-up. Skeletal Radiol 2008;37(7):609–617
18 Kröner AH, Berger CE, Kluger R, Oberhauser G, Bock P, Engel A.
Influence of high tibial osteotomy on bone marrow edema in the
knee. Clin Orthop Relat Res 2007;454(454):155–162
19 Healy WL, Della Valle CJ, Iorio R, et al. Complications of total knee
arthroplast y: standardized list and definitions of the Knee Society.
Clin Orthop Relat Res 2013;471(1):215–220
20 Kurtz S, Mowat F, Ong K, Chan N, Lau E, Halpern M. Prevalence of
primary and revision total hip and knee ar throplasty in the United
States from 1990 through 2002. J Bone Joint Surg Am 2005;87(7):
1487–1497
21 Kurtz SM, Lau E, Ong K, Zhao K, Kelly M, Bozic KJ. Future young
patient demand for primary and revision joint replacement:
national projections from 2010 to 2030. Clin Orthop Relat Res
2009;467(10):2606–2612
22 Franklin PD, Li W, Ayers DC. The Chitranjan Ranawat Award:
functional outcome after total knee replacement varies with
patient attribu tes. Clin Orthop Relat Res 2008;466(11):2597–2604
The Journal of Knee Surgery Vol. 29 No. 7/2016
Subchondroplasty for Treating Bone Marrow Lesions Cohen, Sharkey562
23 Mizner RL, Petterson SC, Cleme nts KE, Zeni JA Jr, Irrgang JJ, Snyder-
Mackler L. Measuring functional improvement after total knee
arthroplasty requires both performance-based and patient-report
assessments: a longitudinal analysis of outcomes. J Arthroplasty
2011;26(5):728–737
24 Browne JP, Bastaki H, Dawson J. What is the optimal time point to
assess patient-reported recovery after hip and knee replacement?
A systematic review and analysis of routinely reported outcome
data from the English patient-reported outcome measures pro-
gramme. Health Qual Life Outcomes 2013;11:128
25 Singh JA, O’Byrne M, Harmsen S, Lewallen D. Predictors of moder-
ate-severe functional limitation after primary total knee arthro-
plasty (TKA): 4701 TKAs at 2 years and 2935 TKAs at 5 years.
Osteoarthritis Cartilage 2010;18(4):515–521
26 Mastbergen SC, Lafeber FP. Changes in subchondral bone early in
the development of osteoarthritis. Arthritis Rheum 2011;63(9):
2561–2563
27 Lim YZ, Wang Y, Wluka AE, et al. Association of obesity and
systemic factors with bone marrow lesions at the knee: a system-
atic review. Semin Arthritis Rheum 2014;43(5):600–612
28 Moore WR, Graves SE, Bain GI. Synthetic bone graft substitutes.
ANZ J Surg 2001;71(6):354–361
29 TofighiA,RosenbergA,SutariaM,BalataS,ChangJ.New
generation of synthetic, bioresorbable and injectable calcium
phosphate bone substitute materials: Alpha-bsm®, Beta-
bsmTM and Gamma-bsmTM. J Biomimet Biomat Tissue Engi-
neer 2009;2:39–55
30 Sharkey PF, Cohen SB, Leinberry CF, Parvizi J. Subchondral bone
marrow lesions associated with knee osteoarthritis. Am J Orthop
2012;41(9):413–417
31 Bajammal SS, Zlowodzki M, Lelwica A, et al. The use of calcium
phosphate bone cement in fracture treatment. A meta-analysis of
randomized trials. J Bone Joint Surg Am 2008;90(6):1186–1196
32 Higgins LD, Taylor MK, Park D, et al; International Knee Documen-
tation Committee. Reliability and validity of the International
Knee Documentation Committee (IKDC) Subjective Knee Form.
Joint Bone Spine 2007;74(6):594–599
33 Browne JE, Branch TP. Surgical alternatives for treatment of articular
cartilage lesions. J Am Acad Orthop Surg 2000;8(3):180–189
34 Tubach F, Ravaud P, Baron G, et al. Evaluation of clinically relevant
changes in patient reported outcomes in knee and hip osteoar-
thritis: the minimal clinically important improvement. Ann
Rheum Dis 2005;64(1):29–33
35 Irrgang JJ, Anderson AF, Boland AL, et al; International Knee
Documentation Committee. Responsiveness of the International
Knee Documentation Committee Subjective Knee Form. Am J
Sports Med 2006;34(10):1567–1573
36 Grilo RM, Treves R, Preux PM, Vergne-Salle P, Bertin P. Clinically
relevant VAS pain score change in patients with acute rheumatic
conditions. Joint Bone Spine 2007;74(4):358–361
37 Chatterjee D, McGee A, Strauss E, Youm T, Jazrawi L. Subchondral
calcium phosphate is ineffective for bone marrow edema lesion s in
adults with advanced osteoarthritis. Clin Orthop Relat Res 2015;
473(7):2334–2342
38 Mitsou A, Vallianatos P, Piskopakis N, Maheras S. Anterior
cruciate ligament reconstruction by over-the-top repair com-
bined with popliteus tendon plasty. J Bone Joint Surg Br 1990;
72(3):398–404
39 Bengtsson J, Möllborg J, Werner S. A study for testing the sensitiv-
ity and reliabilit y of the Lysholm knee scoring scale. Knee Surg
Sports Traumatol Arthrosc 1996;4(1):27–31
40 U.S. Agency for Healthcare Research and Quality. National and
regional estimates on hospital use for all patients from the HCUP
Nationwide Inpatient Sample (NIS) for ar throplasty of knee
(surgical reconstruction or replacement of knee). 2012. http://
hcupnet.ahrq.gov/HCUPnet.jsp
The Journal of Knee Surgery Vol. 29 No. 7/2016
Subchondroplasty for Treating Bone Marrow Lesions Cohen, Sharkey 563
