ArticlePDF Available

Subchondroplasty for Treating Bone Marrow Lesions

Authors:

Abstract and Figures

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 (n = 66) 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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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;29:555563.
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) nding 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.25These 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 inammation, 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 uoroscopic 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 signicant 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 insignicant 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 identied 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 signicant 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.2225
The deciencies 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 specically 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 uoroscopic guidance by
injecting a owable, synthetic, calcium phosphate (CaP) bone
void ller6,9,30 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 aps, 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 ndings 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 signicant
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-
inammatory 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 conned to the same compartment as the BML
Pain in compartment of BML at least 4/10
Moderate to severe joint disease conned 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-inammatory
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 uoroscopic 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 aps, 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 convertedto
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 postoperativemeasure used was
the nal measurement available in the chart for each
instrument and patient. Because of variable patient partic-
ipation per visit, the nal IKDC measure may have been
obtained at a different follow-up interval than the nal 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 35.076.0), and
the average body mass index (BMI) was 30.1 kg/m
2
(range
20.353.2 kg/m
2
). Prior to surgery, patients had an average of
22.4 months duration of symptoms (range 2.0180.0
months). The modied 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 uoroscopic
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 uoroscopic image showing
placement of cannulas in the medial femoral condyle and tibial
plateau. (D) Intraoperative lateral uoroscopic 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 14.955.2).
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
nal follow-up VAS ¼27.2 months). As illustrated in Fig. 2A,
50 of these 57 patients exhibited pain improvement on nal
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 (35.076.0)
Sex (% female) 52%
Mean height, in (range)
a
67.0 (59.074.0)
Mean weight, lb (range)
a
195.0 (115.0350.0)
Mean BMI, kg/m
2
(range)
b
30.1 (20.353.2)
Mean length of symptoms before subchondroplasty, mo (range)
a
22.4 (2.0180.0)
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: 05 degrees
Flexion: 100135 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, 410)
Baseline IKDC scores, mean (SD, range)
c
30.5 (10, 14.955.2)
Abbreviations: BMI, body mass index; IKDC, International Knee Documentation Committee; NSAID, nonsteroidal anti-inammatory 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, nal VAS, and postoperative duration at nal
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 nal 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, nal IKDC, and postoperative duration at nal
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 (nal 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 nal follow-up VAS score was obtained, for each patient. (C) Baseline and nalVASscores,forallpatientswhose
nal follow-up VAS score was at least 6 months postsurger y (n¼44). (D) Box-and-whiskers plots of baseline and nal 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 ve
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 (nal 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 nal follow-up IKDC score was obtained, for each patient. (C) Baseline and nal
IKDC scores, for all patients whose nal follow-up IKDC score was at least 6 months postsurger y (n¼44). (D) Box-and-whiskers plots of baseline
and nal 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
47.076.0), 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
signicant 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 excellentpain 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 unidentied 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 nal follow-up data were collected
at varying time points. This makes it difcult 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
efcacy. 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 signicantly
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 dened clinical failurebased 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 difculty of using
revision to an elective surgery for assessing efcacy.
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, 612
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 efcacy of using SCPa technique for applying a CaP
bone substitute to the BML defectwith arthroscopy, as a less
invasive, joint-preserving option in patients with BMLs associat-
ed with advanced OA. We observed clinically signicant and
durable improvements in pain and function in most patients in
our investigation. Understanding the limitations of retrospective
case studies, this rst 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):575584
2Radke S, Kirschner S, Seipel V, Rader C, Eulert J. Treatment of
transient bone marrow oedema of the hipa comparative study.
Int Orthop 2003;27(3):149152
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):210216
4Shubin Stein BE, Ahmad CS, Pfaff CH, Bigliani LU, Levine WN. A
comparison of magnetic resonance imaging ndings of the acro-
mioclavicular joint in symptomatic versus asymptomatic patients.
J Shoulder Elbow Surg 2006;15(1):5659
5Orr JD, Sabesan V, Major N, Nunley J. Painful bone marrow edema
syndrome of the foot and ankle. Foot Ankle Int 2010;31(11):949953
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):170175
7Jimenez-Boj E, Nöbauer-Huhmann I, Hanslik-Schnabel B, et al.
Bone erosions and bone marrow edema as dened by magnetic
resonance imaging reect true bone marrow inammation in
rheumatoid arthritis. Arthritis Rheum 2007;56(4):11181124
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):4753
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):138143
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):24132419
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):
13921396
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):541549
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 ndings, and histopathology. Skeletal
Radiol 2008;37(5):423431
14 Moseley JB, OMalley K, Petersen NJ, et al. A controlled trial of
arthroscopic surgery for osteoarthritis of the knee. N Engl J Med
2002;347(2):8188
15 Kirkley A, Birmingham TB , Litcheld RB, et al. A randomized tr ial of
arthroscopic surgery for osteoarthritis of the knee. N Engl J Med
2008;359(11):10971107
16 Thorlund JB, Juhl CB, Roos EM, Lohmander LS. Arthroscopic
surgery for degenerative knee: systematic review and meta-
analysis of benets 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):609617
18 Kröner AH, Berger CE, Kluger R, Oberhauser G, Bock P, Engel A.
Inuence of high tibial osteotomy on bone marrow edema in the
knee. Clin Orthop Relat Res 2007;454(454):155162
19 Healy WL, Della Valle CJ, Iorio R, et al. Complications of total knee
arthroplast y: standardized list and denitions of the Knee Society.
Clin Orthop Relat Res 2013;471(1):215220
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):
14871497
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):26062612
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):25972604
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):728737
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, OByrne 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):515521
26 Mastbergen SC, Lafeber FP. Changes in subchondral bone early in
the development of osteoarthritis. Arthritis Rheum 2011;63(9):
25612563
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):600612
28 Moore WR, Graves SE, Bain GI. Synthetic bone graft substitutes.
ANZ J Surg 2001;71(6):354361
29 ToghiA,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;2:3955
30 Sharkey PF, Cohen SB, Leinberry CF, Parvizi J. Subchondral bone
marrow lesions associated with knee osteoarthritis. Am J Orthop
2012;41(9):413417
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):11861196
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):594599
33 Browne JE, Branch TP. Surgical alternatives for treatment of articular
cartilage lesions. J Am Acad Orthop Surg 2000;8(3):180189
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):2933
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):15671573
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):358361
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):23342342
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):398404
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):2731
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
... It has been proven in animal models that at both a cellular and molecular level the BSM will form a macroporous nanocrystalline matrix similar to native bone and overtime, through cell mediated remodeling, the BSM will be resorbed allowing new bone deposition [8]. Within the literature, however, there are mixed results on its efficacy [5,9,10]. To our knowledge there is no study that provides a histological analysis of bone after subchondroplasty in human subjects to evaluate its claims for BSM resorption and bone deposition at a histological level, as this can correlate with the procedures overall efficacy and patient improvement. ...
... After preparation, the tibial specimen was observed to contain BSM of calcium phosphate from subchondroplasty procedure, as well as adjacent normal bone (Figure 2a). Nine representative areas of the proximal tibia were chosen and labeled zones one through nine, which helped to analyze the interface between the BSM and surrounding medullary bone (Figure 2b) [1][2][3][4][5][6]8,11,12]. Following a standard decalcification process, each area underwent multiple histologic sections. ...
... It is also typically performed in conjunction with arthroscopy to improve accuracy of the injection, as well as, to diagnose and treat any intra-articular pathologies that could be causing pain. Sharkey performed a subchondroplasty in patients with primarily grade 3 or 4 OA changes diagnosed by arthroscopy [5]. At 2 years follow up patients demonstrated a significant decrease in subjective pain scores performed a mid-term follow up study of 32 months on patients who recently underwent subchondroplasty diagnosed BMLs on MRI. ...
Article
In our series of 227 patients who underwent prior Subchondroplasty of the knee wiht bone substitute material (BSM) we had the opportunity to review 4 cases which returned for conversion to Total Knee Arthroplasty (TKA). The average time to convert to a TKA was 23.5 months (18-35 months).
... Therefore, authors have proposed hip arthroscopy with subchondroplasty in these patients [5,6]. In recent years, subchondroplasty of the knee has shown to be a safe procedure while alleviating pain and decreasing the exacerbation of osteoarthritis [7,8]. Furthermore, patients who underwent SCP and later necessitated a THA showed no difference in outcomes compared to those who underwent THA as an index procedure [9]. ...
... Increased subchondral pressure due to the focalization of load as mentioned earlier, either from direct trauma to the acetabular dome or FAIS, could lead to pressure necrosis of the underlying cancellous bone. In either case, histologic analyses of the subchondral cyst are consistent with fibrous tissues often seen with chronic, nonhealing stress reactions [7,13]. Hence, it is posited that increasing mechanical support through the injection of void fillers such as calcium phosphate cement would allow for osteoconductive remodeling and eventual healing of the inflammatory or cystic lesions [7,14,15]. ...
... In either case, histologic analyses of the subchondral cyst are consistent with fibrous tissues often seen with chronic, nonhealing stress reactions [7,13]. Hence, it is posited that increasing mechanical support through the injection of void fillers such as calcium phosphate cement would allow for osteoconductive remodeling and eventual healing of the inflammatory or cystic lesions [7,14,15]. ...
... One such study reported an improvement of VAS of 4.3 points in 50 of the 57 individuals studied at the 6-month follow-up after CaP injection of bone marrow lesions. 9 Additionally, a report of 5 cases in the distal medial femoral condyle and tibial plateau reported a decrease in VAS from a mean 7.8 preoperatively to a mean 2.2 post-operatively at the 24-week follow-up. 10 These results are consistent with what we have obtained through use of our technique in insufficiency fractures of the foot. ...
... In this study, the patient noted a decrease in VAS from 9 preoperatively to 1-2 at the 6-week follow-up. 9 The CaP provides the scaffold for bony ingrowth while BMA provides the ability to add mesenchymal stem cells, osteoprogenitor cells, and hematopoietic stem cells. Platelets also contribute important growth factors in the like of transforming growth factor beta (TGF-B), platelet derived growth factor (PDFG), and vascular endothelial growth factor (VEGF) to achieve a superior healing environment. ...
... Avascular necrosis of the talus has been managed successfully with core decompression with and without the addition of the calcium phosphate conduit. 9,15 The use of CaP in this study was performed to provide additional scaffolding for the insufficient metatarsals and allow for immediate weight bearing postoperatively. Additional studies should compare the efficacy of BMA with and without CaP to determine the necessity of this additional structural graft. ...
Article
Full-text available
The treatment of metatarsal stress fractures typically involves a period of immobilization and offloading to allow bone to remodel. For those resistant to conservative therapy, surgical treatment options are limited. The purpose of this study is to investigate the efficacy of an injection of calcium phosphate and bone marrow aspirate for treatment of metatarsal stress fractures. A retrospective chart review was performed over a 5-year period. Four patients with lesser metatarsal stress fractures resistant to conservative therapy had undergone a percutaneous injection of a calcium phosphate and bone marrow aspirate. The Visual Analog Scale scores for pain at the pre-operative, 5-day, 2-week, 4-week, 8-week, 3-month and 6-month post-operative visits were evaluated for mean improvement. Additionally, a radiographic review was performed to evaluate any adverse outcomes or failure of fixation. A mean Visual Analog Scale pain score of 7.5 ± 1.5 was obtained from patients prior to operation and decreased to a mean 1 ± 1.15 at the 6-month follow-up. There was a progressive improvement at each follow-up with statistical significance (p ≤ 0.05) at each time point. Patients were weight bearing as tolerated post-operatively in protective device with return to a supportive sneaker at a mean 4 weeks. This study shows excellent results with the injectable calcium phosphate and bone marrow aspirate combination for treatment of lesser metatarsal stress fractures. Although current literature is limited in surgical treatment of these insufficiency fractures, this novel technique supports the consideration of this modality for use in clinical practice.
... 6 Promising results have been recently reported with the advent use of calcium phosphate (CaPO 4 ) solution in subchondral lesions around the knee. 7,8 A similar approach has been described in the hip, but clinical outcomes are less evaluated. 6,9 Concomitant central compartment pathology, including femoroacetabular impingement (FAI) as well as chondral and labral lesions, is frequently present in the context of femoral head AVN. ...
... 28 Subchondroplasty, which includes the injection of CaPO 4 material in addition to CD, is an emerging surgical technique with good outcomes in subchondral lesions around the knee. 7,8 Data regarding clinical outcomes in the hip are still lacking, but a few studies showed promising results in the short and mid-term follow-up. 29-31 Subchondroplasty also seems effective in preventing further collapse of the femoral head. ...
Article
Full-text available
Avascular necrosis (AVN) of the hip is a devastating disease that affects middle-aged adults with poor outcomes if not treated in its early stages. In recent years, subchondroplasty with calcium phosphate solution has shown promising results. Concomitant intra-articular pathologies, including femoroacetabular impingement and chondral lesions, have been described in hips affected by AVN. These should be addressed at the time of surgery to lower the risk of failure. In this Technical Note, we describe an arthroscopic approach to femoral head subchondroplasty with precollapse lesion in AVN affected hip, combined with labral reconstruction and acetabular chondral treatment.
... 20 Operative management of bone marrow lesions was first developed and popularized in the knee area, with literature supporting and, at times, refuting its use. 2,3,8,18 Operative socalled stabilization of BME lesions involves percutaneous injections of calcium phosphate (with or without marrow or biologic augmentation) under fluoroscopic guidance. 3,8,18 Some studies have shown that the synthetic injected calcium phosphate is resorbed and replaced with endogenous healthy trabecular bone on an average of 6-22 months postoperatively. ...
Article
Full-text available
Background Treatment of chronic refractory heel pain has evolved to consider calcaneal structural fatigue as a component of the symptom profile. While concomitant calcium phosphate injection has become a method of addressing the accompanying calcaneal bone marrow edema (BME) frequently seen in this population, there is no literature supporting its use compared to traditional fasciotomy. Methods Consecutive patients with symptoms of refractory infracalcaneal heel pain and calcaneal BME were treated in our practice by either surgical fasciotomy (n = 33) or fasciotomy plus calcium phosphate injection (n = 31) between 2014 and 2019. Outcomes were retrospectively assessed via Foot and Ankle Outcome Scores (FAOS), return to activity, and complication rate. Results Sixty-four patients (64 feet) were included with a mean age of 50.3 ± 12.9 years and mean follow-up of 23.2 ± 22.3 months. No differences were observed between groups preoperatively. Significant improvements in 4 of 5 FAOS subscales were observed postoperatively in both groups ( P < .05 for all, paired t test). However, patients undergoing concomitant calcium phosphate injection reported significantly better scores for both activities of daily living (ADL; mean difference +10.2; 95% confidence interval [CI] 0.07-20.2) and foot-specific QOL (mean difference +21.9, 95% CI 7.0-36.6) at final follow-up compared with those undergoing plantar fasciotomy alone. All patients returned to their desired level of activity, and the frequency of complications did not differ between groups ( P > .05, Fisher exact test). Conclusion In patients presenting with recalcitrant infracalcaneal heel pain accompanied by calcaneal BME, calcium phosphate injection into the calcaneus, when combined with plantar fasciotomy, was safe and more effective than traditional plantar fasciotomy alone. Level of Evidence Level III, retrospective comparative study.
... 6 Operative management of BME lesions was developed and popularized in the knee arena, with early ample literature supporting its use. 2,5,7,8 Operative subchondral stabilization of BME lesions involves percutaneous injections of calcium phosphate (with our without marrow or biologic augmentation) under uoroscopic guidance. 2,5,8 Studies show that the synthetic injected calcium phosphate is resorbed and replaced with endogenous healthy trabecular bone on an average of 6-22 months postoperatively. ...
Preprint
Full-text available
Disabling foot pain is often accompanied by MRI evidence of bone marrow edema which may represent early structural fatigue. Emerging evidence suggests subchondral stabilization with injectable calcium phosphate can alleviate pain associated with bone marrow edema in the hindfoot, ankle and knee; however, there is no data supporting its use or safety for midfoot or forefoot lesions. We identified 54 patients who underwent SS of various midfoot/forefoot osseous structures in our practice over a four-year period. All patients proved recalcitrant to standard conservative measures, and all had advanced imaging appreciating BME. VAS for pain at 1, 3, 6, and 12 months postoperatively served as the primary outcome measure. 41 patients were included with a mean age of 54.3 ± 14.9 years and mean follow up of 14.1 ± 6.9 months. Patients saw a significant decrease in VAS pain as early as 1 month postoperatively (p<0.05). Mean postoperative VAS at 12 months was 2.11 ± 2.50, and the mean reduction in VAS pain from preop to 12 months postop was -5.00 (95% CI -3.44 to -6.56, p<0.05). Fourteen patients (34%, 14/41) were pain free at 12 months. Treatment of more than one bone (unadjusted OR 6.23 [95% CI 1.39 to 27.8], P=0.017) was associated with a greater likelihood of not achieving a pain free status at 12 months. Initial experience suggests that SS was both safe and effective in our patient population. Simultaneous treatment of multiple bones should be entered into with caution, and further research on the subject is necessary. Level of Evidence: IV (Retrospective Case Series)
Article
Case: A 23-year-old male patient presented with symptomatic, high-grade medial tibial plateau bone marrow edema unresponsive to conservative treatment. After the injection of intralesional viscous bone cement, the patient had resolution of his symptoms and returned to running. Conclusion: The use of intralesional viscous bone cement has grown in popularity for the treatment of bone marrow edema in individuals older than 40 years but is uncommon in younger individuals. This case demonstrates that intralesional viscous bone cement may be considered in the treatment of high-grade bone marrow edema in young, active patients who are unresponsive to extensive conservative management.
Chapter
Spontaneous osteonecrosis of the knee (SONK) presents a challenging treatment scenario as the etiology of these lesions has been poorly defined, and therefore appropriate treatment remains uncertain. More recently, it has been proposed that these lesions are better characterized as the culmination of subchondral insufficiency fractures of the knee (SIFK). As a result, treatment options better aimed at reversing or halting this pathophysiologic process have been considered. The use of injectable orthobiologics, such as platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and calcium phosphate, has become of interest for treating such lesions. However, the efficacy of these treatment modalities remains poorly understood. The purpose of the current chapter is to provide a comprehensive and evidence-based review of the pathophysiology of and risk factors for SIFK. Additionally, this chapter discusses the most recent evidence surrounding the use of orthobiologics to treat SIFK and future directions for research pertaining to this pathology.
Article
Objective Intraarticular (IA) administration of platelet-rich plasma (PRP) has been proposed as a new strategy to halt osteoarthritis (OA) progression. In patients with severe OA, its potential is limited because it is unable to reach the subchondral bone, so a new strategy is needed, and intraosseous (IO) infiltration has been suggested. The purpose is to assess the impact of IA together with IO infiltration of plasma rich in growth factors (PRGF) in serum hyaluronic acid (HA) and type II collagen cleavage neoepitope (C2C) levels. Design A total of 32 rabbits were included in the study and randomly divided into 2 groups: control and treatment. A 4-mm chondral defect was created in the medial femoral condyle and IA followed by IO infiltration were performed. Serum C2C and HA levels were measured using enzyme-linked immunosorbent assay (ELISA) tests before infiltration and 28, 56, and 84 days post-infiltration. Results Significant lower C2C serum levels were obtained in treatment group (IA + IO infiltration of PRGF) at 84 days post-infiltration than in control group (IA infiltration of PRGF + IO infiltration of saline solution), while no significant differences between groups were reported at any other study times. Regarding HA, at 56 days post-infiltration, greater significant levels were seen in the treatment group. However, at 84 days post-infiltration, no significant differences were obtained, although lower levels were reported in the treatment group. Conclusions Despite inconclusive, the results suggest that the combination of IA and IO infiltration with PRGF may enhance cartilage and subchondral bone regeneration, but further studies are needed.
Article
The subchondral bone is a structure present underneath articular cartilage consisting of two major parts: the bone plate and the spongiosa. It is responsible for cartilage nutrition and plays an essential role in the healing of chondral lesions. 1 Focal changes in the subchondral bone, termed bone marrow lesions (BMLs), are features detected by magnetic resonance imaging (MRI). In patients with knee osteoarthritis (OA), BMLs can correlate with faster joint degeneration 2, 3 and increased pain. 4-6 Recent research has focused on using biologic therapeutics to help maintain and improve cartilage health; 7-10 however, treatment options taking into account the subchondral bone are still limited. Osteo-core plasty is a new, minimally invasive procedure for treating subchondral pathologies to prevent the progression of osteoarthritis.11
Article
Full-text available
Objective To determine benefits and harms of arthroscopic knee surgery involving partial meniscectomy, debridement, or both for middle aged or older patients with knee pain and degenerative knee disease. Design Systematic review and meta-analysis. Main outcome measures Pain and physical function. Data sources Systematic searches for benefits and harms were carried out in Medline, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to August 2014. Only studies published in 2000 or later were included for harms. Eligibility criteria for selecting studies Randomised controlled trials assessing benefit of arthroscopic surgery involving partial meniscectomy, debridement, or both for patients with or without radiographic signs of osteoarthritis were included. For harms, cohort studies, register based studies, and case series were also allowed. Results The search identified nine trials assessing the benefits of knee arthroscopic surgery in middle aged and older patients with knee pain and degenerative knee disease. The main analysis, combining the primary endpoints of the individual trials from three to 24 months postoperatively, showed a small difference in favour of interventions including arthroscopic surgery compared with control treatments for pain (effect size 0.14, 95% confidence interval 0.03 to 0.26). This difference corresponds to a benefit of 2.4 (95% confidence interval 0.4 to 4.3) mm on a 0–100 mm visual analogue scale. When analysed over time of follow-up, interventions including arthroscopy showed a small benefit of 3–5 mm for pain at three and six months but not later up to 24 months. No significant benefit on physical function was found (effect size 0.09, −0.05 to 0.24). Nine studies reporting on harms were identified. Harms included symptomatic deep venous thrombosis (4.13 (95% confidence interval 1.78 to 9.60) events per 1000 procedures), pulmonary embolism, infection, and death. Conclusions The small inconsequential benefit seen from interventions that include arthroscopy for the degenerative knee is limited in time and absent at one to two years after surgery. Knee arthroscopy is associated with harms. Taken together, these findings do not support the practise of arthroscopic surgery for middle aged or older patients with knee pain with or without signs of osteoarthritis. Systematic review registration PROSPERO CRD42014009145.
Article
Full-text available
To determine benefits and harms of arthroscopic knee surgery involving partial meniscectomy, debridement, or both for middle aged or older patients with knee pain and degenerative knee disease. Systematic review and meta-analysis. Pain and physical function. Systematic searches for benefits and harms were carried out in Medline, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to August 2014. Only studies published in 2000 or later were included for harms. Randomised controlled trials assessing benefit of arthroscopic surgery involving partial meniscectomy, debridement, or both for patients with or without radiographic signs of osteoarthritis were included. For harms, cohort studies, register based studies, and case series were also allowed. The search identified nine trials assessing the benefits of knee arthroscopic surgery in middle aged and older patients with knee pain and degenerative knee disease. The main analysis, combining the primary endpoints of the individual trials from three to 24 months postoperatively, showed a small difference in favour of interventions including arthroscopic surgery compared with control treatments for pain (effect size 0.14, 95% confidence interval 0.03 to 0.26). This difference corresponds to a benefit of 2.4 (95% confidence interval 0.4 to 4.3) mm on a 0-100 mm visual analogue scale. When analysed over time of follow-up, interventions including arthroscopy showed a small benefit of 3-5 mm for pain at three and six months but not later up to 24 months. No significant benefit on physical function was found (effect size 0.09, -0.05 to 0.24). Nine studies reporting on harms were identified. Harms included symptomatic deep venous thrombosis (4.13 (95% confidence interval 1.78 to 9.60) events per 1000 procedures), pulmonary embolism, infection, and death. The small inconsequential benefit seen from interventions that include arthroscopy for the degenerative knee is limited in time and absent at one to two years after surgery. Knee arthroscopy is associated with harms. Taken together, these findings do not support the practise of arthroscopic surgery for middle aged or older patients with knee pain with or without signs of osteoarthritis. PROSPERO CRD42014009145. © Thorlund et al 2015.
Article
Full-text available
Injury to subchondral bone is associated with knee pain and osteoarthritis (OA). A percutaneous calcium phosphate injection is a novel approach in which subchondral bone marrow edema lesions are percutaneously injected with calcium phosphate. In theory, calcium phosphate provides structural support while it is gradually replaced by bone. However, little clinical evidence supports the efficacy of percutaneous calcium phosphate injections. We asked: (1) Does percutaneous calcium phosphate injection improve validated patient-reported outcome measures? (2) What proportion of patients experience failure of treatment (defined as a low score on the Tegner Lysholm Knee Scoring Scale)? (3) Is there a relationship between outcome and age, sex, BMI, and preoperative grade of OA? Between September 2012 and January 2014, we treated 33 patients with percutaneous calcium phosphate injections. Twenty-five satisfied our study inclusion criteria; of those, three patients were lost to followup and 22 (88%; 13 men, nine women) with a median age of 53.5 years (range, 38-70 years) were available for retrospective chart review and telephone evaluation at a minimum of 6 months (median, 12 months; range, 6-24 months). Our general indications for this procedure were the presence of subchondral bone marrow edema lesions observed on MR images involving weightbearing regions of the knee associated with localized pain on weightbearing and palpation and failure to respond to conservative therapy (> 3 months). Patients with pain secondary to extensive nondegenerative meniscal tears with a flipped displaced component at the level of bone marrow edema lesions, or with mechanical axis deviation greater than 8° were excluded. All patients had Grades III or IV chondral lesions (modified Outerbridge grading system for chondromalacia) overlying MRI-identified subchondral bone marrow edema lesions. Percutaneous calcium phosphate injection was performed on the medial tibial condyle (15 patients), the medial femoral condyle (five patients), and the lateral femoral condyle (two patients). Concomitant partial meniscectomy was performed in 18 patients. Preoperative and postoperative scores from the Knee Injury and Arthritis Outcome Score (KOOS) and the Tegner Lysholm Knee Scoring Scale were analyzed. For patients available for followup, the outcome scores improved after treatment. The KOOS improved from a mean of 39.5 ± 21.8 to 71.3 ± 23 (95% CI, 18.6-45.2; p < 0.001) and the Tegner and Lysholm score from 48 ± 15.1 to 77.5 ± 20.6 (95% CI, 18.8-40.2; p < 0.001). However, seven of the 22 patients had poor clinical outcomes as assessed by the Tegner Lysholm Knee Scoring Scale, whereas three had fair results, five had good results, and seven had excellent results. The postoperative Tegner Lysholm score was inversely related to the preoperative Kellgren-Lawrence OA grade (R(2) = 0.292; F (1.20) = 9.645; p = 0.006). We found no relationship between outcome scores and age, sex, or BMI. In a study that would have been expected to present a best-case analysis (short-term followup, loss to followup of patients with potentially unsatisfactory results, and use of invasive cotreatments including arthroscopic débridements), we found that percutaneous calcium phosphate injection in patients with symptomatic bone marrow edema lesions of the knee and advanced OA yielded poor results in a concerning proportion of our patients. Based on these results, we advise against the use of percutaneous calcium phosphate injections for patients with advanced osteoarthritic changes. Level IV, therapeutic study.
Article
Full-text available
It is unclear if there is a clinically important improvement in the six to 12-month recovery period after hip and knee replacement. This is an obvious gap in the evidence required by patients undergoing these procedures. It is also an issue for the English PROMs (Patient-Reported Outcome Measures) Programme which uses 6-month outcome data to compare the results of hospitals that perform hip and knee replacements. A systematic review of studies reporting the Oxford Hip Score (OHS) or Oxford Knee Score (OKS) at 12 months after surgery was performed. This was compared with six-month outcome data collected for 60,160 patients within the English PROMs programme. A minimally important difference of one standard error of the measurement, equivalent to 2.7 for the OHS and 2.1 for the OKS, was adopted. Six studies reported OHS data for 10 different groups containing 8,308 patients in total. In eight groups the change scores reported were at least 2.7 points higher than the six-month change observed in the PROMs programme (20.2 points). Nine studies reported OKS data for 13 different groups containing 4,369 patients in total. In eight groups the change scores reported were at least 2.1 points higher than the six-month change observed in the PROMs programme (15.0 points). There is some evidence from this systematic review that clinically important improvement in the Oxford hip and knee scores occurs in the six to 12 month recovery period. This trend is more apparent for hip than knee replacement. Therefore we recommend that the English Department of Health study the impact on hospital comparisons of using 12- rather than six-month outcome data.
Article
Bone marrow lesions (BMLs) are a recently identifiable cause of knee pain in patients with degenerative joint disease. BMLs are understood to be a stress reaction, bone defect, or fracture of the knee. A potential opportunity exists to healing and relief of patient symptoms through treatment of BMLs. In this report, we describe a method of treatment for these bone defects known as BMLs. Notwithstanding our promising results with this technique, further study is required to determine the most appropriate candidates who would benefit from this treatment.
Article
Alpha-bsm® is a first generation self-setting, injectable and moldable apatitic calcium phosphate cement (CPC) based on amorphous calcium phosphate (ACP). ACP was prepared using low temperature double decomposition technique, from a calcium solution (0.16 M), and phosphate solution (0.26 M) in a basic (pH~13) media. ACP was than stabilized using three crystal growth inhibitors (CO32-, Mg2+, P2O74-), freeze-dried, and heated (450 °C, 1h) to remove additional moisture and some inhibitors. Dicalcium phosphate dehydrate (DCPD) was also prepared using wet chemistry at room temperature from calcium and phosphate solution, respectively, 0.3 M and 0.15 M. ACP and DCPD powder were combined at a 1:1 ratio and ground to produce Alpha-bsm® bone cement. The cement is supplied as a powder and when mixed with an appropriate amount (0.8 ml/g) of physiological saline at room temperature, forms an injectable putty-like paste. The paste has a working time of about 45 minutes at room temperature, when stored in a moist environment. The setting reaction proceeds isothermically at body temperature (37°C) in less than 20 minutes, forming a hardened, porous (total porosity 50 to 60%), low crystalline (40% comparing with HA), apatitic calcium phosphate cement with a compressive strength range of 10 to 12 MPa. Extensive pre-clinical studies (rabbit radius critical sized defect, canine tibia osteotomy, sheep tibia, primate fibula fracture healing, and primate fibula critical size defect) demonstrate that Alpha-bsm® undergoes remodeling in conjunction with new bone formation. The next generation of Bone Substitute Materials (Beta-bsmTM and Gamma-bsm TM) are formulated based on the Alpha-bsm® chemistry but differ in powder processing (e.g. milling) technique. These materials are also self-setting, injectable and/or moldable apatitic calcium phosphate cements with improved handling and mechanical properties. The setting & hardening reaction of these new CPCs proceeds isothermically in less than 5 minutes at 37°C and once hardened demonstrate a compressive strength of 30 to 50 MPa. The final product (after full conversion) is a low crystalline (40% compared with Hydroxyapatite), calcium deficient (Ca/P atomic ratio = 1.45) carbonated apatite similar to the composition and structure of natural bone mineral (crystal size: length = 26 nm, width thickness = 8 nm). A desirable feature of these cements is their high surface chemistry (with specific surface area of about 180-200 m2/g) which is ideal for remodeling and controlled release of growth factors. A pilot rabbit critically sized femoral defect study comparing the three synthetic family products demonstrate that they share similar remodeling and resorption characteristics up to 52 weeks. Physico-chemical and mechanical performance of these next generation CPCs are favorable when compared with existing CPCs in the market, specifically material working time (at room temperature), cohesivity in a wet environment and fast setting & hardening rate (at body temperature).