0753 Core Decompression for Avascular Necrosis · 10/15/2019 · Avascular necrosis (AVN), also...

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Core Decompression for Avascular Necrosis

Clinical Policy Bulletins Medical Clinical Policy Bulletins

Number: 0753

*Please see amendment for Pennsylvania Medicaid at the end of this CPB.

Aetna considers core decompression medically necessary for the treatment of early/pre-collapse

(stage I or II; before X-ray changes are evident) avascular necrosis of the hip (femoral head

and/or neck).

Aetna considers core decompression experimental and investigational for the treatment of the

following indications (not an all-inclusive list) because its effectiveness for these indications has

not been established.

Avascular necrosis of other joints (e.g., the ankle, elbow, knee, mandibular condyle, and

shoulder)

Late/post-collapse (stage III or higher; when X-ray changes have occurred) avascular

necrosis of the hip

Post-arthroscopic osteonecrosis

Aetna considers the following adjunctive treatments experimental and investigational for the

treatment of avascular necrosis of any joint because the effectiveness of these approaches has

not been established (not an all-inclusive list):

Last Review

10/15/2019

Effective: 04/25/2008

Next

Review: 08/13/2020

Review

History

Definitions

Additional

Clinical Policy

Bulletin

Notes

P 1/39

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www.aetna.com/cpb/medical/data/700_799/0753.html Proprietary

Autologous bone marrow mononuclear cells/bone marrow concentrate/bone marrow

stem cells

Autologous platelet concentrate

Bisphosphonates

Bone morphogenic proteins (e.g., rhBMP-2)

Demineralized bone matrix

Erythropoietin

Growth factors

Laser therapy

Mesenchymal stem cells

Ozone therapy

Parathyroid hormone

Platelet-rich fibrin

Platelet-rich plasma (PRP)

PRP combined with stem cells

PRP combined with mesenchymal stem cells and synthetic bone graft

Synthetic bone graft substitute (e.g., calcium sulphate and calcium phosphate).

Note: According to the Ficat Classification of Avascular Necrosis of the Femoral Head, the

presence of cysts is considered stage II. (Ficat Classification of Avascular Necrosis (AVN) of

the Femoral Head (http://roentgenrayreader.blogspot.com/2010/05/ficat-classification-of

avascular.html)).

See also CPB 0287 - Total Hip Replacement (../200_299/0287.html), and

CPB 0661 - Joint Resurfacing (../600_699/0661.html).

Avascular necrosis (AVN), also known as osteonecrosis, aseptic necrosis and ischemic bone

necrosis, is a relatively common disease characterized by death of cellular elements of bone or

marrow. Most of the 10,000 to 20,000 Americans who develop AVN annually are between the

ages of 20 and 50 years. The hip (femoral head) is the most commonly affected site for clinically

significant AVN. There are many risk factors for the disease including hemoglobinopathies,

dislocation of the hip, alcoholism, fracture of the femoral neck, use of corticosteroid, as well

as collagen vascular disease. With secondary collapse of the femoral head, disabling hip pain

may result in the need for total hip replacement. For non-traumatic AVN, the disease is often

bilateral, which further increases the extent of disability. Various approaches have

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http://roentgenrayreader.blogspot.com/2010/05/ficat-classification-of-avascular.html






been employed for treating different stages of AVN of the hip. Non-operative treatments include

rest, non-weight-bearing exercises, protected weight-bearing, pharmacotherapy (e.g., non-

steroidal anti-inflammatory drugs and bisphosphonate medications such as alendronate or

residronate), and electrical stimulation. Operative treatments include fusion, osteotomy, hemi-

resurfacing, hemi-arthroplasty, debridement and grafting, core decompression with or without

grafting, as well as total hip arthroplasty (Shannon and Trousdale, 2004; DeSmet et al, 2005;

McKown, 2007).

Core Decompression of the Hip

Core decompression of the hip is usually employed before collapse and fracture of the femoral

head and/or neck to delay or avoid reconstructive surgery of the affected joint. It is

generally carried out to preserve the function and the structure of the hip as well as to relieve

pain associated with AVN. Core decompression entails repair of the necrotic site by coring,

followed by filling the cored area with a bone graft, which is optional. A lateral trochanteric

approach is used in this procedure: an 8-mm to 10-mm cylindrical core of bone is removed from

the antero-lateral segment of the femoral head, which creates an open cylindrical channel. This

open channel serves to relieve pressure. The open channel may be filled with either a

vascularized or a non-vascularized bone graft. The former is used to aid in the ingrowth of

vascular cellular tissue into the necrotic area; thus enhancing re-vascularization, which may

arrest the progression of the necrosis. The latter is used to provide structural stability to the hip

during the healing process. There is adequate evidence that core decompression is effective in

treating early stages (I or II) of AVN of the hip.

Castro and Barrack (2000) performed a metaanalysis of data on core decompression and

conservative treatment for avascular necrosis (AVN) of the femoral head. MEDLINE was

searched from 1966 to 1998 using the MeSH terms 'femoral head necrosis' and 'osteonecrosis',

and the reference from retrieved articles were examined for additional studies. The search was

restricted to citations in the English language. Study designs of evaluations included in the

reviewStudies with at least 10 participants and a minimum average follow-up of 12 months were

eligible for inclusion. Studies where patient selection protocols created sample biases were

excluded. The average length of follow-up was 43 months (SE=6 months). Surgical core

decompression, i.e. the removal of a single core of bone from the avascular segment of the

femoral head, was compared with conservative treatment, i.e. a period of protected weight

bearing with crutches. Studies in which participants received additional treatments, such as iliac

crest bone graft, vascularised fibular grafting, or pulsed electromagnetic stimulation, in addition

to core decompression, were excluded from the analysis. Patients with AVN of the femoral head,

as determined by radiographic staging according to the Steinberg classification (stages 0 to V) or

an equivalent classification system were included. The three most common causes of AVN were

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steroid use (344 hips), alcohol abuse (153 hips) and idiopathic (127 hips). The average age of

the participants presenting was 40 years (standard error, SE=2 years). Bilateral disease was

present in 31% of the participants undergoing core decompression and in 62% of those

undergoing conservative treatment. Successful treatment, defined as no further surgical

intervention implemented or recommended, was assessed. Radiographic progression from stage

I to stage II was not considered a failure, since radiographs significantly lag behind the

physiological condition in the femoral head. Steinberg stage 0 outcomes were not compared

since prophylactic core decompression of an asymptomatic, normal hip was not recommended

by most authors. The stage III hips were not compared because their advanced disease

predisposes them to failure, regardless of the intervention. A meta-analysis was performed to

compare the success rates for core decompression and conservative treatment for Steinberg

stages I and II. A sensitivity analysis was used to compare the 22 studies included in the meta-

analysis with the 9 studies excluded on account of highly selected patient groups; this compared

year of publication, distribution of Steinberg stages, and percentage of bilateral cases. The

sensitivity analysis was performed in order to determine whether the variables used to select

patients were predictive of core decompression failure. Twenty-two studies (n=818) using a

single surgical core decompression technique, and 8 studies (n=264) using a conservative

technique, were included. Eleven studies were non-randomised prospective, 10 were

retrospective, and 1 was randomized prospective. An additional 9 studies that were excluded on

account of highly selected patient groups were used in a further sensitivity analysis. The most

significant finding was that, with an average follow-up time of 42 months, core decompression

was 23% more successful than conservative treatment for hips with Steinberg stage I AVN. The

success rates for surgical core decompression were 84, 63 and 29% for Steinberg stages I, II,

and III, respectively. Conservatively- treated patients with stage 0, I, II and III AVN demonstrated

success rates of 86, 61, 59 and 25%, respectively. Chi-squared analysis showed that for stage I

hips only, the success rate of core decompression (84%) was statistically significantly higher

than that for conservative treatment (61%) (p=0.001). Several significant differences were found

in the sensitivity analyses. Studies with selection biases tended to be performed earlier than non-

biased studies (1,986 versus 1,992; p=0.0068). Studies on specific groups also had

proportionately fewer patients in Steinberg stage I (21 versus 48%; p=0.02), more patients in

Steinberg stage III (42 versus 18%; p=0.03), and more patients with bilateral disease (86 versus

31%; p=0.0001). When 70% or more of the sample patients had bilateral disease, the success

rates for Steinberg stages I, II and III were 50, 60 and 44%, respectively. There were 33 (5%)

complications in the 688 cases reported in the 13 studies. Reported complications were

intertrochanteric fracture (n=14), technical errors in surgery (n=6), seromas and wound infections

(n=8), femoral head fractures (n=3), deep vein thrombosis (n=1) and pulmonary embolus (n=1).

The authors state that the 23% difference between core decompression and conservatively-

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treated patients with Steinberg stage I AVN was interpreted cautiously. Although many authors

agree that core decompression provides excellent and immediate pain relief, core

decompression did not alter the progression of AVN in Steinberg stage II hips.

Steinberg (1995) evaluated the safety and effectiveness of core decompression in the treatment

of AVN of the femoral head. All patients with AVN of the femoral head, stages I to IVA, were

included regardless of the cause of the necrosis. A total of 300 hips were available for analysis.

The follow-up ranged from 2 to 12 years. Main outcome measures included antero-posterior and

lateral radiographs, taken immediately before surgery and at the final follow-up, clinical hip

evaluation according to the Harris scoring system, and the need for total hip replacement. One

patient sustained a subcapital fracture 1 month after surgery due to a fall. There was 1 case of

non-fatal pulmonary embolism, 1 case of pneumonia, and 1 case of thrombo-phlebitis of the

thigh. A total of 46 % of operatively managed hips showed no radiographical progression of

disease compared with only 19 % of non-operatively managed hips. Moreover, 35 % of the

operatively managed hips required total hip replacement compared with 77 % of non-operatively

managed hips. The results in hips with early (stages I and II) AVN were only slightly better than

those of hips with advanced (stages III and IVA) disease. However, the results in hips with small

areas of necrosis in both stages I and II were much better than those with larger lesions; only 7

% of the former group required total hip replacement after decompression and cancellous bone

grafting. The authors concluded that core decompression with cancellous bone grafting is a safe

and effective procedure for the treatment of early AVN of the femoral head. Results with this

form of treatment are considerably better than those obtained in patients treated non-operatively.

Steinberg et al (2001) reviewed the results of a prospective study of 406 hips in 285 patients

treated by one surgeon with core decompression and bone grafting. Patients were followed-up

for 2 to 14 years. The outcome was determined by the change in the Harris hip score,

quantitative radiographical measurements, and the need for total hip replacement. These hips

were compared with 55 hips in 39 patients treated non-operatively and with historic controls.

Five complications occurred after 406 procedures including 2 fractures that resulted from falls

during the first post-operative month. Of the 312 hips in 208 patients with a minimum 2-year

follow-up, 36 % of hips (113 hips in 90 patients) required hip replacement at a mean of 29

months: 18 of 65 hips (28 %) with stage I disease; 45 of 133 hips (34 %) with stage II disease; 3

of 13 hips (23 %) with stage III disease; and 45 of 92 hips (49 %) with stage IV disease. Before

femoral head collapse (stages I and II combined) hip replacement was performed in 10 of 77

hips (14 %) with small lesions, 33 of 68 hips (48 %) with intermediate lesions, and 20 of 48 hips

(42 %) with large lesions. Results as determined by changes in Harris hip scores and

radiographical progression were similar. Patients who underwent core decompression and bone

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grafting have a very low complication rate. In patients treated before femoral head collapse, the

outcome is significantly better than in patients who received symptomatic treatment. The results

were correlated with the stage and the size of the necrotic lesion.

Simank et al (2001) assessed and compared the results of core decompression and inter-

trochanteric osteotomy for non-traumatic osteonecrosis of the femoral head using Cox

regression and survivorship analysis. A total of 177 cases with a mean age of 41 years at

surgery were treated for osteonecrosis (94 core decompressions and 83 osteotomies). Any

further surgery was defined as failure and endpoint. Significant risk factors for treatment failure

were age over 40 years at surgery (p = 0.022), corticosteroid intake (p < 0.001), advanced stage

of necrosis (Steinberg stage greater than or equal to III, p = 0.04), and core decompression (p =

0.084). To analyze the influence of the surgical procedure, patients with corticosteroid treatment

were excluded, and survival analysis was performed. This analysis revealed survival rates of 74

% after osteotomy and 78 % after core decompression 6 years post-operatively in early, pre-

collapse stages (p = 0.819). In advanced stages, the rate of survival for hips after core

decompression was lower (56 %) than in hips after osteotomy (76 %) (p = 0.056). These

findings indicated that core decompression may be as effective as inter-trochanteric osteotomy in

pre-collapse stages but is less traumatizing and is cost-effective. For post-collapse hips, inter-

trochanteric osteotomy should be considered.

Bellot and associates (2005) studied retrospectively a series of 32 cases (25 patients) of femoral

head osteonecrosis treated by core decompression. These researchers examined the

epidemiological and clinical features as well as the laboratory findings, and compared cases

requiring secondary hip replacement and those that had a favorable outcome. The series

included 32 hips, 1 case was lost to follow-up. Mean age at decompression was 41.3 years (22

to 55). In 8 hips, osteonecrosis was favored by corticosteroid treatment, in 3 by chronic

alcoholism, and in 1 by hypertriglyceridemia. No favoring factors were present for 20 hips.

According to the Association Research Circulation Osseous (ARCO) classification there were 15

stage I hips, 13 stage II, 3 stage III, and 1 stage IV. Core decompression was centered in 24

hips and mean time to decompression was 6.4 months (14 days to 40 months). These

investigators reviewed hips without a total prosthesis using the Postel-Merle-d'Aubigne function

score and for the radiological assessment the ARCO stage and the Koo index. Favorable

outcome was noted in 12 hips. Total hip arthroplasty was required for 19, 1 hip was lost to

follow-up. Mean follow-up in the success group was 82 months (26 to 176) and mean "time of

participation" in the failure group was 11 months (1 to 38). Mean survival after core

decompression was 14 months. Time between onset of symptoms and decompression did not

influence outcome. Lesions that remained asymptomatic before decompression remained

stable. Stage I hips did not have more favorable outcome than stage II hips (p < 0.05). Stage III

or IV hips had unfavorable outcome. Hips with a Koo index greater than 40 had a poor outcome

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(p < 0.05). The authors concluded that early disease (stage I or II) is an ideal indication for

decompression, but is insufficient alone to guarantee success. Furthermore, they

considered late disease (stage III or IV and a Koo index greater than 40) an contraindication for

decompression.

Israelite and co-workers (2005) stated that early treatment of osteonecrosis of the femoral head

yielded better results than late treatment. Because osteonecrosis is frequently bilateral, it often

is advisable to treat both hips simultaneously. Core decompression is one of the more common

methods of treatment; however the safety of doing simultaneous bilateral core decompression

has been questioned. These researchers sought to evaluate the safety and effectiveness of

simultaneous bilateral core decompression compared with unilateral core decompression. A

total of 193 patients (276 hips) who had core decompression with bone grafting were followed up

for 24 to 145 months; 124 procedures were unilateral and 152 were bilateral. Patients were

evaluated by change in Harris hip score, radiographical progression, post-operative

complications, and conversion to total hip arthroplasty. Total hip arthroplasty was required in 56

of 124 (45 %) of hips in the unilateral, and 48 of 152 (32 %) of hips in the bilateral group. Post-

operative complications were similar. In the unilateral group there were 2 major and 9 minor

complications; in the bilateral group there were 3 major and 10 minor complications. When

bilateral core decompression is indicated, it can be done simultaneously on both hips, allowing

earlier treatment of the contralateral hip without risk of increased complications and possibly with

a better outcome. Simultaneous bilteral deompression required only one hospitalization and

decreased recovery time compared with two separate procedures. Therefore, it provided

advantages over procedures that can not be done simultaneously on both hips.

Keizer and associates (2006) described the long-term results of core decompression and

placement of a non-vascularized bone graft in the management of AVN of the femoral head.

These investigators treated 80 hips in 65 patients, 18 by a cortical tibial autograft and 62 by a

fibular allograft. The mean age of the patients was 36 years. A total of 78 hips were available

for evaluation of which pre-operatively 6 were Ficat-Arlet stage 0, 3 stage I, 31 stage IIA, 16

stage IIB, 13 stage III and 9 stage IV. A total of 34 hips (44 %) were revised at a mean of 4

years (SD 3.8). Survivorship analysis using a clinical end-point showed a survival rate of 59 % 5

years after surgery. These researchers found a significant difference (p = 0.002) in survivorship,

when using a clinical and radiological end-point, between the 2 grafts, in favor of the tibial

autograft. They considered this difference to be the result of the better quality and increased

volume of tibial bone compared with that from the trochanteric region used with the fibular

allograft. This is a relatively simple, extra-articular and reproducible procedure. In the authors'

view core decompression, removal of the necrotic tissue and packing of the cancellous grafts

into the core track are vital parts of the procedure.

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von Stechow and Drees (2007) stated that osteonecrosis of the femoral head eventually leads to

its destruction if it remains untreated. Depending on the location and the extent of the

osteonecrosis, several surgical options are available. For early small and medium-sized pre-

collapse lesions, core decompression is the treatment of choice. Osteotomies and bone grafting

procedures can be utilized in medium pre-collapse, as well as in small post-collapse lesions.

Cartilage lesions of the femoral head allow limited femoral resurfacing arthroplasty. If the

acetabulum reveals cartilage lesions, a total hip replacement should be preformed.

Mont and co-workers (2007) noted that when osteonecrosis of the femoral head is diagnosed in

its early stages (before collapse of the femoral head), various procedures such as core

decompression (with and without bone grafting), osteotomies, as well as non-vascularized and

vascularized bone grafting can be used to preserve the joint. The effectiveness of core

decompression has been peer-reviewed in more than 40 studies. In general, this treatment is

most successful for patients with early stage, small- and medium-sized lesions, before collapse

of the femoral head. Various methods of non-vascularized bone grafting have been used.

Results have varied; however, a 60 % to 80 % success rate has been achieved at 5- to 10-year

follow-up.

Other techniques such as infusion/implantation of autologous bone-marrow mononuclear cells

(BMMC) have also been used in an attempt to improve the outcomes of core decompression.

Gangji and Hauzeur (2005) studied the implantation of autologous BMMC in a necrotic lesion of

the femoral head to determine the effect on the clinical symptoms and the stage and volume of

osteonecrosis. They studied 13 patients (18 hips) with stage I or II osteonecrosis of the femoral

head, according to the ARCO classification. The hips were allocated to a program of either core

decompression (the control group) or core decompression and implantation of autologous

BMMC (the bone-marrow-graft group). Both patients and assessors were blind with respect to

treatment-group assignment. The primary outcomes studied were safety, clinical symptoms, and

disease progression. After 24 months, there was a significant reduction in pain (p = 0.021) and

in joint symptoms measured with the Lequesne index (p = 0.001) and the WOMAC index (p =

0.013) within the bone-marrow-graft group. At 24 months, 5 of the 8 hips in the control group

had deteriorated to stage III, whereas only 1 of the 10 hips in the bone-marrow-graft group had

progressed to this stage. Survival analysis showed a significant difference in the time to collapse

between the two groups (p = 0.016). Implantation of BMMC was associated with only minor side

effects. The authors concluded that implantation of autologous BMMC appeared to be a safe

and effective treatment for early stages of osteonecrosis of the femoral head. Although the

findings of this study are promising, their interpretation is limited because of the small number of

patients and the short duration of follow-up. Further study is needed to confirm the results.

8/39



Yan and colleagues (2006) assessed the safety and effectiveness of the treatment of

osteonecrosis of the femoral head by percutaneous decompression and autologous BMMC

infusion. A total of 44 hips in 28 patients with AVN at early stage were treated by percutaneous

multiple holes decompression followed by autologous BMMC infusion. Autologous BMMC were

concentrated from bone marrow that was taken from the posterior iliac crest of the patient.

Patients were followed-up at least 2 years. Results were determined by the changes in the

Harris hip score and the progression in the radiographical stages. No complications were

observed after the operation. Before operation, there were stage I of femoral head necrosis in 8

hips, stage II in 15 hips, stage III in 14 hips, stage IV in 7 hips, and the post-operative stages at

the most recent follow-up were stage O in 1 hip, stage I in 6 hips, stage II in 13 hips, stage III in

13 hips, stage IV in 7 hips, stage V in 4 hips. The mean pre-operative Harris hip score was 58

(46 to 89), and improved to 86 (70 to 94) post-operatively. All the femoral head collapsed pre-

operatively showed that the necrotic size was at least more than 30 %. The authors concluded

that percutaneous multiple holes decompression combined with autologous BMMC is a new way

to treat AVN of the femoral head. The earlier the stage, the better the result. They noted that

randomized prospective studies are needed to compare this combination approach with routine

core decompression.

Gangji et al (2011) examined the effectiveness of bone marrow cell implantation into the necrotic

lesion of the femoral head on clinical symptoms and the progression of osteonecrosis of the

femoral head in comparison with core decompression. These investigators studied 19 patients

and 24 hips with early stage osteonecrosis of the femoral head. The hips were allocated to

either core decompression only or core decompression and implantation of bone marrow cells.

Both patients and assessors were blind with respect to treatment group assignment. The

primary outcomes were clinical symptoms and disease progression. Bone marrow implantation

afforded a significant reduction in pain and in joint symptoms and reduced the incidence of

fractural stages. At 60 months, 8 of the 11 hips in the control group had deteriorated to the

fractural stage whereas only 3 of the 13 hips in the bone marrow graft group had progressed to

that stage. Survival analysis showed a significant difference in the time to failure between the 2

groups at 60 months. Patients had only minor side effects after the treatments. The authors

concluded that this long-term follow-up study confirmed that implantation of autologous bone

marrow cells in the necrotic lesion might be an effective treatment for patients with early stages

of osteonecrosis of the femoral head.

In a Cochrane review on the treatment for AVN of bone in individuals with sickle cell disease

(SCD), Martí-Carvajal and colleagues (2009) found no evidence that adding hip core

decompression to physical therapy achieves clinical improvement compared to physical therapy

alone. However, these investigators highlighted that their conclusion was based on 1 trial with

high attrition rates. They stated that further randomized controlled trials are needed to assess

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the role of hip-core depression for this clinical condition. Endpoints should focus on participants'

subjective experience (e.g., quality of life and pain) as well as more objective "time-to-event"

measures (e.g., mortality, survival, hip longevity).

Bakhshi and colleagues (2012) stated that osteonecrosis of femoral head (ONFH) is a

challenging disease. Regardless of underlying causes, the ultimate result in all cases is

disruption of femoral head blood supply. Once the disease starts, it is progressive in 80 % of

cases. Since the majority of the affected individuals are young, every effort should be focused

on preserving the patients own femoral head. In recent years, the role of angiogenic growth

factors has been studied with promising results in animal models of ONFH. Erythropoietin (EPO)

is a well-known hormone that has been used in treatment of chronic anemia for many years with

few side effects. Considering the angiogenic properties of EPO, the authors hypothesized that

local delivery of recombinant human EPO during core decompression will enhance bone

regeneration in ONFH.

Helbig et al (2012) evaluated patients after core decompression combined with an augmentation

by a demineralized bone matrix, and particularly aimed to report long-term conversion rates to

total hip replacement (THR). A total of 14 patients with 18 hips suffering from ONFH (Ficat stage

I to IIB) underwent this surgical procedure. All patients underwent radiographical and magnetic

resonance imaging (MRI) investigations at baseline and at follow-up periods of 12 and 24

months. The clinical follow-up was done using the Merle d'Aubigné-score for an average period

of 9 years after surgery. Fourteen of the 18 subjects (77 %) achieved at least a good clinical

result after 2 years. The Merle d'Aubigné-score improved significantly after 12 (p = 0.0001) and

24 months (p = 0.0002). However, the MRI volumetric analysis showed an increased necrotic

bone volume from 3.16 +/- 0.54 to 3.88 +/- 0.62 cm(3) (p = 0.04). Within 9 years, 13 out of 18

cases (72 %) required further surgery by THR. Only 7 out of 18 subjects (39 %) reported an

ongoing post-operative clinical benefit, and would retrospectively redo the same surgical

approach again. The 5 patients who did not require THR were still satisfied after 9 years.

Theauthors concluded that in patients with early-stage ONFH, core decompression combined

with the implantation of a demineralized bone matrix leads to a limited, temporary pain relief as

seen in core decompression alone. However, long-term results were not encouraging with a

high rate of conversion to arthroplasty. Therefore, core decompression with implantation of a

demineralized bone matrix may be not appropriate to avoid THR in the long-term.

Wang et al (2012) examined the effectiveness of core decompression surgery for the treatment

of steroid-induced femoral head osteonecrosis. The rabbit femoral head osteonecrosis model

was established by the administration of steroids in combination with horse serum. Magnetic

resonance imaging was applied to screen for the animal femoral head osteonecrosis. The

rabbits with bilateral femoral head osteonecrosis were randomly selected to do the one side of

10/39



core decompression. The other side was used as the sham. Quantitative reverse transcription

polymerase chain reaction (RT-PCR) and western blot techniques were used to measure the

local expression of bone morphogenetic protein-2 (BMP-2) and peroxisome proliferator-activated

receptor gamma (PPAR-gamma) mRNAs and proteins. Bone tissues of femoral head from the

normal control group and operation group (with or without lateral decompression) were

histologically analyzed by H and E staining. The comparisons of the local expression of BMP-2

and PPAR-gamma mRNAs and proteins and the bone regeneration were further analyzed

between different groups at each time point (2, 4 and 8 weeks post-operation, respectively). The

expression of BMP-2 mRNA and protein in the steroid-induced femoral head osteonecrosis with

or without core decompression was significantly lower than that in normal animals. And BMP-2

expression in femoral head osteonecrosis with and without lateral decompression both showed

the decreasing trend with the increased post-operation time. There was no significant difference

of BMP-2 expression between femoral head osteonecrosis with and without lateral

decompression. The expression of PPAR-gamma mRNA and protein in steroid-induced femoral

head osteonecrosis with and without core decompression both were significantly higher than that

in normal animals. The PPAR-gamma expression in the steroid-induced femoral head

osteonecrosis with and without lateral decompression both showed a significantly increased

trend with the increased post-operation time. However, there was no significant difference of

PPAR-gamma expression between the femoral head osteonecrosis with and without lateral

decompression at each time point. Histopathological analysis revealed that new trabecular bone

and a large number of osteoblasts were observed in the steroid-induced femoral head

osteonecrosis with lateral decompression at 8 weeks after surgery, but there still existed

phenomenon of trabecular bone fractures and bone marrow cell necrosis. The authors

concluded that although core decompression takes partial effect in promoting bone regeneration

in the early treatment of femoral head osteonecrosis, such an effect does not significantly

improve or reverse the pathological changes of femoral marrow cell necrosis. Thus, the long-

term effect of core decompression in the early treatment of steroid-induced femoral head

osteonecrosis is not satisfactory.

Guadilla et al (2012) described a non-invasive arthroscopic procedure as an alternative to open

surgery for avascular necrosis of the hip. Patients with grade I or IIA AVN of the hip were treated

by core decompression performed by drilling under fluoroscopic guidance. Liquid platelet-rich

plasma (PRP) is delivered through a trocar, saturating the necrotic area. In more severe

conditions, the necrotic bone is decompressed and debrided, through a cortical window at the

head-neck junction. A composite graft made of autologous bone and PRP is delivered by

impactation through the core decompression track. Fibrin membranes were applied to enhance

healing of the head-neck window and arthroscopic portals. Platelet-rich plasma was infiltrated in

the central compartment. This arthroscopic approach aided in making diagnosis of the labrum

and articular cartilage and allowed intra-operative treatment decisions. Visual control provided

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the precise localization and treatment for the necrotic area allowing cartilage integrity to be

preserved. The authors concluded that arthroscopic management of AVN of the femoral head is

viable and has significant advantages. They stated that clinical studies should justify the

theoretical additional benefits of this approach.

Abrisham et al (2013) examined the value of core decompression in treating the AVN; this study

was performed on patients with symptomatic AVN with different etiologies who were treated with

core decompression. This study was carried out on 25 patients (with the total number of 37

femoral head) who were diagnosed AVN using X-ray and MRI. Core decompressions for these

patients were started soon after the diagnosis. The results were considered as a success if

there was no progression of disease confirmed by X-ray or no subsequent operation was

required. Modified Ficat staging was used to record changes before and 2 years after core

decompression treatment. Twenty five patients were participated in this study in which 68 % (n =

17) were female, 32 % (n = 8) were male, and the average of the age of the patients were 29.58

± 4.58. Eight of these patients had systemic lupus erythematous (SLE) (32 %), 4 rheumatoid

arthritis (RA) (16 %), 3 with kidney transplant (12 %), 1 Takayasu's vasculitis (4 %) and 1

Wegner vasculitis (4 %). Eight of patients had a history of intravenous injection of Temgesic (32

%). In patients using Temgesic the changes in Modified Ficat staging were significantly different

before and after core decompression (p = 0.03) in comparison with other groups; and in all 8

Temgesic users AVN progressed to the stage 3 and 4 after core decompression. The authors

concluded that this study demonstrated that core decompression to prevent the changes in the

femoral head has been more effective in patients with collagen vascular diseases and kidney

transplant than patients using intravenous Temgesic. These patients, in spite of early operation,

showed no benefit of core decompression to prevent the changes in the femoral head.

Zalavras and Lieberman (2014) stated that osteonecrosis of the femoral head may lead to

progressive destruction of the hip joint. Although the etiology of osteonecrosis has not been

definitely delineated, risk factors include corticosteroid use, alcohol consumption, trauma, and

coagulation abnormalities. Size and location of the lesion are prognostic factors for disease

progression and are best assessed by MRI. The effectiveness of medical management of

osteonecrosis with pharmacologic agents and biophysical modalities requires further

investigation. Surgical management is based on patient factors and lesion characteristics.

Preservation of the femoral head may be attempted in younger patients without head collapse by

core decompression with vascularized bone grafts, avascular grafts, bone morphogenetic

proteins, stem cells, or combinations of the above or rotational osteotomies. The authors

concluded that the optimal treatment modality has not been identified. When the femoral head is

collapsed, arthroplasty is the preferred option.

Core Decompression of Other Joints (e.g., Knee, Ankle, and Shoulder)

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The knee is the second most common location for osteonecrosis with about a 10 % incidence of

the disease in the hip. The disease can be classified into 4 stages -- stage I: progression from

no radiographical findings; stage II: a slight flattening of the medial condyle; stage

III: appearance of a radiolucent lesion: and stage IV: articular cartilage collapse (Soucacos et al,

1997). There are two distinctive entities: (i) spontaneous osteonecrosis of the knee (SPONK),

and (ii) secondary osteonecrosis of the knee. They are differentiated by age of presentation,

associated risk factors (e.g., use of corticosteroid and alcoholism), location, laterality, and

condylar involvement. Each of these two entities has several distinct surgical treatment options,

which include osteotomy, arthroscopic debridement, core decompression, unicompartmental

knee arthroplasty, and total knee arthroplasty. It is essential to diagnose these two entities as

early as possible, and use appropriate treatment to avoid osteoarthritis, joint destruction, and

ultimately joint collapse (Ragland et al, 2004).

While available evidence indicates that core decompression is effective in treating early stages of

AVN of the hip, there is currently insufficient evidence that this procedure is effective in treating

AVN of the knee, ankle, and shoulder. The quality as well as the quantity of the evidence for

core decompression for these joints is poor and limited. In particular, the majority of studies

involved a small number of patients and lacked appropriate control groups. Furthermore, several

of the studies were pulbished by the same group of investigators. Prospective, well-designed,

randomized, controlled trials are needed to ascertain the clinical value of core decompression for

joints other than the hip.

Jacobs et al (1989) performed 28 core decompressions of the distal femur for pathologically

confirmed AVN. At a mean follow-up of 54 months (range of 20 to 140 months) and using the

Ficat stages, all 7 cases in stage I and stage II had good results. Of 21 cases in stage III, 11

cases had good results, 4 had poor results, and 6 needed total knee replacement. There were

no significant orthopedic complications. The authors noted that core decompression is

worthwhile and will be more accurate with new methods ofimaging.

Mont and colleagues (1997) reported the long-term results of core decompression for the

treatment of AVN of the distal femur. A total of 79 knees (45 patients) were evaluated. All

patients had a corticosteroid association (had been treated with more than 30 mg of prednisone

for over 2 weeks predating by at least 6 months the onset of AVN). A total of 32 knees were

managed with rest and protected weight-bearing. Core decompression was performed at a

minimum of 3 months after the onset of symptoms in another 47 knees. Knees treated with

protected weight-bearing had an average asymptomatic period of only 11 months and all but 6

(18 %) proceeded to total knee replacement within 6 years. Core decompression yielded good

or excellent results in 73 % of the knees at an average follow-up of 11 years (range of 4 to 16

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years). Of the 13 knees with failed core decompression, 7 were asymptomatic for greater than 5

years. A subset of 26 knees from each group was matched for age, gender, diagnosis, Ficat and

Arlet Stage, and length of follow-up. The matched non-core group had 23 % survival as

compared with 74 % survival in the core group. These long-term follow-up findings suggested

that core decompression may slow the rate of symptomatic progression of AVN of the knee.

Furthermore, core decompression may extend the symptom-free interval in certain patients and

may delay the need for more extensive procedures such as total knee arthroplasty.

Forst et al (1998) reported their findings on early core decompression in patients with

spontaneous AVN of the knee/femoral condyle. In 16 patients with an average age of 64.6 +/-

9.8 years and sudden onset of severe knee pain, the initial stage of Ahlbäck disease

(spontaneous AVN of a femoral condyle) was verified by MRI and subsequent histology. The first

radiological sign of AVN (flattening of the affected femoral condyle) was present in only 1 case.

All patients were treated surgically by extra-articular drilling into the affected femoral condyle to

achieve core decompression. Knee pain disappeared immediately after surgery in all patients.

Successful healing was confirmed by normalization of the bone marrow on MRI (on average,

35.8 months follow-up). Core decompression by extra-articular drilling into the femoral condyle

can be recommended as an effective treatment in initial AVN of the knee (still radiologically

invisible). However, if radiological flattening of the affected femoral condyle becomes apparent,

progression of this disease can not be avoided.

Mont et al (2000a) defined the clinical, demographical, and radiographical patterns of

atraumatic AVN of the distal part of the femur and the proximal part of the tibia at presentation

and reported the outcome of treatment of this condition. A total of 248 knees in 136 patients who

were younger than the age of 55 years were treated. Results of non-operative treatments, core

decompression, arthroscopic debridement, and total knee arthroplasty were evaluated. There

were 106 female patients and 30 male patients, and their mean age was 36 years (range of 15 to

54 years) at the time of diagnosis. A total of 101 patients (74 %) had involvement of other large

joints, with 18 (13 %) presenting initially with knee symptoms. A total of 101 patients (74 %) had

a disease that affected the immune system; 67 of them had systemic lupus erythematosus. A

total of 123 patients (90 %) had a history of corticosteroid use. Technetium-99m bone-scanning

missed lesions in 16 (29 %) of 56 knees. Eight (20 %) of 41 initially symptomatic knees treated

non-operatively had a successful clinical outcome (a Knee Society score of at least 80 points

and no additional surgery) at a mean of 8 years. The knees that remained severely symptomatic

for 3 months were treated with either core decompression (91 knees) or total knee arthroplasty

(7 knees). Seventy-two (79 %) of the 91 knees treated with core decompression had a good or

excellent clinical outcome at a mean of 7 years. Efforts to avoid total knee arthroplasty with

repeat core decompression or arthroscopic debridement led to a successful outcome in 15 (60

%) of 25 knees. Thirty-four (71 %) of 48 knees treated with total knee arthroplasty had a

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successful clinical outcome at a mean of 9 years. The authors concluded that atraumatic AVN of

the knee affects women predominantly, and was associated with corticosteroid use in 90 % of

the patients. Evaluation should include standard radiographical and MRI of all symptomatic

joints. Prognosis was negatively related to large juxta-articular lesions. Non-operative

treatments should be reserved for asymptomatic knees only. Core decompression was

successful (a Knee Society score of at least 80 points and no additional surgery) in 79 % of the

knees in which the disease was in an early stage. Total knee arthroplasty was successful in only

71 % of the knees.

Delanois et al (1998) reported their findings of 37 ankles in 24 patients who were treated for

atraumatic AVN of the talus. There were 21 women and 3 men, and their mean age was 40

years (range of 26 to 62) at the time of the diagnosis. Thirteen (54 %) of the 24 patients had

bilateral involvement. Sixteen patients (67 %) had a disease that affects the immune system,

including systemic lupus erythematosus (n = 13), scleroderma (n = 1), insulin-dependent

diabetes mellitus (n = 1), and multiple sclerosis (n = 1). Four patients had a history of regular

alcohol use, and 4 patients had a history of moderate smoking. One patient had a protein-S

deficiency, 1 patient had had a renal transplant, and 1 patient had a history of asthma. Two

patients had no identifiable risk factors for osteonecrosis. Fifteen patients (63 %) had

involvement of other large joints. The mean duration of symptoms before the patients were seen

was 5.4 months (range of 2 months to 2 years). The mean ankle score at the time of

presentation was 34 points (range of 2 to 75) according to the system of Mazur et al. A

radiographical review revealed that, according to the system of Ficat and Arlet, 8 ankles had

stage III or IV disease of the talus at presentation. The remaining 29 ankles had stage II

disease. Osteonecrosis was seen in the postero-lateral aspect of the talar dome (zones III and

IV on the sagittal images; and zones II, III, and IV on the coronal images) in 22 of the 23 ankles

for which MRI were available. Osteonecrosis was seen in the antero-medial aspect of the talar

dome (zones I and II on the sagittal images; and zone I on the coronal images) in the remaining

ankle. Bone scans, available for 11 ankles, revealed increased uptake in the talus. All patients

were initially managed non-operatively with restricted weight-bearing, an ankle-foot orthosis, and

use of analgesics; 2 ankles responded to this regimen. Thirty-two ankles that remained severely

symptomatic were treated with core decompression, which was useful in the treatment of pre-

collapse (stage II) disease. Twenty-nine of these ankles had a fair-to-excellent clinical outcome

a mean of 7 years (range of 2 to 15 years) post-operatively; the remaining 3 ankles had an

arthrodesis after the core decompression failed. Three ankles were treated initially with an

arthrodesis for post-collapse (stage III or IV) disease. All 6 of the ankles that had an arthrodesis

fused, at a mean of 7 months (range of 5 to 9 months) post-operatively.

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Mont et al (2000b) described the epidemiology, clinical and radiographical presentation,

treatment, and prognosis of atraumatic AVN of the shoulder/humeral head. Of the 1,056 patients

managed for AVN of any joint between July 1, 1974, and December 1, 1996, 127 shoulders in 73

patients were treated for atraumatic AVN of the proximal humerus. There were 47 women and

26 men with a mean age of 41 years (range of 20 to 60). Numerous associated factors were

noted: alcohol use (38 %), moderate smoking (30 %), asthma (8 %), and nephrosis (3 %). A

corticosteroid association was noted in 60 patients (82 %) and 42 of the patients (58 %) had an

immuno-compromising disease. The severity of humeral head AVN did not correlate with dose

or duration of corticosteroid therapy. According to the modified Ficat and Arlet radiographical

staging system, there were 20 shoulders with Stage I disease, 55 shoulders with stage II

disease, and 52 shoulders with Stage III or IV disease. Seventy-four of the shoulders treated

with core decompression (78 %) had good to excellent clinical outcomes at a mean follow-up of

6 years (range of 2 to 21). Fourteen of the 16 patients (88 %) treated with hemi-arthroplasty or

total shoulder arthroplasty were clinically successful at a mean follow-up 4 years (range of 2 to

11). The authors concluded that there was a low incidence of humeral head involvement in

the AVN patient cohort (7 % of all AVN patients), and a high incidence of corticosteroid use (82

%), hip involvement (81 %), and bilateral disease (74 %).

Harreld et al (2009) stated that osteonecrosis of the humeral head is considerably less common

than osteonecrosis of the hip. However, as in the hip, the interaction between a genetic

predisposition and certain risk factors may lead to increased intra-osseous pressure, loss of

circulation, and eventual bone death. The most common risk factor remains corticosteroid use,

which accounts for most reported cases. Radiographical staging and measurement of lesion

size are predictive of disease progression and can be used to determine appropriate

intervention. Recent studies have reported the use of various treatment modalities such as

pharmacotherapy, core decompression with small-diameter drilling, arthroscopic-assisted core

decompression, as well as bone grafting. The authors concluded that prospective,

randomized trials are needed to determine the effectiveness of these joint-preserving

procedures. Hemiarthroplasty and total shoulder arthroplasty are recommended for patients with

end-stage disease.

Innes and Strauch (2010) performed a systematic review of the treatment of Kienbock's disease

to test the hypothesis that none of the reported treatments for Kienbock's disease is superior with

respect to outcomes of pain, motion, grip strength, and radiographic measures. These

investigators searched PubMed, Medline, and the Cochrane Review for articles published

between 1998 and 2008 reporting outcomes of treatment for Kienbock's disease. Patients were

grouped by stage of disease. Early stages were defined as Lichtman stage I, II, and IIIa, and

"late" stages as IIIb and IV. The groups were then analyzed on the basis of treatment;

procedures performed on subjects in the early group included vascularized bone grafting (VBG),

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metaphyseal core decompression, and radial osteotomy, whereas the procedures performed on

subjects in the late group included VBG, radial osteotomy, partial arthrodesis, proximal row

carpectomy, tendon ball arthroplasty, and non-surgical treatment. These researchers found no

statistically significant difference between any of the treatment groups for subjective pain

outcomes. In terms of objective measures, statistically significant improvement (p < 0.05) was

seen in range of motion after radial osteotomy and VBG in early-stage patients and after all

interventions, except partial arthrodesis and non-surgical treatment, for late-stage patients. Grip

strength was significantly improved in early-stage patients after radial osteotomy and VBG and

for all late-stage patients, except among those managed non-surgically. Changes in Stahl and

carpal height index scores were not statistically significant regardless of intervention, except after

radial osteotomy in the early group, where they statistically worsened. The authors concluded

that based on retrospective data from uncontrolled studies, no active treatment is superior in the

treatment of Kienbock's disease and there are insufficient data to determine whether the

outcomes of any intervention are superior to placebo or the natural history of the disease.

Chuong et al (1995) stated that deviations of the condylar form are usually ascribed to

"degenerative arthritis" or "osteoarthritis". More recently, osteonecrosis has been discussed as a

possible cause of condylar degeneration and pain. These researchers presented a review of the

literature on osteonecrosis, emphasizing the spectrum of degenerative osseous disease, which

includes osteoarthrosis, condylsis, osteomyelitis, and osteonecrosis. Preliminary results of

mandibular core decompression with and without bone grafting were presented suggesting a

therapeutic benefit. Moreover, the authors concluded that further study is needed to elucidate

this process.

Lieberman et al (2014) stated that there is no consensus with respect to the best procedures to

preserve the knee joint in patients with osteonecrosis of the knee. These investigators

performed a systematic review of the literature between 1999 and 2012. Only 10 of 1,057

studies met inclusion criteria. Core decompression prevented additional surgical treatment in

pre-collapse knees with a failure rate of 10.4 % (7 of 67 knees). Autogenous and osteochondral

grafts decreased the need for additional surgery in both pre-collapse (0 %, 20 of 20) and post-

collapse knees (10.5 %, 8 of 76 knees). The authors concluded that although these results are

quite promising, multi-center randomized trials are needed to identify the optimal procedures to

treat this disease.

Gross et al (2014) identified and summarized all available evidence for the treatment of talar

AVN; provided treatment recommendations; and highlighted gaps in the literature. These

investigators searched Medline and Embase using a unique algorithm. The Oxford Level of

Evidence Guidelines and GRADE recommendations were used to rate the quality of evidence

and to make treatment recommendations. A total of 19 studies fit the inclusion criteria

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constituting 321 ankles at final follow-up. The interventions of interest included hind-foot fusion,

conservative measures, bone grafting, vascularized bone graft, core decompression, and talar

replacement. All studies were Level IV evidence. Due to study quality, imprecise and sparse

data, and potential for reporting bias, the quality of evidence is "very low". Studies investigating

conservative therapy showed that prolonged protective weight-bearing provided the best

outcomes in early talar AVN. The authors concluded that given the "very low" GRADE

recommendation, understanding of talar AVN would be significantly altered by higher quality

studies. Early talar AVN seems best treated with protected weight-bearing and possibly in

combination with extracorporeal shock-wave therapy. If that fails, core decompression may be

an attractive treatment option. Arthrodesis should be saved as a salvage procedure. Moreover,

they stated that future prospective, randomized studies are needed to guide the conservative

and surgical management of talar AVN.

In a Cochrane review, Marti-Carvajal et al (2014) determined the impact of any surgical

procedure compared with other surgical interventions or non-surgical procedures, on AVN of

bone in people with SCD in terms of safety and effectiveness. These investigators searched the

Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register,

comprising references identified from comprehensive electronic database searches and hand-

searches of relevant journals and abstract books of conference proceedings. Additional trials

were sought from the reference lists of papers identified by the search strategy. Date of the most

recent search of the Group's Haemoglobinopathies Trials Register: March 17, 2014.

Randomized clinical trials comparing specific therapies for AVN of bone in people with SCD were

selected for analysis. Each author independently extracted data and assessed trial quality.

Since only 1 trial was identified, meta-analysis was not possible. One trial (46 subjects) was

eligible for inclusion. After randomization, 8 participants were withdrawn, mainly because they

declined to participate in the trial. Data were analyzed for 38 participants at the end of the trial.

After a mean follow-up of 3 years, hip core decompression and physical therapy did not show

clinical improvement when compared with physical therapy alone using the score from the

original trial (an improvement of 18.1 points for those treated with intervention therapy versus an

improvement of 15.7 points with control therapy). There was no significant statistical difference

between groups regarding major complications (hip pain, relative risk [RR] 0.95 (95 %

confidence intervals [CI]: 0.56 to 1.60; vaso-occlusive crises, RR 1.14 (95 % CI: 0.72 to 1.80;

very low quality of evidence); and acute chest syndrome, RR 1.06 (95 % CI: 0.44 to 2.56; very

low quality of evidence)). This trial did not report results on mortality or quality of life. The

authors found no evidence that adding hip core decompression to physical therapy achieved

clinical improvement in people with SCD with AVN of bone compared to physical therapy alone.

However, they highlighted that the conclusion was based on 1 trial with high attrition rates. They

stated that further randomized controlled trials are needed to evaluate the role of hip-core

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depression for this clinical condition; end-points should focus on participants' subjective

experience (e.g. quality of life and pain) as well as more objective “time-to-event” measures (e.g.

mortality, survival, hip longevity).

Villa and colleagues (2016) reviewed the literature evaluating core decompression (CD) with

BMMCs, CD alone, and bisphosphonate treatment in pre-collapse ONFH by focusing just on

randomized controlled trials (RCTs) reporting functional and radiologic outcomes. These

investigators determined if the literature provides evidence supporting any single approach.

Using PubMed and Embase databases, these researchers reviewed the clinical evidence of

treatments for pre-collapse ONFH following Preferred Reporting Items for Systematic Reviews

and Meta-Analyses (PRISMA) guidelines; 12 RCTs met the inclusion criteria. Results showed

that CD with BMMCs had lower risk of femoral head collapse when compared to the CD alone

excluding hips lost to follow-up (RR [95 % CI]: 0.25 [0.11 to 0.60]; p = 0.002) and when assumed

that hips lost to follow-up experienced collapse (RR [95 % CI]: 0.11 [0.03 to 0.47]; p = 0.003).

Neither CD nor bisphosphonate treatments showed lower risk to femoral head collapse when

compared to control treatments (p = 0.46 and 0.31, respectively). The authors concluded that

current literature showed that there is a lower risk of femoral head collapse in patients with

ONFH treated with CD combined with BMMCs when compared to CD alone; however, there was

no robust evidence to determine the effect on functional outcomes. They stated that more RCTs

assessing new combination therapies and using standardized outcome measures are needed.

An UpToDate review on “Osteonecrosis (avascular necrosis of bone)” (Jones and Mont, 2017)

states that “Core decompression for osteonecrosis of the shoulder has not been subjected to

prospective, well-designed studies. A retrospective report describing core decompression of 95

shoulders with osteonecrosis reported “good to excellent clinical outcomes” in 74 (78 %) after a

mean follow-up period of 6 years. Of those shoulders with Ficat and Arlet radiographic stage I,

II, III, or IV osteonecrosis, symptomatic relief after decompression was noted in 94, 92, 71, and

13 %, respectively … In those with stage IV lesions and in those who have less severe

radiographic disease but continued symptoms, total shoulder arthroplasty is the treatment of

choice”.

Adjunctive Treatments

Yu and associates (2015) reviewed the outcomes of using synthetic bone graft substitute

(calcium sulfate and calcium phosphate) for the treatment of late-stage osteonecrosis of the

femoral head. From November 2008 to May 2009, a total of 19 hips in 18 patients with

osteonecrosis of the femoral head [6 hips in ARCO stage IIC and 13 hips in stage IIIA] were

treated with core decompression combined with PRO-DENSE (injectable regenerative graft).

The average age of the patients at the time of surgery was 48 years (range of 25 to 67 years); 12

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patients (13 hips) overused alcohol, 4 patients (4 hips) were idiopathic, 1 patient (1 hip) used

corticosteroids, and 1 patient (1 hip) was post-traumatic. The clinical failure was defined as

conversion to total hip arthroplasty or progression in head collapse. At the conclusion of the

study, 3 in the 6 stage IIC hips and 8 in the 13 stage IIIA hips were converted to total hip

arthroplasty in an average of 8.5 months (range of 4 to 30 months) post-operatively. Advanced

collapse of the femoral head awaiting for total hip arthroplasty was observed in the other 6 hips.

Of the 19 hips, only 2 hips (10.5 %) survived without further collapse in the 5-year follow-up. This

resulted in 89.5 % failure rate with early resorption of the grafting in an average of 5.3 months.

The authors concluded that core decompression combined with an injectable calcium sulfate and

calcium phosphate composite graft (PRO-DENSE) were associated high failure rates in the early

post-operative period. They stated that this approach is not recommended for the treatment of

ARCO stage IIC and IIIA osteonecrosis of the femoral head.

Pierce and colleagues (2015) carried out a review of core decompression in the treatment of

osteonecrosis of the femoral head. These investigators described the following: (i) how

traditional core decompression is performed; (ii) adjunctive treatments; (iii) multiple

percutaneous drilling techniques; and (iv) overall outcomes of these procedures. The

authors concluded that core decompression has optimal outcomes when used in the earliest,

pre-collapse disease stages. More recent studies have reported excellent outcomes with

percutaneous drilling. Furthermore, they stated that adjunct treatments combining core

decompression with growth factors, bone morphogenic proteins, stem cells, and bone grafting

have demonstrated positive results; however, larger RCTs are needed to evaluate their overall

effectiveness.

Autologous Platelet Concentrate

Lopez-Jornet and colleagues (2016) performed a systematic literature review to determine the

effectiveness of autologous platelet concentrate (APC) application, for prevention or treatment of

medication-related osteonecrosis of the jaw (MRONJ) together with surgical debridement. An

electronic search was performed using Medline (PubMed), Embase, and Cochrane databases

until January 2015 using the following search terms: osteonecrosis, bisphosphonates,

antiresorptive, antiangiogenic therapy, BRONJ, platelet concentrate, PRP, PRF, and PRGF. Two

reviewers assessed the eligibility of articles independently and extracted key data. The

methodology used met PRISMA criteria. The Newcastle-Ottawa scale was used to assess the

quality of the articles. Preventive applications of PRP were reported in 697 dental extractions in

patients taking bisphosphonates (BPs) intravenously, of whom 7 patients developed

osteonecrosis (5 mandibular and 2 maxillary). In cases of established osteonecrosis, 8 studies

reported treatment by surgery combined with APC (7 with PRP and 1 with leukocyte-rich and

platelet-rich fibrin) in 123 patients (34 men and 89 women) with ONJ, who received 157

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treatments, of which 135 achieved complete resolution (85.98 %). The authors concluded that

there are no published scientific data to sufficiently support any specific treatment protocol,

including the use of APC together with surgical debridement, for the management of MRONJ.

They stated that RCTs of the use of APC are needed

Bisphosphonates and Mesenchymal Stem Cells (MSCs)

In a retrospective study, Gianakos et al (2016) examined if core decompression (CD) with

mesenchymal stem cells combined with BP therapy can improve the clinical outcomes and

reduce the risk of hip replacement when compared to treatment with BP therapy alone. Between

2006 and 2014, a total of 84 consecutive patients who were diagnosed with ONFH were

identified from the authors’ institution's registry. Of these 84 patients, 49 patients (62 hips) fit

inclusion/exclusion criteria; 29 patients (40 hips) were treated with BP therapy only; 20 patients

(20 hips) were treated with BP, core decompression, and mesenchymal stem cells. Functional

outcomes were assessed using the Modified Harris Hip Score (MHHS), the visual analog score

(VAS), and evaluation of support system. Clinical failure was defined as deterioration of the

MHHS/VAS scores and support system used severe enough to require THR. Radiologic

outcome measures included the XR and MR imaging staging of the hip. Survival analysis was

performed with total hip replacement as the end-point failure. Collapse was defined as

progression from Ficat stage I or II to stage III and from Steinberg I, II, III to IV, V, VI. Failure

requiring THR occurred in 21/40 (52.5 %) of BP-treated hips at a mean follow-up of 25.3 ± 11.5

months and 5/22 (22.73%) of BP + CD + MSC-treated hips at a mean follow-up of 22.7 ± 19.5

months. The median (Q1, Q3) time to collapse was 24.9 (7.4, 33.0) months in BP-treated hips

and 27.3 (27.3) months in BP + CD + MSC-treated hips. There was no evidence of a difference

in functional outcomes between the 2 treatment groups. After adjusting for baseline Ficat stage,

age, and sex, an un-replaced hip treated with BP + CD + MSC had 0.42 (95 % CI: 0.11 to 1.57)

times the risk of being replaced in the next moment compared to an un-replaced hip treated with

BP only (p = 0.196). The authors concluded that these findings demonstrated that treatment with

BP alone or BP + CD + MSC can postpone the need for total hip arthroplasty (THA) in the first

24 months in patients with ONFH compared to previously reported data, but there is no

statistically significant difference between the 2 treatment groups. Combination therapy of BP +

CD + MSC may be more effective in delaying the progression of collapse in early stage ONFH.

Moreover, they stated that future prospective studies are needed to ascertain the effectiveness

of these treatment strategies in the long-term.

Papakostidis and colleagues (2016) noted that the value of CD for treatment of ONFH is unclear.

These researchers investigated by a literature review whether implantation of autologous bone

marrow aspirate, containing high concentrations of pluripotent MSCs, into the CD track would

improve the clinical and radiological results compared with the classical method of CD alone.

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The primary outcomes of interest were structural failure (collapse) of the femoral head and

conversion to THR. All RCTs and non-RCTs comparing simple CD with autologous bone marrow

cell implantation into the femoral head for the treatment of ONFH were considered eligible for

inclusion. The methodological quality of the studies included was assessed independently by 2

reviewers using the Cochrane Collaboration tool for assessing risk of bias in randomized studies.

Of 496 relevant citations identified, 7 studies formed the basis of this review. The pooled

estimate of effect size for structural failure of the femoral head favored the cell therapy group, as,

in this treatment group, the odds of progression of the femoral head to the collapse stage were

reduced by a factor of 5 compared to the CD group (OR = 0.2, 95 % CI: 0.08 to 0.6; p = 0.02).

The respective summarized estimate of effect size yielded halved odds for conversion to THR in

the cell therapy group compared to CD group (odds ratio [OR] = 0.6, 95 % CI: 0.3 to 1.02; p =

0.06). The authors concluded that these findings suggested that implantation of autologous

MSCs into the core decompression track, particularly when employed at early (pre-collapse)

stages of ONFH, would improve the survivorship of femoral heads and reduce the need for hip

arthroplasty. Moreover, they stated that better designed RCTs with adequate sample sizes,

based on power calculations, are needed to further determine the exact role of cytotherapy in the

management of ONFH.

Bone Marrow Concentrate / Aspirate

In a prospective and randomized clinical trial, Pepke and associates (2016) examined the safety

of injection of bone marrow aspirate concentrate during core decompression and studied its

clinical (VAS; HHS) and radiological outcomes (MRI). These investigators evaluated 24

consecutive patients with non-traumatic femoral head necrosis (FHN) during a period of 2 years

after intervention. In-vitro analysis of mesenchymal stem cells was performed by evaluating the

fibroblast colony forming units (CFU-Fs). Post-operatively, significant decrease in pain

associated with a functional benefit lasting was observed. However, there was no difference in

the clinical outcome between the 2 study groups. Over the period of 2 years there was no

significant difference between the head survival rate between both groups. In contrast to that,

these researchers could not perceive any significant change in the volume of FHN in both

treatment groups related to the longitudinal course after treating. The number of CFU showed a

significant increase after centrifugation. The authors concluded that this trial could not detect a

benefit from the additional injection of bone marrow concentrate with regard to bone

regeneration and clinical outcome in the short-term.

Cabrolier and Molina (2016) noted that ONFH leads to degeneration of the head and finally to

osteoarthritis of the hip. Decompression is the most widely used treatment, but its effectiveness

is limited. These researchers stated that it has been proposed instillation of stem cells in

addition to decompression, would lead to better results. Searching in Epistemonikos database,

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which is maintained by screening 30 databases, these investigators identified 2 systematic

reviews including 2 randomized trials. They combined the evidence using meta-analysis and

generated a summary of findings table following the GRADE approach. The authors concluded

that instillation of bone marrow stem cells at the time of core decompression probably slowed

progression to osteoarthritis of the hip in patients with ONFH and might reduce the need of

subsequent surgeries. However, they stated that it is unclear whether it has any effect on the

functionality because the certainty of the evidence is very low.

Yuan and co-workers (2016) evaluated the clinical outcomes of ONFH after autologous bone

marrow stem cell implantation. These investigators searched the PubMed, Embase and Web of

Science databases and included all case-control trials that reported on the clinical outcomes of

osteonecrosis progression, incidence of THA and improvement in HHS. Overall, 7 case-control

trials were included. Compared with the controls, patients treated with the bone marrow stem

cells implantation treatment showed improved clinical outcomes with delayed osteonecrosis

progression (OR = 0.17, 95 % CI: 0.09 to 0.32; p < 0.001), a lower THA incidence (OR = 0.30, 95

% CI: 0.12 to 0.72; p < 0.01) and increased HHS (mean difference = 4.76, 95 % CI: 1.24 to 8.28;

p < 0.01). The heterogeneity, publication bias, and sensitivity analyses showed no statistical

difference significant differences between studies. The authors concluded that the findings of

this study suggested that autologous bone marrow stem cells implantation has a good

therapeutic effect on ONFH, resulting in beneficial clinical outcomes. However, they stated that

trials with larger sample sizes are needed to confirm thesefindings.

Gangii and associates (2011) determined the efficacy of bone marrow cell implantation into the

necrotic lesion of the femoral head on clinical symptoms and the progression of osteonecrosis of

the femoral head in comparison with core decompression. These researchers studied 19

patients and 24 hips with early stage osteonecrosis of the femoral head. The hips were

allocated to either core decompression only or core decompression and implantation of bone

marrow cells. Both patients and assessors were blind with respect to treatment group

assignment. The primary outcomes were clinical symptoms and disease progression. Bone

marrow implantation afforded a significant reduction in pain and in joint symptoms and reduced

the incidence of fractural stages. At 60 months, 8 of the 11 hips in the control group had

deteriorated to the fractural stage whereas only 1 of the 13 hips in the bone marrow graft group

had progressed to that stage. Survival analysis showed a significant difference in the time to

failure between the 2 groups at 60 months. Patients had only minor side-effects after the

treatments. The authors concluded that this long-term follow-up study confirmed that

implantation of autologous bone marrow cells in the necrotic lesion might be an effective

treatment for patients with early stages of osteonecrosis of the femoral head. These

investigators stated that larger studies are need to fully understand the results of this trial.

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In a randomized control study, Sen and colleagues (2012) reported the findings of 51

osteonecrotic hips in 40 patients who were randomly divided into 2 treatment groups. Patients in

group A (25 hips) were treated with core decompression, and those in group B (26 hips) received

autologous bone marrow mononuclear cell instillation into the core tract after core

decompression. Outcome between the 2 groups were compared clinically (Harris Hip score),

radiographically (x-ray and magnetic resonance imaging [MRI]), and by Kaplan-Meier hip

survival analysis after 12 and 24 months of surgical intervention. The clinical score and mean

hip survival were significantly better in group B than in group A (p < 0.05). Patients with adverse

prognostic features at initial presentation, that is, poor Harris Hip score, x-ray changes, edema,

and/or effusion on MRI had significantly better clinical outcome and hip survival in group B than

in group A. The authors concluded that further studies with larger sample size and longer follow-

up are needed to establish the role of stem cell therapy in the treatment of osteonecrosis. This

was a small study (n = 26 hips in the bone marrow mononuclear cell instillation group) with

relatively short-term follow-up (up to 24 months).

Tabatabaee and co-workers (2015) stated that the management of early-stage osteonecrosis of

the femoral head (ONFH) remains challenging. These researchers examined the effects of core

decompression and concentrated bone marrow implantation on ONFH. The study recruited 28

hips with early ONFH randomly assigned into 2 groups of core decompression with (group A)

and without (group B) bone marrow injection. Patients were evaluated using the Western

Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, visual analog

scale (VAS) pain index, and MRI. The mean WOMAC and VAS scores in all patients improved

significantly (p < 0.001); MRI showed a significant improvement in group A (p = 0.046) and

significant worsening in group B (p < 0.001). The authors concluded that bone marrow stem cell

injection with core decompression could be effective in early ONFH. These researchers stated

that more studies with larger sample size and longer follow-up are needed to accept the role of

stem cell therapy in the treatment of ONFH.

Laser and Ozone Therapies

In a systematic review, Fliefe and colleagues (2015) evaluated the available treatments for

bisphosphonate-related osteonecrosis of the jaws (BRONJ) and their outcomes. A literature

search of PubMed, Cochrane Library, and Web of Science databases was conducted in

accordance with the PRISMA statement, search phrases were “jaw osteonecrosis” OR

“bisphosphonate-related osteonecrosis” OR “bisphosphonate osteonecrosis” AND “treatment”

OR “outcomes”. A total of 97 articles published between 2003 and February 2014 were

reviewed. The studies reported 4,879 cases of BRONJ. The mean age of the patients was 66.5

± 4.7 years. The male to female ratio was 1:2. The mean duration of BP administration was

38.2 ± 15.7 months. The quality of the publications was good, with some moderate and poor.

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Minimally invasive surgical treatment was the treatment most used. Medical treatment was also

used. Adjunctive treatments included laser, growth factors, hyperbaric oxygen and ozone. The

authors concluded that the articles provided a broad range of outcome variables to assess the

treatment of BRONJ and the outcomes of each treatment; considerable heterogeneity was found

regarding study design, sample size, and treatment modalities. They stated that clinical trials

with larger samples are needed to provide sufficient information for each treatment modality to

predict the outcomes of each treatment.

Latifyan et al (2016) noted that ONJ resulting from administration of BP or denosumab is a rare

but severe complication in cancer patients. Complete remission depends on the stage of ONJ; it

can be estimated in the range of 20 to 30 %. Low-level laser therapy (LLLT) has been

advocated as a logical additional option; LLLT irradiation has anti-inflammatory actions and thus

can help to control pain, as well as bio-stimulating properties with favorable actions on bacterial

control and wound healing. These investigators reviewed the results of 7 published studies of

LLLT in BP-associated ONJ; LLLT resulted in an overall response rate of 55 % superior to that

observed in controls (30 %). The findings suggested that there might be an advantage to add

LLLT to the "classical" management of ONJ. The authors concluded that further research is

needed to remove any doubt of protection or enhancement of carcinogenic processes; they

believe that prospective well-controlled studies of LLLT in ONJ are needed. If the positive results

are confirmed, it would represent a great improvement for the quality of life of many patients.

Platelet-Rich Fibrin (PRF)

Gonen and Yılmaz Asan (2017) stated that platelet-rich fibrin (PRF) is a second generation

platelet concentrate, and has the ability of regulating the inflammation and stimulation of

chemotactic agents. These researchers presented the treatment of stage-III BRONJ by PRF. A

77-year old male patient with stage-III BRONJ was treated with minimal surgical operations and

PRF membrane. The patient was followed-up for 18 months, and there was no recurrence or

exposure. The authors concluded that PRF may promote the healing of both bone and soft

tissues even in stage-III patients. They stated that this technique is an alternative treatment

modality for the closure of bone exposure and tissue healing in BRONJ patients. The findings of

this sing-case study need to be validated by well-designedstudies.

Norholt and Hartlev (2016) evaluated the outcome of the surgical treatment of osteonecrosis of

the jaw (ONJ) with the additional use of autologous membranes of PRF. The study population

consisted of 15 patients with ONJ lesions in the maxilla (n = 3), mandible (n = 11), or both (n =

1); 8 patients had malignant disease and were treated with high-dose anti-resorptive medication;

7 were treated with low-dose anti-resorptive drugs for osteoporosis; 13 patients had grade 2 ONJ

lesions and 2 had grade 3 lesions. The following standardized surgical technique was applied:

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resection of necrotic bone, mobilization of mucoperiosteal flaps, and multiple layer coverage of

bone with PRF membranes. At follow-up of 7 to 20 months after surgery, complete mucosal

healing and an absence of symptoms were found in 14 of the 15 patients (93 %). The patient

with persistent bone exposure had a grade 3 ONJ lesion before surgery. The authors concluded

that the findings of this study suggested that the use of PRF membranes in the surgical

treatment of grade 2 ONJ may be a contributing factor to a successful outcome. These

preliminary findings need to be further investigated.

Bone Morphogenic Proteins

Pan and co-workers (2014) examined the effect of recombinant human bone morphogenetic

protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of

rabbit femoral head necrosis. Bilateral femoral head necrosis models of rabbit were established

by steroid injection. A total of 48 rabbits (96 femoral head necrosis) were randomly divided into 4

groups: Group A, control group with 12 rabbits, 24 femoral head necrosis; Group B, treated with

rhBMP-2/PLGA implantation after core depression, with 12 rabbits, 24 femoral head necrosis;

Group C, treated with rhBMP-2 implantation after core depression, with 12 rabbits, 24 femoral

head necrosis; and Group D treated with core depression group without implantation, with 12

rabbits, 24 femoral head necrosis. All animals were sacrificed after 12 weeks. The ability of

repairing bone defect was evaluated by X-ray radiograph. Bone mineral density analysis of the

defect regions were used to evaluate the level of ossification. The morphologic change and bone

formation was assessed by hematoxylin and eosin (HE) staining. The angiogenesis was

evaluated by vascular endothelial growth factor (VEGF) immunohistochemistry. The osteogenetic

ability and quality of femoral head necrosis in group B were better than those of other groups

after 12 weeks by X-ray radiograph and morphologic investigation. And the angiogenesis in

group B was better than other groups. Group C had similar osteogenetic quality of femoral head

necrosis and angiogenesis with group D. The authors concluded that the treatment of rhBMP-

2/PLGA implantation after core depression can promote the repair of rabbit femoral head

necrosis. They noted that it is a promising and efficient synthetic bone material to treat the

femoral head necrosis.

Gao and colleagues (2016) evaluated the effectiveness of CD combined with implantation of

bone marrow-derived cells (BMDC) and rhBMP-2 for the treatment of ONFH after femoral neck

fractures in children and adolescents. This study included 51 patients (aged 11.4 to 18.1 years)

with ARCO stages I to III ONFH after femoral neck fractures between 2004 and 2010. The hips

were divided into 2 groups based on whether the lateral pillar of the femoral head (LPFH) was

preserved: (i) LPFH and (ii) non-LPFH groups. All patients were followed-up clinically and

radiographically for a minimum of 5 years. A total of 44 patients (86.3 %) had improved clinical

outcome. Radiologically, 9 of the 51 hips (17.6 %) exhibited collapse onset or progression of the

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femoral head or narrowing of the hip joint space, and 1 patient in the non-LPFH group required

hip arthroplasty due to the worsened syndrome. The authors concluded that the technique

provided an effective therapeutic option for children and adolescents with ONFH following

femoral neck fractures; it relieved hip pain and prevented the progression of osteonecrosis in

young patients lasting more than 5 years after surgery. Moreover, they stated that further

prospective, multi-center studies are needed to indicate a therapeutic potential of the combined

technique for osteonecrosis after femoral neck fracture in the special age group.

The authors stated that this study had several drawbacks. It was limited by virtue of the

retrospective analysis. Because osteonecrosis after femoral neck fractures is relatively

uncommon in children and adolescents, it would have been difficult to mount a RCT. The sample

size of this study was relatively small (n = 51). Due to the limited number of cases, it was

believed that the cell transplantation plus BMP-2 enhanced the success rate of CD compared

with other researches, which should be further confirmed by future high-quality, multi-center

case-control studies. Considering the impact of the radiation, the CT scan was not used in

regular follow-up, which may influence the radiological observation of the state of osteogenesis.

They stated that despite these limitations, however, it was considered that this retrospective

study might be valuable to clarify a hypothesis, provided an available method, and focus on the

study question.

Parathyroid Hormone[1-34] (PTH[1-34])

Zhou and colleagues (2017) noted that steroid-associated osteonecrosis (SAON) might induce

bone collapse and subsequently lead to joint arthroplasty. Core decompression is regarded as

an effective therapy for early-stage SAON, but the prognosis is unsatisfactory due to incomplete

bone repair. Parathyroid hormone[1-34] (PTH[1-34]) has demonstrated positive efficacy in

promoting bone formation. These researchers evaluated the effects of PTH on improving the

effects of CD in early-stage SAON. Distal femoral CD was performed 2 weeks after

osteonecrosis induction or vehicle injection, with 10 of the ON-induced rabbits being subjected to

6-week PTH[1-34] treatment and the others, including ON-induced and non-induced rabbits,

being treated with vehicle; MRI confirmed that intermittent PTH administration improved SAON

after CD therapy. Micro-CT showed increased bone formation within the tunnel. Bone repair

was enhanced with decreased empty osteocyte lacunae and necrosis foci area, resulting in

enhanced peak load and stiffness of the tunnel. Additionally, PTH enlarged the mean diameter

of vessels in the marrow and increased the number of vessels within the tunnels, as well as

elevated the expression of BMP-2, RUNX2, IGF-1, bFGF and VEGF, together with serum OCN

and VEGF levels. The authors concluded that PTH[1-34] enhanced the effectiveness of CD on

osteogenesis and neovascularization, thus promoting bone and blood vessels repair in the

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SAON model. They stated that these results might provide a potential therapeutic strategy for

patients with early-stage SAON. These preliminary findings need to be further investigated in

well-designed studies.

Synthetic Bone Graft substitute (e.g., Calcium Sulphate and Calcium Phosphate)

Landgraeber and colleagues 920170 stated that advanced core decompression (ACD) is a new

technique for treatment of ONFH that includes removal of the necrotic tissue using a

percutaneous expandable reamer followed by refilling of the drill hole and the defect with an

injectable, hard-setting, composite calcium sulphate (CaSO4)-calcium phosphate (CaPO4) bone

graft substitute. As autologous bone has been shown to be superior to all other types of bone

grafts, the aim of the study was to present and evaluate a modified technique of ACD with

impaction of autologous bone derived from the femoral neck into the necrotic defect. A cohort of

patients with an average follow-up of 30.06 months (minimum of 12 months) was evaluated for

potential collapse of the femoral head and any reasons that led to replacement of the operated

hip. Only patients in stages 2a to 2c according to the Steinberg classification were included in

the study. In 75.9 % the treatment was successful with no collapse of the femoral head or

conversion to a THR. Analysis of the results of the different subgroups showed that the success

rate was 100 %, 84.6 % and 61.5 % for stages 2a, 2b and 2c lesions, respectively. The authors

concluded that previous studies with a comparable follow-up reported less favorable results for

ACD without autologous bone. Especially in stages 2b and 2c the additional use of autologous

bone had a positive effect. They stated that in comparison to other hip-preserving techniques,

the modified ACD technique is a very promising and minimally invasive method for treatment of

ONFH. These researchers noted that even if it is still too early to draw final conclusions, the

modified technique of ACD appeared to be superior to the previous one; further long-term follow-

up is needed to receive final assurance.

Autologous Stem Cells

Xu and co-workers (2017) evaluated the safety and efficacy of CD combined transplantation of

autologous bone marrow stem cells (CDBMSCs) for treatment of avascular necrosis of the

femoral head (ANFH); RCTs regarding effectiveness of CDBMSCs for treating ANFH were

searched in 8 comprehensive databases prior to September 2016. The data analysis was

performed by using the RevMan version 5.3. A total of 11 studies with 507 participants were

included. Results showed that CDBMSCs group was more effective than CD group in increasing

HHS, decreasing necrotic area of femoral head, collapse of femoral head, and conversion to

THR incidence. In the subgroup analysis, the results did not change in different intervention

measure substantially. In addition, the safety of CDBMSCs for ANFH was reliable. The authors

concluded that this systematic review found that BMSCs implantation into the CD track appeared

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to be more effective in the treatment of ANFH than CD only, delayed ANFH progression, reduced

necrotic area of femoral head, decreased the need for THA, and improved HHS. However, they

stated that more rigorously designed and higher quality trials with larger sample size are needed

for confirming the effectiveness of CD combined with BMSCs on ANFH.

The authors stated that this study had several drawbacks that should be taken into consideration

when accepting the findings of this review. First, the vast majority of the included trials failed to

describe detailed information about randomization, allocation concealment, and blinding, as

these are the core standards of a well-designed RCT. It was hard to randomly allocate the

patients' hip joint that most of clinical studies failed to randomize. These reasons contributed to

risk of bias of included studies. Second, all trials reported positive effects in the CDBMSCs for

the treatment of ANFH, while negative findings were less likely to be published, implying that

publication bias may have existed. Third, except for 1 study, the remainder of the studies

ignored the sample size estimation. All included studies were of small sample sizes, which

weakened the validity of statistical analysis. Lastly, these investigators failed to generate a

funnel plot for outcomes to detect potential publication bias due to the limited number of included

trials.

Bone Grafting

Yoon and colleagues (2018) stated that CD has been used to treat early-stage (pre-collapse)

ONFH in an attempt to prevent collapse. Recently, other adjunctive treatments including bone

grafting (BG) and bone marrow mononuclear cells (BMMC) were combined to traditional CD to

improve the results. These investigators examined the efficacy of various CD modalities and

non-operative treatment through a network meta-analysis (NMA). A total of 9 RCTs with a

minimum 2 year follow-up were retrieved from PubMed, Embase, and Cochrane Library search.

Treatment modalities were categorized into 5: traditional CD alone, CD combining BG, CD

combining BMMC, CD combining BG and BMMC, and non-operative treatment. The rate of

conversion to THA and the radiologic progression were compared among the 5 treatments. A

total of 453 hips were included in the NMA; 151 hips in CD, 70 hips in CD combining BG, 116

hips in CD combining BMMC, 25 hips in CD combining BG and BMMC, and 91 hips in non-

operative treatment. There were no differences in the rate of THA conversion across all 5

treatment modalities. The pooled risk ratio compared with non-operative treatment for THA

conversion was 0.92 (95 % CI: 0.19 to 4.43; p = 0.915) in traditional CD; 4.10 (95 % CI: 0.37 to

45.42; p = 0.250) in CD combining BG; 0.30 (95 % CI: 0.04 to 2.49; p = 0.267) in CD combining

BMMC; and 1.78 (95 % CI: 0.05 to 63.34; p = 0.750) in CD combining BG and BMMC. No

significant differences were found in terms of the radiologic progression across all treatments.

The authors concluded that in the current NMA, they did not find any differences in the rates of

THA conversion and radiologic progression across all CD modalities and non-operative

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treatment. They stated that these findings question the assumption that CD changes the natural

course of ONFH. Considering that size of necrotic portion was the major determinant of future

collapse of the necrotic femoral head and the collapse did not occur in small lesions even without

any treatment, a large-scale RCT is needed to confirm the effectiveness of CD.

Platelet-rich Plasma Combined with Stem Cells

Houdek and colleagues (2018) reported the results in a preliminary series of patients with ONFH

treated with PRP plus bone marrow-derived mesenchymal stem cells (BmMSCs). A total of 22

consecutive patients (35 hips; 11 men and 11 women) with corticosteroid-induced osteonecrosis

who met study inclusion criteria were enrolled; none declined participation, and none was lost to

follow-up, although 1 patient (2 hips) died within a year of the procedure for reasons unrelated to

it, and 5 patients (7 hips) did not undergo MRI at the 1-year follow-up. All patients had pre-

collapse osteonecrosis, rated either University of Pennsylvania Stage 1 (n = 4) or Stage 2 (n =

31 hips). Mean age and body mass index (BMI) were 43 years and 31 kg/m, respectively.

Patients underwent pre- and post-operative radiography and MRI to assess femoral head

involvement using the modified Kerboul angle. Absolute cell count and colony-forming unit

(CFU) assays were used to assess MSC abundance and viability of the bone marrow obtained at

the time of surgery. Patients were followed at regular intervals to assess clinical response to

treatment with a mean follow-up of 3 years (range of 2 to 4 years). The change in femoral head

involvement was assessed with the modified Kerboul angle; the HHS was used to assess clinical

outcome; and conversion to THA, re-operation, and survivorship free from femoral head collapse

were analyzed with the Kaplan-Meier method on a per-hip basis. Survivorship free from THA,

any procedure, and femoral head collapse was 84 % (95 % CI: 75 % to 93 %), 67 % (95 % CI:

55 % to 79 %), and 93 % (95 % CI: 76 % to 98 %), respectively, at 3 years post-operatively; 2

patients (4 hips) underwent a 2nd decompression and MSC injection for persistent pain without

signs of radiographic collapse. All patients with collapse underwent THA. The mean modified

Kerboul angle improved from 205° ± 47° to 172° ± 48° post-operatively (mean change of -30° ±

6°, p = 0.01). A greater proportion of patients who underwent an additional procedure had a

modified Kerboul grade of 3 or 4 pre-operatively (80 % [4 of 5] versus 13 % [4 of 30 Grade 1 or

2; OR, 26; 95 % CI: 2 to 296; p = 0.005). Pre-operatively the mean HHS was 57 ± 12, which

improved to 85 ± 15 (mean change of 28 ± 3, p < 0.001) at most recent follow-up. Patients

undergoing a re-operation or THA had a lower mean concentration of nucleated cells/ml (5.5 x

10 ± 2.8 x 10 cells/mL versus 2.3 x 10 ± 2.2 x 10 cells/ml, p = 0.02) and lower mean CFUs (13 ±

6 versus 19 ± 7, p = 0.04) compared with those who did not. The authors concluded that core

hip decompression with injection of PRP plus concentrated bone marrow improved pain and

function; greater than 90 % of hips in this series were without collapse at a minimum of 2 years.

They stated that in this preliminary study, successful results were seen when nucleated cell

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count was high and modified Kerboul grade was low. Moreover, these researchers stated that

further randomized studies are needed to determine this procedure's efficacy versus core

decompression or non-operative treatment alone.

Platelet-Rich Plasma Combined with Mesenchymal Stem Cells, and Synthetic Bone Graft

D'Ambrosi and colleagues (2018) reported the rate of survivorship in patients with ONFH treated

with CD in association with MSCs implantation, PRP injection, and synthetic bone graft. These

researchers evaluated 24 hips in 16 patients, according to Ficat classification, treated by CD,

injection of PRP and MSCs, and back-filling of the core tract with synthetic bone graft.

Survivorship was estimated using Kaplan-Meier curves. The survivorship of CD in association

with the procedure was 50 % at 75 months of follow-up. The survival rate was 80 % for patients

in early stage and 28.6 % for patients in advanced stage at 75 months. When these

investigators compared Kaplan-Meier survival curves of patients in stage III + IV and patients in

stage I + II, they noticed that the survival functions were statistically different (p < 0.05, log-rank

test), particularly in stage I + II where we had a greater surviving core decompression, in

comparison to patients in stage III + IV. The authors concluded that these findings suggested

that the technique was safe and good preliminary results were obtained in patients with early

stages of the disease with no reported complications.

The authors stated that this study had 2 main drawbacks. First, small number of patients (n =

16). Second, these researchers mixed 4 different techniques (core decompression, PRP, MSCs,

and synthetic bone graft); thus, it was impossible to clearly know which of the procedures was

truly effective in improving outcomes.

Core Decompression for the Treatment of Post-Arthroscopic Osteonecrosis

Sargeant and colleagues (2019) stated that post-arthroscopic osteonecrosis is a rare

complication that mostly occurs in individual over 50 years of age. It most commonly occurs in

the medial femoral condyle, followed by the lateral femoral condyle then medial tibial plateau.

These investigators reported the 1st case of lateral tibial plateau osteonecrosis in a young

patient after arthroscopic lateral meniscectomy. This patient developed progressively

deteriorating symptoms following uncomplicated arthroscopy; with a subsequent MRI showing

bone edema and some overlying cartilage damage. Conservative measures were unsuccessful,

so core decompression was undertaken. This has resulted in improved symptoms and

subsequent follow-up MRI demonstrated resolution of edema with no progressive cartilage

change. These investigators stated that post-arthroscopic osteonecrosis of the lateral tibial

plateau is a rare condition with a poor outcome, usually resulting in arthroplasty. The authors

concluded that the findings of this study suggested that core decompression may be successful

31/39



in younger patients, however, larger studies with long-term follow-up are needed to confirm these

preliminary findings, and that patients must be advised that this approach often leads to joint

replacement surgery.

CPT Codes / HCPCS Codes / ICD-10 Codes

Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+":

Code Code D escription

CPT codes not covered for indications listed in the CPB:

Core decompression, bone morphogenic proteins, evaluation of growth factors, mesenchymal stem cells, - no specific code:

0232T Injection(s), platelet rich plasma, any site, including image guidance, harvesting and

preparation when performed

0481T Injection(s), autologous white blood cell concentrate (autologous protein solution),

any site, including image guidance, harvesting and preparation, when performed

38232 Bone marrow harvesting for transplantation; autologous

Other CPT codes related to the CPB:

20955 Bone graft with microvascular anastomosis; fibula

27071 Partial excision, wing of ilium, symphysis pubis, or greater trochanter of femur,

(craterization, saucerization) (eg, osteomyelitis or bone abcess); deep (subfascial or

intramuscular)

27170 Bone graft, femoral head, neck, intertrochanteric or subtrochanteric area (includes

obtaining bone graft)

38230 Bone marrow harvesting for transplantation; allogenic

38241 Hematopoietic progenitor cell (HPC); autologous transplantation

HCPCS codes covered if selection criteria are met:

S2325 Hip core decompression

HCPCS codes not covered for indications listed in the CPB::

C1763 Connective tissue, non-human (includes synthetic)

J1436 Injection, etidronate disodium, per 300 mg

J1740 Injection, ibandronate sodium, 1 mg

J2430 Injection, pamidronate disodium, per 30 mg

J3489 Injection, zoledronic acid, 1 mg

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Code Code Description

P9020 Platelet rich plasma, each unit

S8948 Application of a modality (requiring constant provider attendance) to one or more

areas; low-level laser; each 15 minutes

ICD-10 codes covered if selection criteria are met:

M87.051 -

M87.059, M87.151

- M87.159

M87.251

M87.256, M87.351

- M87.353

M87.851

M87.859, M90.551

- M90.559

Osteonecrosis of femur [early/pre-collapse (stage I or II; before X-ray changes are

evident)] [not covered for bone morphogenic proteins, growth factors, synthetic bone

substitute]

ICD-10 codes not covered for indications listed in the CPB:

M87.00 - M87.050;

M87.061 -

M87.150; M87.161

- M87.166;

M87.174 -

M87.179; M87.188

- M87.219;

M87.231 -

M87.250; M87.261

- M87.319;

M87.331 -

M87.350; M87.361

- M87.366;

M87.374 -

M87.819; M87.831

- M87.850;

M87.861 -

M87.869; M87.874

- M87.9; M90.511 -

M90.549; M90.561

- M90.58 - M90.59

Osteonecrosis of bone [excluding femur]

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Core Decompression of the Hip

1. Steinberg ME. Core decompression of the femoral head for avascular necrosis: Indications

and results. Can J Surg. 1995;38 Suppl 1:S18-S24.

2. Castro FP, Barrack RL. Core decompression and conservative treatment for avascular

necrosis of the femoral head: A meta-analysis. Am J Orthoped. 2000;29(3):187-194.

3. Steinberg ME, Larcom PG, Strafford B, et al. Core decompression with bone grafting for

osteonecrosis of the femoral head. Clin Orthop Relat Res. 2001;(386):71-78.

4. Simank HG, Brocai DR, Brill C, Lukoschek M. Comparison of results of core decompression

and intertrochanteric osteotomy for nontraumatic osteonecrosis of the femoral head using

Cox regression and survivorship analysis. J Arthroplasty. 2001;16(6):790-794.

5. Shannon BD, Trousdale RT. Femoral osteotomies for avascular necrosis of the femoral

head. Clin Orthop Relat Res. 2004;(418):34-40.

6. DeSmet AA, Dalinka MK, Alazraki NP, et al; Expert Panel on Musculoskeletal Imaging.

Avascular necrosis of the hip. Reston, VA: American College of Radiology (ACR); 2005.

7. Bellot F, Havet E, Gabrion A, et al. Core decompression of the femoral head for avascular

necrosis. Rev Chir Orthop Reparatrice Appar Mot.2005;91(2):114-123.

8. Israelite C, Nelson CL, Ziarani CF, et al. Bilateral core decompression for osteonecrosis of

the femoral head. Clin Orthop Relat Res. 2005;441:285-290.

9. Keizer SB, Kock NB, Dijkstra PD, et al. Treatment of avascular necrosis of the hip by a non-

vascularised cortical graft. J Bone Joint Surg Br.2006;88(4):460-466.

10. Gangji V, Hauzeur JP. Treatment of osteonecrosis of the femoral head with implantation of

autologous bone-marrow cells. Surgical technique. J Bone Joint Surg Am. 2005;87 Suppl

1(Pt 1):106-112.

11. Yan ZQ, Chen YS, Li WJ, et al. Treatment of osteonecrosis of the femoral head by

percutaneous decompression and autologous bone marrow mononuclear cell infusion. Chin

J Traumatol. 2006;9(1):3-7.

12. McKown K and reviewed by the American College of Rheumatology (ACR) Patient

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Available at: http://www.rheumatology.org/public/factsheets/osteonecrosis.asp. Accessed

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13. von Stechow D, Drees P. Surgical treatment concepts for femoral head necrosis.

Orthopade. 2007;36(5):451-457.

14. Mont MA, Marulanda GA, Seyler TM, et al. Core decompression and nonvascularized bone

grafting for the treatment of early stage osteonecrosis of the femoral head. Instr Course

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15. Martí-Carvajal AJ, Solà I, Agreda-Pérez LH. Treatment for avascular necrosis of bone in

people with sickle cell disease. Cochrane Database Syst Rev. 2009;(3):CD004344.

16. Govaers K, Meermans G, Bortier H, Londers J. Endoscopically assisted core

decompression in avascular necrosis of the femoral head. Acta Orthop Belg.

2009;75(5):631-636.

17. Mukisi-Mukaza M, Manicom O, Alexis C, et al. Treatment of sickle cell disease's hip

necrosis by core decompression: A prospective case-control study. Orthop Traumatol Surg

Res. 2009;95(7):498-504.

18. Gangji V, De Maertelaer V, Hauzeur JP, et al. Autologous bone marrow cell implantation in

the treatment of non-traumatic osteonecrosis of the femoral head: Five year follow-up of a

prospective controlled study. Bone. 2011;49(5):1005-1009.

19. Bakhshi H, Rasouli MR, Parvizi J. Can local erythropoietin administration enhance bone

regeneration in osteonecrosis of femoral head? Med Hypotheses. 2012;79(2):154-156.

20. Helbig L, Simank HG, Kroeber M, et al. Core decompression combined with implantation of

a demineralised bone matrix for non-traumatic osteonecrosis of the femoral head. Arch

Orthop Trauma Surg. 2012;132(8):1095-1103.

21. Guadilla J, Fiz N, Andia I, Sánchez M. Arthroscopic management and platelet-rich plasma

therapy for avascular necrosis of the hip. Knee Surg Sports Traumatol Arthrosc.

2012;20(2):393-398.

22. Wang W, Liu L, Dang X, et al. The effect of core decompression on local expression of

BMP-2, PPAR-γ and bone regeneration in the steroid-induced femoral head osteonecrosis.

BMC Musculoskelet Disord. 2012;13(1):142.

23. Gangji V, De Maertelaer V, Hauzeur JP. Autologous bone marrow cell implantation in

the treatment of non-traumatic osteonecrosis of the femoral head: Five year follow-up

of a prospective controlled study. Bone. 2011;49(5):1005-1009.

24. Sen RK, Tripathy SK, Aggarwal S, et al. Early results of core decompression and

autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis:

A randomized control study. J Arthroplasty. 2012;27(5):679-686.

25. Tabatabaee RM, Saberi S, Parvizi J, et al. Combining concentrated autologous bone

marrow stem cells injection with core decompression improves outcome for patients

with early-stage osteonecrosis of the femoral head: A comparative study. J

Arthroplasty. 2015;30(9 Suppl):11-15.

26. Lakshminarayana S, Dhammi IK, Jain AK, et al. Outcomes of core decompression with

or without nonvascularized fibular grafting in avascular necrosis of femoral head: Short

term followup study. Indian J Orthop. 2019;53(3):420-425.

Core Decompression of the Other Joints

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1. Jacobs MA, Loeb PE, Hungerford DS. Core decompression of the distal femur for avascular

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Causal treatment by early core decompression. Arch Orthop Trauma Surg. 1998;117(1-

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Orthop Surg. 2009;17(6):345-355.

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and late stages. J Hand Surg Am. 2010;35(5):713-717,717.e1-e4.

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people with sickle cell disease. Cochrane Database Syst Rev. 2012;5:CD004344.

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preservation procedures work? J Arthroplasty. 2014;29(1):52-56.

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Med Iran. 2013;51(4):250-253.

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talus: A systematic review. Foot Ankle Spec.2014;7(5):387-397.

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osteonecrosis of the lateral tibial plateau. Knee Surg Relat Res. 2019;31(1):76-80.

Adjunctive Treatments

1. Pan ZX, Zhang HX, Wang YX, et al. Effect of recombinant human bone morphogenetic

protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on

repair of rabbit femoral head necrosis. Asian Pac J Trop Med. 2014;7(11):895-899.

2. Yu PA, Peng KT, Huang TW, et al. Injectable synthetic bone graft substitute combined

with core decompression in the treatment of advanced osteonecrosis of the femoral

head: A 5-year follow-up. Biomed J. 2015;38(3):257-261.

3. Pierce TP, Jauregui JJ, Elmallah RK, et al. A current review of core decompression in the

treatment of osteonecrosis of the femoral head. Curr Rev Musculoskelet Med.

2015;8(3):228-232.

4. Fliefel R, Tröltzsch M, Kühnisch J, et al. Treatment strategies and outcomes of

bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of

patients: A systematic review. Int J Oral Maxillofac Surg. 2015;44(5):568-585.

5. Gianakos AL, Moya-Angeler J, Duggal S, et al. The efficacy of bisphosphonates with core

decompression and mesenchymal stem cells compared with bisphosphonates alone in

the treatment of osteonecrosis of the hip: A retrospective study. HSS J. 2016;12(2):137

144.

6. Pepke W, Kasten P, Beckmann NA, et al. Core decompression and autologous bone

marrow concentrate for treatment of femoral head osteonecrosis: A randomized

prospective study. Orthop Rev (Pavia). 2016;8(1):6162.

7. Cabrolier J, Molina M. Is instillation of bone marrow stem cells at the time of core

decompression useful for osteonecrosis of the femoral head? Medwave. 2016;16 Suppl

1:e6406.

8. Yuan HF, Zhang J, Guo CA, Yan ZQ. Clinical outcomes of osteonecrosis of the femoral

head after autologous bone marrow stem cell implantation: A meta-analysis of seven

case-control studies. Clinics (Sao Paulo). 2016;71(2):110-113.

9. Lopez-Jornet P, Sanchez Perez A, Amaral Mendes R, Tobias A. Medication-related

osteonecrosis of the jaw: Is autologous platelet concentrate application effective for

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prevention and treatment? A systematic review. J Craniomaxillofac Surg.

2016;44(8):1067-1072.

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review of the potential efficacy of low-level laser therapy. Support Care Cancer.

2016;24(9):3687-3693.

11. Gonen ZB, Yılmaz Asan C. Treatment of bisphosphonate-related osteonecrosis of the

jaw using platelet-rich fibrin. Cranio. 2017;35(5):332-336.

12. Norholt SE, Hartlev J. Surgical treatment of osteonecrosis of the jaw with the use of

platelet-rich fibrin: A prospective study of 15 patients. Int J Oral Maxillofac Surg.

2016;45(10):1256-1260.

13. Gao F, Sun W, Guo W, et al. Combined with bone marrow-derived cells and rhBMP-2 for

osteonecrosis after femoral neck fractures in children and adolescents: A case series.

Sci Rep. 2016;6:30730.

14. Papakostidis C, Tosounidis TH, Jones E, Giannoudis PV. The role of "cell therapy" in

osteonecrosis of the femoral head. A systematic review of the literature and meta-

analysis of 7 studies. Acta Orthop. 2016;87(1):72-78.

15. Zhou CH, Meng JH, Zhao CC, et al. PTH[1-34] improves the effects of core

decompression in early-stage steroid-associated osteonecrosis model by enhancing

bone repair and revascularization. PLoS One.2017;12(5):e0178781.

16. Landgraeber S, Warwas S, Claßen T, Jäger M. Modifications to advanced Core

decompression for treatment of avascular necrosis of the femoral head. BMC

Musculoskelet Disord. 2017;18(1):479.

17. Xu S, Zhang L, Jin H, et al. Autologous stem cells combined core decompression for

treatment of avascular necrosis of the femoral head: A systematic meta-analysis.

Biomed Res Int. 2017;2017:6136205.

18. Hauzeur JP, De Maertelaer V, Baudoux E, et al. Inefficacy of autologous bone marrow

concentrate in stage three osteonecrosis: A randomized controlled double-blind trial.

Int Orthop. 2018;42(7):1429-1435.

19. Houdek MT, Wyles CC, Collins MS, et al. Stem cells combined with platelet-rich plasma

effectively treat corticosteroid-induced osteonecrosis of the hip: A prospective study.

Clin Orthop Relat Res. 2018;476(2):388-397.

20. D'Ambrosi R, Biancardi E, Massari G, et al. Survival analysis after core decompression in

association with platelet-rich plasma, mesenchymal stem cells, and synthetic bone

graft in patients with osteonecrosis of the femoral head. Joints. 2018;6(1):16-22.

21. Yoon BH, Lee YK, Kim KC, et al. No differences in the efficacy among various core

decompression modalities and non-operative treatment: A network meta-analysis. Int

Orthop. 2018;42(12):2737-2743.

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AETNA BETTER HEALTH® OF PENNSYLVANIA

Amendment to Aetna Clinical PolicyBulletin Number: 0753 Core

Decompression for Avascular Necrosis

There are no amendments for Medicaid.

www.aetnabetterhealth.com/pennsylvania revised10/10/2019

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