Abstract
Background
Avascular necrosis (AVN) of femoral head is commonly seen in middle age groups and in its advanced stages, it is a common indication for total hip replacements (THRs). These patients invariably require revision surgeries in their lifetime and modalities to delay the first arthroplasty are necessary. Core decompression (CD) with bone marrow aspirate concentrate (BMAC) have proved successful in early stages of AVN, but their role in advanced stages remains unclear. The present review was done to assess the same.
Research question
Is CD and BMAC combination effective in delaying radiographic progression and THRs in post collapse stages of AVN hip?
Methodology
A systematic review and meta-analysis was conducted to determine the overall efficacy of CD and BMAC in post collapse stages of AVN hip and to specifically compare primary outcomes like radiographic progression along with need of THR, with CD alone.Three data bases (PubMed, EMBASE and SCOPUS) were searched to identify relevant articles.
Results
The present review included 12 studies with 3 studies included in the meta-analysis. There were 270 hips across the 12 studies out of which 196 hips were treated with CD + BMAC.
Primary outcomes
39.8% cases worsened from stage 3 to stage 4, while the overall incidence of THR in stages 3 and 4 was 38.3%. On comparison with CD alone the combination of CD + BMAC did not show any enhanced efficacy in either delaying progression (Odds ratio of 1.41 (95% CI = 0.55–3.62) or in conversion to THR (Odds Ratio: 0. 92; 95% CI = 0.41–2.06)
Conclusion
CD can be considered in stage 3 of AVN in younger population to delay the need of arthroplasty, before severe head distortion and arthritis sets in, and can be supplemented with bone strut grafts or tantalum rods, for supporting the articular cartilage. BMAC that has shown better results in early AVN, has not shown any additional benefits when compared to CD alone in advanced cases.
Keywords: Advanced AVN, Avascular necrosis, core decompression, Bone marrow aspirate concentrate, Stem cells, Subchondral collapse
1. Introduction
Avascular necrosis of the femoral head (AVN) is a common multifactorial hip pathology, characterized by increased intra-osseous pressure and damage to the femoral blood supply.1,2 It results in ischemic necrosis of the subchondral bone, resulting subsequently into its collapse and further to more advanced stages of joint space narrowing and arthritis, affecting functional status and quality of life.3
The disease is of added concern in terms of its demography, as it commonly affects the young and middle aged population, with a long remaining life span.4 Therefore it becomes increasingly important to stop the progression of the disease in the early stages itself, so as to preserve the femoral head and prevent arthroplasty, as long as possible. Various techniques have been tried with variable beneficial results for early stages of AVN (Ficat Arlet 2b i.e. up to stage of crescent sign/subchondral collapse). These include core decompression (CD) alone or with adjuvants like orthobiologics (platelet rich plasma or PRP, bone marrow aspirate concentrate or BMAC, recombinant bone morphogenetic proteins 2 and 7 or rh- BMP 2 and 7) and/or autologous bone grafting.5, 6, 7
However, once the supporting bone collapses and damages the articular cartilage, the role of these modalities is controversial. At present, the gold standard of treatment in the advanced AVN is total hip replacement (THR). Despite excellent results of arthroplasty, the survival of the prosthesis remains an issue in young and middle aged population and revision surgeries are a given in most of the cases.8Hence, there have been various attempts at delaying the process of arthritis and subsequent THRs, which include rotational osteotomies, vascularised bone grafting and CD plus BMAC. Benefits have been seen with vascularised grafting, however they are associated with donor site morbidity and adverse reactions.9 Rotational osteotomies have been useful in selective patients, especially in hands of the surgeons who have described these surgeries; however the need for intact areas of the head and difficult reproduction of the technique, precludes it use.10,11
The effect of instillation of BMAC is increased presence of osteoprogenitor cells in the necrotic area to aid in tissue regeneration.12,13 CD alone has been reported to be beneficial in up to 84-95 % in stage 1 and 65% in stage 2 as per Ficat Arlet staging; effects are unpredictable in advanced stages.6, 14,15Subsequently, BMAC has been used as an adjuvant and reported more beneficial results in early stages of AVN. This prompted the trials of BMAC in the advanced stages with collapsed subchondral bone beyond the crescent stage, to evaluate its feasibility as a hip preserving surgery.
This present study was conceptualised to review the literature to determine efficacy of core decompression and BMAC combination in advanced stages of AVN (post collapse) and assess whether this modality has a role in delaying the progression of disease into osteoarthritis and delaying total hip replacement.
2. Methodology
2.1. Study design
A systematic review of literature and meta-analysis were performed through specified search engines of PubMed, Embase and Scopus according to the PRISMA guidelines.16
2.2. Search methodology
The primary search was conducted on the PubMed, Embase and SCOPUS databases on 24th June 2020 using specific keywords [Table 1]. Relevant articles published from the inception of the databases were scrutinised and a total number of 2397 results were obtained. A secondary search was done from the references sections of identified publications for any missed articles.
Table 1.
Search strategy.
| Database | Search No. | Period - Inception to 24-06-2020 with keywords | Results |
|---|---|---|---|
| PubMed | 1 | (“femur head necrosis" [MeSH Terms] OR (“femur" [All Fields] AND “head" [All Fields] AND “necrosis" [All Fields]) OR “femur head necrosis" [All Fields] OR (“avascular" [All Fields] AND “necrosis" [All Fields] AND “femoral" [All Fields] AND “head" [All Fields]) OR “avascular necrosis femoral head" [All Fields]) AND post [All Fields] AND (“shock" [MeSH Terms] OR “shock" [All Fields] OR “collapse" [All Fields]) | 1748 |
| 2 | 1 AND core [All Fields] AND (“decompression" [MeSH Terms] OR “decompression" [All Fields]) | 357 | |
| 3 | 2 AND (“bone marrow" [MeSH Terms] OR (“bone" [All Fields] AND “marrow" [All Fields]) OR “bone marrow" [All Fields]) AND aspirate [All Fields] AND concentrate [All Fields] | 64 | |
| 4 | 2 AND mononuclear [All Fields] AND (“stem cells" [MeSH Terms] OR (“stem" [All Fields] AND “cells" [All Fields]) OR “stem cells" [All Fields]) | 108 | |
| Scopus | 1 | TITLE-ABS-KEY (avascular AND necrosis AND femoral AND head AND core AND decompression AND bone AND marrow AND aspirate AND concentrate) | 3 |
| 2 | TITLE-ABS-KEY (avascular AND necrosis AND femoral AND head AND core AND decompression AND stem AND cells) | 51 | |
| 3 | TITLE-ABS-KEY (avascular AND necrosis AND femoral AND head AND post AND collapse AND core AND decompression) | 11 | |
| Embase | 1 | avascular necrosis femoral head core decompression bone marrow aspirate concentrate’ OR (post AND (‘collapse’/exp OR collapse) AND avascular AND (‘necrosis’/exp OR necrosis) AND femoral AND (‘head’/exp OR head) AND core AND (‘decompression’/exp OR decompression) AND (‘bone’/exp OR bone) AND (‘marrow’/exp OR marrow) AND (‘aspirate’/exp OR aspirate) AND concentrate) | 5 |
| 2 | avascular necrosis femoral head core decompression stem cells’ OR (avascular AND (‘necrosis’/exp OR necrosis) AND femoral AND (‘head’/exp OR head) AND core AND (‘decompression’/exp OR decompression) AND (‘stem’/exp OR stem) AND (‘cells’/exp OR cells)) | 50 | |
| Total | 2397 | ||
2.3. Inclusion & exclusion criteria
Articles pertaining to core decompression plus BMAC for conserving femoral heads affected by avascular necrosis were included. The focus was primarily on cases included in post collapse stages of AVN hip; Ficat Arlet stage 3 and ARCO stage 3b onwards. We excluded cases in crescent phase of the disease and ARCO early stage 3, as modified by Nijmegen et al.17 Studies describing usage of other orthobiologics like rh BMP 2,7 or PRP or BMAC in combination with PRP were excluded. Studies that only included early stages of the disease (pre-collapse) were excluded. Cadaveric studies, animal/biomechanical studies, conference abstracts, case reports, and any studies not published in English language were all excluded.
2.4. Data collection and analysis
The study results were assessed for inclusion independently by 2 authors (PK and KJ). Discrepancies in assessments were resolved by discussions and consensus. The data extracted were tabulated; names of the authors, year of publishing, relevant demographic parameters, type of studies and outcome measures of interest including functional outcomes, pain relief and hip survival rates/conversion to hip arthroplasties. Radiological progression and conversion to arthroplasty were considered as the primary outcomes in the present review.
For risk of bias The Cochrane Collaboration’s risk of bias tool was used to assess randomized trials, whereas the MINORS tool was used to assess non-randomized studies.18,19
Meta-analysis was performed if two or more studies reported on the outcome of interest, with statistical heterogeneity determined using the I2 test. Reasons for clinical heterogeneity, if any, were also explored. The Review Manager Software (RevMan 5.4) was used for statistical analysis.20 Open MetaAnalyst was used for pooled analysis and forest plots were constructed to provide a visual summary.21
3. Results
3.1. Search and screening
Using our specified key words, the total number of hits in the databases was 2397 out of which 283 studies were identified after excluding duplications and irrelevant titles for further evaluation. After screening of titles and abstracts, 34 studies were isolated and full texts were read. Finally, 12 studies were identified for inclusion in the review22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33[Fig. 1]
Fig. 1.
PRISMA flowchart depicting selection of articles.
3 studies that compared core decompression + BMAC with core decompression alone were meta analysed to assess the primary outcomes.23,24,27
3.2. Characteristics of the studies
A total of 12 studies were included in the review [Table 2]. 5 were retrospective and 7 were prospective studies, out of which only 3 were randomized clinical trials. 6 studies were comparative trials; they compared CD + BMAC with CD alone (n = 3), with CD + unprocessed marrow (n = 1) and with CD + bone grafting (n = 2).
Table 2.
Characteristics of the study.
| S. No | Author | Study (Prospective /Retrospective) (RCT/Non RCT) |
Comparative /Non Comparative |
Intervention | Additional Intervention | Number of patients | Gender (M/F) | Age and SD | No. of MSCs | No. of CFU | Average Follow up |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Aoyama 2014 [22] | Prospective/Non RCT | Non Comparative | CD + BMAC | Mixed with beta-TCP plus vascularised fibula graft | 4 | 4/0 | 35 ± 10.48 | 1.2 × 108 | 2 years | |
| 2 | Hauzer 2018 [23] |
Prospective/RCT | Comparative | CD + BMAC | – | 19 (23 hips) | 14/5 | 48.0 ± 2.8 | 3.46 ± 0.36 × 109 | 19.45 ± 3.51 × 106 | 2 years |
| CD | – | 19 (23 hips) | 13/6 | 49.7 ± 3.2 | |||||||
| 3 | Kang 2018 [24] | Retrospective/Non RCT | Comparative | CD + BMAC | – | 23 | – | 13.97 ± 13.8 × 106 | 21.6 ± 11.01 × 106 | 4.53 years | |
| CD | – | 23 | – | 4 years | |||||||
| 4 | Lim 2013 [25] | Retrospective/Non RCT | Comparative | CD + BMAC | – | 49 | – | 8.7 ± 4.6 × 108 | 16.9 ± 13.0 × 106 | 5 years | |
| CD + BG | – | 8 | – | ||||||||
| 5 | Ma 2014 [26] | Prospective/RCT | Comparative | CD + BMAC | Bone marrow buffy coat implantation | 5 | – | 3 × 109 | 2 years | ||
| CD + BG | – | 5 | – | ||||||||
| 6 | Pilge 2016 [27] | Retrospective/Non RCT | Comparative | CD + BMAC | Iloprost intravenous | 3 | 3/0 | 39 ± 21.28 | 2 years 36 months |
||
| CD | Iloprost intravenous | 3 | 2/1 | 41.67 ± 21.36 | 27 months | ||||||
| 7 | Rastogi 2013 [28] | Prospective/RCT | Comparative | CD + BMAC | – | 12 | – | 1.1 × 108 | 2 years | ||
| CD + unprocessed marrow | – | 12 | – | ||||||||
| 8 | Tomaru 2018 [29] | Retrospective/Non RCT | Non Comparative | CD + BMAC | – | 11 | – | 2.82 ± 1.8 × 107 | 1.09 ± 1.37 × 106 | 5 years | |
| 9 | Yoshioka 2011 [32] | Retrospective/Non RCT | Non Comparative | CD + BMAC | – | 2 | 0/2 | 42.5 ± 13.23 | 5.32 × 107 | 48.5 months | |
| 10 | Wang T 2013 [31] | Prospective/Non RCT | Non Comparative | CD + BMAC | Bone grafting | 1 | – | 2 years | |||
| 11 | Zhao 2015 [33] | Prospective/Non RCT | Non Comparative | CD + BMAC | Tantalum rod implantation with vascularised iliac grafting | 24 (31 hips) | 13/11 | 33.21 ± 6.09 | 2 × 106 | 64.35 months | |
| 12 | Hernigou 2002 [30] | Prospective/Non RCT | Non Comparative | CD + BMAC | Bone grafting | 32 hips | – | 16.4 × 106 | 12.4 ± 3.4 × 106 | 5–10 years |
(RCT: Randomized Control Trial); (M/F: Male/Female); MSC: Mesenchymal Stem Cells; CFU: Colony Forming Unit; CD: Core Decompression; BMAC: Bone Marrow Aspirate Concentrate; BG: Bone Grafting; TCP: Tricalcium phosphate).
A total of 270 hips were included in the review, out of which 196 hips were treated with CD + BMAC. 178 hips were classified as ARCO stage 3b or Ficat Arlet stage 3 and 18 hips of ARCO stage 4 were also included. The mean age reported in the studies ranged from 35 to 49 years signifying that AVN is a disease more common in the young and the middle aged. The average follow up ranged from a minimum of 24 months to a maximum of 64 months.
3.3. Risk of bias
Overall risk of bias of the included RCTs and comparative non randomized studies were low. However for non-comparative studies the overall bias risk was moderate owing to a number of retrospectively designed studies. It was calculated by two authors independently reading each article about randomization, blinding methods and outcome reporting and risk of bias was calculated separately for randomized control studies and non-randomized studies[Fig. 2, Fig. 3].
Fig. 2.
Risk of bias graphs.
Fig. 3.
Risk of bias summary.
4. Results of meta-analysis of primary outcomes
4.1. Radiographic progression (Table 3)
Table 3.
Outcomes and Survival Analysis of various studies.
| S. No | Author | Intervention | Number of hips | Functional Outcomes | Radiographic Progression | Conversion to THR | Inference | |
|---|---|---|---|---|---|---|---|---|
| 1 | Aoyama 2014 [22] | CD + BMAC | ARCO Stage 3B: 4 | JOA: 52.25 ± 23.5 | 76.5 ± 25.28 | 2 | – | Safe; trial with more patients to determine efficacy of use of adjuvants like TCP and growth factors |
| 2 | Hauzer 2018 [23] |
CD + BMAC | ARCO Stage 3 : 23 | WOMAC A: 7.7 ± 0.6 WOMAC B: 3.2 ± 0.4 VAS: 58.4 ± 4.5 | WOMAC A score evolution: −1.5 ± 1.0 WOMAC B score evolution: −1.5 ± 1.3; VAS: 50.7 ± 1.4 | 10 at 9.9 ± 2.6 months | 15 | No significant improvement with BMAC in stage 3 when added to CD. |
| CD | ARCO Stage 3 : 23 | WOMAC A: 7.1 ± 1.1 WOMAC B: 3.8 ± 0.5 VAS: 46.7 ± 5.7 | WOMAC A score evolution: −0.6 ± 0.9 WOMAC B score evolution: −0.1 ± 0.4; VAS: 44.4 ± 0.7 | 9 at 9.3 ± 2.2 months | 15 | |||
| 3 | Kang 2018 [24] | CD + BMAC | ARCO Stage 3:19; ARCO Stage 4 : 4 |
- | - | 5 | Stage 3 : 8 Stage 4 : 1 |
BMAC lowers THR conversion rates in early stages but no significant change in collapse stages. |
| CD | ARCO Stage 3:19; ARCO Stage 4 : 4 |
– | – | 3 | Stage 3 : 10 Stage 4 : 1 |
|||
| 4 | Lim 2013 [25] | CD + BMAC | Ficat Arlet Stage 3 : 49 | - | - | 28 | 23 | BMAC does not appear to alter the natural course of AVN. |
| CD + BG | Ficat Arlet Stage 3 : 8 | – | – | 5 | 1 | |||
| 5 | Ma 2014 [26] | CD + BMAC | Ficat Arlet Stage 3 : 5 | - | - | 2 | 2 | Strategy of CD + BG + marrow enriched buffy coat should be evaluated for post collapse stages. |
| CD + BG | Ficat Arlet Stage 3 : 5 | – | – | 2 | 0 | |||
| 6 | Pilge 2016 [27] | CD + BMAC | ARCO Stage 3 : 3 | MDA: 13.33 ± 2.51 | 13 ± 2.64 | – | 2 | Additional iloprost therapy with BMAC to be evaluated for post collapse |
| CD | ARCO Stage 3 : 3 | 13 ± 3.6 | 12.67 ± 2.51 | – | 1 | |||
| 7 | Rastogi 2013 [28] | CD + BMAC | ARCO Stage 3 : 12 | – | – | 3 | 0 | Mononuclear cells aid in healing process of necrotic zone better than unprocessed bone marrow cells. |
| CD + unprocessed marrow | ARCO Stage 3 : 12 | – | – | 3 | 3 | |||
| 8 | Tomaru 2018 [29] | CD + BMAC | ARCO Stage 3: 9 ARCO Stage 4 : 2 |
– | – | – | Stage 3 : 4 Stage 4 : 1 |
BMAC with additional adjuvants should be evaluated for post collapse. |
| 9 | Yoshioka 2011 [32] | CD + BMAC | ARCO Stage 3 : 2 | – | – | 1 | 1 | BMAC is effective in early stages, role in post collapse needs evaluation. |
| 10 | Wang T 2013 [31] | CD + BMAC | ARCO Stage 3 : 1 | HHS: 55 | HHS: 71 | 0 | 1 | BMAC is effective in early stages, role in post collapse needs evaluation. |
| 11 | Zhao 2015 [33] | CD + BMAC | ARCO Stage 3 : 19 ARCO Stage 4 : 12 |
HHS: Stage 3 : 39.84 ± 4.86 Stage 4 : 37.00 ± 7.08 |
Stage 3 : 79.11 ± 11.64 Stage 4 : 74.25 ± 18.86 |
Stage 3 : 3/19 | Stage 3:2 Stage 4 : 3 |
BMAC with tantalum rod and vascularised graft is promising for end stage AVN. |
| 12 | Hernigou 2002 [30] | CD + BMAC | Steinberg Stage 4 : 32 | HHS: 68 | 74 | 12 | 12 | BMAC with additional growth factors could be considered for advanced stages. |
(CD: Core Decompression; BMAC: Bone Marrow Aspirate Concentrate; BG: Bone Grafting; TCP: Tricalcium phosphate; JOA: Japan Orthopaedic Association; MDA: Merle d’Aubigné Score; HHS: Harris Hip Score; VAS: Visual Analog Scale; WOMAC: Western Ontario and McMaster Universities Arthritis Index).
The radiographic progression was assessed as worsening of AVN from stage 3 to stage 4. 10 studies reported this in 66/166 patients (39.8%) (95% CI = 25.1%–46.9%); the heterogeneity for this event was moderate (I2 = 48.75%, p = 0.041) [Fig. 4].
Fig. 4.
Pooled analysis of studies reporting radiographic progression.
4.2. Conversion to THR (Table 3)
We assessed conversion to THR separately for ARCO stages 3 and 4. Pooled analysis of AVN collapse in stage 3 showed conversion in 70/178 patients (39.3%) (95% CI = 21.6%–51.4%); however the heterogeneity for this event was high (I2 = 81.13%, p < 0.001)[Fig. 5]. For stage 4 cases, as reported by 3 studies, in a pool of 5/18 patients (27.8%), needed THR(95% CI = 6.9%–47.4%); the heterogeneity for this event was low (I2 = 0%; p = 0.796) [Fig. 6].
Fig. 5.
Pooled analysis of studies reporting conversion to THR in stage 3.
Fig. 6.
Pooled analysis of studies reporting conversion to THR in stage 4.
4.3. Comparative Analysis
This was done between core decompression and CD + BMAC in 3 studies. There was no significant benefit seen with CD + BMAC in terms of radiographic progression compared to CD alone; Odds ratio of 1.41 (95% CI = 0.55–3.62) [Fig. 7 A].
Fig. 7.
Comparative Analysis between CD + BMAC vs core decompression alone A) radiographic progression B) conversion to THR.
In terms of conversion to THR also, there was no additional benefit seen with BMAC added with core decompression; Odds Ratio: 0. 92; 95% CI = 0.41–2.06 [Fig. 7 B].
5. Discussion
Avascular necrosis of hip is a progressive entity that if unchecked, leads to femoral head distortion and arthritis, for which hip arthroplasties offer considerable success. Theories related to its pathogenesis highlight the fact that osteogenesis in the femoral head decreases due to diminished numbers of mesenchymal mononuclear cells; thereby instillation of such cells could help in trabecular regeneration.34,35 Its efficacy in pre collapse stages has been proven in literature, however whether or not the indication can be expanded to include the advanced forms of AVN hip, where the subchondral bone and articular cartilage have already collapsed, is a matter of debate.6 Hernigou et al. were the first to evaluate the efficacy of the CD and BMAC in a study that included 32 Steinberg stage 4 AVN hips, out of which 12 cases progressed, requiring THR; the mean Harris Hip Score (HHS) also did not show much improvements (68–74 postoperatively).30
In the present review the aim was to ascertain the effect of this treatment modality in post collapse stages of AVN hip, by determining the radiographic worsening of stage and need of THR as the primary outcomes. Moreover, comparison of this combination therapy with CD alone was also done to deduce any additional benefits for the patients in delaying that progression. 39.8% of stage 3 cases worsened to stage 4, despite the given treatment, which are serious numbers, particularly considering the associated cost factors of preparing and instilling BMAC with CD in these patients. Moreover, the average follow up ranged between 2 and 5 years, therefore this might not be the actual number of failures and could have been under reported. In terms of patients requiring THR, 70/178 stage 3 and 5/18 stage 4 hips eventually needed arthroplasty, which again show below par outcomes.
On comparing CD alone with the combination, there was no significant difference with no obvious additional benefits of BMAC in post collapse stages. However, only 3 studies could be assessed for this comparison, and more studies are needed for conclusive evidence23,24,27
An improvisation with CD and BMAC in post collapse stages could be addition of strut grafts or tantalum rods, that could support the articular cartilage till the osteogenesis sets in, reforming the subchondral trabecular architecture. Zhao et al. had excellent results in their study of 31 hips in ARCO 3 and 4 stages, where they used tantalum rods with iliac graft along with BMAC and only 3 cases in stage 3 progressed, despite a long mean follow up of more than 5 years.33 Their patients also showed remarkable improvements in HHS with doubling of average scores. Overall only 5 cases needed THR. This aspect of enhancing the overall effect could be an area where focus of further research could be placed at.
It was also observed in the present review that radiographic progression does not necessarily correlate with the need for THR. Thus, we advise that the need for THR should be delayed in a young patient as much as possible to prolong longevity and core decompression can be tried for this. Role of additional BMAC remains doubtful and its cost effectiveness should be considered.
There were some limitations in this study. There were only 3 studies available for comparative meta-analysis. Moreover, the number of patients included in the studies were low. Additionally, a high statistical heterogeneity was noted for some of the outcomes reported in our analysis.
The moderate risk of bias associated with the non comparative studies further decreases the strength of the evidence. Therefore further RCTs are warranted to strengthen the findings of this review.
6. Conclusion
The role of CD + BMAC in the post collapse stages of AVN appears to be inconclusive. The use of this technique can be considered in stage 3, especially with added use of bone graft or tantalum rods. However, total hip replacement remains the only viable option once arthritis sets in.
Funding
Nil.
Source of funding
Nil.
Availability of data and material
Not applicable.
Declaration of competing interest
None.
References
- 1.Jones K.B., Seshadri T., Krantz R., Keating A., Ferguson P.C. Cell-based therapies for osteonecrosis of the femoral head. Biol Blood Marrow Transplant. 2008;14(10):1081–1087. doi: 10.1016/j.bbmt.2008.06.017. [DOI] [PubMed] [Google Scholar]
- 2.Marker D.R., Seyler T.M., Ulrich S.D., Srivastava S., Mont M.A. Do modern techniques improve core decompression outcomes for hip osteonecrosis? Clin Orthop Relat Res. 2008;466(5):1093–1103. doi: 10.1007/s11999-008-0184-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Fan M., Peng J., Qin L., Lu S. Experimental animal models of osteonecrosis. Rheumatol Int. 2011;31(8):983–994. doi: 10.1007/s00296-011-1819-9. [DOI] [PubMed] [Google Scholar]
- 4.Mont M.A., Jones L.C., Hungerford D.S. Nontraumatic osteonecrosis of the femoral head: ten years later. JBJS. 2006;88(5):1117–1132. doi: 10.2106/JBJS.E.01041. [DOI] [PubMed] [Google Scholar]
- 5.Mont M.A., Marulanda G.A., Seyler T.M., Plate J.F., Delanois R.E. Core decompression and nonvascularized bone grafting for the treatment of early stage osteonecrosis of the femoral head. Instr Course Lect. 2007;56:213–220. [PubMed] [Google Scholar]
- 6.Kumar P., Shetty V.D., Dhillon M.S. Efficacy of orthobiologic adjuvants to core decompression for hip preservation in avascular necrosis hip. J Hip Preserv Surg. 2020 doi: 10.1093/jhps/hnaa051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Lieberman J.R., Conduah A., Urist M.R. Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein. Clin Orthop Relat Res. 2004;429:139–145. doi: 10.1097/01.blo.0000150312.53937.6f. [DOI] [PubMed] [Google Scholar]
- 8.Hernigou P., Poignard A., Nogier A., Manicom O. Fate of very small asymptomatic stage-I osteonecrotic lesions of the hip. JBJS. 2004;86(12):2589–2593. doi: 10.2106/00004623-200412000-00001. [DOI] [PubMed] [Google Scholar]
- 9.Zhao D., Xu D., Wang W., Cui X. Iliac graft vascularization for femoral head osteonecrosis. Clin Orthop Relat Res. 2006;442:171–179. doi: 10.1097/01.blo.0000181490.31424.96. [DOI] [PubMed] [Google Scholar]
- 10.Miyanishi K., Noguchi Y., Yamamoto T. Prediction of the outcome of transtrochanteric rotational osteotomy for osteonecrosis of the femoral head. J Bone Joint Surg. 2000;82(4):512–516. doi: 10.1302/0301-620x.82b4.10065. [DOI] [PubMed] [Google Scholar]
- 11.Sugioka Y. Transtrochanteric anterior rotational osteotomy of the femoral head in the treatment of osteonecrosis affecting the hip: a new osteotomy operation. Clin Orthop Relat Res. 1978;(130):191–201. [PubMed] [Google Scholar]
- 12.Baksh D., Song L., Tuan R.S. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med. 2004;8(3):301–316. doi: 10.1111/j.1582-4934.2004.tb00320.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Gao Y.-S., Zhang C.-Q. Cytotherapy of osteonecrosis of the femoral head: a mini review. Int Orthop. 2010;34(6):779–782. doi: 10.1007/s00264-010-1009-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Castro F., Barrack R. Centre for Reviews and Dissemination; UK: 2000. Core Decompression and Conservative Treatment for Avascular Necrosis of the Femoral Head: A Meta-Analysis. Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] [PubMed] [Google Scholar]
- 15.Ficat R. Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment. J Bone Joint Surg. 1985;67(1):3–9. doi: 10.1302/0301-620X.67B1.3155745. [DOI] [PubMed] [Google Scholar]
- 16.Shamseer L., Moher D., Clarke M. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. Br Med J Int Ed. 2015:349. doi: 10.1136/bmj.g7647. [DOI] [PubMed] [Google Scholar]
- 17.Koo K.-H., Mont M.A., Jones L.C. Springer; 2014. Osteonecrosis. [Google Scholar]
- 18.Higgins J.P., Altman D.G., Gøtzsche P.C. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Br Med J Int Ed. 2011;343:d5928. doi: 10.1136/bmj.d5928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Slim K., Nini E., Forestier D., Kwiatkowski F., Panis Y., Chipponi J. Methodological index for non-randomized studies (MINORS): development and validation of a new instrument. ANZ J Surg. 2003;73(9):712–716. doi: 10.1046/j.1445-2197.2003.02748.x. [DOI] [PubMed] [Google Scholar]
- 20.Review Manager (RevMan) The Cochrane Collaboration; 2020. [Computer Program]. Version 54. [Google Scholar]
- 21.Wallace B.C., Dahabreh I.J., Trikalinos T.A., Lau J., Trow P., Schmid C.H. Closing the gap between methodologists and end-users: R as a computational back-end. J Stat Software. 2012;49(5):1–15. [Google Scholar]
- 22.Aoyama T., Goto K., Kakinoki R. An exploratory clinical trial for idiopathic osteonecrosis of femoral head by cultured autologous multipotent mesenchymal stromal cells augmented with vascularized bone grafts. Tissue Eng B Rev. 2014;20(4):233–242. doi: 10.1089/ten.teb.2014.0090. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Hauzeur J.-P., De Maertelaer V., Baudoux E., Malaise M., Beguin Y., Gangji V. Inefficacy of autologous bone marrow concentrate in stage three osteonecrosis: a randomized controlled double-blind trial. Int Orthop. 2018;42(7):1429–1435. doi: 10.1007/s00264-017-3650-8. [DOI] [PubMed] [Google Scholar]
- 24.Kang J.S., Suh Y.J., Moon K.H. Clinical efficiency of bone marrow mesenchymal stem cell implantation for osteonecrosis of the femoral head: a matched pair control study with simple core decompression. Stem Cell Res Ther. 2018;9(1):274. doi: 10.1186/s13287-018-1030-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Lim Y.W., Kim Y.S., Lee J.W., Kwon S.Y. Stem cell implantation for osteonecrosis of the femoral head. Exp Mol Med. 2013;45(11):e61–e. doi: 10.1038/emm.2013.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Ma Y., Wang T., Liao J. Efficacy of autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of femoral head: a prospective, double-blinded, randomized, controlled study. Stem Cell Res Ther. 2014;5(5):1–8. doi: 10.1186/scrt505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Pilge H., Bittersohl B., Schneppendahl J. Bone marrow aspirate concentrate in combination with intravenous iloprost increases bone healing in patients with avascular necrosis of the femoral head: a matched pair analysis. Orthop Rev. 2016;8(4) doi: 10.4081/or.2016.6902. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Rastogi S., Sankineani S., Nag H. Intralesional autologous mesenchymal stem cells in management of osteonecrosis of femur: a preliminary study. Musculoskeletal surgery. 2013;97(3):223–228. doi: 10.1007/s12306-013-0273-0. [DOI] [PubMed] [Google Scholar]
- 29.Tomaru Y., Yoshioka T., Sugaya H. Mid-term results of concentrated autologous bone marrow aspirate transplantation for corticosteroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus. Int Orthop. 2018;42(7):1623–1630. doi: 10.1007/s00264-018-3959-y. [DOI] [PubMed] [Google Scholar]
- 30.Hernigou P., Beaujean F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res. 2002;405:14–23. doi: 10.1097/00003086-200212000-00003. [DOI] [PubMed] [Google Scholar]
- 31.Wang T., Wang W., Yin Z.S. Treatment of osteonecrosis of the femoral head with thorough debridement, bone grafting and bone-marrow mononuclear cells implantation. Eur J Orthop Surg Traumatol. 2014;24(2):197–202. doi: 10.1007/s00590-012-1161-2. [DOI] [PubMed] [Google Scholar]
- 32.Yoshioka T., Mishima H., Akaogi H., Sakai S., Li M., Ochiai N. Concentrated autologous bone marrow aspirate transplantation treatment for corticosteroid-induced osteonecrosis of the femoral head in systemic lupus erythematosus. Int Orthop. 2011;35(6):823–829. doi: 10.1007/s00264-010-1048-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Zhao D., Liu B., Wang B. Autologous bone marrow mesenchymal stem cells associated with tantalum rod implantation and vascularized iliac grafting for the treatment of end-stage osteonecrosis of the femoral head. BioMed Res Int. 2015;2015 doi: 10.1155/2015/240506. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Hernigou P., Poignard A., Manicom O., Mathieu G., Rouard H. The use of percutaneous autologous bone marrow transplantation in nonunion and avascular necrosis of bone. J Bone Joint Surg. 2005;87(7):896–902. doi: 10.1302/0301-620X.87B7.16289. [DOI] [PubMed] [Google Scholar]
- 35.Xiao Z-m, Jiang H., Zhan X-l, Wu Z-g, Zhang X-l. Treatment of osteonecrosis of femoral head with BMSCs-seeded bio-derived bone materials combined with rhBMP-2 in rabbits. Chin J Traumatol. 2008;11(3):165–170. doi: 10.1016/s1008-1275(08)60035-8. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Not applicable.