Abstract
Synthetic bone grafts (SBGs) potentially add structural stability after core decompression (CD) for osteonecrosis of the femoral head (ONFH). This systematic review assessed the evidence supporting the (i) radiographic efficacy, (ii) revision rates, and (iii) safety of CD and CD with SBG for the treatment of ONFH. A total of 6549 papers were screened. Inclusion criteria were met by 12 studies for CD and by 14 studies for CD + SBG. This study included 931 hips with Stages I or II of ONFH—414 treated with CD, 379 treated with CD + SBG, and 138 treated with CD + SBG with adjuvant therapies (CD + SBG + ADJ). The radiographic progression was 37% for CD, 33% for CD + SBG, and 32% for CD + SBG + ADJ, with no differences between subgroups (P = .922). The mean total hip arthroplasty conversion rate was 31% for CD, 17% for CD + SBG, and 15% for CD + SBG + ADJ, with no differences between subgroups (P = .08). The complication rates were 0.9% for CD and 2.8% for CD + SBG and CD + SBG + ADJ groups combined. There is no clear evidence that SBGs improve outcomes over CD alone.
INTRODUCTION
Osteonecrosis of the femoral head (ONFH) is a debilitating disease that primarily affects patients between 30 and 50 years of age. ONFH is responsible for about 5%–12% of total hip arthroplasties (THAs) performed yearly in the USA [1, 2]. The aetiology of the disease remains unclear. Recent reports suggest that ONFH develops due to an impaired subchondral blood supply, which leads to a cortical bone collapse [2]. If untreated, ONFH causes significant disability for young patients. Therefore, early diagnosis and hip-preserving treatment remain crucial [3].
THA is a definitive treatment in an advanced stage of ONFH. However, THA performed at a young age is associated with a higher risk of revision [4, 5]. Several invasive and non-invasive therapeutic procedures have proven effective in the early stage of ONFH [6].
Ficat and Arlet proposed core decompression (CD) in 1962 as a treatment option for early-stage disease [7]. The CD is performed by drilling a subchondral necrotic lesion in the femoral head, reducing what they thought was increased venous pressure, and stimulating blood reperfusion and bone tissue regeneration [7–11]. However, removing a significant amount of cancellous bone during the CD procedure can often lead to a structural insufficiency [12, 13]. Therefore, synthetic bone grafts (SBGs) have recently been implemented as an addition to CD procedures. This systematic review and meta-analysis aimed to assess and compare the evidence supporting the structural modifying effect (evaluated radiographically), revision rates, and safety of CD and CD with SBG for treating ONFH.
MATERIALS AND METHODS
Reporting
The systematic review and meta-analysis were conducted following the 2009 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement and was registered in the PROSPERO database in advance [14].
Search strategy
Computer-assisted searches utilizing Cochrane, Embase, and MEDLINE databases were conducted on 4 July 2023 and were limited to time from 1 January 1990 to 4 July 2023.
For CD studies, a search string included terms: CD, osteonecrosis, avascular necrosis, femoral head necrosis, and hip. For CD + SBG studies, the search included terms: bone substitutes, biocompatible materials, hip, osteonecrosis, and avascular necrosis, femoral head necrosis. Search strings are provided in Appendix A.
Study titles and abstracts were analysed for eligibility. We specified inclusion criteria as follows: patients included in the study were diagnosed with ONFH; patients were treated with CD, CD with SBG, or CD with SBG and adjuvant therapies (ADJs); follow-up more than 6 months; clinical or radiological outcomes measured; Level of Evidence of four or higher [15], study was conducted after year 2000. We excluded animal studies, case reports, systematic reviews, papers missing relevant data, and studies published in languages other than English. After a preliminary search, the authors reviewed selected articles and hand-searched references for additional publications. The most recent study was selected when patient groups overlapped. Two independent authors (M.D., M.K.W.) completed the study selection separately. Any differences in opinions were resolved by consensus.
Data extraction and synthesis
The following data were extracted: the first author’s name, publication date, journal title, demographic characteristics (number of hips, sex, and age), ONFH stage, follow-up time, intervention type, SBG type, clinical efficacy evaluation, radiographic outcomes, conversion to THA rate, and adverse effects. The data were recorded in a custom information extraction table [16]. ADJ included in the analysis were bone marrow concentrate (BMC), platelet-rich plasma (PRP), and bone morphogenic proteins, when used alongside CD and SBG.
Clinical and radiological results data and conversion rate to THA were synthesized. Radiological evaluation was collected and presented as radiological progression (RP) rate. Finally, the THA conversion rate was recorded as a mean value and percentage at the latest follow-up.
Data analyses
The meta-analysis compared the CD, the CD + SBG and the CD + SBG + ADJ groups. Data from separate studies were combined and analysed using meta-analysis methods. The RP and THA conversion rate estimates in the CD, the CD + SBG, and the CD + SBG + ADJ groups were pooled using a random-effects model with the restricted maximum-likelihood estimator of between-study variance (τ2). This model was chosen since we assumed that the actual effect size may vary from study to study [17]. The inverse variance method pooled the results, and the Freeman-Tukey double arcsine transformation was used for rate estimates [18]. The Clopper–Pearson confidence intervals (95% CIs) were calculated for individual studies. Heterogeneity between studies was assessed using Cochran’s Q test and I2 statistic. We also estimated prediction intervals (95%) to provide a range of expected proportions.
To compare a treatment effect for variants of therapies, we performed subgroup analyses using the Q test [19].
To assess publication biases, the funnel plots were analysed and Egger’s regression test of funnel plot asymmetry was conducted. Studies with missing observations were omitted. Sensitivity analysis was done using the trim and fill method and leave-one-out method (pooled estimates were calculated, omitting one study at a time).
All analyses were performed using R statistical software version 4.1.2 with the package meta.
Quality assessment
The methodological quality of the case series and cohort studies was assessed using the Institute of Health Economics checklist (Appendix B). The quality of randomized control trials was assessed with version 2 of the Cochrane risk-of-bias tool [20] (Appendix A).
RESULTS
Study selection and results presentation
The initial search yielded 4306 studies for CD (Fig. 1), of which 12 met the inclusion criteria. There were 2243 studies for CD + SBG (including ADJs) (Fig. 2), of which 14 met the inclusion criteria. One study was Level 1b, and 13 papers were Level 4+ in the SBG group (including ADJs), and three were Level 1b and nine Level 4 in the CD group. Results are presented in forest plots. A description of data presentation is included in Appendix D.
Figure 1.
Identification of studies on core decompression via databases and registers.
Figure 2.
Identification of studies on core decompression with synthetic bone grafts via databases and registers.
Patient demographics and study design
Core decompression
The CD group included 414 hips with ONFH from 12 studies. The mean patient age was 38.7 years. Four classification systems were adopted: Ficat, University of Pennsylvania Classification of Osteonecrosis, ARCO, and Japanese Orthopaedic Association Score. All the included patients were classified as pre-collapse stage (I and II) of the disease, regardless of the system used (Table 1). The mean follow-up was 66 months (range 16–144 months).
Table 1.
Demographic data for core decompression studies.
| Author | Year | Journal | EV | Study design | Type | Treatment | Men | Women | Number of pre-collapse hips | Mean age | Mean FU (months) | Etiogenic | Ficat classification | ARCO classification | Japanese Orthopaedic Association Staging | The University of Pennsylvania Classification of Osteonecrosis | Clinical assessment |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Aggarwal (C) | 2020 | The Journal of Arthroplasty | 1b | RCT | Control | CD | 19 | 2 | 28 | 35.2 | 63.7 | N/A | I (6h), II (22h) | I (6), II (22) | N/A | N/A | Harris Hip Score |
| Boontanapibul (C) | 2021 | The Journal of Arthroplasty | 4 | Case–control | Control | CD | 12 | 14 | 31 | 43 | 38 | Steroid (13), steroid and chemo (5), alcohol (4), idiopathic (8), sickle cell (3) | I (6h) II (25h) IIIa (2h) | N/A | N/A | N/A | N/A |
| Lakshminarayana (C) | 2019 | Indian Journal of Orthopaedics | 4 | Case–control | Control | CD | N/A | N/A | 36 | 30 | 53.5 | N/A | I (36h) | N/A | N/A | N/A | Harris Hip Score, VAS |
| Martinot (C) | 2020 | International Orthopaedics | 4 | Case–control | Control | CD | 19 | 5 | 23 | 41 | 64 | Chronic disease (2), alcohol (6), steroid (5), tobacco (6), transplant (2), hypercholesterolaemia (1) | I (1h) II (22h) III (1h) | N/A | N/A | N/A | Harris Hip Score, d’Aubigné Hip Score, UCLA Score, Devane Score |
| Tan | 2022 | Journal of Orthopaedic Surgery and Research | 4 | Case series | N/A | CD | 18 | 6 | 32 | 47.1 | 25.9 | Steroid (8), alcohol (10), idiopathic (14) | N/A | N/A | N/A | IA (4h) IB (6h) IC (4h) IIA (4h) IIB (4h) IIC (10h) | Harris Hip Score, VAS, Oxford Hip Score |
| Wang (C) | 2022 | Orthopaedic Surgery | 4 | Case–control | Control | CD | N/A | N/A | 71 | 38.6 | 60 | Steroid (14), alcohol (33), idiopathic (6) | N/A | N/A | Stage I (19h), Stage II (52h), Type C1 (24h), Type C2 (47h) | N/A | Oxford Hip Score, UCLA Score |
| Zhao (C) | 2023 | Journal of Orthopaedic Surgery and Research | 4 | Case–control | Control | CD | 34 | 26 | 80 | 37.7 | 24 | Steroid (23), alcohol (17), idiopathic (20) | N/A | I (21), II (59) | N/A | N/A | Harris Hip Score, VAS |
| Liang (C) | 2023 | International Orthopaedics | 4 | Case–control | Control | CD | 17 | 3 | 18 | 37.5 | 40.5 | Steroid (4), alcohol (9), idiopathic (7) | N/A | IIA (3), IIB (7), IIC (8), IIIA (2) | N/A | N/A | Harris Hip Score, VAS |
| Jayankura (C) | 2023 | Clinical Orthopaedics and Related Research | 1b | RCT | Control | CD | 26 | 4 | 26 | 45 | 24 | Steroid (7), alcohol (24), idiopathic (26) | N/A | I (3), II (24), IV (2) | N/A | N/A | WOMAC |
| Gangji (C) | 2011 | Bone | 4 | Case–control | Control | CD | N/A | N/A | 11 | 45.7 | 60 | Steroid (9), alcohol (1), idiopathic (1) | N/A | I (2), II (9) | N/A | N/A | Lequesne Index, WOMAC, VAS |
| Zhao (C) | 2012 | Bone | 4 | Case–control | Control | CD | 24 | 26 | 44 | 33.3 | 60 | Steroid (13), alcohol (8), idiopathic (13), trauma (12), Caisson disease (5) | N/A | IC (2), IIA (15), IIB (22), IIC (12) | N/A | N/A | Harris Hip Score |
| Pepke (C) | 2016 | Orthopaedic Reviews | 1b | RCT | Control | CD | 12 | 2 | 14 | 44.4 | 24 | Chemotherapy (2), immunosuppression (3) | N/A | II (14) | N/A | N/A | Harris Hip Score, VAS |
RCT—randomized controlled trial; CD—core decompression; EV—Study evaluation in Oxford Centre for Evidence-Based Medicine Levels of Evidence; FU—follow-up; ARCO—Association Research Circulation Osseous classification; (C)—control group; UCLA—University of California Los Angeles; VAS—Visual Analogue Scale; HSS—Hospital for Special Surgery; WOMAC—Western Ontario and McMaster University Osteoarthritis index; N/A—not applicable.
Core decompression + synthetic bone graft
Overall, 517 hips with ONFH from 14 studies that utilized SBG were included in the review. Of these, 379 were treated with CD + SBG, and 138 with CD + SBG + ADJ. The mean patient age was 44 years. There were five different classification systems that were adopted: Ficat classification, Steinberg classification, ARCO classification, and Japanese Orthopaedic Association Score. All the included patients were classified as pre-collapse stage (I and II) of the disease, regardless of the system used. The mean follow-up was 31.4 months (range 12–69 months) (Tables 2 and 3).
Table 2.
Demographic data for core decompression with synthetic bone grafts and ADJs studies.
| Author | Year | Journal | EV | Study design | Type | Treatment | Men | Women | Number of pre-collapse hips | Mean age | Mean FU (months) | Etiogenic | Ficat classification | ARCO classification | Japanese Orthopaedic Association Staging | Steinberg classification |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Classen | 2015 | Journal of Tissue Engineering And Regenerative Medicine | 4 | Case series | N/A | CD + calcium sulphate/calcium phosphate composite | 43 | 17 | 57 | 47.4 | 29.1 | Alcohol (6p), nicotine (7p), pregnancy (2p), steroid (7p), plasmacytoma (2p), chemotherapy (5p), post-trauma (1p), drugs (1p), haemochromatosis (1p), Factor V deficiency (1p) | N/A | N/a | N/A | 1 (9), 2 (48), 3 (15) |
| Liu | 2012 | Archives of Orthopaedic and Trauma Surgery | 4 | Case–control | Control | CD + n-HA/PA66 | 14 | 3 | 27 | 38.1 | 24.9 | Steroid (9), idiopathic (4), alcohol (14) | N/A | IIB (12p), IIC (15p) | N/A | N/A |
| Lu | 2018 | International Orthopaedics | 4 | Case series | N/A | CD + calcium phosphate/PMMA bioceramic rod | 45 | 17 | 43 | 44.5 | 26.7 | Steroid (15p/15h), idiopathic (11p/12h), alcohol (30p/39h), post-trauma (6p/6h) | N/A | II (43h), III (29) | N/A | N/A |
| Sionek | 2018 | International Orthopaedics | 4 | Case series | N/A | CD + calcium sulphate/calcium phosphate composite | 45 | 8 | 38 | 35.5 | 50.4 | Steroid (24p/26h), alcohol (29p/32h) | II (38h), III (20h) | N/A | N/A | N/A |
| Yang | 2013 | Archives of Orthopaedic and Trauma Surgery | 4 | Case–control | Study | CD + n-HA/PA66 rod + bioglass bone graft | 21 | 8 | 33 | 35.5 | 21.8 | Steroid (17 patients), idiopathic (7 patients), alcohol (5 patients) | N/A | N/A | N/A | IB (3p), IC (4p), IIA (8p), IIB (10p), IIC (8p), IIIA (5p) |
| Yu | 2015 | Biomedical Journal | 4 | Case series | N/A | CD + calcium sulphate/calcium phosphate composite | 14 | 4 | 6 | 48 | 17.7 | Steroid (1 hip/1 patient), idiopathic (4 hips/4 patients), alcohol (12 patients/13 hips) | N/A | IIC (6h), IIIA (13h) | N/A | N/A |
| Zhao | 2018 | Medicine/sciences | 4 | Case series | N/A | CD + calcium sulphate | 48 | 28 | 76 | 51.2 | 12 | Steroid (30 patients), alcohol (27p), idiopathic (19p) | I (26p), II (50p) | N/A | N/A | N/A |
| Jameel | 2022 | Cureus | 4 | Case–control | Study | CD + calcium sulphate hydroxyapatite bioceramic paste | 17 | 3 | 23 | 29.2 | 21.6 | Idiopathic (17 patients/23 hips) | I (18h), II (5h) | N/A | N/A | N/A |
| Lyu. | 2023 | BMC Musculoskeletal Disorders | 4 | Case–control | Control | CD + calcium phosphate | 16 | 8 | 29 | 45.8 | 62.1 | Steroid (14 hips), alcohol (12 hips), other (3 hips) | I (7), II (22) | N/A | N/A | N/A |
| Wan | 2022 | International Orthopaedics | 4 | Case–control | Study | CD + calcium phosphate | 24 | 22 | 47 | 30.5 | 44.6 | N/A | N/A | IIA (22), IIB (25) | N/A | N/A |
RCT—randomized controlled trial; CD—core decompression; SBG—synthetic bone grafts; ADJ—adjuvant therapies; EV—Study evaluation in Oxford Centre for Evidence-Based Medicine Levels of Evidence; FU—follow-up; ARCO—Association Research Circulation Osseous classification; n-HA/PA66—nano-hydroxyapatite/polyamide 66; IP-CHA—Interconnected porous hydroxyapatite ceramics; N/A—not applicable.
Table 3.
Demographic data for core decompression with synthetic bone grafts and ADJs studies.
| Author | Year | Journal | EV | Study design | Type | Treatment | Men | Women | Number cases (Hips) | Mean age | Mean FU (months) | Etiogenic | Ficat classification | ARCO classification | Japanese Orthopaedic Association Staging | Steinberg classification |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Biancardi | 2018 | Joints | 4 | Case series | N/A | CD + PRP + BMC + calcium sulphate/calcium phosphate composite | 14 | 2 | 24 | 41.9 | 50.4 | Steroid (3p), HIV (2p), alcohol (3p), idiopathic (8p) | I (2), II (8), III (10), IV (6) | N/A | N/A | N/A |
| Civinini | 2012 | International Orthopaedics | 4 | Case series | N/A | CD + BMC + calcium sulphate/calcium phosphate composite | 17 | 14 | 37 | 43.8 | 20.6 | Steroid (14p/17h), pharmacological treatment of bone marrow transplantation (4p/6h), alcohol (10p/13h), systemic lupus erythematosus (1p/1h), idiopathic (6h) | N/A | N/A | N/A | 1c (3), 2a (7), 2b (11), 2c (9), 3a (7) |
| Hernandez | 2020 | Clinics in Orthopaedic Surgery | 4 | Case series | N/A | CD + BMC + calcium phosphate | 7 | 3 | 17 | 37.8 | 68.9 | Steroid (6p), alcohol (4p) | N/A | I (6), II (4) | N/A | N/A |
| Liu | 2012 | Archives of Orthopaedic and Trauma Surgery | 4 | Case–control | Study | CD + BMC + n-HA/PA66 | 13 | 4 | 26 | 38 | 26.7 | Steroid (10 hips), idiopathic (3 hips), alcohol (15 hips) | N/A | IIB (13p), IIC (15p) | N/A | N/A |
| Yamasaki | 2010 | The Journal of Bone and Joint Surgery (Br) | 4 | Case–control | Study | CD + BMC + IP-CHA | 14 | 8 | 30 | 41 | 29 | Steroid (14p/22h), idiopathic (2p/2h), alcohol (6p/6h) | N/A | N/A | N/A | 1 (2h), 2 (25h), 3A (3h), B (2h), C1 (13h), C2 (15h) |
| Lyu. | 2023 | BMC Musculoskeletal Disorders | 4 | Case–control | Study | CD + calcium phosphate + PRP | 16 | 5 | 25 | 45.8 | 59.3 | Steroid (14 hips), alcohol (7 hips), Other (4 hips) | I (6), II (19) | N/A | N/A | N/A |
RCT—randomized controlled trial; CD—core decompression; SBG—synthetic bone grafts; ADJ—adjuvant therapies; EV—Study evaluation in Oxford Centre for Evidence-Based Medicine Levels of Evidence; FU—follow-up; ARCO—Association Research Circulation Osseous classification; PRP—platelet-rich plasma; BMC—bone morphogenic cells; n-HA/PA66—nano-hydroxyapatite/polyamide66; IP-CHA—interconnected porous hydroxyapatite ceramics; N/A—not applicable.
Synthetic bone grafts and adjuvant therapies
Different types of SBGs and ADJs utilized in the studies are highlighted in Tables 2 and 3.
Radiographic progression
Core decompression
Structural modifying effects were reported in 12 studies within the CD group [3, 21–31]. The mean RP in the CD group was 37% (range 23%–73%) (Fig. 3).
Figure 3.
Radiological progression rate; Events—hips that progressed radiologically; Total—total number of treated hips; CD—core decompression; SBG—synthetic bone grafts; (C)—control group; (T)—treatment group.
Core decompression + synthetic bone graft
Radiographic progression at the latest follow-up was described in 10 out of 14 studies in CD + SBG and CD + SBG + ADJ groups [32–41] (Table 4). At the latest follow-up, progression was observed in 33% (range 4%–100%) of the hips in CD + SBG and 32% (range 10%–88%) in CD + SBG + ADJ. The RP rates across the CD, CD + SBG, and CD + SBG + ADJ groups are summarized in Figure 3. The test for subgroup differences indicated no significant subgroup effect (P = .92), suggesting no differences in RP between the CD, CD + SBG, and CD + SBG + ADJ groups (Fig. 3).
Table 4.
Radiological assessment for core decompression with synthetic bone grafts and core decompression with synthetic bone grafts and ADJs studies.
| Author | Group | Treatment | Number of pre-collapse ONFH | Baseline assessment (hips) | Follow-up assessment | Mean FU (months) | Lesion size baseline | Lesion size follow-up |
|---|---|---|---|---|---|---|---|---|
| Biancardi | N/A | CD + PRP + BMC +calcium sulphate/calcium phosphate composite | 10 | Ficat: I (2), II (8), III (10), IV (6) | Survival rate—50% | 50.4 | N/A | N/A |
| Civinini | N/A | CD + BMC + calcium sulphate/calcium phosphate composite | 30 | Steinberg: 1c (3), 2a (7), 2b (11), 2c (9), 3a (7) | 78.6% of the hips improved radiologically or had no radiological progression./radiological progression—21.6% | 20.6 | N/A | N/A |
| Classen | N/A | CD + calcium sulphate/calcium phosphate composite | 57 | Steinberg: 1 (9), 2 (48), 3 (15) | 77% of heads without collapse/33% radiological progression | 29.1 | N/A | N/A |
| Hernandez | N/A | CD + BMC + calcium phosphate | 17 | ARCO: I (11), II (6) | 88% of the hips progressed to ARCO III | 68.9 | N/A | N/A |
| Liu | Study | CD + BMC + n-HA/PA66 | 26 | ARCO: IIB (13), IIC (15) | Radiological progression 21.4% of the hips | 26.7 | N/A | N/A |
| Control | CD + n-HA/PA66 | 27 | ARCO: IIB (12), IIC (15) | Radiological progression 59.3% of the hips | 24.9 | N/A | N/A | |
| Lu | N/A | CD + calcium phosphate/PMMA bioceramic rod | 43 | ARCO: II (43), III (29) | Radiological improvement in 31.95% hips, 33.33% stable, 34.72% presented radiological progression | 26.7 | N/A | N/A |
| Sionek | N/A | CD + calcium sulphate/calcium phosphate composite | 38 | Ficat: II (38), III (20) | Radiological progression in 27.6% | 50.4 | N/A | N/A |
| Yamasaki | Study | CD + BMC + IP-CHA | 30 | Japanese Orthopaedic Association Scale: 1 (2), 2 (25), 3A (3), B (2), C1 (13), C2 (15) | <2 mm collapse 33.3%, >2 mm collapse—10% | 29 | Steinberg method 21% (3%–36%) | N/A |
| Yang | Study | CD + n-HA/PA66 rod + bioglass bone graft | 33 | Steinberg: IB (3), IC (4, IIA (8), IIB (10), IIC (8), IIIA (5) | Radiological progression in 21.05% hips | 21.8 | N/A | N/A |
| Yu | N/A | CD + calcium sulphate/calcium phosphate composite | 6 | ARCO: IIC (6), IIIA (13) | Survival rate—42.1% | 17.7 | N/A | N/A |
| Zhao | N/A | CD + calcium sulphate | 76 | Ficat: I (26), II (50) | No radiological assessment | 12 | N/A | N/A |
| Jameel | Study | CD + calcium sulphate hydroxyapatite bioceramic paste | 23 | Ficat: I (18), II (5) | Survival rate—96.59% | 21.6 | N/A | N/A |
| Lyu | Study | CD + calcium phosphate + PRP | 29 | Ficat I (6), II (19) | Survival rate—84% | 59.3 | N/A | N/A |
| Control | CD + calcium phosphate | 25 | Ficat I (7), II (22) | Survival rate—86.2% | 62.1 | N/A | N/A | |
| Wan | Study | CD + calcium phosphate | 47 | ARCO IIA (22), IIB (25) | Femoral head collapse in 3 hips | 44.6 | N/A | N/A |
CD—core decompression; ONFH—osteonecrosis of femoral head; ARCO—Association Research Circulation Osseous classification; PRP—platelet-rich plasma; BMC—bone morphogenic cells; n-HA/PA66—nano-hydroxyapatite/polyamide66; IP-CHA—interconnected porous hydroxyapatite ceramics; N/A—not applicable.
Conversion to total hip arthroplasty
Core decompression
In the CD group, conversion to THA was reported in eight studies [3, 21, 23, 25, 27, 29–31]. The mean conversion rate to THA was 31% (range 11%–55%) (Fig. 4).
Figure 4.
THA conversion rate; Events—hips that were converted to THA; Total—total number of treated hips; CD—core decompression; SBG—synthetic bone grafts; THA—total hip arthroplasty; (C)—control group; (T)—treatment group.
Core decompression + synthetic bone graft
In 11 CD + SBG studies, the survival rate was evaluated with conversion to THA as an endpoint [32–39, 42–44] (Table 5). The mean conversion to THA rate was 17% (range 7%–50%) in CD + SBG and 15% (range 3%–53%) in CD + SBG + ADJ. The test for subgroup differences indicated no significant subgroup effect (P = .08), suggesting no differences in THA conversion rate for CD + SBG and CD + SBG + ADJ (Fig. 4).
Table 5.
Total hip replacement conversion rate for core decompression with synthetic bone grafts and core decompression with synthetic bone grafts and ADJs studies.
| Author | Type | Treatment | Number of pre-collapse cases (ONFH—hips) | Conversion to THA rate (%) |
|---|---|---|---|---|
| Biancardi | N/A | CD + PRP + BMC + calcium sulphate/calcium phosphate composite | 10 | 50 |
| Civinini | N/A | CD + BMC + calcium sulphate/calcium phosphate composite | 30 | 8.1 |
| Classen | N/A | CD + calcium sulphate/calcium phosphate composite | 57 | 33 |
| Hernandez | N/A | CD + BMC + calcium phosphate | 17 | 53 |
| Liu | Study | CD + BMC + n-HA/PA66 | 26 | 14.3 |
| Control | CD + n-HA/PA66 | 27 | 18.5 | |
| Lu | N/A | CD + calcium phosphate/PMMA bioceramic rod | 43 | 9.8 |
| Sionek | N/A | CD + calcium sulphate/calcium phosphate composite | 38 | 20.8 |
| Yamasaki | Study | CD + BMC + IP-CHA | 30 | 3.3 |
| Yang | Study | CD + n-HA/PA66 rod + bioglass bone graft | 33 | 21 |
| Yu | N/A | CD + calcium sulphate/calcium phosphate composite | 6 | 57.9 |
| Zhao | N/A | CD + calcium sulphate | 76 | N/A |
| Jameel | Study | CD + calcium sulphate hydroxyapatite bioceramic paste | 23 | N/A |
| Lyu | Study | CD + calcium phosphate + PRP | 29 | 13.8 |
| Control | CD + calcium phosphate | 25 | 16 | |
| Wan | Study | CD + calcium phosphate | 47 | N/a |
CD—core decompression; ONFH—osteonecrosis of femoral head; THA—total hip replacement; PRP—platelet-rich plasma; BMC—bone morphogenic cells; n-HA/PA66—nano-hydroxyapatite/polyamide66; IP-CHA—interconnected porous hydroxyapatite ceramics; N/A—not applicable.
Safety
Complications were reported in one study (two patients) in the CD group, with an overall complication rate of 0.9%. Four studies reported complications in 12 patients, with an overall complication rate of 2.8% in the CD + SBG and CD + SBG + ADJ groups.
Risk of bias
Analysis of funnel plots suggests low risk of bias due to missing results and presence of small-study effect. Egger’s regression test of funnel plot asymmetry indicates no significant asymmetry in the case of THA conversion rate estimates in the CD, the CD + SBG, and the CD + SBG + ADJ groups and in the case of RP rate estimates in the CD group. For RP rate estimates in the CD + SBG and the CD + SBG + ADJ groups, Egger’s test P-value was .04, suggesting that the distribution of study sizes and their effect sizes might not be symmetrical, which could be indicative of potential publication bias.
Sensitivity analysis using trim and fill methods and the leave-one-out method was done to assess the robustness of results. None of the studies omitted had made a significant difference in the pooled proportion estimate, the 95% CI, or the heterogeneity measures.
Limitations
This study has several limitations that should be considered when interpreting the results. As already mentioned, the majority of included studies were case series with varying study designs, follow-up durations, and patient characteristics, which introduces potential heterogeneity and limits the strength of pooled estimates.
In addition to these general limitations, several methodological factors were not consistently reported across the studies, further restricting the depth of comparative analysis. Differences in the surgical technique, including the diameter or number of CD tracks, were not uniformly described and were therefore not analysed in this review. Likewise, the size and location of necrotic lesions, which can influence disease progression and treatment outcomes, were not consistently reported and thus could not be quantitatively assessed.
Furthermore, definitions of clinical failure varied considerably among studies. While some defined failure as conversion to THA, others used thresholds based on the Harris Hip Score or patient-reported pain. This heterogeneity limits direct comparability of clinical outcomes across studies.
Despite limitations, this review offers relevant data and insights into the role of SBGs for CD in early-stage ONFH.
DISCUSSION
The most important findings of this study were that adding SBG to CD in the treatment of ONFH provides no statistically significant differences between CD, CD + SBG, and CD + SBG + ADJ groups in the case of RP and THA conversion rates.
When conducting our meta-analysis, studies that used only SBG and those that used ADJs in addition to SBG were analysed separately. This decision was based on the existing literature, which suggests that adding other therapies, such as BMC, may result in better outcomes in CD therapy for ONFH [45, 46]. However, our results did not reveal significant differences between patients treated with CD + SBG + ADJ and those treated with CD + SBG.
Among the adjuvant cell therapies used in the reviewed studies, bone morphogenic cells (BMCs) and PRP were the most commonly employed. BMCs have been shown to enhance osteogenic differentiation and promote better bone regeneration in necrotic lesions, potentially improving the outcomes of CD procedures [47, 48]. PRP, known for its high concentration of growth factors, is believed to stimulate angiogenesis and bone healing [49]. Despite the theoretical benefits of these therapies, our analysis did not reveal a significant difference in RP or THA conversion rates between CD + SBG and CD + SBG + ADJ groups. While BMC and PRP may support bone healing, their effectiveness in ONFH remains uncertain and warrants further investigation.
The reviewed studies used synthetic grafts such as calcium sulphate, phosphate, and bioceramics. Calcium sulphate is a resorbable bone graft substitute that provides a temporary scaffold for bone regeneration and is often used in combination with other materials to enhance osteoconductivity [50, 51]. However, its rapid resorption rate may limit its long-term structural support in ONFH treatment [50]. Calcium phosphate, on the other hand, has a slower degradation rate and more closely mimics the mineral composition of natural bone, making it a favourable option for bone regeneration [52]. Bioceramics, including hydroxyapatite and tricalcium phosphate, have been extensively studied due to their excellent biocompatibility and osteoconductive properties [53]. Despite these potential advantages, variability in study outcomes suggests that the effectiveness of different SBG materials may depend on patient-specific factors, surgical techniques, and postoperative rehabilitation protocols.
Our study had limitations. Most of the included studies were case series. However, case series are commonly performed in orthopaedics and can provide valuable data. Studies included in the review evaluated patients with different stages of ONFH. This heterogeneity may have had an impact on the findings. Differences between studies were found in the type, preparation, and administration of the bone substitutes and postoperative aftercare. We could not compare different SBGs due to the limited number of studies. Studies differed in mean follow-up time; thus, conclusions regarding the efficacy of different therapies may lack comparable follow-up. The CD + SBG group had fewer trials and participants contributing data compared to the CD group; thus, the analysis may not be able to detect subgroup differences. Furthermore, significant unexplained heterogeneity between trials within these subgroups makes the validity of the treatment effect estimate for each subgroup uncertain. Finally, conversion to THA, determined as a treatment failure in most studies, may not be a good indicator of the efficacy of treatment. Despite all the limitations, our review provides plausible data, and initial conclusions concerning the use of SBG in the treatment of ONFH can be drawn.
Although the conversion to THA rate was considerably low, RP was ~32% in studies that used CD + SBG + ADJ and 33% in studies that used CD + SBG, with no statistical difference between those two rates. Yu et al. [36] reported a low survival rate and a high conversion to THA rate (50%). The authors observed loss of structural integrity of the SBG without bone remodelling during THA procedures. Hernandez et al. [32] reported high rates of RP and conversion to THA. These results may be influenced by the small number of included hips.
Case–control trials reported by Liu et al. [38] and Yamasaki et al. [37] concluded that adding bone marrow cells (BMCs) to CD + SBG produced better radiological results with a lower conversion to THA rate in the treatment group. The authors claim that adding BMC may have contributed to better bone resorption in the necrotic area.
Finally, our review demonstrated a low overall rate of complications, with no complications directly related to SBG utilization.
Different studies attempted to improve structural support and bone remodelling after CD procedures. Hua et al. [6], in their meta-analysis, analysed CD with SBG implantation and CD with cell therapies and presented that those treatments have better results than CD alone. Piuzzi et al. [45] also reached similar conclusions in their systematic review, reporting lower RP and lower conversion to THA rate when adding cell-based therapy to a CD procedure. Corresponding results were presented in the study by Hernigou et al. [46] on 125 consecutive patients with bilateral corticosteroid-induced ONFH. The authors performed bilateral CDs by adding bone marrow injections to the more advanced side. Significantly improved outcomes [54] were observed in the bone marrow injection sides after 20 to 30 years of follow-up [46]. RP was 72% in CD hips and only 28% in the hips treated with CD with bone marrow. The THA conversion rate was reported to be approximately three times higher in the hips treated with CD (76%) than in those treated with CD and bone marrow (24%) [46].
In conclusion, while the addition of SBGs to the treatment of ONFH may result in a moderate risk of conversion to THA and a low complication rate, there is no clear evidence that adding SBGs to CD produces better results than CD alone.
Supplementary Material
Contributor Information
Michał Dębiński, Departments of Trauma and Orthopaedic Surgery and Rehabilitation, Mazovian Bródnowski Hospital, Kondratowicza 8, 03-242 Warsaw, mazowieckie, Poland; Department of Trauma and Orthopaedic Surgery, The Dr. Jozef Psarski Masovian Specialist Hospital in Ostroleka, Aleja Jana Pawła II 120A, 07-410, Ostrołęka, mazowieckie, Poland.
Stuart B Goodman, Department of Orthopaedic Surgery, Stanford University, 450 Broadway Street, Redwood City, California 94063, United States.
Jerzy Walecki, Department of Radiology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, mazowieckie, Poland.
Konstancja Bobecka-Wesołowska, Faculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, mazowieckie, Poland.
Marcin K Waśko, Department of Radiology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, mazowieckie, Poland; Health Sciences Department, Ignacy Mościcki University of Applied Sciences in Ciechanów, Wojska Polskiego 51, 06-400 Ciechanów, mazowieckie, Poland.
ACKNOWLEDGEMENTS
The authors would like to express their sincere gratitude to Ms. Katarzyna Krucz-Pyrka and Ms. Dorota Gula for their valuable assistance in literature retrieval and support in accessing relevant sources. Their help significantly contributed to the preparation of this manuscript.
CONFLICT OF INTEREST
The authors declare that they have no competing interests.
FUNDING
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
DATA AVAILABILITY
The data supporting the findings of this systematic review and meta-analysis are available from the corresponding author upon reasonable request. Due to the nature of the study, which is based on previously published data, individual participant-level data were not collected. The dataset used for data extraction and synthesis was compiled manually from eligible studies and is available upon request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data supporting the findings of this systematic review and meta-analysis are available from the corresponding author upon reasonable request. Due to the nature of the study, which is based on previously published data, individual participant-level data were not collected. The dataset used for data extraction and synthesis was compiled manually from eligible studies and is available upon request.