TY - JOUR
AU - Betsch, Marcel
AB - Abstract Introduction Osteonecrosis of the femoral head (ONFH) often leads to secondary osteoarthritis and total hip arthroplasty. Source of data Recent published literatures. Areas of agreement There has been increasing focus on the early intervention in ONFH patients to preserve the native hip articulation, reduce pain and improve function. Areas of controversy Efficacy of surgical strategies for ONFH is debated. Several clinical studies showed controversial results, and the best treatment has not yet been clarified. Growing points To provide an overview over current treatment options for ONFH compares their failure rates and conversion to total hip arthroplasty (THA) rates. Areas timely for developing research Core decompression (CD) augmented with autologous bone grafting plus the implantation of bone marrow concentrate can decrease the rate of failure and progression to THA rates compared to CD alone. hip, femoral head osteonecrosis, failure, arthroplasty Introduction Atraumatic osteonecrosis of the femoral head (ONFH) produces ischemic ONFH without trauma or sepsis, and progression to secondary osteoarthritis after collapse of the femoral head.1,2 ONFH occur in 10 000–20 000 adults per year in the USA alone, and in many Asian countries the prevalence is even higher.3,4 It is a painful, progressive and difficult to manage condition, primarily found patients aged 20–60 years, with an average age of 38 years.5–7 Although the exact pathophysiology of ONFH is still unknown, it may result from a clotting disorder or genetic abnormality which leads to vascular compromise in the femoral head.8–13 A further explanation is that increased intramedullary pressure in the femoral head leads to decreased blood flow and cell death via a mechanism similar to that of compartment syndrome.14–16 Once the disease has progressed to subchondral fractures, femoral head collapse and painful osteoarthritis, a total hip arthroplasty (THA) is often required.17,18 Just in North America, ONFH accounts for 5–18% of the more than 500 000 annually performed THA.7 However, the outcomes of THA for the much younger and active ONFH patients have been inferior to those reported in typical osteoarthritis patients, because of the limited lifetime and durability of THA.19 Therefore, there has been increasing focus on early intervention in ONFH patients to preserve the native hip articulation, reduce pain and improve function. In the early stages of ONFH, the most commonly performed procedure to increase blood flow to the necrotic bone area, by decreasing the intraosseous pressure, are core decompression (CD) and percutaneous drilling; however, their efficacy has been recently debated.20,21 Given the limitations of CD, various adjunctive techniques, e.g. medical treatment, cell-based and bone grafting therapies, have been described to inject harvested cells into the necrotic areas of the femoral head to enhance bone healing and remodeling.22–28 This systematic review and Bayesian network meta-analysis provides an overview of the current treatment options for ONFH and compares their failure and conversion to THA rates. Method Search strategy This Bayesian network meta-analysis was conducted following the PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions.29 A guide protocol was preliminary drafted: P (population): femoral head osteonecrosis; I (intervention): medical and surgical treatments; O (outcomes): rate of failure, rate of progression to THA Data source and extraction Two independent authors (**; **) performed the literature search in January 2020. The following databases were accessed: PubMed, Google Scholar, Embase and Scopus. The following keywords were used in combination: hip, pain, femoral head, osteonecrosis, necrosis, avascular necrosis, core decompression, drilling, bone, autograft, allograft, bone marrow cells, stem cells, blood cells, mononuclear cells, tantalum rod, conservative, light bulb technique, bisphosphonates, statin, drugs, transplant, grafts, scaffolds, transplantation, aspirate, total hip arthroplasty, failure, collapse and subchondral bone. Initial screening of the resulting articles was consequently performed by the same authors. The full-text of the articles of interest was accessed. References of the articles were also screened. Disagreements were debated and solved by a third author (NM). Eligibility criteria All the clinical trials that compare two or more treatments for femoral head osteonecrosis were accessed. Articles with level of evidence I to III, according to Oxford Centre of Evidence-Based Medicine,30 were considered. According to the authors’ language capabilities, articles in English, German, Italian, French and Spanish were eligible. Only comparative studies, either prospective or retrospective were eligible. Studies that evaluated the effect of alternative medicine (e.g. traditional Chinese medicine) were not included for inclusion. Studies involving less than five patients were not considered. Articles that report data on arthroscopic bone graft and/or labrum repair and/or femoroplasty were not eligible. Only articles reporting quantitative data under the outcomes of interest were considered for inclusion. Missing data under the outcomes of interest warranted the exclusion from this study. Outcomes of interest Two authors independently (**; **) performed data extraction. Study generalities (author and year, journal, study design) and patients baseline demographic information (number of samples and procedures, mean BMI and age, duration of the follow-up, percentage of female, side and etiology) were collected. The outcomes of interest were to evaluate the risk of failure and progression to THA. Failure was defined as the presence of new subchondral fracture and/or pain that does not allow a normal quality of life. Methodology quality assessment For the methodological quality assessment, two reviewers (**;**) performed the Coleman Methodology Score (CMS).31 The CMS assess methodological quality of systematic reviews and meta-analyses, and is highly reliable.32–34 The included studies were evaluated under several point of interest: study size, follow-up duration, surgical approach, type of study, description of diagnosis, surgical technique and rehabilitation, outcome criteria assessment, procedure of assessing outcomes and subject selection process were also evaluated. The CMS scored the included articles between 0% (poor) and 100% (excellent). Values > 60% are considered satisfactory. Statistical analysis The statistical analyses were performed by the main author (**). Baseline comparability was assessed through the IBM SPSS software. The analysis of variance (ANOVA) was used for analysis, with P values > 0.1 was considered satisfactory. The STATA Software/MP, Version 14.1 (StataCorporation, College Station, Texas, USA) was used for the statistical analyses. The NMA was performed through the STATA routine for Bayesian hierarchical random-effects model analysis. The log odd ratio (LOR) effect measure was adopted for analysis of dichotomic data. The overall inconsistency was evaluated through the equation for global linearity via the Wald test. If the P value > 0.5, the null hypothesis cannot be rejected, and the consistency assumption could be accepted at the overall level of each treatment. Both confidence (CI) and percentile (PrI) intervals were set at 95%. Edge plot and interval plots were obtained and evaluated. The funnel plot was also performed to assess publication bias. Egger’s linear regression test35 was performed to assess plot asymmetry. Values of PEgger > 0.05 demonstrated no statistical evidence of asymmetrical distribution. Fig. 1 Open in new tabDownload slide Flow chart of the literature search. Fig. 1 Open in new tabDownload slide Flow chart of the literature search. Results Search result The literature search resulted in 1570 articles. Of them, 701 were duplicates. A further 827 articles were excluded: not matching the topic (N = 401); language limitations (N = 31); not comparative study (N = 217); using less differentiated stem cells (N = 15); performing intra-arterial cells infusion and/or non in-situ transplantation (N = 18); using human bone morphogenetic protein and/or performing extracorporeal shockwave therapy (N = 6); using a synthetic bone graft of calcium sulfate and/or electromagnetic field (N = 8); evaluating alternative medicine (N = 7); reporting data on arthroscopic bone graft and/or labrum repair and/or femoroplasty (N = 8); lacking quantitative data under the outcomes of interest (N = 74); high risk of bias, e.g. uncertain results, too small population (N = 42). This left 32 articles for the present study. The literature search results are shown in Figure 1. Methodological quality assessment The CMS evidenced some limitations and strengths of the present study. Study size and follow-up were adequate. Surgical approach, diagnosis and rehabilitation description were adequately described by most of articles. Outcome measures and related timing of assessment were often defined and reliable. General health measures were rarely reported. The procedure of assessing outcomes and the subject selection processes were often biased and not satisfactory described. Concluding, the CMS scored 74.28%, attesting good methodology quality. The CMS is reported in Table 1. Table 1 Coleman methodology score Endpoints . Mean . SD . Range . Part A: Only one score to be given for each of the 7 sections  1. Study size 6.23 2.2 4–10  2. Mean follow-up 5.55 2.2 4–10  3. Surgical approach 9.35 2.5 0–10  4. Type of study 8.55 6.7 0–10  5. Description of diagnosis 4.84 0.9 0–10  6. Descriptions of surgical technique 7.81 2.3 5–15  7. Description of postoperative rehabilitation 3.39 2.4 0–5 Part B: Scores may be given for each option in each of the 3 sections if applicable  1. Outcome criteria 1.1 Outcome measures clearly defined 1.77 0.6 0–2 1.2 Timing of outcome assessment clearly stated 1.52 0.7 0–2 1.3 Use of outcome criteria that has reported reliability 2.97 0.2 0–3 1.4 General health measure included 0.90 1.1 0–3  2. Procedure of assessing outcomes 2.1 Participants recruited 4.97 0.2 0–5 2.2 Investigator independent of surgeon 2.52 1.2 0–5 2.3 Written assessment 2.84 0.6 0–3 2.4 Completion of assessment with minimal assistance 2.94 0.4 0–3  3. Description of subject selection process 3.1 Selection criteria reported and unbiased 4.39 1.3 0–5 3.2 Recruitment rate reported > 80% 3.26 2.3 0–5 3.3 Recruitment rate reported < 80% 3.61 2.2 0–5 Endpoints . Mean . SD . Range . Part A: Only one score to be given for each of the 7 sections  1. Study size 6.23 2.2 4–10  2. Mean follow-up 5.55 2.2 4–10  3. Surgical approach 9.35 2.5 0–10  4. Type of study 8.55 6.7 0–10  5. Description of diagnosis 4.84 0.9 0–10  6. Descriptions of surgical technique 7.81 2.3 5–15  7. Description of postoperative rehabilitation 3.39 2.4 0–5 Part B: Scores may be given for each option in each of the 3 sections if applicable  1. Outcome criteria 1.1 Outcome measures clearly defined 1.77 0.6 0–2 1.2 Timing of outcome assessment clearly stated 1.52 0.7 0–2 1.3 Use of outcome criteria that has reported reliability 2.97 0.2 0–3 1.4 General health measure included 0.90 1.1 0–3  2. Procedure of assessing outcomes 2.1 Participants recruited 4.97 0.2 0–5 2.2 Investigator independent of surgeon 2.52 1.2 0–5 2.3 Written assessment 2.84 0.6 0–3 2.4 Completion of assessment with minimal assistance 2.94 0.4 0–3  3. Description of subject selection process 3.1 Selection criteria reported and unbiased 4.39 1.3 0–5 3.2 Recruitment rate reported > 80% 3.26 2.3 0–5 3.3 Recruitment rate reported < 80% 3.61 2.2 0–5 Open in new tab Table 1 Coleman methodology score Endpoints . Mean . SD . Range . Part A: Only one score to be given for each of the 7 sections  1. Study size 6.23 2.2 4–10  2. Mean follow-up 5.55 2.2 4–10  3. Surgical approach 9.35 2.5 0–10  4. Type of study 8.55 6.7 0–10  5. Description of diagnosis 4.84 0.9 0–10  6. Descriptions of surgical technique 7.81 2.3 5–15  7. Description of postoperative rehabilitation 3.39 2.4 0–5 Part B: Scores may be given for each option in each of the 3 sections if applicable  1. Outcome criteria 1.1 Outcome measures clearly defined 1.77 0.6 0–2 1.2 Timing of outcome assessment clearly stated 1.52 0.7 0–2 1.3 Use of outcome criteria that has reported reliability 2.97 0.2 0–3 1.4 General health measure included 0.90 1.1 0–3  2. Procedure of assessing outcomes 2.1 Participants recruited 4.97 0.2 0–5 2.2 Investigator independent of surgeon 2.52 1.2 0–5 2.3 Written assessment 2.84 0.6 0–3 2.4 Completion of assessment with minimal assistance 2.94 0.4 0–3  3. Description of subject selection process 3.1 Selection criteria reported and unbiased 4.39 1.3 0–5 3.2 Recruitment rate reported > 80% 3.26 2.3 0–5 3.3 Recruitment rate reported < 80% 3.61 2.2 0–5 Endpoints . Mean . SD . Range . Part A: Only one score to be given for each of the 7 sections  1. Study size 6.23 2.2 4–10  2. Mean follow-up 5.55 2.2 4–10  3. Surgical approach 9.35 2.5 0–10  4. Type of study 8.55 6.7 0–10  5. Description of diagnosis 4.84 0.9 0–10  6. Descriptions of surgical technique 7.81 2.3 5–15  7. Description of postoperative rehabilitation 3.39 2.4 0–5 Part B: Scores may be given for each option in each of the 3 sections if applicable  1. Outcome criteria 1.1 Outcome measures clearly defined 1.77 0.6 0–2 1.2 Timing of outcome assessment clearly stated 1.52 0.7 0–2 1.3 Use of outcome criteria that has reported reliability 2.97 0.2 0–3 1.4 General health measure included 0.90 1.1 0–3  2. Procedure of assessing outcomes 2.1 Participants recruited 4.97 0.2 0–5 2.2 Investigator independent of surgeon 2.52 1.2 0–5 2.3 Written assessment 2.84 0.6 0–3 2.4 Completion of assessment with minimal assistance 2.94 0.4 0–3  3. Description of subject selection process 3.1 Selection criteria reported and unbiased 4.39 1.3 0–5 3.2 Recruitment rate reported > 80% 3.26 2.3 0–5 3.3 Recruitment rate reported < 80% 3.61 2.2 0–5 Open in new tab Risk of publication bias The risk of publication bias was assessed using the funnel plots (Fig. 2). Both funnel plots showed good overall distribution of the referral points. According to the Egger’s test, no statistically significant asymmetry was detected in both plots (PEgger > 0.05), thus attesting to the present study acceptable risk of publication bias. Fig. 2 Open in new tabDownload slide Overall network comparisons: edge (left), funnel (middle) and interval (right) plots. Fig. 2 Open in new tabDownload slide Overall network comparisons: edge (left), funnel (middle) and interval (right) plots. Patients demographics Data from 1898 patients (2367 procedures) were retrieved. Mean duration of symptoms before intervention was 7.27 ± 4.5 months, while the mean follow-up was 51.2 (11.3–360) months. The mean age of the patients was 38.12 ± 7.8 years, the mean BMI 24.59 ± 1.0. 31.5% (586 of 1862 patients) were female. 46.5% (588/1265) were bilateral, 26.6% (336/1265) left and 26.9% (/1898) right side. The etiology were steroids in 39.5% (750/1898), idiopathic 19.2% (365/1898), alcohol 32.9% (625/1898), traumatic 5.0% (94/1898) and 8.0% (151/1898) other or unknown. The ANOVA test found good baseline comparability (P > 0.1). Studies generalities and patient demographics are shown in Table 2. Outcomes of interest CD combined with bone autograft and BMC (LOR –0.83; 95% CI –3.14 to 1.48; 95% PrI –3.92 to 2.26) showed a lower rate of failure, followed by CD combined with MSC (LOR 0.08; 95% CI –2.57 to 2.72; 95% PrI –3.31 to 3.46). Conservative management resulted in the worse outcomes in terms of failure rates (LOR 4.30; 95% CI 1.94–6.66; 95% PrI 1.17–7.43). The equation for global linearity via the Wald test found no statistically significant inconsistency (P = 0.7). Concerning the rate of progression to THA, CD combined with bone autograft and BMC performed better (LOR –1.08; 95% CI –4.33 to 2.16; 95% PrI –4.74 to 2.57), followed by CD combined with bone autograft and PRP (LOR 1.07; 95% CI –1.76 to 3.89; 95% PrI –2.16 to 4.29). Conservative management resulted in the highest rates of THA progression (LOR 4.70; 95% CI 2.42–6.97; 95% PrI 2.03–7.36). The equation for global linearity via the Wald test found any statistically significant inconsistency (P = 0.9). The network comparisons are shown more in detail in Figure 2. Discussion There is growing interest in the development of hip preserving treatment options for ONFH. This Bayesian network meta-analysis compares failure and progression to THA rates of currently available treatment options for ONFH (core decompression, bone marrow concentrate, bone auto- and allograft, mesenchymal stem cells, mononuclear cells, light-bulb technique, tantalum rods, bisphosphonates, statins and conservative treatment). Included were 32 studies with a total of 1898 patients, considering only studies with evidence levels I–III. CD combined with autologous bone grafting and the implantation of bone marrow concentrate results in lower overall failure and lower progression to THA rates than most other treatment options for ONFH. Conservative treatment of ONFH was associated with the highest overall failure and progression to THA rates. Table 2 Generalities and patients baseline of the included studies Author, year . Journal . Study design . CMS . Treatment . Follow-up (months) . Patients (n) . Procedures (n) . Female (%) . Age (mean) . Bi et al., 201936 J Orthop Surg Res Prospective 72 Robot assisted CD, local cancellous bone graft autologous 26.8 9 16 22.2 34.9 Conventional CD, local cancellous bone graft autologous 26.4 11 20 27.3 35.3 Cao et al., 201837 Int J Clin Exp Med Prospective 75 Multi-directional CD apparatus with impaction bone grafting fibula apparatus with impaction bone grafting 41.1 27 30 37.0 37.7 CD fibula allograft 43.9 26 28 30.8 36.9 Cao et al., 201738 Clin Orthop Related Res Retrospective 80 CD, autologous bone grafting 36.0 21 21 23.8 31.0 CD free vascularized fibula allograft 36.0 21 21 23.8 31.0 Gangji et al., 201139 Bone Prospective, double blinded 73 CD, autologous bone marrow cell implantation 60.0 13 13 52.6 42.2 CD isolated 60.0 11 11 52.6 45.7 Gianakos et al., 201640 HSS J Retrospective 64 Bisphosphonates 22.7 29 40 38.0 43.0 Bisphosphonates, CD, MSC 25.3 20 20 55.0 38.0 Hauzeur et al., 201841 Int Orthop Prospective, Randomized 78 CD, BMA 12.0 19 23 26.3 48.0 CD isolated 12.0 19 23 31.6 49.7 Hernigou et al., 201842 Int Orthop Randomized 90 CD, MSC 360.0 125 125 37.6 36.0 CD isolated 360.0 125 125 37.6 36.0 Huang et al., 201943 Annals Translational Medicine Prospective, Randomized 76 CD, Tantalum Rod (Runze) 38.2 19 21 21.1 43.4 CD, Tantalum Rod (Zimmer) 39.5 20 20 30.0 41.6 Kang et al., 201844 Stem Cell Res Ther Retrospective 67 CD isolated 48.0 50 53 24.0 47.3 CD, BMMSC 54.4 50 53 28.0 46.0 Kang et al., 201245 Joint Bone Spine Prospective, Randomized 88 CD isolated 62.0 52 52 30.9 45.3 CD, bisphosphonate 62.0 55 55 32.7 43.8 Koo et al., 199546 J bone Joint Surg Prospective, Randomized 68 CD, cancellous bone graft 24.0 18 5.6 42.5 Conservative 24.0 19 5.6 49.7 Lakatos et al., 201747 J Osteopor Phys Act Retrospective 52 CD, autogenous bone impaction, platelet rich Plasma 73.2 16 17 5.9 45.3 CD isolated 70.8 12 12 50.0 46.3 Li et al., 201648 Indian J Orthop Prospective, Randomized 78 CD, cancellous bone grafting 30.0 20 23 CD, quadratus femoris muscle pedicle bone grafting 30.0 19 24 Li et al., 201749 J Orthop Sci Retrospective 71 CD, neck fenestration, autogenous bone grafting 36.0 71 83 15.7 38.2 CD, bone grafting 36.0 75 90 13.3 39.6 Li et al., 201850 Int J Clin Exp Med Retrospective 79 Non-vascularized bone grafting via trapdoor 45.4 17 17 35.0 15.2 Conservative 43.6 20 20 20.0 14.9 Lim et al., 201351 Experimental Molecular Medicine Retrospective 74 CD, MSC 87.0 86 128 20.0 36.3 CD, bone graft 87.0 21 31 24.0 34.3 Liu et al., 201552 Int Orthop Retrospective 73 CD, tantalum rod 48.2 42 52 11.9 40.7 CD, composite bone grafting 71.6 36 49 16.7 41.0 Ma et al., 201453 Stem Cell Res Ther Prospective, Randomized 83 CD, autologous bone graft, BMC 24.0 21 25 28.6 34.8 CD, autologous bone graft 24.0 18 24 27.8 35.6 Miao et al., 201554 Open Orthop J Prospective 70 CD isolated 18.1 30 34 56.7 35.2 CD, tantalum rod 19.8 30 36 60.0 32.6 Mohanty et al., 201655 Musculoskelet Surg Retrospective 65 CD isolated 36.0 24 33 29.2 36.7 CD, non-vascularized free fibula graft 36.0 22 35 13.6 34.1 Mukisi-Mukaza et al., 200956 Orthop Traumatol Surg Res Prospective 75 Conservative 13.4 16 23 68.8 36.5 CD isolated 11.3 26 42 61.5 30.3 Neumayr et.al, 200657 J Bone J Surg Prospective 59 CD isolated 37.2 17 17 53.0 24.7 Conservative 36.0 21 21 48.0 26.4 Ou et al., 201958 Int J Clin Exp Med Retrospective 70 CD, free fibular graft 41.5 46 62 43.5 55.0 CD isolated 41.5 44 60 50.0 55.1 Pepke et al., 201659 Orthopedic Rev Prospective, Randomized 80 CD isolated 24.0 14 14 14.3 44.5 CD, BMA 24.0 11 11 9.1 44.3 Rastogi et al., 201360 Musculoskelet Surg Prospective, Randomized 81 CD, MNC 24.0 30 30 13.0 34.7 CD, BMA 24.0 30 30 20.0 33.0 Sallam et al., 201761 Hip Int Retrospective 73 CD isolated 94.3 38 38 44.7 33.2 CD, inverted femoral head graft 94.3 33 33 48.5 32.7 Sen et al., 201262 Arthroplasty Prospective, Randomized 81 CD isolated 24.0 20 25 28.0 CD, MNC 24.0 20 26 26.9 Stulberg et al.,199163 Clin Orthop Rel Res Prospective, Randomized 76 Conservative 26.8 17 26 CD isolated 26.8 19 29 Tabatabaee et al., 201564 Arthroplasty Prospective, Randomized 80 CD, BMA 24.0 14 14 35.7 31.0 CD, autologeous cancellous bone grafting, non-vascularized fibula grafting 104.5 25 28 Wang et al., 201965 Arthroplasty Retrospective 73 Light bulb technique 48.0 66 21.2 38.1 CD 48.0 59 25.4 39.1 Yin et al., 201666 BMC Musculoskelet Dis Retrospective 66 CD, Statin 36.0 20 32 35.0 39.1 CD isolated 36.0 16 26 18.8 44.7 Zhao et al., 20129 Bone Prospective, Randomized 87 CD, MSC 60.0 50 53 46.0 32.7 CD isolated 60.0 50 51 48.0 33.8 Author, year . Journal . Study design . CMS . Treatment . Follow-up (months) . Patients (n) . Procedures (n) . Female (%) . Age (mean) . Bi et al., 201936 J Orthop Surg Res Prospective 72 Robot assisted CD, local cancellous bone graft autologous 26.8 9 16 22.2 34.9 Conventional CD, local cancellous bone graft autologous 26.4 11 20 27.3 35.3 Cao et al., 201837 Int J Clin Exp Med Prospective 75 Multi-directional CD apparatus with impaction bone grafting fibula apparatus with impaction bone grafting 41.1 27 30 37.0 37.7 CD fibula allograft 43.9 26 28 30.8 36.9 Cao et al., 201738 Clin Orthop Related Res Retrospective 80 CD, autologous bone grafting 36.0 21 21 23.8 31.0 CD free vascularized fibula allograft 36.0 21 21 23.8 31.0 Gangji et al., 201139 Bone Prospective, double blinded 73 CD, autologous bone marrow cell implantation 60.0 13 13 52.6 42.2 CD isolated 60.0 11 11 52.6 45.7 Gianakos et al., 201640 HSS J Retrospective 64 Bisphosphonates 22.7 29 40 38.0 43.0 Bisphosphonates, CD, MSC 25.3 20 20 55.0 38.0 Hauzeur et al., 201841 Int Orthop Prospective, Randomized 78 CD, BMA 12.0 19 23 26.3 48.0 CD isolated 12.0 19 23 31.6 49.7 Hernigou et al., 201842 Int Orthop Randomized 90 CD, MSC 360.0 125 125 37.6 36.0 CD isolated 360.0 125 125 37.6 36.0 Huang et al., 201943 Annals Translational Medicine Prospective, Randomized 76 CD, Tantalum Rod (Runze) 38.2 19 21 21.1 43.4 CD, Tantalum Rod (Zimmer) 39.5 20 20 30.0 41.6 Kang et al., 201844 Stem Cell Res Ther Retrospective 67 CD isolated 48.0 50 53 24.0 47.3 CD, BMMSC 54.4 50 53 28.0 46.0 Kang et al., 201245 Joint Bone Spine Prospective, Randomized 88 CD isolated 62.0 52 52 30.9 45.3 CD, bisphosphonate 62.0 55 55 32.7 43.8 Koo et al., 199546 J bone Joint Surg Prospective, Randomized 68 CD, cancellous bone graft 24.0 18 5.6 42.5 Conservative 24.0 19 5.6 49.7 Lakatos et al., 201747 J Osteopor Phys Act Retrospective 52 CD, autogenous bone impaction, platelet rich Plasma 73.2 16 17 5.9 45.3 CD isolated 70.8 12 12 50.0 46.3 Li et al., 201648 Indian J Orthop Prospective, Randomized 78 CD, cancellous bone grafting 30.0 20 23 CD, quadratus femoris muscle pedicle bone grafting 30.0 19 24 Li et al., 201749 J Orthop Sci Retrospective 71 CD, neck fenestration, autogenous bone grafting 36.0 71 83 15.7 38.2 CD, bone grafting 36.0 75 90 13.3 39.6 Li et al., 201850 Int J Clin Exp Med Retrospective 79 Non-vascularized bone grafting via trapdoor 45.4 17 17 35.0 15.2 Conservative 43.6 20 20 20.0 14.9 Lim et al., 201351 Experimental Molecular Medicine Retrospective 74 CD, MSC 87.0 86 128 20.0 36.3 CD, bone graft 87.0 21 31 24.0 34.3 Liu et al., 201552 Int Orthop Retrospective 73 CD, tantalum rod 48.2 42 52 11.9 40.7 CD, composite bone grafting 71.6 36 49 16.7 41.0 Ma et al., 201453 Stem Cell Res Ther Prospective, Randomized 83 CD, autologous bone graft, BMC 24.0 21 25 28.6 34.8 CD, autologous bone graft 24.0 18 24 27.8 35.6 Miao et al., 201554 Open Orthop J Prospective 70 CD isolated 18.1 30 34 56.7 35.2 CD, tantalum rod 19.8 30 36 60.0 32.6 Mohanty et al., 201655 Musculoskelet Surg Retrospective 65 CD isolated 36.0 24 33 29.2 36.7 CD, non-vascularized free fibula graft 36.0 22 35 13.6 34.1 Mukisi-Mukaza et al., 200956 Orthop Traumatol Surg Res Prospective 75 Conservative 13.4 16 23 68.8 36.5 CD isolated 11.3 26 42 61.5 30.3 Neumayr et.al, 200657 J Bone J Surg Prospective 59 CD isolated 37.2 17 17 53.0 24.7 Conservative 36.0 21 21 48.0 26.4 Ou et al., 201958 Int J Clin Exp Med Retrospective 70 CD, free fibular graft 41.5 46 62 43.5 55.0 CD isolated 41.5 44 60 50.0 55.1 Pepke et al., 201659 Orthopedic Rev Prospective, Randomized 80 CD isolated 24.0 14 14 14.3 44.5 CD, BMA 24.0 11 11 9.1 44.3 Rastogi et al., 201360 Musculoskelet Surg Prospective, Randomized 81 CD, MNC 24.0 30 30 13.0 34.7 CD, BMA 24.0 30 30 20.0 33.0 Sallam et al., 201761 Hip Int Retrospective 73 CD isolated 94.3 38 38 44.7 33.2 CD, inverted femoral head graft 94.3 33 33 48.5 32.7 Sen et al., 201262 Arthroplasty Prospective, Randomized 81 CD isolated 24.0 20 25 28.0 CD, MNC 24.0 20 26 26.9 Stulberg et al.,199163 Clin Orthop Rel Res Prospective, Randomized 76 Conservative 26.8 17 26 CD isolated 26.8 19 29 Tabatabaee et al., 201564 Arthroplasty Prospective, Randomized 80 CD, BMA 24.0 14 14 35.7 31.0 CD, autologeous cancellous bone grafting, non-vascularized fibula grafting 104.5 25 28 Wang et al., 201965 Arthroplasty Retrospective 73 Light bulb technique 48.0 66 21.2 38.1 CD 48.0 59 25.4 39.1 Yin et al., 201666 BMC Musculoskelet Dis Retrospective 66 CD, Statin 36.0 20 32 35.0 39.1 CD isolated 36.0 16 26 18.8 44.7 Zhao et al., 20129 Bone Prospective, Randomized 87 CD, MSC 60.0 50 53 46.0 32.7 CD isolated 60.0 50 51 48.0 33.8 Open in new tab Table 2 Generalities and patients baseline of the included studies Author, year . Journal . Study design . CMS . Treatment . Follow-up (months) . Patients (n) . Procedures (n) . Female (%) . Age (mean) . Bi et al., 201936 J Orthop Surg Res Prospective 72 Robot assisted CD, local cancellous bone graft autologous 26.8 9 16 22.2 34.9 Conventional CD, local cancellous bone graft autologous 26.4 11 20 27.3 35.3 Cao et al., 201837 Int J Clin Exp Med Prospective 75 Multi-directional CD apparatus with impaction bone grafting fibula apparatus with impaction bone grafting 41.1 27 30 37.0 37.7 CD fibula allograft 43.9 26 28 30.8 36.9 Cao et al., 201738 Clin Orthop Related Res Retrospective 80 CD, autologous bone grafting 36.0 21 21 23.8 31.0 CD free vascularized fibula allograft 36.0 21 21 23.8 31.0 Gangji et al., 201139 Bone Prospective, double blinded 73 CD, autologous bone marrow cell implantation 60.0 13 13 52.6 42.2 CD isolated 60.0 11 11 52.6 45.7 Gianakos et al., 201640 HSS J Retrospective 64 Bisphosphonates 22.7 29 40 38.0 43.0 Bisphosphonates, CD, MSC 25.3 20 20 55.0 38.0 Hauzeur et al., 201841 Int Orthop Prospective, Randomized 78 CD, BMA 12.0 19 23 26.3 48.0 CD isolated 12.0 19 23 31.6 49.7 Hernigou et al., 201842 Int Orthop Randomized 90 CD, MSC 360.0 125 125 37.6 36.0 CD isolated 360.0 125 125 37.6 36.0 Huang et al., 201943 Annals Translational Medicine Prospective, Randomized 76 CD, Tantalum Rod (Runze) 38.2 19 21 21.1 43.4 CD, Tantalum Rod (Zimmer) 39.5 20 20 30.0 41.6 Kang et al., 201844 Stem Cell Res Ther Retrospective 67 CD isolated 48.0 50 53 24.0 47.3 CD, BMMSC 54.4 50 53 28.0 46.0 Kang et al., 201245 Joint Bone Spine Prospective, Randomized 88 CD isolated 62.0 52 52 30.9 45.3 CD, bisphosphonate 62.0 55 55 32.7 43.8 Koo et al., 199546 J bone Joint Surg Prospective, Randomized 68 CD, cancellous bone graft 24.0 18 5.6 42.5 Conservative 24.0 19 5.6 49.7 Lakatos et al., 201747 J Osteopor Phys Act Retrospective 52 CD, autogenous bone impaction, platelet rich Plasma 73.2 16 17 5.9 45.3 CD isolated 70.8 12 12 50.0 46.3 Li et al., 201648 Indian J Orthop Prospective, Randomized 78 CD, cancellous bone grafting 30.0 20 23 CD, quadratus femoris muscle pedicle bone grafting 30.0 19 24 Li et al., 201749 J Orthop Sci Retrospective 71 CD, neck fenestration, autogenous bone grafting 36.0 71 83 15.7 38.2 CD, bone grafting 36.0 75 90 13.3 39.6 Li et al., 201850 Int J Clin Exp Med Retrospective 79 Non-vascularized bone grafting via trapdoor 45.4 17 17 35.0 15.2 Conservative 43.6 20 20 20.0 14.9 Lim et al., 201351 Experimental Molecular Medicine Retrospective 74 CD, MSC 87.0 86 128 20.0 36.3 CD, bone graft 87.0 21 31 24.0 34.3 Liu et al., 201552 Int Orthop Retrospective 73 CD, tantalum rod 48.2 42 52 11.9 40.7 CD, composite bone grafting 71.6 36 49 16.7 41.0 Ma et al., 201453 Stem Cell Res Ther Prospective, Randomized 83 CD, autologous bone graft, BMC 24.0 21 25 28.6 34.8 CD, autologous bone graft 24.0 18 24 27.8 35.6 Miao et al., 201554 Open Orthop J Prospective 70 CD isolated 18.1 30 34 56.7 35.2 CD, tantalum rod 19.8 30 36 60.0 32.6 Mohanty et al., 201655 Musculoskelet Surg Retrospective 65 CD isolated 36.0 24 33 29.2 36.7 CD, non-vascularized free fibula graft 36.0 22 35 13.6 34.1 Mukisi-Mukaza et al., 200956 Orthop Traumatol Surg Res Prospective 75 Conservative 13.4 16 23 68.8 36.5 CD isolated 11.3 26 42 61.5 30.3 Neumayr et.al, 200657 J Bone J Surg Prospective 59 CD isolated 37.2 17 17 53.0 24.7 Conservative 36.0 21 21 48.0 26.4 Ou et al., 201958 Int J Clin Exp Med Retrospective 70 CD, free fibular graft 41.5 46 62 43.5 55.0 CD isolated 41.5 44 60 50.0 55.1 Pepke et al., 201659 Orthopedic Rev Prospective, Randomized 80 CD isolated 24.0 14 14 14.3 44.5 CD, BMA 24.0 11 11 9.1 44.3 Rastogi et al., 201360 Musculoskelet Surg Prospective, Randomized 81 CD, MNC 24.0 30 30 13.0 34.7 CD, BMA 24.0 30 30 20.0 33.0 Sallam et al., 201761 Hip Int Retrospective 73 CD isolated 94.3 38 38 44.7 33.2 CD, inverted femoral head graft 94.3 33 33 48.5 32.7 Sen et al., 201262 Arthroplasty Prospective, Randomized 81 CD isolated 24.0 20 25 28.0 CD, MNC 24.0 20 26 26.9 Stulberg et al.,199163 Clin Orthop Rel Res Prospective, Randomized 76 Conservative 26.8 17 26 CD isolated 26.8 19 29 Tabatabaee et al., 201564 Arthroplasty Prospective, Randomized 80 CD, BMA 24.0 14 14 35.7 31.0 CD, autologeous cancellous bone grafting, non-vascularized fibula grafting 104.5 25 28 Wang et al., 201965 Arthroplasty Retrospective 73 Light bulb technique 48.0 66 21.2 38.1 CD 48.0 59 25.4 39.1 Yin et al., 201666 BMC Musculoskelet Dis Retrospective 66 CD, Statin 36.0 20 32 35.0 39.1 CD isolated 36.0 16 26 18.8 44.7 Zhao et al., 20129 Bone Prospective, Randomized 87 CD, MSC 60.0 50 53 46.0 32.7 CD isolated 60.0 50 51 48.0 33.8 Author, year . Journal . Study design . CMS . Treatment . Follow-up (months) . Patients (n) . Procedures (n) . Female (%) . Age (mean) . Bi et al., 201936 J Orthop Surg Res Prospective 72 Robot assisted CD, local cancellous bone graft autologous 26.8 9 16 22.2 34.9 Conventional CD, local cancellous bone graft autologous 26.4 11 20 27.3 35.3 Cao et al., 201837 Int J Clin Exp Med Prospective 75 Multi-directional CD apparatus with impaction bone grafting fibula apparatus with impaction bone grafting 41.1 27 30 37.0 37.7 CD fibula allograft 43.9 26 28 30.8 36.9 Cao et al., 201738 Clin Orthop Related Res Retrospective 80 CD, autologous bone grafting 36.0 21 21 23.8 31.0 CD free vascularized fibula allograft 36.0 21 21 23.8 31.0 Gangji et al., 201139 Bone Prospective, double blinded 73 CD, autologous bone marrow cell implantation 60.0 13 13 52.6 42.2 CD isolated 60.0 11 11 52.6 45.7 Gianakos et al., 201640 HSS J Retrospective 64 Bisphosphonates 22.7 29 40 38.0 43.0 Bisphosphonates, CD, MSC 25.3 20 20 55.0 38.0 Hauzeur et al., 201841 Int Orthop Prospective, Randomized 78 CD, BMA 12.0 19 23 26.3 48.0 CD isolated 12.0 19 23 31.6 49.7 Hernigou et al., 201842 Int Orthop Randomized 90 CD, MSC 360.0 125 125 37.6 36.0 CD isolated 360.0 125 125 37.6 36.0 Huang et al., 201943 Annals Translational Medicine Prospective, Randomized 76 CD, Tantalum Rod (Runze) 38.2 19 21 21.1 43.4 CD, Tantalum Rod (Zimmer) 39.5 20 20 30.0 41.6 Kang et al., 201844 Stem Cell Res Ther Retrospective 67 CD isolated 48.0 50 53 24.0 47.3 CD, BMMSC 54.4 50 53 28.0 46.0 Kang et al., 201245 Joint Bone Spine Prospective, Randomized 88 CD isolated 62.0 52 52 30.9 45.3 CD, bisphosphonate 62.0 55 55 32.7 43.8 Koo et al., 199546 J bone Joint Surg Prospective, Randomized 68 CD, cancellous bone graft 24.0 18 5.6 42.5 Conservative 24.0 19 5.6 49.7 Lakatos et al., 201747 J Osteopor Phys Act Retrospective 52 CD, autogenous bone impaction, platelet rich Plasma 73.2 16 17 5.9 45.3 CD isolated 70.8 12 12 50.0 46.3 Li et al., 201648 Indian J Orthop Prospective, Randomized 78 CD, cancellous bone grafting 30.0 20 23 CD, quadratus femoris muscle pedicle bone grafting 30.0 19 24 Li et al., 201749 J Orthop Sci Retrospective 71 CD, neck fenestration, autogenous bone grafting 36.0 71 83 15.7 38.2 CD, bone grafting 36.0 75 90 13.3 39.6 Li et al., 201850 Int J Clin Exp Med Retrospective 79 Non-vascularized bone grafting via trapdoor 45.4 17 17 35.0 15.2 Conservative 43.6 20 20 20.0 14.9 Lim et al., 201351 Experimental Molecular Medicine Retrospective 74 CD, MSC 87.0 86 128 20.0 36.3 CD, bone graft 87.0 21 31 24.0 34.3 Liu et al., 201552 Int Orthop Retrospective 73 CD, tantalum rod 48.2 42 52 11.9 40.7 CD, composite bone grafting 71.6 36 49 16.7 41.0 Ma et al., 201453 Stem Cell Res Ther Prospective, Randomized 83 CD, autologous bone graft, BMC 24.0 21 25 28.6 34.8 CD, autologous bone graft 24.0 18 24 27.8 35.6 Miao et al., 201554 Open Orthop J Prospective 70 CD isolated 18.1 30 34 56.7 35.2 CD, tantalum rod 19.8 30 36 60.0 32.6 Mohanty et al., 201655 Musculoskelet Surg Retrospective 65 CD isolated 36.0 24 33 29.2 36.7 CD, non-vascularized free fibula graft 36.0 22 35 13.6 34.1 Mukisi-Mukaza et al., 200956 Orthop Traumatol Surg Res Prospective 75 Conservative 13.4 16 23 68.8 36.5 CD isolated 11.3 26 42 61.5 30.3 Neumayr et.al, 200657 J Bone J Surg Prospective 59 CD isolated 37.2 17 17 53.0 24.7 Conservative 36.0 21 21 48.0 26.4 Ou et al., 201958 Int J Clin Exp Med Retrospective 70 CD, free fibular graft 41.5 46 62 43.5 55.0 CD isolated 41.5 44 60 50.0 55.1 Pepke et al., 201659 Orthopedic Rev Prospective, Randomized 80 CD isolated 24.0 14 14 14.3 44.5 CD, BMA 24.0 11 11 9.1 44.3 Rastogi et al., 201360 Musculoskelet Surg Prospective, Randomized 81 CD, MNC 24.0 30 30 13.0 34.7 CD, BMA 24.0 30 30 20.0 33.0 Sallam et al., 201761 Hip Int Retrospective 73 CD isolated 94.3 38 38 44.7 33.2 CD, inverted femoral head graft 94.3 33 33 48.5 32.7 Sen et al., 201262 Arthroplasty Prospective, Randomized 81 CD isolated 24.0 20 25 28.0 CD, MNC 24.0 20 26 26.9 Stulberg et al.,199163 Clin Orthop Rel Res Prospective, Randomized 76 Conservative 26.8 17 26 CD isolated 26.8 19 29 Tabatabaee et al., 201564 Arthroplasty Prospective, Randomized 80 CD, BMA 24.0 14 14 35.7 31.0 CD, autologeous cancellous bone grafting, non-vascularized fibula grafting 104.5 25 28 Wang et al., 201965 Arthroplasty Retrospective 73 Light bulb technique 48.0 66 21.2 38.1 CD 48.0 59 25.4 39.1 Yin et al., 201666 BMC Musculoskelet Dis Retrospective 66 CD, Statin 36.0 20 32 35.0 39.1 CD isolated 36.0 16 26 18.8 44.7 Zhao et al., 20129 Bone Prospective, Randomized 87 CD, MSC 60.0 50 53 46.0 32.7 CD isolated 60.0 50 51 48.0 33.8 Open in new tab Meta-analyses are considered valuable tools for analyzing different studies; however, they only allow a pair-wise assessment of treatments. In contrast, network meta-analysis blend together information over a network of comparisons to compare the relative effects of different treatments used for the same condition. Network meta-analyses provide vital clinical information by ranking the relative efficacy of all interventions, even those which have not been compared with one another previously. Corticosteroid use and alcoholism (which lead to significant changes in the lipid metabolism) are the most common causes for ONFH (72.4% of all ONFH cases).67–69 This may result in higher rates of fat embolism, which plays an important role in the process of ONFH.70 CD is commonly performed in patients with early stages of ONFH. CD promotes angiogenesis in necrotic bone areas, improves blood circulation of the bone bed, stimulates bone repair in the femoral head, thereby delaying or avoiding THA.71,72 In previous studies, CD results in favorable clinical outcomes, when this procedure is performed in the early stages of ONFH with small lesion sizes.62,63,73,74 However, there is wide variability in surgical techniques between the studies, paucity of randomized clinical trials, and a small number of patients included in each study, all limiting the efficacy of CD. Based on the findings of this network meta-analysis, we conclude that CD only provides moderate failure and progression rates as compared to other treatment options. To further improve the effectiveness of CD, this technique has been combined with various bone and cell grafting procedures, as well as with additional pharmaceutical interventions. The majority of the included studies combined CD with bone grafting (autologous and allogenic), bone marrow concentrate, mononuclear and mesenchymal stem cells, as well as bisphosphonates, statins and tantalum rods. These treatment options have different success rates, in terms of failure and progression to THA rates. CD with bone autograft plus BMC had the lowest overall failure rate, followed by CD combined with MSCs and MNCs. The overall lowest progression to THA rates were shown for CD with bone autograft plus BMC, followed by CD with bone autograft plus PRP, and finally CD with BMC. Based on these findings, it can be assumed that the encouraging result mainly arise from the effects of autologous bone grafting of the necrotic bone area and from the effects of cytotherapy. Stem cells from the bone marrow can differentiate into osteoblasts and vascular endothelial cells, and secrete various cytokines to repair and reconstruct the necrotic lesion in the femoral head.44,75,76 These findings support the role of cytotherapy and bone grafting in combination with CD in the treatment of ONFH; however, there is great variability in treatment protocols, and cell types/numbers used. Therefore, future studies should focus on the establishment of standardized protocols and cell treatment processes. Tantulum rods can be used in the treatment of ONFH as a mechanical substitute of fibular grafts following CD.77 A meta-analysis showed that tantalum rods are a safe and minimally invasive treatment method for ONFH with satisfactory clinical outcomes.77 However, we demonstrate that CD combined with the implantation of tantalum rods did not have significantly lower failure and progression to THA rates than CD alone. Bisphosphonates are used in the treatment of ONFH by inhibiting osteoclast formation and promoting osteoclast apoptosis. A meta-analysis showed that, although bisphosphonates suggest improvement in bone morphology in some animal models, this is not supported by clinical studies mostly because of the high heterogeneity in study protocols.78 Our results confirm these findings. CD with bisphosphonate therapy and bisphosphonates alone lead to only minor improvements in failure and progression to THA rates. Similar results were found for statin use in combination with CD in the treatment of ONFH in our network analysis. Strengths of this Bayesian network analysis are the comprehensive literature search of multiple databases in multiple languages, which led to the inclusion of 32 studies with a total of 1898 patients. We also performed a vigorous review process. Our methodological quality assessment did show overall good methodology quality; however, the assessment of outcomes and the subject selection processes were often biased. Finally, we summarized and analyzed the latest evidence in a network analysis for most currently available treatment options of ONFH. Limitations of this network meta-analysis include the focus on the effects of therapeutic options for ONFH without an assessment of clinical or radiographic outcomes. The present analysis was performed at the study level and not at an individual level. Furthermore, we did not study the patients by disease stage. Finally, given the lack of comparator and/or quantitative data under the outcomes of interest, some new and emerging methods were not included for analysis. Conclusion Conservative treatment of ONFH is associated with low success rates. However, core decompression is associated with reasonable failure and progression to THA rates in the management of ONFH. 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TI - Failure and progression to total hip arthroplasty among the treatments for femoral head osteonecrosis: a Bayesian network meta-analysis
JO - British Medical Bulletin
DO - 10.1093/bmb/ldab006
DA - 2021-05-18
UR - https://www.deepdyve.com/lp/oxford-university-press/failure-and-progression-to-total-hip-arthroplasty-among-the-treatments-f5DzHSZSpY
SP - 1
EP - 1
VL - Advance Article
IS - 
DP - DeepDyve
ER -