Regenerative therapies for femoral head necrosis in the past two decades: a systematic review and network meta-analysis

Abstract

Background Regenerative techniques combined with core decompression (CD) are commonly used to treat osteonecrosis of the femoral head (ONFH). However, no consensus exists on regeneration therapy combined with CD that performs optimally. Therefore, we evaluated six regenerative therapies combined with CD treatment using a Bayesian network meta-analysis (NMA). Methods We searched PubMed, Embase, Cochrane Library, and Web of Science databases. Six common regeneration techniques were categorized into the following groups with CD as the control group: (1) autologous bone graft (ABG), (2) autologous bone graft combined with bone marrow aspirate concentrate (ABG+BMAC), (3) bone marrow aspirate concentrate (BMAC), (4) free vascular autologous bone graft (FVBG), (5) expanded mesenchymal stem cells (MSCs), and (6) platelet-rich plasma (PRP). The conversion rate to total hip arthroplasty (THA) and progression rate to femoral head necrosis were compared among the six treatments. Result A total of 17 literature were included in this study. In the NMA, two of the six treatment strategies demonstrated higher response in preventing the progression of ONFH than CD: MSCs (odds ratio [OR]: 0.098, 95% confidence interval [CI]: 0.0087–0.87) and BMAC (OR: 0.27, 95% CI: 0.073–0.73). Additionally, two of the six treatment strategies were effective techniques in preventing the conversion of ONFH to THA: MSCs (OR: 0.062, 95% CI: 0.0038–0.40) and BMAC (OR: 0.32, 95% CI: 0.1–0.074). No significant difference was found among FVBG, PRP, ABG+BMAC, ABG, and CD in preventing ONFH progression and conversion to THA (P>0.05). Conclusions Our NMA found that MSCs and BMAC were effective in preventing ONFH progression and conversion to THA among the six regenerative therapies. According to the surface under the cumulative ranking value, MSCs ranked first, followed by BMAC. Additionally, based on our NMA results, MSCs and BMAC following CD may be necessary to prevent ONFH progression and conversion to THA. Therefore, these findings provide evidence for the use of regenerative therapy for ONFH.

1. Introduction

Osteonecrosis of the femoral head (ONFH) is a common refractory disease in joint orthopedics. More than 10,000 new patients are affected with ONFH annually in the United States, accounting for approximately 10% of total hip arthroplasties (THAs) [1]. The cumulative number of patients with ONFH in China reached 8.12 million in 2013 [2]. According to statistics, the prevalence rate of ONFH is increasing yearly [3]. ONFH is a progressive disease typically caused by insufficient blood supply to the femoral head, which leads to increased pressure in it, eventually culminating in its collapse. The femoral head usually develops into secondary arthritis when it collapses [4].

Core decompression (CD) is a commonly used procedure for treating femoral head necrosis despite some controversy; it is a simple procedure that treats ONFH by drilling into the necrotic area of the femoral head [5–8]. The theoretical advantage of CD is in relieving the pain by reducing venous congestion and bone marrow pressure. Blood flow increases in the osteonecrosis area with the decrease in intraosseous pressure, thereby alleviating the pathology and promoting bone regeneration in the osteonecrosis area [9, 10]. CD combined with regeneration therapy appears to accelerate the healing of osteonecrosis and reduce the risk of femoral head collapse [11]. Recently, studies have shown that bone marrow aspirate concentrate (BMAC), expanded mesenchymal stem cells (MSCs), autologous bone graft (ABG), and other regenerative therapies show gratifying outcomes in the treatment of bone diseases [12–17]. In addition to BMAC, MSCs, and ABG, common regeneration therapies also include platelet-rich plasma (PRP), autologous bone graft combined with bone marrow aspirate concentrate (ABG+BMAC), and free vascular autologous bone graft (FVBG).