Benjie Wang

Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells

BACKGROUND Treatment of early-stage osteonecrosis of the femoral head (ONFH) with autologous implantation of iliac crest bone marrow-derived mononuclear cells, which contain tens of thousands of bone marrow mesenchymal stem cells (BMMSCs), recently achieved a promising outcome. METHODS One hundred patients with early-stage ONFH were recruited and randomly assigned to BMMSC treatment or core decompression (CD) treatment. Each BMMSC-treated hip received femoral head (FH) implantation of 2×10(6) autologous subtrochanteric bone marrow-derived and ex vivo expanded BMMSCs. The radiographic stage of ONFH according to the Association Research Circulation Osseous classification, Harris hip score (HHS), and the volume of the necrotic lesion or the low signal intensity zone (LowSIZ) in the FH were assessed before and 6, 12, 24, and 60 months after the initial operation. RESULTS Sixty months after the operation, only 2 of the 53 BMMSC-treated hips progressed and underwent vascularized bone grafting. In CD group, 7 hips lost follow-up, and 10 of the rest 44 hips progressed and underwent vascularized bone grafting (5 hips) or total hip replacement (5 hips). Compared with the CD group, BMMSC treatment significantly improved the HHS as well as decreased the volume of femoral head LowSIZ of the hips preoperatively classified at stage IC, IIB, and IIC (P<0.05, respectively; stage IIA, P=0.06, respectively). No complication was observed in both treatment groups. CONCLUSIONS Ex vivo expansion of autologous BMMSCs can reliably provide a greater number of BMMSCs for FH implantation. This intervention is safe and effective in delaying or avoiding FH collapse, which may necessitate total hip replacement.

Prevalence of Nontraumatic Osteonecrosis of the Femoral Head and its Associated Risk Factors in the Chinese Population: Results from a Nationally Representative Survey.

Background: Nontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods: A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results: NONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, &khgr; 2 = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, &khgr; 2 = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions: Our findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.

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

Tantalum rod implantation with vascularized iliac grafting has been reported to be an effective method for the treatment of young patients with osteonecrosis of the femoral head (ONFH) to avert the need for total hip arthroplasty (THA). However, there have been unsatisfactory success rates for end-stage ONFH. The authors describe a modified technique using bone marrow mesenchymal stem cells (BMMSCs) associated with porous tantalum rod implantation combined with vascularized iliac grafting for the treatment of end-stage ONFH. A total of 24 patients (31 hips) with end-stage ONFH were treated with surgery; ARCO IIIc stage was observed in 19 hips and ARCO IV stage was observed in 12 hips. All patients were followed for a mean time of 64.35 ± 13.03 months (range 26–78). Operations on only five hips were converted to THA. The joint-preserving success rate of the entire group was 89.47% for ARCO stage IIIc and 75% for ARCO stage IV. The mean Harris hip score of the 31 hips improved significantly from 38.74 ± 5.88 points (range 22–50) to 77.23 ± 14.75 points (range 33–95). This intervention was safe and effective in delaying or avoiding total hip replacement for end-stage ONFH.

Tantalum rod implantation and vascularized iliac grafting for osteonecrosis of the femoral head.

Osteonecrosis of the femoral head is a progressive disease. Without operative intervention, it most often results in collapse and deterioration of the joint. Many joint-preserving surgeries have been implemented, but no uniform treatment exists. The authors report a modified technique of tantalum rod implantation combined with vascularized iliac grafting for the treatment of osteonecrosis of the femoral head. Fifty-two patients (56 hips) with osteonecrosis of the femoral head (Association Research Circulation Osseous classification stage II-IV) treated with this technique were retrospectively reviewed. The major steps of this technique included vascularized iliac graft harvested, necrotic lesion excised, and combined interventions implantation. All patients were followed for a mean of 60 months. Seven hips had to be converted to a total hip arthroplasty. The 5-year joint-preserving success rate of entire group was 87.5%, with 95% for Association Research Circulation Osseous stage II hips, 92% for Association Research Circulation Osseous stage III hips, and 63.6% for Association Research Circulation Osseous stage IV hips. The success rate was lower for stage IV hips compared with stage II and III hips. Mean Harris Hip score of the 49 hips improved significantly from 50 to 91 points. Forty-three (76.8%) of 56 hips remained stable on radiographs. The technique of tantalum rod implantation combined with vascularized iliac grafting may be an effective joint-preserving method for the treatment of intermediate-stage osteonecrosis of the femoral head. A larger group of patients that is compared with a control group is necessary to further research.

Treatment of osteonecrosis of the femoral head by using the greater trochanteric bone flap with double vascular pedicles

The use of the bone flap transfer has been reported to be successful in treatment of patients with early to medium stage (Ficat and Arlet stage I‐III) osteonecrosis of the femoral head (ONFH). We examined the vascular anatomy and blood supply of the greater trochanter area and evaluated the feasibility of revascularization of the femoral head by using the bone flap pedicled with transverse and gluteus medius branches of the lateral circumflex femoral artery. Based on the anatomy study, from January 2002 to May 2004, 32 ONFH patients were treated with the greater trochanteric bone flap pedicled with double blood vessels. Fifteen femoral heads were Ficat and Arlet stage II and 17 were stage III. The mean follow‐up was 99.5 months. Two of the 32 patients required a total hip replacement due to severe hip pain after surgery. The overall Harris hip score improved from a mean of 55.2 points to 85 points. Our data suggest the procedure is relatively easy to perform, less donor‐site morbidity and useful for young patients with stages II to III disease with or without mild collapse of the femoral head.

Digital subtraction angiography in selection of the vascularized greater trochanter bone grafting for treatment of osteonecrosis of femoral head

The aim of this report is to present our experience on the use of the digital subtraction angiography (DSA) in selection of the vascularized greater trochanter bone grafting for the treatment of the osteonecrosis of femoral head (ONFH) in early stages. Between January 2005 and June 2007, DSA was used to evaluate the blood perfusion of the early stages ONFH in 32 patients (45 hips). There were 18 males and 14 females with an average age of 30 years old. Twenty‐one hips were in ARCO stage I, and 24 in ARCO stage II. The arterial blood supply insufficiency was found in 22 hips by DSA, and the venous stasis in 23 hips. The hips with artery blood supply insufficiency received the vascularized greater trochanter bone grafting, and the hips with the venous stasis received the core decompression. All of patients were followed‐up with an average of 4.8 years (ranging 2.4–6.6 years). The preoperative Harris Hip score (HHS) in the patients with arterial blood supply insufficiency was 48.18 ± 7.81 and the postoperative HHS was 93.27 ± 3.03. The preoperative HHS in the patients with venous stasis was 44.04 ± 6.40, and the postoperative HHS 92.65 ± 2.93. The postoperative DSA showed an improved perfusion of the femoral head in 44 hips. Our experience showed that DSA would help to select the appropriate procedure for treatment of ONFH in the early stage.

An epidemiological study of etiology and clinical characteristics in patients with nontraumatic osteonecrosis of the femoral head

Background: Osteonecrosis of the femoral head (ONFH) is a common disease with high disability rate. However, a few studies investigate the etiology and clinical characteristics of nontraumatic ONFH patients in China. Therefore, we conducted this cross-sectional study. Materials and Methods: Totally, information of 7268 nontraumatic ONFH patients treated between August 2005 and August 2015 was extracted from the medical records. The extracted information included the age, gender, diagnostic criteria, cause of nontraumatic ONFH, types of steroid use, and types of alcohol. Results: Among these included patients, there were 5126 (70.5%) male patients with average age of 44.5 years and 2142 (29.5%) female patients with average age of 47.6 years (P = 0.54). The number of steroid-, alcohol-, steroid/alcohol-, and idiopathic-induced nontraumatic ONFH men patients was 1684, 2310, 364, and 768, respectively, and nontraumatic ONFH women patients was 1058, 482, 140, and 462, respectively. Meanwhile, we found that both the levels of triglycerides (P = 0.03) and low-density lipoprotein (P = 0.02) were significantly changed in the idiopathic-induced nontraumatic ONFH patients. Conclusion: These results indicated the earlier onset of nontraumatic ONFH in male patients than in female patients, different main etiology for male (alcohol consumption) and female (steroid use) patients, and close relationship between the lipid metabolism and idiopathic-induced nontraumatic ONFH. Our findings could be helpful for researchers to investigate the pathogenesis of ONFH and aid the clinicians in the early prevention and diagnosis of nontraumatic ONFH.

Omentin-1 prevents cartilage matrix destruction by regulating matrix metalloproteinases

Matrix metalloproteinases (MMPs) play a crucial role in the degradation of the extracellular matrix and pathological progression of osteoarthritis (OA). Omentin-1 is a newly identified anti-inflammatory adipokine. Little information regarding the protective effects of omentin-1 in OA has been reported before. In the current study, our results indicated that omentin-1 suppressed expression of MMP-1, MMP-3, and MMP-13 induced by the proinflammatory cytokine interleukin-1β (IL-1β) at both the mRNA and protein levels in human chondrocytes. Importantly, administration of omentin-1 abolished IL-1β-induced degradation of type II collagen (Col II) and aggrecan, the two major extracellular matrix components in articular cartilage, in a dose-dependent manner. Mechanistically, omentin-1 ameliorated the expression of interferon regulatory factor 1 (IRF-1) by blocking the JAK-2/STAT3 pathway. Our results indicate that omentin-1 may have a potential chondroprotective therapeutic capacity.

Combined vascularized iliac and greater trochanter graftings for reconstruction of the osteonecrosis femoral head with collapse: Reports of three cases with 20 years follow-up

In this report, we present the long‐term results of using combined vascularized iliac and greater trochanter graftings for reconstruction of the osteonecrosis of the femoral head (ONFH) with collapse in three patients. Necrosis over two‐thirds of the femoral head and collapse were observed in these patients, with Harris hip scores (HHS) of 46, 38, and 49 points, respectively. When the patients underwent the femoral head reconstruction procedures, the ages of the patients ranged from 20 to 28 years old. The patients were followed‐up for 20–24 years. X‐ray examinations showed no progress of necrosis or deformity in the femoral head of patients after surgery, with the exception of bone absorption in one patient with persistence of mild pain. The HHS in the three patients were 84, 65, and 86 points at the end of follow‐up, respectively. These results show that the vascularized iliac and greater trochanter graftings may be a valuable option for reconstruction of the ONFH with collapse in younger patients.

Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo

Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum–host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing.