Total Hip Arthroplasty After Failed Hip-Preserving Surgery with Concentrated Autologous Bone Marrow Aspirate Transplantation for Osteonecrosis of the Femoral Head: A Retrospective Study.

Purpose: Since 2003, a hip-preserving technique-concentrated autologous bone marrow aspirate transplantation (CABMAT)-has been applied to treat osteonecrosis of the femoral head (ONFH). We investigated intraoperative and postoperative outcomes of total hip arthroplasty (THA) in patients who underwent CABMAT as hip-preserving surgery for ONFH but developed secondary hip osteoarthritis after progressive femoral head collapse. Methods: A total of 456 hips in 282 patients underwent CABMAT in our hospital between April 2003 and December 2018; 108 hips required THA (THA conversion rate, 23.7%). We enrolled 60 hips (26 hips in 20 men and 34 in 26 women) with a follow-up of over 2 years. We retrospectively analyzed patient background data, time to THA, surgical procedure, postoperative complications, and clinical outcomes from medical records. Results: The disease was steroid-related, alcohol-related, and idiopathic in 48, seven, and five hips, respectively. The mean age at THA was 45.7 years, and mean conversion time was 2.7 years. Cementless THA was performed in all cases; the mean operating time and blood loss were 82.7 min and 210 g, respectively. Postoperative complications were observed in four cases; intraoperative fracture, two cases; superficial infection, one case; and dislocation, one case. The mean follow-up period was 5.7 years; no loosening or deep infections occurred. No patients required revision arthroplasty. Conclusion: We noted no complications related to CABMAT. After a minimum 2-year follow-up, the clinical outcomes were good. CABMAT was found to be an useful hip-preserving surgery, with little effect on conversion to THA, and THA outcomes were good.

Comparison Between Concentrated Autologous Bone Marrow Aspirate Transplantation as a Hip Preserving Surgery and Natural Course in Idiopathic Osteonecrosis of the Femoral Head.

Purpose The purpose is to compare the therapeutic efficacy of concentrated autologous bone marrow aspirate transplantation (CABMAT) with that of observation alone for osteonecrosis of the femoral head (ONFH). Methods This single-center study included patients with idiopathic ONFH that were either treated with CABMAT (CABMAT group) or managed through observation alone (observation group) over a >2-year follow-up period. The Japanese Investigation Committee classification was used to diagnose and classify ONFH. The collapse rates for stages 1 and 2 ONFH (i.e., pre-collapse stages) and the THA conversion rates were compared between the CABMAT and observation groups. Results The CABMAT and observation groups comprised 232 (mean follow-up: 8.2 years) and 106 (mean follow-up: 6.0 years) patients, respectively. No significant intergroup differences were noted in the stages, types, and associated factors of ONFH. The collapse rates for pre-collapse stages in the CABMAT and observation groups were 67.1% and 65.3%, respectively. For stage 1, the collapse rates were significantly lower in the observation group than in the CABMAT group (p<0.05). The overall THA conversion rates in the CABMAT and observation groups were 24.3% and 41.5%, respectively (p<0.0001). For ONFH of stages 3A and 3B (collapse stages), the THA conversion rates were significantly lower in the CABMAT group (p<0.05). Conclusion Collapse rates were significantly higher for stage 1 ONFH; for collapse stages, the THA conversion rates were significantly lower in the CABMAT group than in the observation group. Therefore, observation and CABMAT are recommended for ONFH of stage 1 and for ONFH of higher stages, respectively.

Ten-year results of concentrated autologous bone marrow aspirate transplantation for osteonecrosis of the femoral head: a retrospective study.

BACKGROUND: Idiopathic osteonecrosis of the femoral head (ONFH) occurs at a relatively younger age. It is therefore important to prevent the resultant femoral head collapse and requirement of total hip arthroplasty in these patients. In 2003, we initiated concentrated autologous bone marrow aspirate transplantation (CABMAT), a joint-preserving treatment for ONFH, at our institution. Here, we report the long-term results of CABMAT treatment. METHODS: We retrospectively collated and analyzed the demographic and treatment data of 69 patients (109 hips) with idiopathic ONFH treated with CABMAT between April 2003 and April 2008. RESULTS: Totally, 44 patients (21 men, 23 women, 80 hips) completed the 10-year follow-up. The follow-up rate was 73.4%, and the mean follow-up period was 12.0 (range, 10.0-15.4) years. The mean age of the patients was 42.2 (range, 16.3-70.5) years. Using the Association Research Circulation Osseous (ARCO) classification system for preoperative analysis, 12, 31, 32, and 5 hips were classified as stages 1, 2, 3, and 4, respectively. The overall rate of conversion to total hip arthroplasty (THA) was 34% (27/80 hips). In a multivariate regression analysis, the preoperative stage of ONFH and the body mass index were found to correlate significantly with conversion to THA. Totally, 43 hips (of 80) were classified as belonging to the pre-collapse stage (i.e., stages 1 or 2). The overall collapse rate and the THA-conversion rate of these hips were estimated to be 49% (21/43) and 14% (6/43), respectively. CONCLUSIONS: On the basis of our long-term findings, the minimally invasive and feasible CABMAT therapy can be utilized as one of a joint-preserving treatment for ONFH.

Mid-term results of concentrated autologous bone marrow aspirate transplantation for corticosteroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.

PURPOSE: We had previously established concentrated autologous bone marrow aspirate transplantation (CABMAT), a one-step, low-invasive, joint-preserving surgical technique for treating osteonecrosis of the femoral head (ONFH). This study aimed to evaluate the effects of CABMAT as a hip-preserving surgical approach, preventing conversion to total hip arthroplasty (THA) and femoral head collapse in patients with systemic lupus erythematosus (SLE). METHODS: Since 2003, 52 SLE patients (8 male, 44 female, 92 hips, mean age 35.3 (16-77) (years) were treated with CABMAT. The mean follow-up period was 5.5 (0.7-14) years. Conversion rate to THA and its predicting factors were analyzed. RESULTS: The overall conversion rate to THA was 29% (27/92). Conversion rate to THA was 0% (0/3), 0% (0/4), 22% (9/41), and 41% (18/44) in types A, B, C1, and C2, respectively. Conversion rate to THA was 26% (5/19), 26% (6/23), 28% (11/39), 44% (4/9), and 50% (1/2) in stages 1, 2, 3A, 3B, and 4, respectively. In multivariate logistic regression analysis, sex, body mass index (BMI), pre-operative type, and pre-operative stage were significantly correlated with conversion to THA. CONCLUSION: The conversion rate to THA was lower than that in the natural course and core decompression, but was higher than that seen in other bone marrow transplantation and osteotomy. Since sex, pre-operative type, and pre-operative stage were significantly correlated with conversion to THA, it is suggested that the higher proportion of women, advanced stage (stage 3A or above), and advanced type (type C or above) in this study affected the THA conversion rate.

Hip preserving surgery with concentrated autologous bone marrow aspirate transplantation for the treatment of asymptomatic osteonecrosis of the femoral head: retrospective review of clinical and radiological outcomes at 6 years postoperatively.

BACKGROUND: We had previously established concentrated autologous bone marrow aspirate transplantation (CABMAT), a one-step, low-invasive, joint-preserving surgical technique for treating osteonecrosis of the femoral head (ONFH). The present study aimed to evaluate the effects of CABMAT as a hip preserving surgical approach, preventing femoral head collapse in asymptomatic ONFH. METHODS: In total, 222 patients (341 hips) with ONFH were treated with CABMAT between April 2003 and March 2013. Based on magnetic resonance imaging, we determined that 119 of these patients had bilateral asymptomatic ONFH (238 hips), and 38 further patients had unilateral asymptomatic ONFH (38 hips). In this series, we retrospectively examined 31 hips in 31 patients with unilateral asymptomatic ONFH treated surgically between 2003 and 2012 and followed up for more than 2 years. Clinical and radiological evaluation were performed immediately before the procedure and at the final follow-up. The two-year follow-up rate among patients with unilateral ONFH was 82% (31/38). Therefore, the present study included 31 patients (19 males and 12 females), with a mean age and follow-up period of 40 and 5.8 years, respectively. Of the 31 asymptomatic hips, 5, 6, 10, and 10 had osteonecrosis of types A, B, C1, and C2, respectively. The diagnosis, classification, and staging of ONFH were based on the 2001 Japanese Orthopaedic Association (JOA) classification. RESULTS: Secondary collapse of the femoral head was observed in 6/10 hips and 5/10 hips with osteonecrosis of types C1 and C2, respectively. Total hip arthroplasty was performed in 9.6% of patients (3/31 hips), at an average of 33 months after surgery. Clinical symptoms improved after surgery, and the secondary collapse rate at a mean of 5.8 years after CABMAT was lower than that reported in several previous studies on the natural course of asymptomatic ONFH. CONCLUSIONS: Early diagnosis of ONFH (i.e., before femoral head collapse) and early intervention with CABMAT could improve the clinical outcome of corticosteroid and alcohol-induced ONFH.

Feasibility and Efficacy of Autologous Bone Marrow Aspirate Transplantation Combined with Human Parathyroid Hormone 1-34 Administration to Treat Osteonecrosis in a Rabbit Model.

No studies have examined the transplantation of a bone marrow aspirate (BMA) containing mesenchymal stem cells (MSCs) combined with human parathyroid hormone 1-34 (hPTH1-34) administration. Therefore, we evaluated the feasibility and efficacy of autologous BMA transplantation combined with hPHT1-34 administration in a bone necrosis model. The metatarsal bones of rabbits were necrotized using liquid nitrogen, and the rabbits received a BMA transplantation or saline injection followed by hPTH1-34 (30 µg/kg) or saline administration three times per week (n = 3-4 per group). The rabbits were euthanized at 12 weeks after the initiation of treatment. No systemic adverse effects or local neoplastic lesions were observed. Importantly, the rabbits in the BMA transplantation plus hPTH1-34 group showed the highest bone volumes and histological scores of new bone. These data confirmed the feasibility of BMA transplantation combined with hPTH1-34, at least during the experimental period. The observed efficacy may be explained by a synergistic effect from the stimulation of MSC differentiation to osteoblasts with hPTH1-34-mediated suppression of apoptosis in osteoblasts. These results indicate the promising potential for BMA transplantation combined with hPTH1-34 administration in bone necrosis treatment. Longer term experiments are needed to confirm the safety of this therapeutic strategy.

2. The Effect of Combined Therapy, Percutaneous Autologous Concentrated Bone Marrow Grafting and Low-Intensity Pulsed Ultrasound (LIPUS), on the Treatment of Non-Unions.

We discuss the effect of combined therapy of percutaneous autologous concentrated bone graft and LIPUS on complex non-union treatment. Seventeen of 27 treated patients who had received the therapy at least 1 year before were discussed (10 femurs, 5 tibiae, 1 humerus, and 1 ulna). The average age of the patients was 40.7, and atrophic degeneration was observed in all cases. After 12 months of treatment, bone union was recognized in 76% in all cases, and in 87% of lower long bones. It was reported that LIPUS was effective at improving blood flow, accelerating cytokines which induce angiogenesis, promoting the transport of nutrition and enzymes to living cells, developing the differentiation of osteoblast from mesenchymal stem cells (MSC), inhibiting the differentiation and development of osteoclast, and promoting endochondral ossification. In this study, all patients had been treated with LIPUS for more than 3 months before the grafting was conducted, but the bone union seemed to stop. It was thought that this combined therapy provided a bone marrow cell growth factor sufficient to enable new bone formation to re-start bone union, and then LIPUS worked effectively to promote the initial differentiation, contributing to new bone formation. This combination therapy-less invasive, safe, and low cost-was considered one useful treatment option for non-union.

The safety and efficacy of combined autologous concentrated bone marrow grafting and low-intensity pulsed ultrasound in the treatment of osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is commonly treated with total hip arthroplasty; however, the disadvantages of this form of treatment, especially in young patients, include the need for revision arthroplasty. Here we describe a novel, combined approach to the treatment of ONFH based on autologous concentrated bone marrow grafting and low-intensity pulsed ultrasound (LIPUS). The 7 male and 7 female patients (mean age: 40 years; 22 hips) underwent autologous concentrated bone marrow grafting followed by 6 months of continuous LIPUS. The mean follow-up period was 26 months. We evaluated site-specific bacterial infection of the grafted bone marrow concentrate microbiologically and site-specific cancer by magnetic resonance imaging 24 months after grafting. All patients were assessed using the visual analogue scale (VAS) for pain and the Japanese Orthopedic Association (JOA) hip score. Clinical and plain radiographic evaluations were performed before grafting and at the most recent follow-up. Computed tomography (CT) scans were obtained before and 12 months after grafting. None of the grafted bone marrow concentrates were infected, and none of the patients developed a tumor at the treatment site. The VAS and JOA scores improved in all patients. Collapse progressed in 8 of the 22 hips, but none required total hip arthroplasty. The mean volume of new bone formation 12 months post-grafting as seen on CT was 1256 mm(3). New bone formation was observed in all patients. Our study demonstrates the safety and efficacy of autologous concentrated bone marrow grafting and LIPUS as a joint-preserving procedure for patients with ONFH.

Percutaneous autologous concentrated bone marrow grafting in the treatment for nonunion.

The purpose of this study was to evaluate the clinical and radiographic treatment effects of percutaneous autologous concentrated bone marrow grafting in nonunion cases and to evaluate the effectiveness of this grafting procedure. We enrolled 17 cases those had atrophic changes due to continuous nonunion for over 9 months after injury and had undergone low-intensity pulsed ultrasound treatment for more than 3 months. The site of nonunion was the femur in 10 cases, the tibia in 5 cases, the humerus in 1 case, and the ulna in 1 case. They underwent percutaneous autologous concentrated bone marrow grafting and continued low-intensity pulsed ultrasound stimulation treatment after grafting. Patients were evaluated using the visual analogue scale for pain at immediately before the procedure, 3, 6, and 12 months after grafting. Plain radiographs of the affected site were taken and evaluated about the healing of the nonunion site at each clinical evaluation. As quantitative assessment, CT scans were undertaken before the procedure and 6 months after grafting. The visual analogue scale pain score was reduced consistently after grafting in all patients. About the healing at the nonunion site, 11 and 13 cases of bone union were observed at 6 and 12 months after grafting. The mean volume of callus formation based on CT images was 4,147 (262-27,392) mm3 total between grafting and 6 months. Percutaneous autologous concentrated bone marrow grafting is an effective procedure for the treatment of patients with nonunion.

Concentrated autologous bone marrow aspirate transplantation treatment for corticosteroid-induced osteonecrosis of the femoral head in systemic lupus erythematosus.

The purpose of this study was to evaluate concentrated autologous bone marrow aspirate transplantation (CABMAT) treatment for corticosteroid-induced osteonecrosis of the femoral head (ONFH) in systemic lupus erythematosus (SLE). Bone marrow was aspirated from iliac crests, concentrated on a conventional manual blood bag centrifugation technique that is used to extract buffy coats and then injected into nine hips with drilling. The mean number of nucleated cells for transplantation was 5.32 × 10(7) cells/ml. This cell concentration was significantly higher after concentration, and the mean concentration ratio was 5.5. At follow-up (minimum: three years), significant improvement in pain and Harris Hip Score was observed. For eight of nine hips, we successfully preserved the femoral head. However, one hip required total hip arthroplasty 45 months after the operation. CABMAT using our centrifugation technique is an effective, safe and low-cost procedure of therapeutic osteogenesis for corticosteroid-induced ONFH in SLE.

Rotating three-dimensional dynamic culture of adult human bone marrow-derived cells for tissue engineering of hyaline cartilage.

The method of constructing cartilage tissue from bone marrow-derived cells in vitro is considered a valuable technique for hyaline cartilage regenerative medicine. Using a rotating wall vessel (RWV) bioreactor developed in a NASA space experiment, we attempted to efficiently construct hyaline cartilage tissue from human bone marrow-derived cells without using a scaffold. Bone marrow aspirates were obtained from the iliac crest of nine patients during orthopedic operation. After their proliferation in monolayer culture, the adherent cells were cultured in the RWV bioreactor with chondrogenic medium for 2 weeks. Cells from the same source were cultured in pellet culture as controls. Histological and immunohistological evaluations (collagen type I and II) and quantification of glycosaminoglycan were performed on formed tissues and compared. The engineered constructs obtained using the RWV bioreactor showed strong features of hyaline cartilage in terms of their morphology as determined by histological and immunohistological evaluations. The glycosaminoglycan contents per microg DNA of the tissues were 10.01 +/- 3.49 microg/microg DNA in the case of the RWV bioreactor and 6.27 +/- 3.41 microg/microg DNA in the case of the pellet culture, and their difference was significant. The RWV bioreactor could provide an excellent environment for three-dimensional cartilage tissue architecture that can promote the chondrogenic differentiation of adult human bone marrow-derived cells.

Concentration of bone marrow aspirate for osteogenic repair using simple centrifugal methods.

Bone marrow transplantation can lead to osteogenic repair of intractable bone conditions. To achieve optimal clinical results, it is necessary to transplant as many cells with osteogenetic potential as possible. However, approaches involving special equipment and reagents for the extraction and purification of cells are expensive, and the complicated procedures involved are a hindrance to widespread acceptance of bone marrow transplantation for osteogenic repair. To standardize bone marrow transplantation for bone regeneration, a simple, safe, clean, and low-cost system is required. We describe an easy-to-use method using a conventional manual blood bag centrifugation technique traditionally used for extracting buffy coats, for concentration of cells from bone marrow aspirates (BMAs) to obtain osteogenic progenitors.

Repair of large full-thickness articular cartilage defects by transplantation of autologous uncultured bone-marrow-derived mononuclear cells.

The objective of this study was to investigate the feasibility of autologous uncultured bone marrow-derived mononuclear cell transplantation in large full-thickness cartilage regeneration. After fixing with a hinged external fixator, the entire surface of the left tibial plateau was resected and large full-thickness cartilage defects were formed in 48 rabbits. Animals were divided into four groups: autologous uncultured bone marrow-derived mononuclear cells with fibrin gel (BMC), autologous uncultured peripheral blood-derived mononuclear cells with fibrin gel (PBC), fibrin gel alone (GEL), or nothing (CON) transplanted to the articular cavity 7 days after the operation. The rabbits were killed 8 or 12 weeks after the operation. The repair of defects was investigated histologically and scored using a histological and histochemical grading scale that was modified from the International Cartilage Repair Society Visual Histological Assessment Scale. To evaluate the regenerated cartilage, we also morphometrically measured the staining area positive for Safranin-O or type II collagen and calculated the percentages of the positive staining areas with respect to the regenerated soft tissue area. Histological findings showed that the BMC group had superior cartilage repair compared with the other groups, and that the PBC and CON group showed better cartilage repair than did the GEL group. Histological scores and morphometrical measurements also showed the same results quantitively. The transplantation of autologous uncultured bone marrow-derived mononuclear cells contributes to articular cartilage repair. The easy and safe method used in this study is potentially viable for clinical application.

Repair of large osteochondral defects with allogeneic cartilaginous aggregates formed from bone marrow-derived cells using RWV bioreactor.

Our objective was to examine the technique of regenerating cartilage tissue from bone marrow-derived cells by three-dimensional (3D) culture using the rotating wall vessel (RWV) bioreactor. Three-dimensional and cylindrical aggregates of allogeneic cartilage with dimensions of 10 x 5 mm (height x diameter) formed by the RWV bioreactor were transplanted into osteochondral defects of Japanese white rabbits (Group T, n = 15). For the control, some osteochondral defects were left empty (Group C, n = 18). At 4, 8, and 12 weeks postimplantation, the reparative tissues were evaluated macroscopically, histologically, and biochemically. In Group T at as early as 4 weeks, histological observation, especially via safranin-O staining, suggested that the reparative tissues resembled hyaline cartilage. And we observed no fibrous tissues between reparative tissue and adjacent normal tissues. In the deeper portion of the bony compartment, the osseous tissues were well remodeled. At 4 and 8 weeks postimplantation, the mean histological score of Group T was significantly better than that of Group C (p < 0.05). The glycosaminoglycans (GAG)/DNA ratio in both groups increased gradually from 4 to 8 weeks and then decreased from 8 to 12 weeks. We herein report the first successful regeneration of cartilage in osteochondral defects in vivo using allogeneic cartilaginous aggregates derived from bone marrow-derived cells by 3D culture using the RWV bioreactor.

Stimulation of EP4 receptor enhanced bone consolidation during distraction osteogenesis.

The objective of this study was to confirm whether an agonist of prostaglandin E receptor subtype EP4 can enhance bone consolidation in distraction osteogenesis. A rat distraction osteogenesis model was generated. A unilateral external fixator was fixed to the left femur of the rats of this model after osteotomy. Seven days later, 0.25 mm/12 h or 0.5 mm/12 h elongation was performed for 2 weeks. A systemic administration of an EP4 receptor agonist (ONO 4819 . CD, 3, 10, 30 microg/kg) or normal saline by subcutaneous injection was also performed for 2 weeks. The animals were sacrificed 10, 14, 17, 21, and 42 days after the operation. Radiographic examination, histological examination, and measurements of bone mineral density (BMD) and distraction-callus hardness were performed to qualitatively and quantitatively evaluate new bone formation. Twenty-one days after the operation, the experimental group had a higher BMD and a higher distraction-callus hardness than that of the control group. Forty-two days after the operation, BMD was similar among all of the groups. But the hardness of the experimental groups increased more than that of the control group, so the statistical differences in distraction-callus hardness became more distinct between the two groups, indicating an improved remodeling of the distraction callus. These findings are also supported by histological examination. Subcutaneous injection of an EP4 receptor agonist can promote bone formation and remodeling during distraction osteogenesis. ONO 4819 * CD might be a potential candidate for shortening the treatment time of distraction osteogenesis.

Mechanical stretch inhibits myoblast-to-adipocyte differentiation through Wnt signaling.

Myoblasts are able to differentiate into other mesenchymal lineages including adipocytes and osteoblasts. However, it is not known how this differentiation is normally regulated in intact animals and humans. Here, we subjected cultured C2C12 myoblasts to cyclic mechanical stretch (20% elongation) during differentiation into adipocytes. Mechanical stretch inhibited the myoblast-to-adipocyte differentiation significantly, concurrent with an enhanced expression of Wnt10b mRNA. Inhibition of the Wnt signaling by incubation of the myoblasts with a soluble Wnt ligand, sFRP-2, abolished the inhibitory function of mechanical stretch on adipogenesis. These findings provide evidence that mechanical stretch inhibits myoblast-to-adipocyte differentiation possibly through Wnt signaling.