Femoral Head Ischemia Research Articles

Local administration of bone morphogenetic protein-2 and bisphosphonate during non-weight-bearing treatment of ischemic osteonecrosis of the femoral head: an experimental investigation in immature pigs.

Non-weight-bearing decreases the femoral head deformity but increases bone resorption without increasing bone formation in an experimental animal model of Legg-Calvé-Perthes disease. We sought to determine if local administration of bone morphogenetic protein (BMP)-2 with or without bisphosphonate can increase the bone formation during the non-weight-bearing treatment in the large animal model of Legg-Calvé-Perthes disease. Eighteen piglets were surgically induced with femoral head ischemia. Immediately following the surgery, all animals received an above-the-knee amputation to enforce local non-weight-bearing (NWB). One to two weeks later, six animals received local BMP-2 to the necrotic head (BMP group), six received local BMP-2 and ibandronate (BMP+IB group), and the remaining six received no treatment (NWB group). All animals were killed at eight weeks after the induction of ischemia. Radiographic, microcomputed tomography (micro-CT), and histomorphometric assessments were performed. Radiographic assessment showed that the femoral heads in the NWB, BMP, and BMP+IB groups had a decrease of 20%, 14%, and 10%, respectively, in their mean epiphyseal quotient in comparison with the normal control group. Micro-CT analyses showed significantly higher femoral head bone volume in the BMP+IB group than in the BMP group (p = 0.02) and the NWB group (p < 0.001). BMP+IB and BMP groups had a significantly higher trabecular number (p < 0.01) and lower trabecular separation (p < 0.02) than the NWB group. In addition, the osteoclast number per bone surface was significantly lower in the BMP+IB group compared with the NWB group. Calcein labeling showed significantly higher bone formation in the BMP and BMP+IB groups than in the NWB group (p < 0.05). Heterotopic ossification was found in the capsule of four hips in the BMP+IB group but not in the BMP group. Administration of BMP-2 with bisphosphonate best decreased bone resorption and increased new bone formation during non-weight-bearing treatment of ischemic osteonecrosis in a pig model, but heterotopic ossification is a concern. This preclinical study provides new evidence that BMP-2 with bisphosphonate can effectively prevent the extreme bone loss associated with the non-weight-bearing treatment and increase new bone formation in the femoral head in this animal model of ischemic osteonecrosis.

Acetabular changes associated with avascularnecrosis of the femoral head in a piglet model.

ObjectivesAn experimental piglet model induces avascular necrosis (AVN) and deformation of the femoral head but its secondary effects on the developing acetabulum have not been studied. The aim of this study was to assess the development of secondary acetabular deformation following femoral head ischemia.MethodsIntracapsular circumferential ligation at the base of the femoral neck and sectioning of the ligamentum teres were performed in three week old piglets. MRI was then used for qualitative and quantitative studies of the acetabula in operated and non-operated hips in eight piglets from 48 hours to eight weeks post-surgery. Specimen photographs and histological sections of the acetabula were done at the end of the study. ResultsThe operated-side acetabula were wider, shallower and misshapen, with flattened labral edges. At eight weeks, increased acetabular cartilage thickness characterised the operated sides compared with non-operated sides (p < 0.001, ANOVA). The mean acetabular width on the operated side was increased (p = 0.015) while acetabular depth was decreased anteriorly (p = 0.007) and posteriorly (p = 0.44). The cartilage was thicker, with delayed acetabular bone formation, and showed increased vascularisation with fibrosis laterally and focal degenerative changes involving chondrocyte hypocellularity, chondrocyte cloning, peripheral pannus formation and surface fibrillation. ConclusionsWe demonstrate that femoral head AVN in the young growing piglet also induced, and was coupled with, secondary malformation in acetabular shape affecting both articular and adjacent pelvic cartilage structure, and acetabular bone. The femoral head model inducing AVN can also be applied to studies of acetabular maldevelopment, which is less well understood in terms of developing hip malformation.Cite this article: Bone Joint Res 2014;3:130–8.

Idiopathic ischemic necrosis of an accessory carpal bone in a dog

A 6-year-old neutered female mixed-breed dog was evaluated because of a 6-week history of left forelimb lameness that varied in severity. Radiography revealed expansile and lytic changes of the left accessory carpal bone (ACB). Results of histologic evaluation of ACB core biopsy specimens indicated areas of bone necrosis. The entire left ACB was excised and submitted for histologic evaluation; results confirmed a diagnosis of idiopathic ischemic necrosis. Left pancarpal arthrodesis was performed to treat carpal hyperextension and persistent lameness. The dog had an excellent functional outcome with no other problems related to the carpus until its death 4 years later, further decreasing suspicion that the problem was attributable to an undetected neoplasm or bacterial or fungal osteomyelitis. The radiographic and histologic findings for the dog of this report were similar to previously reported findings for dogs with ischemic femoral head necrosis and humans with ischemic carpal (pisiform or lunate bone) necrosis. The etiology of the ischemic ACB necrosis in this dog was not determined. To the authors' knowledge, this is the first report of a dog with idiopathic ischemic ACB necrosis. Idiopathic ischemic necrosis should be included as a differential diagnosis for dogs with lameness and destructive and expansile ACB radiographic lesions. An excellent functional outcome may be attained by means of ACB excision and pancarpal arthrodesis.

Effects of Non-Weight-Bearing on the Immature Femoral Head Following Ischemic Osteonecrosis

Local non-weight-bearing as a treatment for Legg-Calvé-Perthes disease remains controversial since a clear scientific basis for this treatment is lacking. The purpose of this study was to determine the effects of non-weight-bearing on decreasing the femoral head deformity following ischemic osteonecrosis and to investigate its biological effects. Unilateral femoral head ischemia was induced in sixteen piglets by placing a ligature around the femoral neck and transecting the ligamentum teres. Eight animals received a hind-limb amputation to prevent weight-bearing on the ischemic side (NWB group). The remaining eight piglets were allowed to bear weight as tolerated (WB group). The contralateral femoral heads of the WB group were used as normal controls. All animals were killed at eight weeks after induction of ischemia, when a deformity is expected in this model. Radiographic, microcomputed tomographic (micro-CT), and histomorphometric assessments were performed. Radiographic and micro-CT assessments showed significantly greater flattening of the infarcted epiphysis in the WB group compared with the NWB group. The mean epiphyseal quotient (ratio of femoral head height to diameter) was significantly lower in the WB group (0.29 ± 0.06) compared with the NWB group (0.41 ± 0.06, p < 0.001). Histomorphometric analyses showed that the mean percentage revascularization of the infarcted epiphysis was significantly greater in the NWB group (95% ± 14%) compared with the WB group (34% ± 33%, p < 0.0004), suggesting that revascularization was more rapid in the NWB group. Both histomorphometric and micro-CT analyses of trabecular bone parameters showed significantly decreased bone volume and decreased trabecular number in the infarcted epiphysis of the NWB group compared with the WB group (p < 0.05). Local non-weight-bearing decreased the deformity following ischemic femoral head osteonecrosis and increased the rates of revascularization and resorption of the infarcted epiphysis.

Regulation of VEGF expression by HIF-1α in the femoral head cartilage following ischemia osteonecrosis

Juvenile femoral head osteonecrosis is due to disruption of blood supply which results in ischemic injury. Angiogenesis is an essential component for the healing of damaged head. Hypoxia-inducible factor-1α (HIF-1α) is a master regulator of cellular response to hypoxia. Our histological studies showed increased vessel formation in cartilage in the ischemic group compared to the control group in a pig model of femoral head osteonecrosis. Microarray and RT-PCR indicated that VEGF expression was upregulated along with HIF-1α in the ischemic side. Immunohistochemistry assay demonstrated that HIF-1α and VEGF were upregulated in chondrocytes in ischemic femoral heads. Both HIF-1α and VEGF expression increased in primary chondrocytes under hypoxia station. Interestingly, an HIF-1α activator DFO further enhanced VEGF expression. Moreover, transfection of siRNA directed against HIF-1α led to inhibition of VEGF expression. Taken together, our data indicated that upregulation of VEGF during hypoxia in chondrocyte is mediated partially through HIF-1α.

Microcrack density and nanomechanical properties in the subchondral region of the immature piglet femoral head following ischemic osteonecrosis

Development of a subchondral fracture is one of the earliest signs of structural failure of the immature femoral head following ischemic osteonecrosis, and this eventually leads to a flattening deformity of the femoral head. The mechanical and mineralization changes in the femoral head preceding subchondral fracture have not been elucidated. We hypothesized that ischemic osteonecrosis leads to early material and mechanical alterations in the bone of the subchondral region. The purpose of this investigation was to assess the bone of the subchondral region for changes in the histology of bone cells, microcrack density, mineral content, and nanoindentation properties at an early stage of ischemic osteonecrosis in a piglet model. This large animal model has been shown to develop a subchondral fracture and femoral head deformity resembling juvenile femoral head osteonecrosis. The unoperated, left femoral head of each piglet (n=8) was used as a normal control, while the right side had a surgical ischemia induced by disrupting the femoral neck vessels with a ligature. Hematoxylin and eosin (H&E) staining and TUNEL assay were performed on femoral heads from 3 piglets. Quantitative backscattered electron imaging, nanoindentation, and microcrack assessments were performed on the subchondral region of both control and ischemic femoral heads from 5 piglets. H&E staining and TUNEL assay showed extensive cell death and an absence of osteoblasts in the ischemic side compared to the normal control. Microcrack density in the ischemic side (3.2±0.79 cracks/mm2) was significantly higher compared to the normal side (0.27±0.27 cracks/mm2) in the subchondral region (p<0.05). The weighted mean of the weight percent distribution of calcium (CaMean) also was significantly higher in the ischemic subchondral region (p<0.05). Furthermore, the nanoindentation modulus within localized areas of subchondral bone was significantly increased in the ischemic side (16.8±2.7GPa) compared to the normal control (13.3±3.2GPa) (p<0.05). Taken together, these results support the hypothesis that the nanoindentation modulus of the subchondral trabecular bone is increased in the early stage of ischemic osteonecrosis of the immature femoral head and makes it more susceptible to microcrack formation. We postulate that continued loading of the hip joint when there is a lack of bone cells to repair the microcracks due to ischemic osteonecrosis leads to microcrack accumulation and subsequent subchondral fracture.

Treatment of Early Avascular Necrosis of Femoral Head by Small Intestinal Submucosal Matrix With Peripheral Blood Stem Cells

Background Avascular necrosis of the femoral head (ANFH) is a highly mutilating disease. There are no effective ways to treat early femoral head ischemia. Peripheral blood stem cell (PBSC) transplantation may be superior to conventional bone marrow transplantation. Small intestinal submucosae matrix (SIS) is composed of highly conserved collagens, glycoproteins, proteoglycans, and glycoaminoglycans in their natural configuration and concentrations. When implanted in a number of microenvironments in vivo, SIS has been used to induce proliferation, remodeling, and regeneration of host tissues. This study was designed to verify the curative effects of PBSC and SIS transplantation–induced vascular regeneration to improve ischemic femoral head necrosis in rabbits. Methods 32 New Zealand white rabbits underwent ischemic femoral head necrosis modeling in both hindlimbs by liquid-nitrogen refrigeration. All rabbits were intraperitoneally injected with grannlocytectomy–stimulating factor (250 μg/kg/d), except for normal control subjects injected with equivalent saline solution. After separation of peripheral blood stem cells (PBSCs), 64 femoral heads in 32 rabbits were randomly divided into 4 groups: group A, cancellous bone and peripheral blood stem cells cultured with small intestinal submucosa; group B, cancellous bone and PBSCs; group C, cancellous bone autografts; and group D, no treatment. The specimens were harvested at 4 and 8 weeks after surgery. All specimens were examined to observe angiogenesis and osteogenesis repairing the avascular necrosis of the femoral head by using gross observation, x-ray, histology, and immunohistochemical staining. Results In 4 weeks after peripheral stem cell transplantation, the standing ability and activity of the transplanted hindlimbs were improved remarkably, but there were no obvious changes in the control limbs. X-rays showed a greater density of grafts than the host bone in groups A,B, and group C was unchanged at 4 weeks. Histology revealed many osteoprogenitor cells and osteoblasts and no inflammatory cell infiltration at 4 weeks with much new bone formed at 8 weeks in group A and at 4 weeks in group B. The cancellous bone autograft was absorbed completely at 8 weeks in group C. There was little osteoid tissue formed in group D at 8 weeks. The zone of new bone formation in group A was greater than that in group B ( P < .05), but there was no significant difference between groups A and C ( P > .05). Immunohistochemical staining with CD31 mouse antibody showed greater amounts and zones of new blood vessels in groups A and B at 4 and 8 weeks and little evidence in group D. There was no significant difference between groups A and B ( P > .05) and significant differences between groups A and B versus C and D ( P < .05). Conclusion Transplantation of PBSCs cultured with SIS effectively improved ischemic femoral head necrosis.

Surgical treatment of developmental dysplasia of the hip presenting in children above 10 years

BackgroundManagement of developmental dysplasia of the hip in older children remains controversial. The objective of this study was to evaluate the results of surgical treatment of developmental dysplasia of the hip in children older than 10 years. MethodSixty-three patients (75 hips) whose mean age at the time of surgery was 11.5 years (range 10–19 years) were treated using Salter osteotomy, Pemberton acetabuloplasty, Dega osteotomy, or Westin osteotomy. Subtrochanter transverse femoral shortening and derotation osteotomy were performed for all patients. A long leg cast, rather than a spica cast, was applied postoperation, and progressive flexion and extension exercises of the hip joint were initiated 2 weeks after the surgery. ResultAll 63 patients (75 hips) were followed for an average of 7.6 years (range 5–10 years) after surgery. According to the McKay criteria and Severin X-ray criteria, the fineness ratios were 82.7 and 82.6%, respectively. After surgery, there were 4 cases of semiluxation (6.3%); 4 of femoral head ischemia necrosis (6.3%), and 9 of hip joint stiffness (14.3%). ConclusionWe believe that preoperation overall evaluation and personalized operation plans, experience with the surgical procedure, and commencement of functional exercise soon after the operation are the main reasons for the satisfactory therapeutic effects achieved in this study after surgery for developmental dysplasia of the hip presenting in children older than 10 years.

Hypoxia-inducible factor-1 is a positive regulator of Sox9 activity in femoral head osteonecrosis

Legg–Calve–Perthes disease (LCPD) is a juvenile form of ischemic osteonecrosis of the femoral head leading to femoral head deformity and premature osteoarthritis. Femoral head osteonecrosis occurs due to blood supply disruption which results in hypoxic injury to the femoral head. Hypoxia-inducible factor-1 α (HIF-1α) is a master regulator of cellular response to hypoxia. A pig model of ischemic osteonecrosis of femoral head has been shown to have radiographic and histopathologic changes resembling LCPD. Our preliminary studies showed that the cartilage layer was thicker in the hypoxia group compared to the control group. The mechanism underlying this cartilage response is not known. To explore the hypoxia-induced downstream gene activity following the femoral head ischemia, porcine microarray analysis of gene profiles of chondrocytes from normal and ischemic femoral heads was performed. In the ischemic side, the expression of Sox9, a transcription factor required for chondrocyte differentiation, was upregulated along with HIF-1α. Expressions of Sox9 target genes, such as type II collagen and aggrecan, were also increased. Microarray results were confirmed by quantitative real-time RT-PCR. In addition, immunohistochemistry assay demonstrated that both HIF-1α and Sox9 were upregulated in chondrocytes in ischemic femoral heads compared with normal controls. To investigate the possible molecular mechanisms of hypoxia on Sox9 activity, we tested the effect of HIF-1α on Sox9 expression in vitro. We made a luciferase reporter construct driven by 2 kb Sox9 promoter. Transient transfection assay showed that HIF-1α activated Sox9 promoter activity in a dose-dependent manner. Sox9 is known to activate type II collagen target gene expression. To test the effect of HIF-1α on Sox9-mediated transcription, HIF-1α was cotransfected with Sox9 in type II collagen reporter assay. Our results demonstrated that HIF-1α enhanced Sox9-mediated transcriptional activity. Moreover, coimmunoprecipitation assay showed that HIF-1α associated with Sox9 directly. Taken together, these findings indicate that HIF-1α activates Sox9 expression and enhances Sox9-mediated transcriptional activity and that HIF-1α physically interacts with Sox9. We speculate that HIF-1α upregulation of Sox9 activity may have a chondroprotective role following femoral head ischemia.

Peripheral Blood Stem Cell Transplantation for Ischemic Femoral Head Necrosis

Background Avascular necrosis of the femoral head (ANFH) is a highly mutilating disease. There is no effective way to treat femoral head ischemia. This study was designed to show the curative effects of peripheral blood stem cell transplantation to induce vascular regeneration and improve ischemic femoral head necrosis in rabbits. Methods Twenty New Zealand white rabbits underwent ischemic femoral head necrosis in both hindlimbs using liquid-nitrogen refrigeration. One cohort of rats was intraperitoneally injected with granulocyte-specific colony-stimulating factor (250 μg/kg/d), and control animals received equivalent saline solution. The right side was used as the transplantation group and the left as the control. After separation of peripheral blood, a stem cell suspension was poured into the right femoral artery and saline solution into the left femoral artery. Results At 4 weeks after peripheral stem cell transplantation, standing ability and activity of the the transplanted right hindlimb were remarkably improved, but there were no obvious changes in the control limbs. The experimental rabbits underwent arteriography of bilateral femoral heads, which indicated increased and thickened blood supply to the transplanted right hindlimb compared with the left control. Conclusion Peripheral blood stem cell transplantation improved ischemic femoral head necrosis.

Biphasic threat to femoral head perfusion in abduction: arterial hypoperfusion and venous congestion

Hip abduction can cause avascular necrosis (AVN) of the femoral head in infants. To compare the US perfusion pattern of femoral head cartilage in neutral position with that in different degrees and duration of abduction, testing the venous congestion theory of post-abduction ischemia. In 20 neonates, the Doppler flow characteristics of the posterosuperior (PS) branch of the femoral head cartilage feeding vessels were evaluated in neutral and at 30 degrees, 45 degrees, and 60 degrees abduction. In three neonates the leg was held in 45-degree abduction and flow was assessed at 5, 10, and 15 min. Male/female ratio was 11/9 with a mean age of 1.86 +/- 0.7 weeks. The peak systolic velocities (PSV) declined in all three degrees of abduction. After 15 min of 45-degree abduction, the mean PSV declined and showed an absent or reversed diastolic component and undetectable venous return. No perfusion was detected at 60-degree abduction. Abduction-induced femoral head ischemia is biphasic and degree- and duration-dependent. In phase I there is arterial hypoperfusion and in phase II there is venous congestion. A new pathogeneses for femoral head ischemia is offered.

Increased matrix mineralization in the immature femoral head following ischemic osteonecrosis

Traditionally, it is believed that structural failure of the ischemic epiphysis as well as changes in radiodensity seen in the early stage of Legg–Calvé–Perthes disease is due to the repair process. However, little is known if matrix properties are altered following ischemic injury of the juvenile femoral head. The purpose of this study was to determine the matrix mineralization density, an important determinant of material quality and strength, of the proximal femoral epiphysis in an experimental animal model of Perthes disease.Ten piglets were surgically induced with femoral head ischemia and euthanized at 4 and 8 weeks following surgery. Contralateral, unoperated femoral heads were used as controls. Bone and calcified cartilage mineralization density distribution parameters were determined using quantitative backscattered electron imaging (qBEI) in the epiphyseal calcified articular cartilage, subchondral bone and central trabecular bone region. Histological as well as radiographic assessment was also performed.In the necrotic calcified epiphyseal cartilage matrix, a significant increase in the mean degree of mineralization (CaMean: +24%, p<0.0001) as well as the homogeneity of mineralization (CaWidth: −21%, p<0.05) and a significantly reduced amount of low mineralized matrix (CaLow: −49%, p<0.0001) were already present at 4 weeks post-ischemia induction. Similar changes, but more moderate, were also seen in the subchondral bone region. In contrast, in the necrotic central trabecular region, significant changes in matrix mineralization were found at 8 weeks (CaMean: +4%, p<0.05; CaWidth: −22%, p<0.05; CaLow: −8%, p<0.05) but not at 4 weeks post-ischemia induction.Our findings indicate that the process of matrix mineralization continues in necrotic calcified articular cartilage and bone following femoral head ischemia, which leads to a higher and more homogenous mineralized tissue matrix altering its intrinsic material properties.This may also explain the increased radiodensity seen in the early stage of Perthes disease prior to the initiation of the repair process.

Effects of Disruption of Epiphyseal Vasculature on the Proximal Femoral Growth Plate

Proximal femoral growth disturbance is a major complication associated with ischemic osteonecrotic conditions, such as Legg-Calvè-Perthes disease. The extent of ischemic damage and the mechanisms by which ischemic injury to the growing femoral head produces growth disturbance of the proximal femoral growth plate remain unclear. The purpose of this study was to investigate the effects of disruption of the epiphyseal vasculature on the morphology and function of the proximal femoral growth plate in a porcine model. Ischemic osteonecrosis of the femoral head was surgically induced in sixty-five piglets by placing a ligature tightly around the femoral neck. Radiographic, histological, micro-computed tomographic, cellular viability, hypoxia marker, and cellular proliferation studies were performed. Disruption of the epiphyseal vasculature did not lead to diffuse growth plate damage in the majority of the ischemic femoral heads. One of the twelve femoral heads analyzed at four weeks and six of the twenty-six femoral heads analyzed at eight weeks had severe disruption of the growth plate that precluded histological assessment of the growth plate zones. In the remaining animals, the proximal part of the femur continued to elongate following induction of ischemia, albeit at a slower rate than on the normal side. Histologically, normal developmental thinning of the growth plate was seen to be absent on the ischemic side. Severe hypoxia and cellular death were limited to the area of the growth plate bordering on the infarcted osseous epiphysis. Normal chondrocytic organization and continued proliferation were observed in the proliferative zone of the growth plate. In our porcine model, the proximal femoral growth plate was not diffusely damaged following disruption of the epiphyseal vasculature in the majority of the ischemic femoral heads. The majority of the growth plates remained viable and were able to function despite total disruption of the epiphyseal vasculature. These findings suggest that the source of nutrition for the proximal femoral growth plate is not solely the epiphyseal vasculature as has been traditionally believed.

Femoral head histology subsequent to ischemia, reperfusion and steroid treatment

An episode of ischemia followed by reperfusion of the femoral head (FH) is thought to be a common pathway in the pathogenesis of femoral head necrosis (FHN). Femoral head histology was investigated after short-term high-dose steroid treatment and femoral head ischemia and reperfusion in a large animal model. Twenty-two pigs were randomized to receive methylprednisolone 20 mg/day/kg bodyweight intamuscularly for 3 days followed by methylprednisolone 10 mg/day/kg bodyweight for 11 days ( n=11), whereas the control group ( n=11) received no treatment. After 6 h of unilateral hip-joint pressure increase to 250 mmHg, the pressure was discontinued and reperfusion was allowed for 4 h. Undecalcified histology was performed for the femoral head subchondral region, the mid-region, and the region adjacent to the growth plate. Congestion phenomena were predominantly discerned in femoral head sections of the tamponaded hips. Histomorphometry revealed fat cell hyperthrophy and reduced hemopoetic marrow cells in the femoral heads of the steroid-treated group of animals. The number of blood vessels and bone trabeculae remained unchanged. These characteristics may correlate with early-stage femoral head necrosis.

Osteonecrosis of femoral head: Treatment by core decompression and vascular pedicle grafting.

Background:Femoral head-preserving core decompression and bone grafting have shown excellent result in preventing collapse. The use of vascularized grafts have shown better clinical results. The vascular pedicle bone graft is an easy to perform operation and does not require special equipment. We analyzed and report a series of patients of osteonecrosis of femoral head treated by core decompression and vascular pedicle grafting of part of iliac crest based on deep circumflex iliac vessels.Materials and Methods:The article comprises of the retrospective study of 31 patients of osteonecrosis of femoral head in stage II and III treated with core decompression and vascular pedicle grafting by using part of iliac crest with deep circumflex iliac vessels from January 1990 to December 2005. The young patients with a mean age 32 years (18–52 years) with a minimum follow-up of five years were included for analysis. Sixteen patients had osteonecrosis following alcohol abuse, 12 patients following corticosteroid consumption, 3 patients had idiopathic osteonecrosis. Nine patients were stage IIB, and 22 patients were stage IIIC according to ARCO's system. The core decompression and vascular pedicle grafting was performed by anterior approach by using part of iliac crest with deep circumflex iliac vessels.Results:Digital subtraction arteriography performed in 9 patients at the end of 12 weeks showed the patency of deep circumflex artery in all cases, and bone scan performed in 6 other patients showed high uptake in the grafted area of the femoral head proving the efficacy of the operative procedure. Out of 31 patients, only one patient progressed to collapse and total joint replacement was advised. At the final follow up period of 5–8 years, Harris Hip Score improved mean ± SD of 28.2 ± 6.4 (p < 0.05). Forty-eight percent of patients had an improvement in Harris Hip Score of more that 28 points.Conclusion:The core decompression and vascular pedicle grafting reduces the intraosseous tension to achieve early revascularization of ischemic femoral head. The high percentage of marrow and osteogenic cells survive within a vascularized pedicle graft, which helps in early vascularization and we have been able to achieve good outcome.

Quantitative study of therapeutic efficacy on early intervention of hyperbaric oxygen to model of steroid-induced avascular osteonecrosis of femoral head by multi-slice perfusion imaging

To quantitatively evaluate the hemodynamic status in animal models of steroid-induced avascular osteonecrosis of femoral head (SANFH) by multislice CT (MSCT) perfusion imaging, and estimate the therapeutic efficacy on early intervention of hyperbaric oxygen (HBO) to improve the region blood flow (rBF) of ischemic femoral head. Forty-eight New Zealand male rabbits were injected with Escherichia coli endotoxin and methyl-prednisolone to establish SANFH models and then divided into 3 subgroups to undergo MSCT to measure the rBF, regional blood volume (rBV), and mean transit time (MTT) to obtain perfusion maps at the femoral head epiphysis, metaphysic, and neck of femur, and then were killed to undergo histological examination of the bilateral femoral heads 2, 4, and 6 weeks later respectively (Groups M(2), M(4), and M(6)). Twenty-four rabbits underwent HOB treatment after the second injection of E. c. endotoxin for 1-3 courses respectively (Groups H(1), H(2), and H(3)), and then underwent MSCT and pathological examination as described above. Eight rabbits were used as controls (Group N). (1) The rBF values of Groups M(2), M(4), and M(6) were all significantly lower than that of Group N (P < 0.001, < 0.001, and < 0.002). The rBF value of femoral head epiphysis of Group M(2) was remarkably lower than that of Group N, decreased to the lowest in Group M(4), and re-increased in Group M(6). The rBV value demonstrated similar change pattern in femoral head epiphysis. The MTT values of Groups M(2) and M(4) were longer than that of Group N, and then re-decreased in Group M(6). (2) It did differ significantly between the perfusion data of different femoral head anatomic regions in Groups M(2), M(4), M(6) and N (rBF: F = 52.190, P < 0.001; rBV: F = 42.677, P < 0.001; MTT: F = 3.09, P = 0.048). The changes of the perfusion data in femoral head epiphysis were more significant than those in other anatomic regions. (3) There were no statistically significant differences in the rBF value of the femoral head epiphysis and metaphysis (F = 2.081, P = 0.115; F = 1.142, P = 0.341), in the rBV value of the femoral metaphysis and neck of femur (F = 2.642, P = 0.059; F = 1.568, P = 0.209), and the MTT value of all the anatomic regions (F = 1.111, P = 0.347) among Groups H(1), H(2), H(3), and N. The rBF values of Groups H(1), H(2), and H(3) were statistically higher than those of the corresponding phase model groups (all P < 0.05). Able to detect hemodynamic status of femoral head, MSCT perfusion imaging technique may be used in the early detection of SANFH. Early intervention of HBO therapy can improve the blood perfusion of femoral head.

MR line-scan diffusion imaging in ischemic epiphysis of femoral head:preliminary experimental study in piglets

Objective To observe diffusion changes of epiphysis of femoral head with ischemia of difference phases by line-scan diffusion weighted imaging(LSDWI),and determine whether LSDWI can provide temporal information and severity about ischemia of epiphysis.Methods lschemia was surgically induced in one hip of each piglet(n=25)and the other hip served as a normal control.Piglets were imaged before surgery and at 3 hours,72 hours and 1,3 and 6 weeks after surgery by using LSDWI.Apparent difrusion coefficients(A DC)in epiphysis of the femoral heads were calculated.Significant difierences in ADC values between ischemia group and control group were found by using paired t-test.After scan at individual time points,5 piglets were sacrificed for histological study each time.Results The ADC value in the ischemic femoral heads f(1.22±0.37)×10-3 mm2/s]decreased significantiy at 3 hours after surgery (t=3.914,P＜0.01),compared to that in control[(1.73±0.33)×10-3mm2/s},and increased at 72 hours[(2.15±0.32)×10-3mm2/s versus(1.70±0.22)×10-3 mm2/s](t=3.348,P＜0.01).Then ADC valne kept increasing until 6 weeks after surgery[(1.61±0.27)×10-3mm2/s in ischemia side vs (1.11±0.45)×10-3mm2/s in the control](t=4.136,P＜0.01).rrhe percentage change of the ADC value significandy increased at 3 hours,72 hours,1 and 3 week(s)after the surgery(P＜0.01),compared to that at the prior neighboring time point.No significant increase in the percentage change of ADC value was found between the 3rd week and the 6th week after the surgery(t=2.29.P＞0.05).Histological examinations revealed abnormal thickening within epiphyseal cartilage,and cartilaginous islands within ossified tissues.Growth disturbante wag found in form of focal growth plate disruption.Conclusions Dynamic changes of ADC values were found with the prolonged ischemia of the femoral head by LSDWI.It could serve as a useful marker for evaluating duration and extent of ischemic epiphyseal disruption. Key words: Diffusion magnetic resonance imaging; Epiphyses; Femur head; Ischemia; Animals,laboratory

Dynamic gadoteridol-enhanced MR imaging in the end of growing long bone of piglets

It is of value to identify the non-invasive means that can accurately reflect the blood supply of epiphysis and is more sensitive in detection of early ischemia of epiphysis than the conventional gadoteridol (Gd)-enhanced SE T1WI. The aim of this study was to evaluate the blood supply of various anatomic regions at the end of normal growing long bone using dynamic Gd-enhanced MR imaging and compare the sensitivities between dynamic Gd-enhanced MR imaging and conventional Gd-enhanced SE T1WI in the detection of decreased blood perfusion of early epiphyseal ischemia. Twenty-seven two-week-old piglets were used in this study. For the study of the end of normal growing long bone, unilateral MR imaging of the distal femur and proximal tibia was performed on eleven piglets. The comparison was made among various anatomic regions (physeal and epiphyseal cartilage, metaphyseal spongiosa, the secondary ossification center and metaphysis) using MRI in terms of the enhancement ratio and speed. Their relationships with the histological findings, including RBC/mm(2) and vessel distribution, were evaluated. To examine ischemic femoral head, 16 piglets were divided into two groups, with the control group having 8 piglets (involving 16 normal hips) and an ischemic group having 8 piglets (involving 16 hips with hyperabduction). In the ischemic group, MR imaging was performed on the hips in the hyperabduction immobilized persistently for 30 minutes. After MRI, the piglets were allowed to ambulate freely for 1 day and the same MR scanning was then repeated in a neutral position. The difference in enhancement ratio and speed of the femoral head between the control and ischemic group were evaluated. With regard to the end of normal growing long bone, the enhancement ratio of the metaphyseal spongiosa was greatest among all the anatomic regions (P < 0.001). The enhancement ratio of physeal cartilage was greater than that of epiphyseal cartilage (P < 0. 001), which was the lowest in all tissues (P < 0.001). The enhancement speed of the spongiosa was greater than that of physis but the difference was not significant (P > 0.05). The enhancement speed of physis was greater than that of epiphyseal cartilage (P < 0.05), which was the lowest among all the tissues (P < 0.05). The enhancement ratio and speed were found to be related to the histological findings, including RBC/mm(2) (R > 0.75) and distribution of vessels in the tissues. With ischemic femoral head, the enhancement ratios of physis, anterior part and posterior part of capital femoral epiphysis were significantly lower (P < 0.05) and enhanced more slowly (P < 0.05) than those of normal femoral head on dynamic Gd-enhanced MR imaging. On conventional Gd-enhanced SE T1WI, however, no apparent decrease in enhancement ratio and speed in ischemic hips was found (P < 0.05), when they were compared with those in the normal hips. Dynamic gadoteridol-enhanced MR imaging can reveal the blood supply in various anatomic regions of the end of normal growing long bone. It is more sensitive than conventional Gd-enhanced SE T1WI in the detection of early epiphyseal ischemia.

Normal and ischemic epiphysis of the femur: diffusion MR imaging study in piglets.

To evaluate normal diffusion characteristics in the femur in piglets and changes in diffusion with increasing duration of femoral head ischemia. Normal epiphyses, physes, and metaphyses of piglets were evaluated with line-scan diffusion imaging (n = 12) and diffusion-tensor imaging (n = 4). Apparent diffusion coefficient (ADC) differences between normal proximal and distal femoral structures, epiphyseal and physeal cartilage, and epiphyseal and metaphyseal marrow were compared (Mann-Whitney test). Short-term femoral ischemia was investigated after maximal abduction of the hips for 3 hours (n = 6); ADCs before and after abduction were compared (Wilcoxon signed rank test). Prolonged ischemia was investigated with placement of a ligature around the neck of a femur (n = 7); the ADC of the femur in this condition was compared (Wilcoxon signed rank test) with that of the normal contralateral femur. Changes in ADC ratios at three durations of ischemia (Kruskal-Wallis test) were compared. ADC was greater in epiphyseal cartilage (mean +/- 1 SD, 1.62 x 10(-3) mm2/sec +/- 0.38) than it was in physeal cartilage (1.28 x 10(-3) mm2/sec +/- 0.31) (P <.007) and greater in epiphyseal marrow (1.26 x 10(-3) mm2/sec +/- 0.38) than it was in metaphyseal marrow (0.91 x 10(-3) mm2/sec +/- 0.35) (P <.001). There was columnar arrangement of tensors in the physis. ADC decreased 26% after 3 hours of maximal abduction. After femoral neck ligature, ADC increased a mean of 27% after 6 hours and a mean of 75% after 96 hours. Normal line-scan diffusion imaging findings indicate relative restriction of diffusion in the metaphysis and parallel orientation of tensors in the physis. Diffusion is initially restricted with decreased blood flow but increases if ischemia lasts longer.

Effect of methylprednisolone on reperfusion after femoral head ischemia.

An episode of ischemia and reperfusion of the femoral head is thought to be the common pathway in the pathogenesis of femoral head necrosis. The influence of short-term high-dose steroid treatment on femoral head reperfusion after ischemia was investigated in a porcine model. Twenty-two pigs were randomized to receive methylprednisolone 20 mg/day/kg bodyweight intramuscularly for 3 days followed by methylprednisolone 10 mg/day/kg bodyweight for 11 days (n = 11), whereas the control group (n = 11) received no treatment. Femoral head ischemia was achieved by 6 hours of unilateral intraarticular hip pressure increase to 250 mm Hg. Femoral head blood flow was estimated using radiolabeled microspheres (15 microm in diameter) before ischemia, during hip tamponade, and 4 hours after tamponade release. Femoral head blood flow was lower in the corticosteroid treated pigs. Subtotal femoral head ischemia was documented in both groups during joint tamponade. Apart from two femoral head epiphyses in either group, reperfusion after tamponade release on the average occurred to a blood flow level similar to that before ischemia. Short-term high-dose methylprednisolone treatment depressed bone perfusion in general, but had no effect on reperfusion after femoral head ischemia in the porcine model.