Increased perfusion of the femoral head in transient bone marrow edema syndrome

The pathophysiology of transient bone marrow edema syndrome is not known. Ischemia has been suggested as the pathophysiologic factor, because the histologic findings are similar to those of early stage osteonecrosis. Angiographic studies of osteonecrotic femoral heads have shown arterial interruption and impaired perfusion. The current report describes the angiographic and scintigraphic findings of transient bone marrow edema syndrome of the hip in a 45-year-old man. The nutrient arteries were dilated, and the femoral head perfusion was increased compared with the unaffected contralateral side. These findings suggest that a vasomotor response plays a role in the pathogenesis of transient bone marrow edema syndrome. The disease might be a reversible process after temporary ischemia of the femoral head.     

Histological findings of bone marrow edema pattern on MRI in osteonecrosis of the femoral head

Sequential magnetic resonance imaging (MRI) was performed on a 38-year-old woman with systemic lupus erythematosus who had received corticosteroid and had developed non-traumatic osteonecrosis of the femoral head. The initial MR finding was a band lesion on the T1-weighted image, which had been present before the onset of symptoms. At the onset of symptoms, a diffuse bone marrow edema pattern, with a low signal intensity on T1 and high signal intensity on T2-weighted images, was noted around the band lesion, extending to the femoral neck. Histopathologically, this region was found to consist of serous exudate, focal interstitial hemorrhage, and mild fibrosis, without any evidence of extension of osteonecrosis. It should be noted that extension of a low signal intensity area on MRI after the onset of hip pain may not be the result of the extension of osteonecrosis, but may represent concomitant edema due to collapse. Received: February 25, 2000 / Accepted: May 16, 2000     

髓芯减压联合高压氧治疗髋关节骨髓水肿综合征

目的探讨髓芯减压联合高压氧治疗髋关节骨髓水肿综合征（BMES）的疗效。方法髓芯减压联合高压氧治疗12例髋关节BMES患者。结果12例均获随访,时间6～24个月。患者疼痛均完全消失,术后4～12周髋关节功能恢复正常。随访期间未发现病情复发及股骨头坏死。结论髓芯减压联合高压氧治疗髋关节BMES,创伤小,并发症少,疗效好。     

股骨上端骨髓水肿综合征的MRI表现特点

目的：分析股骨上端骨髓水肿综合征的MRI表现特点以提高对该病的认识。方法;回顾性分析10例股骨上端骨髓水肿综合征患者的MRI表现,男6例,女4例;年龄36～57岁,平均41．5岁;病史1周～3个月。临床表现为突然发作的髋部疼痛9例,行走能力及髋关节活动受限7例;全部病例无明显外伤史,女性患者未在孕期。随访3～12个月,症状消失3个月复查MRI后结束随访。结果：MRI主要表现为弥漫性骨髓水肿,累及股骨头、颈、粗隆间,10例13髋中骨髓水肿1级6髋,2级5髋,3级2髋。合并髋关节积液9髋,I级积液6髋,Ⅱ级1髋,III级2髋。治疗3-12个月后患者髋部疼痛症状消失,股骨内MRI信号恢复正常。     

Decreased osteogenic differentiation of mesenchymal stem cells in alcohol-induced osteonecrosis

We postulated that osteogenic and adipogenic differentiation ability of the mesenchymal stem cells isolated from the bone marrow could be altered in patients with alcohol-induced osteonecrosis of the femoral head. To examine this hypothesis, we investigated the differentiation ability of the mesenchymal stem cells isolated from the bone marrow from the proximal end of the femur during hip replacements in patients with alcohol-induced osteonecrosis of the femoral head and compared it with the differentiation ability of patients with femoral neck fractures. Marrow was collected from the proximal femurs of 33 patients having hip replacement for either alcohol-induced osteonecrosis of the femoral head or femoral neck fractures. The mesenchymal stem cells were isolated and the culture was expanded from the marrow. The cell populations were compared in terms of the doubling time and the differentiation ability to the osteoblasts and adipocytes. The cells obtained from the patients with alcohol-induced osteonecrosis of the femoral head showed a reduced ability to differentiate the osteogenic lineages compared with the cells obtained from the patients with femoral neck fractures. Such changes may play a role in the development of alcohol-induced osteonecrosis of the femoral head. The altered function of mesenchymal stem cells can be responsible for the pathogenesis of osteonecrosis.     

股骨头坏死修复反应区的骨髓水肿及其病理改变

目的探讨股骨头坏死修复反应区骨髓水肿的病理基础和临床意义。方法随机取20个因股骨头坏死行全髋关节置换的股骨头标本，取修复反应区制作成病理切片。根据MRI脂抑像表现分为骨髓水肿组和非水肿组。将两组病理切片的显微镜下结构随机取5个视野，对于所见坏死和崩解骨组织、脂肪组织、造血组织、肉芽组织、纤维组织，进行比较。结果本研究显示骨髓水肿组肉芽组织明显较常见（x^2=13．107，P〈0．05），而无水肿组脂肪组织（x^2=17．755，P〈0．05）和造血组织（x^2=2．838，P〈0．05）较多，两组差异有统计学意义。而坏死骨小梁（x^2=0．457，P〉0．05）、崩解组织（x^2=0．037，P〉0．05）、纤维组织（x^2=0．428，P〉0.05）在两组分布相似，差异无统计学意义。结论股骨头坏死修复反应区的骨髓水肿是一种炎性反应表现，其产生机制可能与股骨头内微骨折有关，对于临床治疗的相关性尚需进一步研究。     

Fatty marrow conversion of the proximal femoral metaphysis in transient bone marrow edema syndrome

Introduction In the proximal femoral metaphysis, hematopoietic marrow is predominant during the adult stage of life. The conversion of hematopoietic marrow to fatty marrow in the proximal femoral metaphysis has been suggested as an etiologic factor of ischemia in the pathogenesis of femoral head osteonecrosis. To determine whether the chronology of fatty marrow conversion of the proximal femoral metaphysis is related to transient bone marrow edema syndrome of the hip, a case control study was conducted on 10 patients with the disease.Materials and methods There were 8 men and 2 women with a mean age of 33 years (range 19–45 years). The 10 patients were matched with 20 controls for gender and age (5-year range). T1-weighted MRI scans of their hips were reviewed. Marrow of the greater trochanter becomes fatty before puberty, and thus, the greater trochanter can be used as a built-in control. The signal intensity of the proximal femoral metaphysis was compared to that of the greater trochanter.Results In all patients, the signal intensity of the proximal femoral metaphysis was isointense (fatty marrow) relative to that of the greater trochanter. In control subjects, the signal intensity was isointense in 8 (40%) and hypointense (hematopoietic marrow) in 12 (60%) (p<0.05).Conclusion The current study shows that the proximal femoral metaphysis is predominantly fatty in transient bone marrow edema syndrome. The conversion of hematopoietic to fatty marrow is known to correlate with decreases in intramedullary blood flow. Thus, the current study suggests that an ischemia of the proximal femur secondary to fatty marrow conversion of the proximal femoral metaphysis might be a cause of transient bone marrow edema syndrome of the hip.     

Cell therapy of hip osteonecrosis with autologous bone marrow grafting

Background:

One of the reasons for bone remodeling leading to an insufficient creeping substitution after osteonecrosis in the femoral head may be the small number of progenitor cells in the proximal femur and the trochanteric region. Because of this lack of progenitor cells, treatment modalities should stimulate and guide bone remodeling to sufficient creeping substitution to preserve the integrity of the femoral head. Core decompression with bone graft is used frequently in the treatment of osteonecrosis of the femoral head. In the current series, grafting was done with autologous bone marrow obtained from the iliac crest of patients operated on for early stages of osteonecrosis of the hip before collapse with the hypothesis that before stage of subchondral collapse, increasing the number of progenitor cells in the proximal femur will stimulate bone remodeling and creeping substitution and thereby improve functional outcome.

Materials and Methods:

Between 1990 and 2000, 342 patients (534 hips) with avascular osteonecrosis at early stages (Stages I and II) were treated with core decompression and autologous bone marrow grafting obtained from the iliac crest of patients operated on for osteonecrosis of the hip. The percentage of hips affected by osteonecrosis in this series of 534 hips was 19% in patients taking corticosteroids, 28% in patients with excessive alcohol intake, and 31% in patients with sickle cell disease. The mean age of the patients at the time of decompression and autologous bone marrow grafting was 39 years (range: 16–61 years). The aspirated marrow was reduced in volume by concentration and injected into the femoral head after core decompression with a small trocar. To measure the number of progenitor cells transplanted, the fibroblast colony forming unit was used as an indicator of the stroma cell activity.

Results:

Patients were followed up from 8 to 18 years. The outcome was determined by the changes in the Harris hip score, progression in radiographic stages, change in volume determined by digitizing area of the necrosis on the different cuts obtained on MRI, and by the need for hip replacement. Total hip replacement was necessary in 94 hips (evolution to collapse) among the 534 hips operated before collapse (Stages I and II). Sixty-nine hips with stage I osteonecrosis of the femoral head at the time of surgery demonstrated total resolution of osteonecrosis based on preoperative and postoperative MRI studies; these hips did not show any changes on plain radiographs. Before treatment, these 69 osteonecrosis had only a marginal band like pattern as abnormal signal and a volume less than 20 cubic centimeters. The intralesional area had kept a normal signal as regards the signal of the femoral head outside the osteonecrosis area. For the 371 other hips without collapse at the most recent follow up (average 12 years), the mean preoperative volume of the osteonecrosis was 26 cm³ (minimum 12, maximum 30 cm³). The mean volume of the abnormal signal measured on MRI at the most recent follow up (mean 12 years) was 12 cm³. The abnormal signal persisting as a sequelae was seen on T1 images as an intralesional area of low intensity signal with a disappearance of the marginal band like pattern.

Conclusion:

According to our experience, best indication for the procedure is symptomatic hips with osteonecrosis without collapse. In some patients who had Steinberg stage III osteonecrosis (subchondral lucency, no collapse) successful outcomes (no further surgery) has been obtained between 5 to 10 years. Therefore in selected patients, even more advanced disease can be considered for core decompression. Patients who had the greater number of progenitor cells transplanted in their hips had better outcomes.     

基于MDLC-MS/MS技术的股骨头缺血性坏死的组织蛋白质组分析

目的:应用组织蛋白质组学方法探寻与成人非创伤性股骨头缺血性坏死(ONFH)相关的蛋白质。方法:自2008年7月至2009年2月,从非创伤性ONFH(男7例,女3例)和新鲜股骨颈骨折(男、女各5例)而行人工髋关节置换术的患者中随机选取10例,平均年龄分别为52岁和63岁。术中取ONFH患者股骨头中坏死骨组织为试验组,取股骨颈骨折患者股骨头中的正常骨组织样品为对照组。用四步溶剂法提取骨组织总蛋白,经SDS-PAGE分离和酶解,应用多维液相色谱与串联质谱联用技术分离鉴定组织蛋白,以TPP软件检测两组蛋白质的差异表达水平,并用Turbo SEQUEST软件鉴定差异表达蛋白质。同时Western免疫印迹验证质谱检测的准确性。结果:试验组和对照组样品中分别鉴定二肽段以上的高可信度蛋白质数量1233个和999个,假阳性率0.8%。试验组中共鉴定差异表达蛋白质192个,其中表达量上调3倍以上的蛋白点107个,下调3倍以上53个,其中34种蛋白质与ONFH密切相关。Western免疫印迹证实试验组样品中GPCR26和CHST2表达量下调,与质谱结果一致。结论:非创伤性ONFH存在复杂的病理生理学过程,本研究发现的差异表达蛋白极有可能成为ONFH早期临床诊断的候选生物学标志物。     

Biochemical markers of bone metabolism in bone marrow edema syndrome of the hip

The aim of this study was to evaluate bone metabolism in patients with bone marrow edema syndrome of the hip. In 37 consecutive patients undergoing core decompression of the femoral head, biochemical markers of bone metabolism were measured in aspirates from cancellous bone and in samples obtained simultaneously from peripheral blood. The diagnosis was made by means of radiographs, magnetic resonance imaging (MRI), and core biopsy specimens. Undecalcified microtome section were available for histopathological evaluation. Bone specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen Type I N-terminal propeptide (PINP), and C-terminal cross-linking telopeptide (ICTP) were studied. Mean serum levels of analytes were 13.1 ng/mL (OC), 11.2 ng/mL (bone ALP), 4.7 ng/mL (ICTP), and 38.8 ng/mL (PINP). In samples obtained from cancellous bone, mean concentrations of all markers were elevated significantly. The mean bone to serum ratios for bone ALP and OC were 14.1 (P=0.005) and 4.1 (P=0.002), respectively. For collagen Type I metabolites, bone to serum ratios averaged 16.3 (P=0.001) for ICTP and 9.6 (P=0.001) for PINP. Markers of bone formation correlated with each other in serum as well as in aspirates from cancellous bone. Elevation of all markers in aspirates from cancellous bone pointed at increased bone turnover, which correlated with histopathological findings of irregularly woven bone, osteoid seams, and lining cells. Mean serum concentrations of all markers, however, were not different from healthy individuals and thus did not provide any useful clue in the diagnosis of this disease. The lack of osteonecrotic regions in our specimens, the marked increase of bone turnover in samples obtained from edematous lesions, and the fact that none of the patients developed osteonecrosis of the femoral head so far seem to further support the contention that transient bone marrow edema syndrome of the hip is a distinct clinical entity.     

Non-traumatic osteonecrosis of the femoral head treated with transtrochanteric anterior rotational osteotomy combined with vascularized iliac bone grafting

A 49-year-old Japanese man who had non-traumatic osteonecrosis of the femoral head with a wide necrotic lesion received transtrochanteric anterior rotational osteotomy combined with vascularized iliac bone grafting. After the bone graft (6 × 1.5 cm) was collected, the femoral head was anteriorly rotated by 90°. A bone tunnel of 1.2 cm in diameter was prepared on the necrotic lesion adjacent to the intact area from the anterior part of the femoral neck to inside the femoral head. The bone graft was trimmed to the size of this bone tunnel, and inserted up to immediately below the articular surface. In the monitoring using T1-weighted magnetic resonance imaging (MRI), the low signal-intensity area between the bone graft and intact area had disappeared, and a high signal-intensity area on the weight-bearing portion of the femoral head had extended. With modifications on the insertion point of the bone graft, transtrochanteric anterior rotational osteotomy combined with vascularized iliac bone graft would be a useful means to preserve the femoral head in large non-traumatic osteonecrosis of the femoral head. Received: December 24, 1999 / Accepted: May 23, 2000     

股骨头骨折后并发股骨头缺血性坏死的治疗

目的 探讨股骨头骨折内固定术后并发股骨头缺血性坏死的治疗.方法 对单侧股骨头骨折内固定术后股骨头缺血性坏死采用带血运骨瓣转移术治疗的26例临床资料进行回顾分析.21例数字减影血管造影(DSA)检查明确股骨头及其周围骨的血供后行内固定物取出、带血运骨瓣转移术.1例内固定物取出后行全髋置换术.结果 施行带血运骨瓣转移术的术后平均随访23个月(12～38个月),根据Harris髋关节功能评分标准进行临床评价.根据手术前后Ficat分期改变进行影像学评价.对其中15例进行术后DSA检查以明确坏死股骨头血运重建情况.术后2髋改行人工全髋关节置换.股骨头得到重建的病例,术后Harris髋关节功能评分提高至平均86.2分(术前平均54分),其中临床成功率为92.0%,影像学成功率为84.0%.15例重建股骨头手术后DSA评估提示血管蒂充盈好,骨瓣血运丰富.结论 股骨头骨折内固定术后股骨头坏死发生率较高(可达40%).在取出内固定物同时行带血运骨瓣转移治疗股骨头缺血性坏死、股骨头血运重建良好,早期疗效满意.     

A new hypothesis for the bone marrow edema pathogenesis during transient osteoporosis

Transient osteoporosis is an infrequent condition of uncertain etiology with pain, limited range of motion and radiographic evidence of osteoporosis affecting one or more joints. It is self-limited, reversible and can involve only the hip (transient osteoporosis of the hip, TOH) or, less frequently, one or more joints contemporaneously or at different times (regional migratory osteoporosis, RMO). We studied four men with transient osteoporosis, including two with TOH and two with RMO. All patients underwent a standard radiographic work-up of the affected joints, arteriovenous Doppler US, computed tomography, magnetic resonance imaging (MRI) and three-phase bone scanning. In all patients, symptoms were related to bone marrow edema demonstrated at MRI and to a transitory regional arterial hyperflow observed at the early scintigraphic analysis. On the basis of our observations, we hypothesize that regional arterial hyperflow may be the cause of the bone marrow edema and therefore of the transient osteoporosis.     

股骨头骨髓水肿综合征的诊治及其与股骨头缺血性坏死的鉴别诊断

目的：通过对股骨头骨髓水肿综合征诊治的观察,分析其疾病特点及其与股骨头缺血性坏死的异同。方法：自2004年1月,股骨头骨髓水肿综合征患者19例,男12例,女7例;平均年龄（46．7±10．36）岁。给予药物及物理治疗,治疗前后按照髋关节Harris评分系统进行评分。结果：治疗前平均（43．17±12．62）分,治疗后平均（86．73±14．29）分,治疗前、后评分差异有统计学意义（P〈0．05）。结论：股骨头骨髓水肿综合征疾病特点不同于股骨头缺血性坏死,是一类独立的疾病。     

Articular collapse and surgical frequency in corticosteroid-associated osteonecrosis of the femoral head and the knee: an MRI-based prospective study

Background

The purpose of this magnetic resonance imaging (MRI)-based prospective study was to clarify the frequency of articular collapse in, and to define the frequency with which surgical interventions are performed for, osteonecrosis of the femoral head and the knee.

Methods

MRI screening for osteonecrosis of the femoral head and the knee was prospectively performed within 1 year after corticosteroid administration. Those patients with osteonecrosis were conservatively followed with MRI to detect articular collapse by bone marrow edema. Several surgical interventions were considered after articular collapse. The frequencies of collapse and of surgical intervention were compared using the Kaplan–Meier method and the log-rank test.

Results

Of 1,239 joints (623 hips and 616 knees) surveyed in the study, osteonecrosis was identified in 370 (191 hips and 179 knees) by MRI. Thus, the incidence of osteonecrosis was 30 % (31 % in hip and 29 % in knee). Of 155 hips and 154 knees followed for more than 2 years, the frequency of articular collapse was significantly higher in osteonecrosis of the femoral head than in osteonecrosis of the knee (p?<?0.05, 38 % [59 hips] versus 5 % [7 knees]). After articular collapse, surgery was performed significantly more often for osteonecrosis of the femoral head than for osteonecrosis of the knee (p?=?0.024, 63 % [37 femoral heads] versus 29 % [2 knees]).

Conclusions

Osteonecrosis of the femoral head can result in clinically more severe sequelae than osteonecrosis of the knee, and surgery is more often performed for osteonecrosis of the femoral head.     

"Transient osteoporosis" as a special reversible form of femur head necrosis

There is still controversy whether transient osteoporosis of the hip joint represents a distinct self-limiting disease, or reflects only an early, reversible subtype of non-traumatic osteonecrosis (ON). Transient osteoporosis has several synonyms: algodystrophy of the hip; transient marrow oedema; or bone marrow oedema syndrome--BMOES. Clinical presentation of BMOES shows mechanical hip joint pain, ON risk factors, and a diffuse bone marrow oedema in MR imaging. Histomorphological changes resemble early ON, but with diffuse sufficient repair in BMOES and focal and insufficient repair only at the border of the necrotic lesion in ON. Therefore the clinical course and outcome are significant different, with restitution occurring in BMOES, while progressive destruction of the joint takes place in ON. So far, the preferred treatment strategies are protected weight bearing for BMOES, but operative treatment for ON. In a prospective study of patients with BMOES, the clinical, radiographic, and MRI course of 43 hip joints after core decompression treatment were investigated. All patients showed immediate relief of pain after surgery and the average duration of symptoms with conservative treatment could be dramatically reduced by core decompression from 6 months down to 2 months. There were no perioperative complications. Based on our experience with over 100 BMOES patients, we are convinced that this syndrome represents not a distinct disease but an early reversible subtype of non-traumatic ON. Due to the excellent clinical results of core decompression, we recommend this operative therapeutical concept in patients with painful BMOES.     

Magnetic resonance imaging and histology of repair in femoral head osteonecrosis

Different repair processes affect the clinical course of nontraumatic avascular femoral head osteonecrosis, not just necrotic lesion size and location. Fourteen femoral heads were retrieved at total hip arthroplasty after core decompression treatment, or after conservative treatment was done on 13 male patients diagnosed with different stages of femoral head osteonecrosis. To determine repair types, features of coronal magnetic resonance images were correlated with light microscopy findings on corresponding coronal undecalcified sections and microradiographs of the retrieved femoral heads. In five femoral heads, repair of necrotic bone and marrow remained restricted to the reactive interface for as many as 63 months, producing the diagnostic osteosclerotic rim with adjacent hypervascularity (limited repair). Nine femoral heads showed extension of the repair process into the necrosis. In five femoral heads, predominant resorption of necrotic bone led to femoral head breakdown within 2 to 50 months (destructive repair). In four femoral heads, reparative bone formation had started from subchondral fractures and/or the reactive interface, definitely reducing the size of the necrotic area (reconstructive repair). In the latter, the disease progressed slowly or stopped for as many as 45 months, irrespective of treatments, but elimination of risk factors seemed beneficial. Although core decompression did not always reach the necrotic area and improve repair, it reduced accompanying bone marrow edema and could delay the disease progress. Osteonecrosis with limited repair can be identified on magnetic resonance images obtained at followup, but the similar signal changes of destructive and reconstructive repair cannot be distinguished on magnetic resonance images alone. The evidence of reconstructive repair in nontraumatic osteonecrosis, however, gives hope for treatments that can improve repair to a sufficient creeping substitution of the affected femoral head.     

Can ischemic hip disease cause rapidly destructive hip osteoarthritis? A case report

Avascular osteonecrosis of the femoral head (AONFH) usually goes through the four stages described by Arlet and Ficat: normal radiographs, heterogeneity and sclerosis of the femoral head, subchondral fracture with an individualized sequestrum, and secondary osteoarthritis. Arlet and Ficat individualized a specific pattern of AONFH which they called ischemic hip disease, in which cartilage damage seen as concentric joint space loss precedes the bony alterations. Although radiological and pathological studies of ischemic hip disease have been published, no clinical data are available. We report the case of a 65-year-old man admitted for a 1-month history of severe hip symptoms with concentric joint space loss but no osteophytes. Laboratory tests and examination of fluid aspirated from the hip ruled out septic arthritis and inflammatory hip disease. Two magnetic resonance imaging (MRI) studies done 1 month apart showed diffuse edema involving not only the femoral head but also the neck and trochanter, as well as major synovial hypertrophy. This atypical MRI appearance prompted synovial membrane and pertrochanteric core biopsies, which showed reactive synovitis and stage IV osteonecrosis, respectively. The pain, disability, and joint space loss worsened. Total hip arthroplasty was performed 1 month after the biopsy. Histological examination of the femoral head showed diffuse necrosis; no evidence of another condition was found on histological sections of the entire synovial membrane. This case corroborates the hypotheses put forward by Lequesne that some cases of rapidly destructive hip osteoarthritis may be ascribable to ischemia.     

Three cases of regional migratory osteoporosis

We examined three patients with regional migratory osteoporosis. Radionucleotide bone scanning and MRI was helpful in the diagnosis of this disease, and all patients recovered with conservative treatment. A biopsy of the femoral head, which was performed in one case, demonstrated bone marrow edema without osteonecrosis. A low intensity area of subchondral bone was observed on a T1-weighted image in two cases, as well as a fracture of the subchondral bone, which might be associated with transient osteoporosis. In one case, the affected region migrated from the medial femoral condyle to the lateral femoral condyle in the same knee joint.