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 ± 2.7 GPa) compared to the normal control (13.3 ± 3.2 GPa) (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.     

Mechanics of femoral head osteonecrosis using three-dimensional finite element method

A three-dimensional finite element model of a femoral head was developed using a surface modeling technique. The distribution of the stress index S (S = effective stress / yield strength, sigma/sigmaY) in various sizes of segmental osteonecrosis was assessed. The stress index of the femoral head was within physiological limits when the necrotic angle was less than 110 degrees. Within both the subchondral region and the deep necrotic region adjacent to the necrotic-viable interface, values of the stress index significantly higher than the normal physiological level (>0.1) appeared when the necrotic angle was 110 degrees or more. In the analysis of 28 osteonecrotic femoral head specimens, fracture appeared in two major locations: the deep necrotic region near the underlying necrotic-viable interface (19 femoral heads) and the subchondral region (7 femoral heads). In 2 femoral heads, the fracture involved both regions. Both sites of fracture coincided with the region of stress index greater than 0.1 in the finite element model study. These results may provide baseline information for predicting the collapse of the femoral head and determining the treatment modality of early stage osteonecrosis.     

Pathology of femoral head collapse following transtrochanteric rotational osteotomy for osteonecrosis

We investigated the pathology of femoral head collapse following transtrochanteric anterior rotational osteotomy. Six femoral heads were obtained during total hip arthroplasty some 2–12 years after osteotomy. In all cases, the preoperatively necrotic lesions exhibited mostly osteonecrosis with accumulation of bone marrow cell debris and trabecular bone with empty lacunae, although repair tissue such as granulation tissue and appositional bone formation were observed in limited areas in some cases. In the transposed intact articular surface of the femoral head, osteoarthritic changes such as fissure penetration to the subchondral bone and osteophyte formation were commonly observed. In newly created subchondral areas at weight-bearing sites, trabecular thickness and the number of trabecular bones had decreased, with few osteoblasts, osteoclasts, and osteocytes being present, resulting in a coarse lamellar structure of the trabecular bone. These findings suggest that transposed areas in cases of failure consist mostly of low-turnover osteoporotic lesions which could cause collapse of the femoral head. Received: 5 October 1999     

人股骨头坏死微观结构及成骨、破骨细胞活性的区域性分布特征

 目的 比较人股骨头坏死标本不同区域的骨微观结构及成、破骨细胞活性。方法 收集2011年3月至2013年5月行全髋关节置换的非创伤性股骨头坏死患者术后的股骨头标本10例（Ficat Ⅳ期）,男6例,女4例;年龄40～57岁,平均47.7岁。Micro-CT扫描后,根据影像学识别骨质密度不同,将每个标本分为软骨下骨区、坏死区、硬化区、健康区,通过病理学检测、纳米压痕、实时荧光定量PCR、免疫组化染色等方法对不同区域的骨微观结构、微观力学性能及成骨、破骨细胞活性进行比较。结果 Micro-CT结果显示,股骨头坏死标本软骨下骨区及坏死区的骨小梁连续性破坏;硬化区的骨小梁数目增多,间隙变窄;正常区域骨小梁结构完整,厚度分布均匀。软骨下骨区、坏死区、硬化区和健康区骨小梁的弹性模量分别为（13.808±4.22） GPa、（13.999±3.816） GPa、（17.266±3.533） GPa和（11.927±1.743） GPa;硬度分别为（0.425±0.173） GPa、（0.331±0.173） GPa、（0.661±0.208） GPa和（0.423±0.088） GPa。抗酒石酸酸性磷酸酶（Trap）染色结果显示,软骨下骨区和坏死区可见Trap染色阳性细胞,硬化区及健康区未见Trap染色阳性细胞。免疫组化染色结果显示,骨形成相关因子Runx2和BMP2在硬化区及健康区表达高于其他区域;骨吸收相关因子RANK和RANKL在软骨下骨区及坏死区表达高于其他区域。结论 股骨头坏死塌陷过程中,骨微观结构发生明显改变,而坏死区骨小梁微观力学强度较健康区无显著降低。股骨头坏死标本中软骨下骨区及坏死区破骨细胞活性增强,硬化区成骨细胞活性增强。     

Microfractures in coxarthrosis

We examined the subchondral bone architecture of the femoral head in relation to trabecular microfracture. Three groups of femoral head specimens were studied. Twenty-eight specimens taken during hip replacement had grade III or IV arthrosis (70 × 8 years). From autopsy, 40 femoral heads were obtained, 18 in a group greater than 50 years of age (72 × 10 years) and 22 in a group less than 50 years of age (25 × 11 years). None of these 40 heads had worse than grade II arthrosis. Coronal slices of the femoral heads were macerated and examined under a dissecting microscope to count trabecular microfractures. For bone histomorphometry, blocks were taken from the subchondral principal compressive and tensile trabeculae. The bone volume, trabecular thickness, and marrow space were quantified. In the subchondral principal compressive region, the arthrotic group had more bone volume, thicker trabeculae, similar trabecular space, and trabecular microfractures when compared with the group greater than 50 years old. In the tensile region, there were no differences except for decreased trabecular microfracture number in the arthrotic group. With the thinnest trabeculae in the compressive region occurring in the greater than 50 years old group, the trabeculae of the younger age group have thinned with age, but with the onset of arthrosis, the thinning is overtaken by pathologic thickening of trabeculae.     

Osteochondritis Dissecans Capituli Humeri) (Untersuchungen an 168 Fällen)

We examined the subchondral bone architecture of the femoral head in relation to trabecular microfracture. Three groups of femoral head specimens were studied. Twenty-eight specimens taken during hip replacement had grade III or IV arthrosis (70 × 8 years). From autopsy, 40 femoral heads were obtained, 18 in a group greater than 50 years of age (72 × 10 years) and 22 in a group less than 50 years of age (25 × 11 years). None of these 40 heads had worse than grade II arthrosis. Coronal slices of the femoral heads were macerated and examined under a dissecting microscope to count trabecular microfractures. For bone histomorphometry, blocks were taken from the subchondral principal compressive and tensile trabeculae. The bone volume, trabecular thickness, and marrow space were quantified. In the subchondral principal compressive region, the arthrotic group had more bone volume, thicker trabeculae, similar trabecular space, and trabecular microfractures when compared with the group greater than 50 years old. In the tensile region, there were no differences except for decreased trabecular microfracture number in the arthrotic group. With the thinnest trabeculae in the compressive region occurring in the greater than 50 years old group, the trabeculae of the younger age group have thinned with age, but with the onset of arthrosis, the thinning is overtaken by pathologic thickening of trabeculae.     

Microfractures in coxarthrosis

We examined the subchondral bone architecture of the femoral head in relation to trabecular microfracture. Three groups of femoral head specimens were studied. Twenty-eight specimens taken during hip replacement had grade III or IV arthrosis (70 +/- 8 years). From autopsy, 40 femoral heads were obtained, 18 in a group greater than 50 years of age (72 +/- 10 years) and 22 in a group less than 50 years of age (25 +/- 11 years). None of these 40 heads had worse than grade II arthrosis. Coronal slices of the femoral heads were macerated and examined under a dissecting microscope to count trabecular microfractures. For bone histomorphometry, blocks were taken from the subchondral principal compressive and tensile trabeculae. The bone volume, trabecular thickness, and marrow space were quantified. In the subchondral principal compressive region, the arthrotic group had more bone volume, thicker trabeculae, similar trabecular space, and trabecular microfractures when compared with the group greater than 50 years old. In the tensile region, there were no differences except for decreased trabecular microfracture number in the arthrotic group. With the thinnest trabeculae in the compressive region occurring in the greater than 50 years old group, the trabeculae of the younger age group have thinned with age, but with the onset of arthrosis, the thinning is overtaken by pathologic thickening of trabeculae.     

股骨头缺血性坏死新月征的形成机制

目的对发生股骨头缺血性坏死出现x线片上“新月征”股骨头的结构改变及与所受应力的对应关系进行研究,探讨“新月征”的形成机制。方法收集1998年3月-2003年4月全髋关节置换术前X线片显示有“新月征”的股骨头16例18髋,进行大体和冠状位断面观察。应用有效压应力原理和应力集中理论对发生在缺血性坏死股骨头上的结构改变原因进行解释和说明。结果松质骨内的骨小梁形成三维立体交互连接的网格结构,孔隙率50％～90％,髓内压20～30mmHg。股骨头内松质骨的构造符合多孔介质的定义,是一种多孔介质。松质骨的变形机制与多孔介质材料变形机制相同。软骨下骨板与松质骨间的断面结构改变使应力易在二者交界处集中。有效压应力原理和应力集中理论可对发生在缺血坏死股骨头上的一些现象及彼此之间的关系进行明确的解释和说明。结论导致“新月征”骨折线正发生在软骨下骨板下的原因是由于在坏死灶外侧软骨下骨板局灶性被吸收发生后,软骨下骨板与未被修复坏死松质骨交界处发生应力集中,集中的应力导致骨折线正位于软骨下骨板下,施加在未被修复坏死松质骨上增加的有效压应力引起未被修复坏死松质骨的体积减小,从而导致新月形空腔在软骨下骨板下形成,新月形空腔在X线片上显示出“新月征”。     

Morphological analysis of collapsed regions in osteonecrosis of the femoral head

In order to investigate the mechanisms of collapse in osteonecrosis of the femoral head, we examined which part of the femoral head was the key point of a collapse and whether a collapsed region was associated with the size of the necrotic lesion. Using 30 consecutive surgically removed femoral heads we retrospectively analysed whole serial cut sections, specimen photographs, specimen radiographs and histological sections. In all of the femoral heads, collapse consistently involved a fracture at the lateral boundary of the necrotic lesion. Histologically, the fractures occurred at the junction between the thickened trabeculae of the reparative zone and the necrotic bone trabeculae. When the medial boundary of the necrotic lesion was located lateral to the fovea of the femoral head, 18 of 19 femoral heads collapsed in the subchondral region. By contrast, when the medial boundary was located medial to the fovea, collapse in the subchondral region was observed in four of 11 femoral heads (p = 0.0011). We found that collapse began at the lateral boundary of the necrotic lesion and that the size of the necrotic lesion seemed to contribute to its distribution.     

RANKL inhibition: a novel strategy to decrease femoral head deformity after ischemic osteonecrosis.

A novel therapeutic strategy to decrease the development of femoral head deformity after ischemic osteonecrosis was studied in a large animal model of total head infarction. RANKL inhibition through exogenous osteoprotegerin administration significantly decreased pathologic bone resorption and deformity during repair of the infarcted head. INTRODUCTION: Legg-Calvé-Perthes disease (LCPD) is a juvenile form of osteonecrosis of the femoral head that can produce permanent femoral head deformity (FHD) and premature osteoarthritis. The development of FHD in LCPD is closely associated with the repair process, characterized by a predominance of bone resorption in its early stage that produces a fragmented appearance and collapse of the femoral head. We present here a novel strategy to preserve the femoral head structure after ischemic osteonecrosis based on inhibition of interaction between RANK and RANKL using exogenous administration of osteoprotegerin (OPG-Fc) in a large animal model of ischemic osteonecrosis. MATERIALS AND METHODS: Ischemic osteonecrosis was surgically induced in 18 male piglets by placing a ligature tightly around the right femoral neck to disrupt the blood flow to the right femoral head. Two weeks after the induction of total head infarction, OPG-Fc or saline was administered subcutaneously to nine animals per group for 6 weeks. The contralateral, normal (left) femoral heads from the animals treated with saline served as normal, nondisease controls. All animals were killed at 8 weeks when severe FHD has been previously shown to occur because of the repair process dominated by osteoclastic bone resorption. Radiographic, histomorphometric, and immunohistochemical assessments were performed. RESULTS: Radiographic assessment showed significantly better preservation of the femoral head structure in the OPG-Fc group compared with the saline group. Epiphyseal quotient (the ratio of epiphyseal height to diameter) was significantly higher in the OPG-Fc group (0.41 +/- 0.09) compared with the saline group (0.24 +/- 0.08, p < 0.001). Histomorphometric assessment revealed a significant reduction in the number of osteoclasts present in the OPG-Fc group (5.9 +/- 5.3mm(-2)) compared with the saline group (39.6 +/- 13.8 mm(-2), p < 0.001). Trabecular bone volume, number, and separation were significantly better preserved in the OPG-Fc group compared with the saline group (p < 0.001). No significant difference in femoral length was observed between the OPG-Fc and saline groups. Immunostaining revealed the presence of OPG-Fc only within the blood vessels, with no apparent staining of bone matrix or trabecular bone surfaces. CONCLUSIONS: To our knowledge, this is the first study to show that RANKL inhibition decreases bone resorption and FHD after ischemic osteonecrosis. Because RANKL inhibitors do not bind to bone, their effects on resorption are reversible as the drug is cleared from circulation. The reversible nature of RANKL inhibitors is very appealing for treating pediatric bone diseases such as LCPD, where the resorptive stage of the disease lasts for 1-2 years.     

Subcapital fractures associated with extensive osteonecrosis of the femoral head

The authors reviewed 10 patients with subcapital fractures associated with extensive osteonecrosis of the femoral head and distinguished these fractures from traumatic femoral neck fractures The mean age of the patients was 52 years (range, 36-68 years). Nine patients were younger than 60 years. Eight patients had risk factors for osteonecrosis. Necrosis was extensive and involved nearly the whole femoral head. Fracture occurred at the junction between a necrotic bone and reparative bone and extended downward through the reparative interface to the healthy inferior cortex of the femoral neck. Patients experienced hip pain that was aggravated gradually during a period of 1 to 24 weeks before diagnosis of the fracture. In all patients, the opposite femoral head was involved with osteonecrosis. In two femoral heads, slight collapse or subchondral fracture (crescent sign) also was observed. No patient had a history of precipitating trauma. In patients younger than 60 years with a subcapital fracture, fracture associated with extensive osteonecrosis of the femoral head should be suspected when a history of trauma is not obvious, when the opposite hip shows findings of osteonecrosis, and when the patient has a risk factor of osteonecrosis. In these fractures, osteosynthesis rarely should be considered because of the high failure rate caused by additional progression of extensive osteonecrosis and the probability of nonunion.     

Development of flattening and apparent fragmentation following ischemic necrosis of the capital femoral epiphysis in a piglet model

BACKGROUND: The repair response that follows ischemic necrosis of the immature femoral head and the biological processes that are responsible for the development of femoral head deformity and fragmentation have not been clearly defined. A piglet model was used to study the radiographic and histopathologic changes that occur prior to and during the development of femoral head deformity and fragmentation following ischemic necrosis. METHODS: Twenty-five male piglets were studied. A nonabsorbable ligature was placed tightly around the femoral neck to disrupt the blood supply to the capital femoral epiphysis. The animals were killed three days to eight weeks following the induction of ischemia. Radiographs of whole and sectioned femoral heads were made, and the radiographic findings were correlated with the histopathologic changes observed in the specimens. RESULTS: Mild femoral head flattening was observed by four weeks after the induction of ischemia, and severe flattening and fragmentation were observed by eight weeks. The predominant repair response observed following revascularization was osteoclastic bone resorption. Prior to the development of flattening, a large area of osteoclastic bone resorption was observed in the central region of the femoral head. Many osteoclasts were present along the revascularization front, which we believe were responsible for active resorption of the necrotic trabecular bone. Appositional new-bone formation, the hallmark of the repair response in adult ischemic necrosis, was not observed in the area of bone resorption. Instead, the areas of resorbed bone were replaced with a fibrovascular tissue that persisted for up to eight weeks. Appositional new-bone formation was observed, but it was limited to small areas in which revascularization was not followed by osteoclastic bone resorption and in which necrotic trabecular bone was still present. The simultaneous presence of the areas of bone resorption and new-bone formation contributed to the fragmented radiographic appearance of the femoral head. CONCLUSIONS: The predominant repair response observed in the piglet model of ischemic necrosis was osteoclastic bone resorption. The early bone loss, the lack of new-bone formation, and the persistence of fibrovascular tissue in the areas of bone resorption compromised the structural integrity of the femoral head and produced progressive femoral head flattening over time. The repair response was different from that observed in femoral heads removed from adult patients with ischemic necrosis and from that observed in the adult rabbit model of ischemic necrosis. Clinical Relevance: The piglet model of ischemic necrosis may be useful for the investigation of the biological processes that lead to the development of femoral head deformity following ischemic necrosis of the immature femoral head.     

Femoral head stress fracture: an unknown complication following Sugioka's transtrochanteric rotational osteotomy

Sugioka's transtrochanteric rotational osteotomy, as a treatment of osteonecrosis of the femoral head, has variable success rates. Its known complications include: progressive varus deformity, femoral neck fracture, and femoral head collapse. However, femoral head stress fracture has not been described as a complication of Sugioka's transtrochanteric rotational osteotomy. This article presents cases of 2 of 64 patients who underwent Sugioka's transtrochanteric rotational osteotomy between 1994 and 2006 and experienced femoral head stress fractures. Both patients were young and active. They presented with acute inability to bear weight and pain on the operated hip after mountain climbing 1 and a half to 3 years following the index surgery. Diagnosis of femoral head stress fracture was established by the presence of an inferolaterally-directed vertical fracture line from the superolateral aspect of the femoral head on computed tomography scans for both patients. One patient was successfully managed with conservative measures, whereas the other underwent total hip replacement after failed conservative treatment. We hypothesize that the direction alteration of the trabecular system due to proximal femoral segment rotation, varus positioning of the proximal femur, and inadequate placement of the screw into the necrotic femoral head may have caused the femoral head stress fractures after transtrochanteric rotational osteotomies. Stress fracture of the femoral head is a potential complication following Sugioka's transtrochanteric rotational osteotomy for osteonecrosis of the femoral head, which may be prevented by avoiding heavy exercises such as mountain climbing, until adequate remodeling of the trabecular system is gained and screws can be inserted into the femoral head subchondral bone as deeply as possible with avoidance of the necrotic area.     

Osteonecrosis in retrieved femoral heads after failed resurfacing arthroplasty of the hip

We present the histological findings of bone retrieved from beneath the femoral components of failed metal-on-metal hip resurfacing arthroplasties. Of a total of 377 patients who underwent resurfacing arthroplasty, 13 required revision; for fracture of the femoral neck in eight, loosening of a component in three and for other reasons in two. None of these cases had shown histological evidence of osteonecrosis in the femoral bone at the time of the initial implantation. Bone from the remnant of the femoral head showed changes of osteonecrosis in all but one case at revision. In two cases of fracture which occurred within a week of implantation, the changes were compatible with early necrosis of the edge of the fracture. In the remaining six fractures, there were changes of established osteonecrosis. In all but one of the non-fracture cases, patchy osteonecrosis was seen. We conclude that histological evidence of osteonecrosis is a common finding in failed resurfaced hips. Given that osteonecrosis is extensive in resurfaced femoral heads which fail by fracture, it is likely to play a role in the causation of these fractures.     

Bilateral femoral head osteonecrosis after septic shock and multiorgan failure.

A case of bilateral femoral head osteonecrosis after septic shock is presented. We suggest that the osteonecrosis was caused by ischemic insults to the proximal femora. The association between septic shock and osteonecrosis has not been previously reported. INTRODUCTION: Osteonecrosis is an uncommon disorder characterized by the in situ death of bone. A diverse range of conditions has been associated with osteonecrosis. We present a case of bilateral femoral head osteonecrosis that occurred after an episode of septic shock. MATERIALS AND METHODS: A 66-year-old woman presented with a left-sided renal stone and a urinary tract infection. Her condition rapidly progressed to a life-threatening illness with septic shock complicated by multiorgan failure, which necessitated prolonged intensive care and inotropic support. She made a full recovery but 3 months later developed bilateral osteonecrosis of the femoral heads requiring bilateral total hip joint replacement. RESULTS AND CONCLUSIONS: We propose that the osteonecrosis was caused by ischemic insults to the femoral heads as a result of the widespread systemic ischemia that occurred during her initial illness. To our knowledge, septic shock has not been previously described as a cause of osteonecrosis. Clinicians should be aware of this association, particularly in patients presenting with bone pain after episodes of sepsis.     

A micro-architectural evaluation of osteoporotic human femoral heads to guide implant placement in proximal femoral fractures

Background and purpose The micro-architecture of bone has been increasingly recognized as an important determinant of bone strength. Successful operative stabilization of fractures depends on bone strength. We evaluated the osseous micro-architecture and strength of the osteoporotic human femoral head.

Material and methods 6 femoral heads, obtained during arthroplasty surgery for femoral neck fracture, underwent micro-computed tomography (microCT) scanning at 30 μm, and bone volume ratio (BV/TV), trabecular thickness, structural model index, connection density, and degree of anisotropy for volumes of interest throughout the head were derived. A further 15 femoral heads underwent mechanical testing of compressive failure stress of cubes of trabecular bone from different regions of the head.

Results The greatest density and trabecular thickness was found in the central core that extended from the medial calcar to the physeal scar. This region also correlated with the greatest degree of anisotropy and proportion of plate-like trabeculae. In the epiphyseal region, the trabeculae were organized radially from the physeal scar. The weakest area was found at the apex and peripheral areas of the head. The strongest region was at the center of the head.

Interpretation The center of the femoral head contained the strongest trabecular bone, with the thickest, most dense trabeculae. The apical region was weaker. From an anatomical and mechanical point of view, implants that achieve fixation in or below this central core may achieve the most stable fixation during fracture healing.     

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.     

Spontaneous osteonecrosis of the knee: the result of subchondral insufficiency fracture

BACKGROUND: Spontaneous osteonecrosis of the knee is a superficial subchondral lesion classically seen in the medial femoral condyle; in general, it is markedly different in its clinicopathological presentation from the classic wedge-shaped subchondral osteonecrotic lesions seen in the hip, knee, and other joints. Recent reports on subchondral insufficiency fracture of the femoral head, which has marked morphological similarities with spontaneous osteonecrosis of the knee, led us to reevaluate a series of patients who had had operative treatment because of a clinical and pathological diagnosis of spontaneous osteonecrosis of the knee. METHODS: We reviewed the cases of fourteen patients who had had operative treatment of spontaneous osteonecrosis of the knee in order to reevaluate the gross and histological morphology of this lesion. The patients included eight women and six men who ranged in age from fifty-nine to eighty-eight years. In all patients, the diagnosis of spontaneous osteonecrosis of the knee had been based on clinical presentation, imaging studies, and pathological findings. The appearance of the lesion on plain radiographs was categorized into four stages, which corresponded to the gross and histological findings. In stage 1, the radiographic appearance is normal; in stage 2, a radiolucent oval area is seen subchondrally or there is slight flattening of the convexity of the condyle, or both; in stage 3, the radiolucent area is expanded and is surrounded by a sclerotic halo; and in stage 4, secondary osteoarthritic changes are apparent. RESULTS: No patient had a stage-1 lesion. Three patients, all of whom had a stage-2 lesion, were considered to have a subchondral insufficiency fracture of the medial femoral condyle. Another six patients, all of whom had a stage-3 lesion, were considered to have a subchondral fracture and associated focal osteonecrosis that was confined to the area between the fracture line and the articular surface. The remaining five patients, three of whom had a stage-3 lesion and two of whom had a stage-4 lesion, had indeterminate findings because the lesion had become detached from the condyle. CONCLUSIONS: Our histopathological findings suggest that the primary event leading to spontaneous osteonecrosis of the knee is a subchondral insufficiency fracture and that the localized osteonecrosis seen in association with this disease is the result of a fracture.     

淫羊藿苷干预兔早期激素性股骨头坏死的实验研究

目的探讨淫羊藿苷对激素诱导的兔早期激素性股骨头坏死干预效果。方法50只成年新西兰兔(体质量2.5~3.0 kg)随机分为对照组(n=10)、模型组(n=20)及实验组(n=20)。模型组和实验组采用脂多糖联合甲泼尼龙注射制备早期激素性股骨头坏死模型;实验组首次注射甲泼尼龙开始每日灌服淫羊藿苷药液1次,对照组及模型组灌服等量生理盐水,连续6周。于6周后取左侧股骨头行大体观察;Micro-CT扫描观察骨小梁微结构,测量骨小梁相对体积(bone volume to total volume,BV/TV)、骨小梁数量(trabecular number,Tb.N)、骨小梁厚度(trabecular thickness,Tb.Tn)及骨小梁分离度(trabecular separation,Tb.Sp),并构建三维图像观察;HE染色观察骨小梁结构、骨细胞及骨髓脂肪细胞形态变化,按照病理学诊断标准检测股骨头坏死模型造模是否成功,计算空骨陷窝率。结果实验期间共7只动物死亡,最终对照组9只、模型组16只、实验组18只纳入研究。大体及Micro-CT扫描、三维重建显示,与对照组相比,模型组股骨头塌陷明显,骨小梁断裂、排列紊乱稀疏;实验组股骨头表面皱褶,塌陷不明显,骨小梁结构轻度退变。与对照组相比,模型组和实验组Tb.N、Tb.Tn、BV/TV下降、Tb.Sp升高;与模型组相比,实验组Tb.N、Tb.Tn、BV/TV升高、Tb.Sp降低;组间比较差异均有统计学意义(P<0.05)。HE染色示模型组骨小梁中骨细胞减少,空骨陷窝较多,骨小梁间脂肪细胞堆积,部分呈囊状融合;实验组骨小梁形态较模型组完整,骨细胞坏死及脂肪细胞肥大不明显。按照股骨头坏死病理学诊断标准,对照组无骨坏死发生,模型组骨坏死发生率为81.3%(13/16),实验组为66.7%(12/18),差异无统计学意义(P=0.448)。模型组和实验组发生坏死的股骨头标本其空骨陷窝率分别为33.1%±1.4%及18.9%±0.8%,均高于对照组12.7%±1.5%,且模型组明显高于实验组,差异均有统计学意义(P<0.05)。结论淫羊藿苷对激素诱导的兔早期激素性股骨头坏死具有保护作用,可以降低骨细胞凋亡,改善骨微结构,延缓骨坏死发生。     

Abnormal subchondral bone microstructure following steroid administration is involved in the early pathogenesis of steroid-induced osteonecrosis

Summary

Loss of bone microstructure integrity is thought to be related to osteonecrosis. But the relationship between the time when bone microstructure integrity loss appears and the onset of osteonecrosis has not yet been determined. Our study demonstrated abnormal changes of subchondral bone microstructure involved in the early pathogenesis of osteonecrosis.

Introduction

Using a rabbit model, we investigated the changes of subchondral bone microstructure following steroid administration to identify the onset of abnormal bone microstructure development in steroid-induced osteonecrosis.

Methods

Fifty-five adult female Japanese White rabbits (mean body weight 3.5 kg; mean age 24 months) were used and randomly divided among three time points (3, 7, and 14 days) consisting of 15 rabbits each, received a single intramuscular injection of methylprednisolone acetate (MP; Pfizer Manufacturing Belgium NV) at a dose of 4 mg/kg, and a control group consisting of 10 rabbits was fed and housed under identical conditions but were not given steroid injections. A micro-CT scanner was applied to detect changes in the trabecular region of subchondral bone of excised femoral head samples. Parameters including bone volume fraction (BV/TV), bone surface (BS), trabecular bone pattern factor (Tb.Pf), trabecular thickness/number/separation (Tb.Th, Tb.N, and Tb.Sp), and structure model index (SMI) were evaluated using the software CTAn (SkyScan). After micro-CT scans, bilateral femoral heads were cut in the coronal plane at a thickness of 4 μm. The sections were then stained with haematoxylin-eosin and used for the diagnosis of osteonecrosis and the rate of development of osteonecrosis.

Results

The BV/TV, BS, Tb.Th and Tb.N demonstrated a time-dependent decline from 3, 7, and 14 days compared with the control group, while the Tb.Pf, Tb.Sp and SMI demonstrated an increase at 3, 7, and 14 days compared with the control group. For the histopathology portion, osteonecrosis was not seen 3 days after steroid treatment, but was present 7 days after treatment and was obvious 14 days after treatment. Furthermore, the rate of osteonecrosis appearing between 7 and 14 days was not significantly different. In addition, the presence and variation of BV/TV, BS, Tb.Pf, Tb.Th, Tb.N, and SMI demonstrated significant changes at 7 days compared with the control group except Tb.Sp (at 14 days) and this is the time when osteonecrosis is thought to occur in this model.

Conclusion

This study demonstrated that osteonecrosis in rabbits is chronologically associated with changes in subchondral bone microstructure.