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Background: Availability of a reliable mouse model of ischemic osteonecrosis could accelerate the development of novel therapeutic strategies to stimulate bone healing after ischemic osteonecrosis; however, no mouse model of ischemic osteonecrosis is currently available., Questions/purposes: To develop a surgical mouse model of ischemic osteonecrosis, we asked, (1) if the blood vessels that contribute to the blood supply of the distal femoral epiphysis are cauterized, can we generate an osteonecrosis mouse model; (2) what are the histologic changes observed in this mouse model, and (3) what are the morphologic changes in the model., Methods: We performed microangiography to identify blood vessels supplying the distal femoral epiphysis in mice, and four vessels were cauterized using microsurgical techniques to induce ischemic osteonecrosis. Histologic assessment of cell death in the trabecular bone was performed using terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) and counting the empty lacunae in three serial sections. Quantitation of osteoclast and osteoblast numbers was performed using image analysis software. Morphologic assessments of the distal femoral epiphysis for deformity and for trabecular bone parameters were performed using micro-CT., Results: We identified four blood vessels about the knee that had to be cauterized to induce total ischemic osteonecrosis of the distal femoral epiphysis. Qualitative assessment of histologic sections of the epiphysis showed a loss of nuclear staining of marrow cells, disorganized marrow structure, and necrotic blood vessels at 1 week. By 2 weeks, vascular tissue invasion of the necrotic marrow space was observed with a progressive increase in infiltration of the necrotic marrow space with the vascular tissue at 4 and 6 weeks. TUNEL staining showed extensive cell death in the marrow and trabecular bone 24 hours after the induction of ischemia. The mean percent of TUNEL-positive osteocytes in the trabecular bone increased from 2% ± 1% in the control group to a peak of 98% ± 3% in the ischemic group 1 week after induction of ischemia (mean difference, 96%; 95% CI, 81%-111%; p < 0.0001). The mean percent of empty lacunae increased from 1% ± 1% in the control group to a peak of 78% ± 15% in the ischemic group at 4 weeks (mean difference, 77%; 95% CI, 56%-97%; p < 0.0001). Quantitative analysis showed that the mean number of osteoclasts per bone surface was decreased in the ischemic group at 1, 2, and 4 weeks (p < 0.0001, < 0.0001, and p = 0.02, respectively) compared with the control group. The mean number of osteoclasts increased to a level similar to that of the control group at 6 weeks (p = 0.23). The numbers of osteoblasts per bone surface were decreased in the ischemic group at 1, 2 and 4 weeks (p < 0.0001 for each) compared with the numbers in the control group. The mean number of osteoblasts also increased to a level similar to that of the control group at 6 weeks (p = 0.91). Mean bone volume percent assessed by micro-CT was lower in the ischemic group compared with the control group from 2 to 6 weeks. The mean differences in the percent bone volume between the control and ischemic groups at 2, 4, and 6 weeks were 5.5% (95% CI, 0.9%-10.2%; p = 0.01), 5.3% (95% CI, 0.6%-9.9%; p = 0.02), and 6.0% (95% CI, 1.1%-10.9%; p = 0.008), respectively. A deformity of the distal femoral epiphysis was observed at 6 weeks with the mean epiphyseal height to width ratio of 0.74 ± 0.03 in the control group compared with 0.66 ± 0.06 in the ischemic group (mean difference, 0.08; 95% CI, 0.00-0.16; p = 0.03)., Conclusion: We developed a novel mouse model of ischemic osteonecrosis that produced extensive cell death in the distal femoral epiphysis which developed a deformity with time., Clinical Relevance: The new mouse model may be a useful tool to test potential therapeutic strategies to improve bone healing after ischemic osteonecrosis.

Background: In patients with corticosteroid treatment, the elbow is a rare site of osteonecrosis; there is little information about the rate and risk factors of disease progression in symptomatic and asymptomatic elbows., Question/purposes: We determined the delay between the beginning of corticosteroid treatment and different stages of osteonecrosis and which stage and dose of steroids influenced disease progression., Methods: Osteonecrosis related to corticosteroids was diagnosed by MRI in 50 elbows of 35 adult patients. Thirty elbows were asymptomatic at initial evaluation (19 with Stage I, 11 with Stage II osteonecrosis). Among the 20 elbows symptomatic at initial evaluation, 13 had radiographic evidence of osteonecrosis without collapse (Stage II) and seven had lesions evident only on MRI (Stage I)., Results: At latest followup (average, 17 years; range, 10-25 years), of the 30 previously asymptomatic elbows, pain developed in 24 and collapse occurred in 14; of the 20 previously symptomatic elbows, 15 showed collapse (seven initially with Stage I, eight with Stage II osteonecrosis). The average time between diagnosis and collapse was 8 and 5 years, respectively, for symptomatic elbows with Stages I and II osteonecrosis. Stage at initial visit, development of pain, and continuation of peak doses of corticosteroids were risk factors for disease progression in asymptomatic elbows. In symptomatic elbows, the extent in contact with the articular surface and lesion location were the main risk factors for disease progression., Conclusions: Untreated asymptomatic and symptomatic elbow osteonecrosis related to corticosteroids has a moderate likelihood of elbow collapse, with decrease in ROM, but none of the patients in this case series followed for 10 to 20 years had elbow arthroplasty., Level of Evidence: Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Background: The literature suggests survivorship of unicompartmental knee arthroplasties (UKAs) for spontaneous osteonecrosis of the knee ranges from 93% to 97% at 10 to 12 years. However, these data arise from small series (23 to 33 patients), jeopardizing meaningful conclusions., Questions/purposes: We determined (1) the longer-term survivorship of UKAs in a larger group of patients with spontaneous osteonecrosis of the knee; (2) their subjective, symptomatic, and functional outcomes; and (3) the percentage of failures and reasons for failures to identify relevant indications, contraindications, and technical parameters for treatment with a modern implant design., Methods: We retrospectively evaluated all 84 patients with late-stage spontaneous osteonecrosis of the knee who had a medial UKA from 1998 to 2005. All patients had preoperative MRI to confirm the diagnosis, exclude metaphyseal involvement, and confirm the absence of major degenerative changes in the lateral and patellofemoral compartments. The mean age of the patients at surgery was 66 years and mean BMI was 28.9. We conducted Kaplan-Meier survival analysis using revision for any reason as the end point. Minimum followup was 63 months (mean, 98 months; range, 63-145 months)., Results: Ten-year survivorship was 89%. Ten revisions were performed; the most common reasons were subsidence of the tibial component (four) and aseptic loosening of the tibial component (three). No patient underwent revision for progression of osteoarthritis in the lateral or patellofemoral compartments., Conclusions: Our data suggest spontaneous osteonecrosis of the knee may be an indication for UKA, provided secondary osteonecrosis of the knee is ruled out, preoperative MRI documents the absence of disease in other compartments, and there is no overcorrection in any plane., Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Background: Limited experimental research has been performed on the treatment of avascular necrosis (AVN) by vascularized bone grafting., Questions/purposes: A new model simulating carpal AVN was created to investigate surgical revascularization of necrotic bone., Methods: In seven mongrel dogs, AVN was induced by removal of the radial carpal bones bilaterally, deep-freezing, coating in cyanoacrylate, and reimplantation. A reverse-flow vascularized bone graft from the distal radius was implanted in the avascular radial carpal bone. The contralateral side served as an untreated ischemic control. Bone blood flow, bone volume, radiography, histomorphometry, histology, and MRI were analyzed at 4 weeks., Results: Blood flow was substantially higher in grafted bones when compared with controls (14.68 ± 15.43 versus 0.27 ± 0.28 mL/minute/100 g). Blood flow correlated with increased osteoid formation and higher levels of bone turnover. T1 and T2 signals on MRI did not correlate with quantitative bone blood flow measurements. Necrotic bones with no blood flow had normal T1 and T2 signals, whereas revascularized bones had signal changes when compared with adjacent carpal bones. No major collapse occurred in any radiocarpal bone., Conclusion: In a canine experimental model, investigation of carpal AVN shows the ability of vascularized bone grafting to revascularize and remodel avascular bone., Clinical Relevance: Surgical revascularization of necrotic bone induced by vascularized bone grafting results in increased bone perfusion and bone remodeling as compared with untreated necrotic bone. MRI T1 and T2 signals can be normal in necrotic avascular bone.

Background: Osteonecrosis is a major treatment complication of pediatric leukemias owing to its potential to cause joint deterioration. Because of potential long-term effects of osteonecrosis on joints, information regarding its progression and collapse in different patients can be used to identify high-risk groups, advise the patients and parents of this complication, and potentially consider the risk for development of osteonecrosis in planning primary treatment., Questions/purposes: We therefore determined: (1) the incidence of joint collapse and/or pain in young patients with hematologic malignancies diagnosed with ON of the knee; (2) risk factors associated with collapse; and (3) the relationship between size and location of osteonecrotic knee lesions and the likelihood of joint collapse., Patients and Methods: We retrospectively reviewed 109 patients with hematologic malignancies and MRI-confirmed knee osteonecrosis. The median age was 11.5 years (range, 2.3-18.8 years) at primary diagnosis of hematologic malignancy and a median age of 13.4 years (range, 2.7-23.3 years) at diagnosis of osteonecrosis of the knee. For analyses, we used the first and last MR images. Minimum clinical followup was 2.3 years after diagnosis of knee osteonecrosis (median, 6 years; range, 2.3-7.17 years)., Results: Joint collapse occurred in 22% (24 of 109). Older age, pain at osteonecrosis presentation, and lesions extending to the articular surface of distal femoral epiphyses were associated with joint collapse., Conclusions: Younger patients and those without extensive femoral epiphyseal involvement have a better prognosis for osteonecrosis of the knee., Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Background: Little is known about the rate and factors of progression of shoulder osteonecrosis (ON) related to corticosteroids., Purpose: We retrospectively evaluated 125 patients (215 shoulders) with humeral head ON diagnosed by MRI to determine the delay between corticosteroid treatment and the different stages and factors influencing the progression of the disease., Methods: Seventy-four of the shoulders had asymptomatic Stage I ON, 58 had asymptomatic Stage II ON, 46 had symptomatic Stage I ON, and 37 had symptomatic Stage II ON. The minimum followup was 10 years (average, 14 years; range, 10-20 years). The delay between the beginning of the corticosteroid treatment and the diagnosis of ON of the humeral head averaged 15 months (range, 6-24 months)., Results: We observed partial or total regression on MRI only in patients with asymptomatic Stage I ON. At last followup, pain had developed in 98 (74%) and collapse had occurred in 71 (54%) of the 132 previously asymptomatic shoulders. Of the 83 symptomatic shoulders, 68 (82%) had collapsed at the final followup. The time between diagnosis and collapse averaged 10 years for patients with symptomatic Stage I ON and 3 years for patients with symptomatic Stage II ON., Conclusions: Stage at initial visit, occurrence of pain, and continuation of peak doses of corticosteroids predicted progression of disease in asymptomatic shoulders, whereas in the symptomatic shoulders, extent and location of the lesion were the main risk factors for progression., Level of Evidence: Level II, prognostic study. See Guidelines for Authors for a complete description of levels.

Osteonecrosis (ON) is commonly caused by high doses of glucocorticoids or ethanol intake. We previously reported suppression of BMP-2 by dexamethasone was more pronounced and enhancement by lovastatin was less pronounced in bone marrow stromal cells (BMSCs) from patients with ON than from patients without ON. We therefore presumed the BMSCs might be dysfunctional in patients with ON and performed this pilot study. We obtained BMSCs from 10 patients with ethanol-induced ON, 10 patients with glucocorticoid-induced ON, and 12 patients without ON as control subjects, checking third passage cells for osteogenic and adipogenic gene expression and differentiation ability. BMSCs from patients with glucocorticoid-induced ON possessed less osteogenic gene expression and less osteogenic differentiation, whereas BMSCs from patients with ethanol-induced ON possessed more adipogenic gene expression and more adipogenic differentiation. Dysfunction of BMSCs may be one of the causes of ON, with differing dysfunction in ethanol-induced ON and glucocorticoid-induced ON. Glucocorticoids may possess more of a suppressive effect on osteogenesis than ethanol, whereas ethanol may possess a more potent adipogenic effect than glucocorticoids on BMSCs.

Transient osteoporosis is characterized primarily by bone marrow edema. The disease most commonly affects the hip, knee, and ankle in middle-aged men. Its cause remains unknown. The hallmark that separates transient osteoporosis from other conditions presenting with a bone marrow edema pattern is its self-limited nature. Laboratory tests usually do not contribute to the diagnosis. Plain radiographs may reveal regional osseous demineralization. Magnetic resonance imaging is used primarily for early diagnosis and monitoring disease progression. Early differentiation from more aggressive conditions with long-term sequelae is essential to avoid unnecessary treatment. Clinical entities such as transient osteoporosis of the hip and regional migratory osteoporosis are spontaneously resolving conditions. However, early differential diagnosis and surgical treatment are crucial for the patient with osteonecrosis of the hip or knee.

Several animal and human studies suggest pharmacological approaches may prevent steroid-induced osteonecrosis (ON). We asked whether the newly developed 3-hydroxymethyl-3-glutaryl-CoA (HMG-CoA) reductase inhibitor, pitavastatin, could prevent steroid-induced ON in rabbits. We injected 65 adult male Japanese white rabbits once with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. The rabbits were divided into two groups; one group of 35 rabbits received pitavastatins (PS), and the other group of 30 rabbits received no prophylaxis (CTR). Hematological examinations were performed just before the steroid injection (0 weeks) and at 1 and 2 weeks after steroid injection; both the femora and the humeri were histologically examined 2 weeks postinjection. The incidence of histologic changes consistent with early ON in the PS group (13 of 35; 37%) was lower in comparison to the CTR group (21 of 30; 70%). The size of the bone marrow fat cells in the PS group (56.6 +/- 10 microm) was smaller than those in the CTR group (60 +/- 4 microm). The data suggest pitavastatin has the potential to lower the incidence of steroid-induced ON in rabbits.

Although MRI is useful for predicting progression of osteonecrosis (ON) of the femoral head or femoral condyle, predicting outcome of atraumatic osteonecrosis of the humeral head using MRI has not been previously examined. We asked whether the prognosis was related to the extent and location of necrotic lesions on MRI. We investigated 46 radiographically noncollapsed humeral heads in 27 patients, 24 steroid-related and three alcohol-related, using MRI and serial radiographs. The minimum followup was 24 months (mean, 84.9 months; range, 24-166 months). The necrotic lesion was typically located at the medial and superior aspect of the humeral head. The necrotic angle, which expressed the extent of the necrotic lesion, was measured on midoblique-coronal plane (range; 0 degrees -134.7 degrees ) and on midoblique-sagittal plane (range; 0 degrees -150.6 degrees ). Of the 46 lesions, 34 were less than 90 degrees and did not collapse, whereas 11 of the other 12 lesions of more than 90 degrees (92%) collapsed within 4 years. Of these 11 collapsed lesions, four of less than 100 degrees did not progress, followed by reparative reaction on plain radiographs, whereas the other seven of more than 100 degrees progressed to osteoarthritis. The extent of a necrotic lesion on MRI is useful to predict collapse of the humeral head.

The treatment of osteonecrosis of the hip remains a dilemma. Contemporary basic science research focuses on establishing the molecular etiology of this disease with the hope of identifying targets for pharmacologic intervention. Researchers have identified specific genetic polymorphisms that may predispose its development and these may allow early diagnosis and treatment of at-risk patients. Refinements in magnetic resonance imaging aid in the staging of patients with osteonecrosis and findings appear to correlate with clinical outcome. Novel nonoperative and operative modalities for the treatment of osteonecrosis are also under investigation. The results of new pharmacologic and biophysical treatments appear beneficial in delaying, and possibly preventing, the progression of precollapse lesions. New bone grafting strategies may enhance the results of core decompression. Although the results of conventional total hip arthroplasty have improved, newer surface replacement systems provide satisfactory short-term outcomes and may preserve bone stock in younger patients. Further research is needed to clarify the roles of these emerging technologies in the treatment of osteonecrosis of the hip. Until there is convincing evidence of efficacy in randomized clinical trials, we recommend appropriate staging and core decompression with or without bone graft for precollapse lesions and total hip arthroplasty or surface replacement for advanced disease.

Unlabelled: Subchondral fracture of the femoral head has been reported to occur as an insufficiency fracture associated with poor bone quality or as a fatigue fracture in young military recruits. Transient osteoporosis of the hip has clinical and imaging findings that resemble those of a subchondral fracture, but it usually occurs in healthy middle-aged people not involved in sports or similar activities. The clinical aspects of five cases of subchondral fracture of the femoral head occurring in four healthy adults without antecedent trauma were evaluated. Of particular interest were whether subchondral fracture of the femoral head could occur without a sudden increase in daily activity and what differences could be detected from the imaging and clinical courses between subchondral fracture of the femoral head and transient osteoporosis of the hip. Three cases of subchondral fracture of the femoral head occurred without an increase in daily activity. The only difference in imaging findings between subchondral fracture of the femoral head and transient osteoporosis of the hip was the existence of a subchondral fracture line seen on magnetic resonance images of a subchondral fracture of the femoral head. The clinical courses of these disorders were similar. These findings suggest transient osteoporosis of the hip and subchondral fracture of the femoral head are subchondral bone injuries of different severity., Level of Evidence: Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Unlabelled: Unicompartmental knee arthroplasty is a logical procedure when the lesion is limited to one femorotibial compartment. The procedure can now be performed through a mini-incision to provide quicker recovery because the extensor mechanism disruption is minimized. We have found the length of the incision varies according to patient mass and muscle tone. Specific instrumentation limited to the replaced compartment and using either an intra- or extramedullary femoral technique provides femorotibial component alignment and allows slight undercorrection of the deformity. Radiographic assessment demonstrates precise implantation of the components is possible with a mini-incision, which is believed important for the long-term results of the arthroplasty. The functional evaluation of patients implanted with unicompartmental knee arthroplasty performed through a mini-incision suggests appropriate kinematics can be restored after the procedure, enhancing the importance of a functional anterior cruciate ligament., Level of Evidence: Level V, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Age seems to affect the efficacy of radial osteotomies for Kienböck disease. We questioned whether an osteotomy would produce acceptable results in teenagers. We retrospectively identified 11 patients (six males and five females) between 11-19 years of age who were treated with radial osteotomies for Kienböck disease. Preoperatively, three patients had Lichtman Stage II disease, two patients had Stage IIIA disease, and six patients had Stage IIIB disease. Two patients with zero or positive ulnar variance had lateral closing wedge osteotomies, and nine patients with negative ulnar variance had radial shortenings. All patients were evaluated clinically and radiographically. At a mean followup of 50 months, 10 of 11 patients were free from pain, and the remaining one patient had moderate wrist pain during strenuous activity. All patients except one, who had Stage IIIB disease, had an excellent clinical outcome. Radiographic improvement, indicating lunate revascularization, was seen for eight patients. Despite Stage IIIB disease, radial osteotomies produced excellent clinical results in five of six teenage patients. The current results indicate that radial osteotomies are effective in improving not only short-term clinical outcomes, but also radiographic findings in teenage patients with Kienböck disease.

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.

Avascular necrosis of the metacarpal head is a rare condition. Although the condition is associated with trauma, systemic lupus erythematosus, and steroid use, it can occur spontaneously without any obvious cause. Any metacarpal may be affected and the pathologic changes are similar to those described in other bones such as the femur. The diagnosis requires an index of suspicion in a young patient with spontaneous onset of symptoms localized to a metacarpophalangeal joint. Magnetic resonance imaging is a useful early diagnostic tool when the radiographic findings are nonspecific or absent. The natural history of the condition is not known. Although symptoms may resolve with nonoperative treatment, progressive collapse of the metacarpal head and subsequent degenerative arthritis is a possible long-term outcome. Curettage of the lesion and supplementary cancellous bone grafting has been reported to provide symptomatic relief in cases resistant to nonoperative treatment. A case is presented of idiopathic avascular necrosis of the head of the dominant ring finger metacarpal in a 27-year-old woman. The purpose of this report is to highlight the clinical presentation, radiographic features, pathologic findings, and outcome at 2 years after curettage and bone grafting.

In 510 patients with osteosarcoma of the extremity treated at the authors' institute between March 1983 and June 1995 with different regimens of neoadjuvant chemotherapy, factors that influenced the histologic response were investigated. The rate of total necrosis was not related to the patients' gender, age, site, size of tumor, serum of alkaline phosphatase values, or route of cisplatin administration. The histologic response significantly and independently correlated with the number of drugs administered before surgery and with the histologic subtype of the tumor. According to the number of drugs used, the percentage of total necrosis was 31% for a four-drug regimen, 18% for a three-drug regimen, and only 1.5% for a two-drug regimen. According to the histologic type, the rates of total necrosis were 41% for telangiectatic tumors, 36% for fibroblastic tumors, 15% for osteoblastic tumors, and 3% for chondroblastic tumors. The authors concluded that in neoadjuvant therapy of osteosarcoma, the histologic response to preoperative treatment, which correlates with prognosis, depends on the effectiveness of the chemotherapy regimen and on some features intrinsically inherent to the tumor. These data should be considered when selecting the type of treatment (adjuvant or neoadjuvant) and the combinations of drugs to be used in preoperative treatment of patients with osteosarcoma.

The aim of the current study was to test the hypothesis that the induction of an underlying immunologic condition in rabbits may enhance the development of steroid-induced osteonecrosis. Thirty-five adult rabbits were divided into four groups. Group I: 10 rabbits were immunized at 15-day intervals for 2 months by murine antibodies to deoxyribonucleic acid autoantibodies. Four weeks after the end of the immunization, the animals received injections of methylprednisolone for 7 days and then prednisolone per os for 8 months. Group II: 10 animals only received immunizations according to the protocol used in Group I. Group III: 10 animals only were treated with corticosteroids according to the protocol used in Group I. Group IV: five animals were used as controls. Various changes were observed in the proximal metaphysis and diaphysis of the femur in eight of 10 animals in Group I (80%) and in five of 10 animals in Group II (50%) when compared with the animals in Group III and Group IV. The most common feature was evidence of new and old hemorrhage through the sinusoids, exudative reaction and thrombus formation in veins and small arteries. Focal necrotic areas of bone marrow showed an accumulation of cell debris, residue of hemorrhage, and disappearance of marrow elements. These findings suggest that (1) corticosteroids may potentiate the effects of a preexisting condition to increase the risk of osteonecrosis; (2) immunologic reaction may be an important factor in the pathogenesis of necrotic lesions; and (3) repeated intramedullary hemorrhage and thrombus formation may represent early major pathologic findings in bone necrosis.

Relatively few studies investigating the vascular patterns of the carpus have been performed. Technical difficulties in identifying small vessels in three dimensions and in determining their location within the thick ligaments about the wrist have led to conflicting anatomic reports. Studies on cadavers in which improved techniques with arterial injection, chemical debridement, and decalcification were used allowed the arterial anatomy of the carpus to be delineated more accurately. The current authors review these arterial patterns, with attention given to the extraosseous and intraosseous vascularities.

The effects of steroids on a cloned pluripotential cell from bone marrow stroma were examined in vitro in culture and in vivo after the cells were transfected with a traceable gene and transplanted into host mice. Bipedal chickens were treated with steroids to establish a model for osteonecrosis. The effects of a lipid lowering agent, lovastatin, on the prevention of steroid induced adipogenesis in vitro in cell culture, and on adipogenesis and osteonecrosis in vivo in chickens, were evaluated. On treatment with dexamethasone, cloned pluripotential cells began to differentiate into adipocytes and expressed a fat specific gene, whereas the expression of Type I collagen and osteocalcin messenger ribonucleic acid decreased. Addition of lovastatin in culture inhibited steroid induced fat gene expression and counteracted the inhibitory effect of steroids on osteoblastic gene expression. Cloned pluripotential cells were transduced with a traceable retrovirus vector encoding the beta-galactosidase and neomycin resistance genes. The transfected cells were administered to mice either by tail vein or by direct intramedullary injection. Half of the animals in each group were treated with steroids. Histologic sections showed the appearance of transplanted cells in the marrow. Analysis of marrow blowouts by flow cytometry revealed that steroid treatment produced adipogenesis in transplanted cells. Evidence of osteonecrosis was observed in steroid treated chickens, whereas sections from animals treated with steroids and lovastatin showed less adipogenesis and no bone death. The results indicate that steroid induced adipogenesis in the marrow may contribute to osteonecrosis and that lovastatin may be helpful in preventing the development of steroid induced osteonecrosis.

Synovial fluid from the knees of 16 patients undergoing revision knee arthroplasty for aseptic failure was subjected to base digestion and ultrafiltration. Filtered particles were scanned using scanning electron microscopy and analyzed with an image program. Polyethylene particles were identified visually and confirmed with the use of electron diffraction spectroscopy. Averaging more than 1500 particles per patient sample, 25,148 particles were analyzed. This corresponded to a concentration of 3000 polyethylene particles per milliliter of synovial fluid. Three populations of wear debris were identified in the fluid. Small globular particles with a mean area of 75 mu 2 represented 94% of all particles observed. The particles averaged 10 mu in diameter and often were seen in clumps. Long fibrous particles with a mean area of 1164 mu 2 made up 4% of the particle population. Large rhomboidal particles with an area of 557 mu 2 were observed least commonly and comprised the remainder of the particles visualized. All three particle types were observed in each fluid sample regardless of the wear pattern of the retrieved polyethylene liner. There were no differences in absolute particle counts, particle morphologic characteristics, or particle size between patients with and without gross polyethylene wear.

Dysbaric osteonecrosis was induced successfully in adult sheep after 12 to 13, 24-hour exposures to compressed air (2.6-2.9 atmospheres absolute) during a 2-month period. All exposed sheep had decompression sickness and extensive bone and marrow necrosis in their long bones. Radiographic analysis of these progressive lesions showed mottled to distinct medullary opacities and endosteal thickening characteristic of dysbaric osteonecrosis. Six months after the last hyperbaric exposure, neovascularization of once ischemic fatty marrow was centripetal from the diaphyseal cortex. Proliferating endosteal new bone, fatty marrow calcification, and appositional new bone formation were widespread. Juxtaarticular osteonecrosis involved marrow fibrosis and loss of osteocytes in subchondral cortical bone. Tidemark reduplication in juxtaarticular bone and cartilage thinning suggested possible early osteoarthritis induction by recurrent episodes of transient ischemia after multiple hyperbaric exposures. Dysbaric osteonecrosis appears to involve a bone compartment syndrome of elevated intramedullary pressure initiated by decompression induced N2 bubble formation in the fatty marrow of the long bones. An animal model that can be used to investigate the pathogenesis, diagnosis, and treatment of dysbaric osteonecrosis is discussed.

Anterior cruciate ligament reconstruction with patellar tendon was performed in 50 rabbits (two groups of 25 animals) by the outside-in (Group I) and the inside-out (Group II) techniques. Five animals from each group were sacrificed at different times (2 weeks, 1, 3, 6, and 9 months). Histologic analysis showed that the intraarticular part of the graft was morphologically similar to a normal ligament in both groups at 9 months. In Group 1, a newly formed bone-graft junction along the tunnel walls was observed inside the femoral tunnel. At 6 months, this junction resembled a direct type junction. The old bone-tendon junction showed an early disappearance of the fibrocartilage and was differentiated as a direct junction only at 9 months. In Group 2, at the site of the old bone-tendon junction a fibrocartilaginous layer was present during the whole process of remodeling, and at 6 months this area resembled a direct junction. These observations would suggest that when the junction is placed inside the tunnel (outside-in technique) the process of remodeling is more dramatic and slower than when it is placed at the intraarticular exit of the tunnel (inside-out technique), probably because of the formation of a new bone-graft junction along the tunnel walls that partially unload the old junction.

The role of magnetic resonance imaging in the diagnosis and treatment of patients with shoulder pain has increased remarkably in recent years, largely because of improved resolution of images and increased experience of musculoskeletal radiologists. In rotator cuff disease/impingement and instability, magnetic resonance imaging adds a new dimension to the clinical findings through the noninvasive visualization of either the pathology itself or frequently associated abnormalities. It is the associated abnormalities that are depicted in instability: glenoid irregularities, labral tears, capsular laxity, and Hill-Sachs deformities. Glenoid, labral, and Hill-Sachs abnormalities can be assessed with either magnetic resonance imaging or computed tomography arthrography. Magnetic resonance imaging has the advantages of noninvasiveness, multiplanar imaging capability and exquisite soft tissue contrast. In rotator cuff disease, magnetic resonance imaging depicts the status of the rotator cuff itself, revealing partial and full thickness tears, allowing an estimation of size and quality of tendon edges. Possible impingement sites can be identified. Primary instability with secondary impingement may be first suspected on magnetic resonance imaging. Postoperative complications, including recurrent tendon detachment, deltoid dehiscence, and infection, are clarified. Unsuspected but clinically important lesions, such as neoplasm, osteonecrosis, and ganglion with entrapment of the suprascapular nerve, each have characteristic magnetic resonance imaging appearances.

Bacterial endotoxic reactions can cause osteonecrosis in humans by disseminated intravascular coagulation. The authors first used a combination of the Shwartzman reaction and corticoid injections in rabbits to develop a new animal model of osteonecrosis. This model showed a significantly higher incidence and wider area of osteonecrosis in the femur and humerus than that found in rabbits with either Shwartzman reaction or steroid injection alone. Osteonecrosis was observed in several foci that were distributed from the diaphysis to the epiphysis in both bones. Histologically, the bone marrow cells underwent necrosis, whereas the bone trabeculae demonstrated either empty lacunae or pycnotic nuclei of osteocytes. Exogenous steroids appeared to potentiate the Shwartzman reaction and the magnitude of osteonecrosis, perhaps by increasing endothelial damage and hypercoagulability of those intraosseous and extraosseous vessels that subsequently thrombosed. This model may not only be useful in clarifying the etiology and early pathogenesis of human osteonecrosis after corticoid therapy, but also in designing pharmaceuticals for prevention and early treatment.

Dysbaric osteonecrosis (DON) can occur in humans and sheep after a single hyperbaric air exposure with inadequate decompression. The authors hypothesize that DON does not result from primary embolic or compressive effects of nitrogen bubbles on the osseous vasculature, but by secondary injury to the marrow adipose tissue by rapidly expanding nitrogen gas that triggers local, and possibly systemic, intravascular coagulation. A 28-year-old scallop diver remained at a depth of 92 feet in sea water for 4.5 hours on surface-supplied compressed air. Decompression sickness occurred after a no-stop ascent to the surface, and he died 70 minutes later. Autopsy showed multiple gas bubbles, not only within the great vessels, but in the fatty marrow of his femoral and humeral heads. Lipid and platelet aggregates were found on the surface of marrow bubbles. Fibrin-platelet thrombi were detected within dilated venous sinusoids adjacent to bubbles, and in veins, capillaries, and arterioles. Since pulmonary, renal, and intraosseous (subchondral) fat embolism and fibrin thromboses were observed, it is suggested that injured marrow adipocytes can release liquid fat, thromboplastin, and other vasoactive substances, which conceivably can also play a systemic procoagulant role in triggering disseminated intravascular coagulation and additional DON.

A triad of intraosseous fat embolism, intravascular coagulation (both thrombosis and hemorrhage), and osteonecrosis was pathologically demonstrated to coexist for the first time in humans. Specimens were evaluated from the earliest nontraumatic (18 hours) and traumatic (29 hours) femoral head lesions yet reported, and the cause and early pathogenesis were confirmed in a third case. An absolute overload of subchondral fat emboli, with hypercoagulability, stasis, and endothelial damage by free fatty acids, appears to cause end-organ death by triggering intravascular coagulation. This intermediary pathway appears to be capable of producing osteonecrosis by progressive fibrin platelet thromboses, which begin in vulnerable subchondral capillaries and sinusoids, especially when associated with arteriolar vasoconstriction and impaired secondary fibrinolysis (reperfusion of necrotic vessels with peripheral marrow hemorrhages). A relative overload of subperiosteal and subchondral fat emboli, which is below the ischemic/anoxic threshold but insufficient for intravascular coagulation, may cause osteopenia.

In the Swedish Multicenter Study of Knee Arthroplasty, 115 knees in 110 patients with knee osteonecrosis represented all reported cases treated with knee arthroplasty in the period from 1975 to 1986. Primary medial femoral condyle osteonecrosis was the most common osteonecrosis reported (89%). Preoperative roentgenograms were staged according to the type of osteonecrosis and classified according to the grade of arthrosis. Detailed measurements of the size of the lesion were also performed. For primary medial femoral osteonecrosis, the width of the lesion averaged 45% of the condyle. The mean width of the lesion (anteroposterior size) was 21 mm and the mean length (lateral size) was 34 mm. The mean depth on lateral roentgenograms was 6 mm. There was a high correlation of results among the various methods of measurement. Using regression analysis, it was possible to approximate the volume of the lesion even from a single measurement of the width on anteroposterior view. The size of osteonecrosis of the knee can be used to plan resection and select the implant design.

Osteonecrosis (ON) was experimentally induced in rabbits by employing a combined protocol of hypersensitivity vasculitis and administration of high-dose corticosteroids. Thirty-five adult rabbits were used: five were injected twice with horse serum (Group A), five were injected three times with methylprednisolone acetate (Group B), 20 were treated with a combination of horse serum and methylprednisolone acetate (Group C), and five were used as a control (Group D). Both femurs of each rabbit were obtained one to five weeks after the final treatment and were histologically examined. There was no evidence of ON in Groups A, B, and D, whereas vasculitis was prominent in the femurs of Group A rabbits. In Group C, 14 of 20 specimens (70%) showed histologic evidence of ON in the femoral metaphysis: seven showed marrow necrosis and seven marrow and trabecular necrosis. Intramedullary hemorrhage was detected in eight animals. All specimens that showed ON or marrow necrosis revealed arteriopathy (i.e., severe damage to the vascular wall structure of arterioles). These findings were similar to those observed in early ON of clinical materials. The authors conclude that arteriopathy plays an important role in the pathogenesis of ON.

In experimental intraoperative irradiation, 18 adult rabbits received a single, 50-Gy dose of x-radiation at a unilateral knee joint, and subsequent changes in the articular cartilage were examined over a 15-month period by histology, scanning electron microscopy, and autoradiography. Although the subchondral bone showed histologically typical findings of osteonecrosis three to nine months postirradiation, the articular cartilage revealed no obvious degenerative changes during the entire study period. Scanning electron microscopy revealed normal collagen architecture in the irradiated cartilage for as long as 15 months postirradiation. Autoradiography demonstrated active RNA synthesis by the irradiated chondrocytes during the same period. These results indicate that articular cartilage tissue tolerates intraoperative radiotherapy without sustaining serious degenerative changes, unless possible collapse or contracture disturbs its biomechanical integrity. The survival of articular cartilage can be advantageous for this type of limb-salvage surgery in the treatment of malignant bone tumors around a synovial joint.

The percentage of necrosis in a primary osteosarcoma after the patient has received preoperative chemotherapy is prognostic and is usually used to select subsequent chemotherapy. However, the percentage of necrosis that occurs spontaneously, without preoperative chemotherapy, has not been adequately studied. The examination of histologic macrosections of 76 osteosarcomas from patients who had not received preoperative treatment and of 20 patients who had received preoperative chemotherapy revealed a significant difference in the percentage of necrosis. There was minimal spontaneous necrosis, but necrosis after preoperative chemotherapy was usually extensive. The larger the tumor, the greater the percentage of spontaneous necrosis; however, size did not correlate with the percentage of necrosis with preoperative chemotherapy. Survival among those patients who did not receive preoperative treatment correlated with the size and percentage of necrosis. Necrosis in an osteosarcoma in a patient who has received preoperative chemotherapy can be considered the result of chemotherapy and not a spontaneous event.

Sickle cell anemia and Kienböck's disease occurred in an 18-year-old man. The association of the two conditions seems not to have been previously reported.

The effects of liquid nitrogen (LN) and polymethylmethacrylate (PMMA) on normal bone, bone graft incorporation, and reossification were evaluated by simulating a tumor in dogs with experimental bone cavity. Ten skeletally mature mongrel dogs (20 femora) were divided into three groups: Group I, controls; Group II, LN (with and without bone graft); and Group III, PMMA (with and without LN). Roentgenograms, whole-mount histology, and tetracycline fluorescence studies were performed on the distal femur. Correlation of these studies showed that (1) marked trabecular and bone necrosis, extending 7-12 mm around the circumference of the cavity, developed by three and seven weeks after LN but no bony necrosis occurred after PMMA; (2) the pattern of reossification following cryosurgery was delayed and abnormal, demonstrating increased calcification and metaplastic bone formation; (3) cryosurgery decreased the rate of bone graft incorporation; (4) the cryonecrotic rim following cryosurgery correlated with an abortive attempt at peripheral reossification; and (5) cryosurgery had no effect on the articular cartilage. Cryosurgery is effective in causing bone necrosis, whereas PMMA is not, and the pattern of reossification is delayed and altered by freezing. This study suggests that microvascular thrombosis with subsequent ischemic infarction of bone is a major cause of bone necrosis following cryosurgery.

Although viruses have recently been implicated in the pathogenesis of Paget's disease and Perthes' disease, little information is available regarding bone and marrow response to the presence of a noncarcinogenic virus. Vaccinia virus was introduced into the medullary cavity of the femoral shaft of 30 New Zealand White rabbits, and an appropriate control inoculation was performed. Virus was recovered from the inoculation site in 50% of the animals at intervals to one month after inoculation. Histologic abnormalities were observed in 69% of the test femora; similar abnormalities were not observed in the control femora. These abnormalities consisted of bone and marrow necrosis, lymphocyte and plasma cell infiltration, and new bone formation. Some of the newly formed bone was also necrotic. The latter observation suggests an alternative mechanism for the death of new bone, which, in Perthes' disease, has customarily been attributed to repeated ischemic insults.

Thirty-two rabbits were used experimentally to study the effect of cortisone in bone, lungs, kidneys, and liver. Cortisone does induce abnormal increases in the serum cholesterol, fatty metamorphosis of the liver and the fatty emboli of the subchondral vessels of the femoral heads. Clofibrate therapy appeared to modify the cortisone induced changes as evidenced by a lower serum cholesterol level, prevention or lessening of the increase in the marrow fat cell size. This might significantly improve microcirculation of the femoral head.

Scintigraphy, using 99mTc diphosphonate, has the potential for diagnosing osteonecrosis before irreversible changes are visible in routine roentgenograms. If obtained within weeks of an avascular insult, a cold area will appear on scintiscan. However, months later, the revascularization and reparative processes of the dead bone produce a hot area on scintiscan.

New Zealand white rabbits were divided into 4 groups for the study of the etiology of corticosteroid-induced osteonecrosis (avascular necrosis). Group A and B received intramuscular injections of methylprednisolone acetate and methylprednisolone succinate respectively. Group C, on semirestricted diets, and Group D, on ad libitum diets, were controls. Osteocyte death, necrotic debris and intravascular fat emboli were evident in sections of proximal and distal femur by the 2nd week in experimental animals. Blood analysis revealed elevated lipid and prostaglandin levels. Osteoporosis was first observed at 6 weeks. Evidence of advanced osteonecrosis was present histologically at 18 weeks. It is concluded that osteonecrosis probably develops as the result of the interaction of several corticosteroid-induced alterations, including circulating fat emboli and inflammatory unbound free fatty acids or prostaglandins. Osteoporosis may also be a factor in explaining the sporadic nature of the disorder.

Osteonecrosis secondary to sickling disorders differs from most other forms of osteonecrosis, because vaso-occlusive episodes generally involve many other organs. For this reason optimum management and care of these patients requires a team approach. The spectrum of clinical symptoms and bone involvement varies widely from one patient to another, even among patients with the same abnormal hemoglobin patterns. Although the efficacy of conservative therapeutic measures has not been definitely established, these may be all that can be offered because of the patient's other problems. Before contemplating surgery, the surgical and anesthetic risks should be evaluated and measures taken to prevent complications. The varus osteotomy, Chiari pelvic osteotomy, prosthetic or total hip replacement, and the Neer shoulder prosthesis may benefit a limited number of carefully selected patients.

Experimental and some clinical evidence suggest that one or more mechanisms, alone or in combination, induce bone necrosis. These include marrow cell hypertrophy, microembolic phenomena, and lipid-induced osteocyte necrosis. Such events may result in local inflammatory exudates and/or vascular impedence. Either may effect an increase in the hydrostatic pressures in bone with the potential to limit blood flow and magnify the initial insult. Further experimental investigations are necessary to gain knowledge of etiologic mechanisms and a rational means of prophylaxis or treatment.

Although the presence of hyperuricemia and avascular necrosis of the hip is well documented, a similar association in the talus seems not to have been previously reported. The clinical and radiographic findings were confirmed by the histologic alterations in bone structure. Successful arthrodesis of the destroyed left ankle joint was accomplished by iliac bone graft.

The history of aseptic bone necrosis includes important contributions by Hunter, Russell, Goodsir, Paget, König, Axhausen, Phemister, and Chandler. Only after Pasteur discovered bacteria in abscesses could a nonbacterial or aseptic necrosis be conceptualized. Techniques and information gained from the study of bone grafts led to important steps in the recognition of aseptic necrosis. The use of the X-ray and careful pathologic correlation enabled a wide group of radiographically distinct lesions to be recognized as bone necroses. Although many identifiable diseases can underlie aseptic necrosis, the cause of most cases is unknown.

The primary method of detecting and recording the changes of dysbaric osteonecrosis is bone and joint radiographic survey. This is not the routine medical and orthopedic roentgen technique, but is a special purpose examination with special technical requirements. The findings indicate selective sites of damage and each should have meticulous study. Fine detail and heavily penetrated radiographs produce needed bony, especially trabecular, and detail and allow the film reviewers to exlude simulating lesions. The incidence of osteonecrosis in American commercial divers has been found to be quite low and considerably less than in other types of compressed gas workers and shell divers. The major radiographic observation is an area of sclerosis, but other changes occur. Juxta-articular lesions can lead to joint damage and are, therefore, potentially disabling. The immediate significance of a lesion in the shaft of a long bone is in its value as a basis for disqualification of an individual for further work in dysbaric environments.