The Contribution of Deleterious Rare Alleles in ENPP1 and Osteomalacia Causative Genes to Atypical Femoral Fracture.

CONTEXT: Atypical femoral fractures (AFFs) are very rare atraumatic or mild trauma fractures in the subtrochanteric region or femoral shaft. Some unique genetic variants in Asian populations might confer susceptibility to AFF, since the incidence of AFFs is higher in Asian populations. OBJECTIVE: Because rare variants have been found to be causative in some diseases and the roles of osteomalacia causative genes have not been reported, we investigated rare variants in genes causing abnormal mineralization. METHODS: Exome sequencing was performed to detect variants in gene coding and boundary regions, and the frequencies of deleterious rare alleles were compared between Japanese patients with AFF (n = 42) and controls of the 4.7KJPN panel of Tohoku Medical Megabank by whole genome sequencing (n = 4773). RESULTS: The frequency of the deleterious rare allele of ENPP1 was significantly increased in AFF (P = .0012, corrected P [Pc] = .0155, OR 4.73, 95% CI 2.15-10.40). In multigene panel analysis, the frequencies of deleterious rare alleles of candidate genes were increased in AFF (P = .0025, OR 2.72, 95% CI 1.49-4.93). Principal component analysis of bone metabolism markers identified a subgroup of patients with AFF with higher frequencies of deleterious rare alleles in ENPP1 (P = 4.69 × 10-5, Pc = .0006, OR 8.47, 95% CI 3.76-19.09) and the candidate genes (P = 1.08 × 10-5, OR 5.21, 95% CI 2.76-9.86). CONCLUSION: AFF is associated with genes including ENPP1 that cause abnormal mineralization, suggesting that osteomalacia is an underlying condition predisposing to AFF and that higher incident rates of AFFs in Asian populations might be explained by the genetic risk factors including ENPP1.

TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts.

BACKGROUND: MicroRNAs (miRNAs) are important regulators of a variety of inflammatory mediators. The present study was undertaken to elucidate the role of miRNAs in the rheumatoid cytokine network. METHODS: We analyzed miRNA expression in rheumatoid synovial fibroblasts (RASFs). miRNA array-based screening was used to identify miRNAs differentially expressed between tumor necrosis factor-α (TNF-α)-activated RASFs and untreated RASFs. Transfection of RASFs with miR-155 was used to analyze the function of miR-155. Real-time polymerase chain reaction (PCR) was used to measure the levels of miR-155 in RASFs. RESULTS: miRNA microarray analysis revealed that miR-155-5p was the most highly induced miRNA in TNF-α-stimulated RASFs. TNF-α-induced miR-155 expression in RASFs was time-dependent and TNFα dose-dependent, whereas, IL-6 stimulation did not affect miR-155 expression in RASFs. Transfection of miR-155 mimics into RASFs resulted in the decrease JAK2/STAT3 phosphorylation in IL-6-treated RASFs. CONCLUSIONS: The current results demonstrate that TNF-α modulated miRNA expressions in RASFs. Our data showed that miR-155, which is highly induced by TNF-α stimulation, inhibits IL-6-mediated JAK2/STAT3 activation in RASFs. These findings suggest that miR-155 contributes to the cross-regulation between TNF-α and IL-6-mediated inflammatory pathways in RA.

Spinal anesthesia increases the risk of venous thromboembolism in total arthroplasty: Secondary analysis of a J-PSVT cohort study on anesthesia.

Clinical guidance on the choice of anesthetic modality vis-à-vis the risk of perioperative venous thromboembolism (VTE) is largely lacking because of a paucity of recent evidence. A comparative effect of general anesthesia and neuraxial blockade on the perioperative incidence of VTE has not been well-investigated.We compared the effects of different types of anesthetic modalities on the risk of VTE after total hip arthroplasty (THA) and total knee arthroplasty (TKA).This is a secondary analysis of the Japanese Study of Prevention and Actual Situation of Venous Thromboembolism after Total Arthroplasty (J-PSVT). Data pertaining to a total of 2162 patients who underwent THA and TKA at 34 hospitals were included in this analysis. We compared the different anesthetic modalities with respect to the incidence of VTE. The composite end-point was asymptomatic/symptomatic deep vein thrombosis detected using scheduled bilateral ultrasonography up to postoperative day (POD) 10 and fatal/non-fatal pulmonary embolism up to POD 10.The study groups were as follows: general anesthesia (n = 646), combined epidural/general anesthesia (n = 1004), epidural anesthesia (n = 87), and spinal anesthesia (n = 425). On multivariate analysis, only spinal anesthesia was associated with a significant increase in the risk of VTE as compared with that associated with general anesthesia. Propensity score-matched analysis for "combined epidural/general anesthesia group" versus "spinal anesthesia group" demonstrated a 48% higher incidence of VTE (relative risk = 1.48, 95% confidence interval [CI] 1.18-1.85) in the latter.Spinal anesthesia was associated with a higher risk of postoperative VTE, as compared with that associated with combined epidural/general anesthesia, in patients undergoing total arthroplasty.

Protracted arthritis in a Japanese patient with familial Mediterranean fever.

The most common arthritic involvement in familial Mediterranean fever (FMF) is acute self- limiting monoarthritis which typically lasts for 72 h. Hip joint involvement is uncommon in FMF and can result either from a process specific to this disease or from a coexisting inflammatory joint disease. We describe a 37-year-old woman with FMF and right osteoarthritis secondary to congenital hip dislocation. Periodic fever with right coxalgia lasting for 6 months was treated using colchicine. Genetic analysis revealed homozygous mutation in the MEFV gene (L110P-E148Q/L110P-E148Q), confirming the FMF diagnosis. Although the clinical presentation and course of FMF arthritis are diverse, delineating these clinical patterns may help with early recognition and treatment to prevent destructive arthritis in FMF. Clinicians should consider the possibility of FMF development in unusual monoarthritis patients with recurrent febrile attacks.

Reduced induction of anti-PF4/heparin antibody in RA patients after total knee arthroplasty.

BACKGROUND: Heparin-induced thrombocytopenia is caused by antibodies (Abs) specific to platelet factor 4 (PF4)/heparin complexes. In this study, we evaluated the rates of seroconversion of anti-PF4/heparin Ab between patients with rheumatoid arthritis (RA) and with osteoarthritis (OA) who underwent total knee arthroplasty. METHODS: The subjects of this randomized controlled trial were 124 patients who underwent total knee arthroplasty (TKA) and received edoxaban with or without a foot pump as thromboprophylaxis. We measured anti-PF4/heparin Abs before and 10 days after surgery, as well as preoperative PF4, using commercially available ELISAs. We also used the database of J-PSVT, a hospital-based, prospective cohort study designed to document the effectiveness of thromboprophylactic agents during arthroplasty. RESULTS: The rates of seroconversion to anti-PF4/heparin Ab were lower in RA patients (4.0 %) than in OA patients (25.5 %). The anti-PF4/heparin IgG optical density (OD) values did not differ before and after surgery in RA patients. In contrast, there was a significant increase in anti-PF4/heparin IgG OD values in OA patients after TKA. In the J-PSVT data, the postoperative seroconversion rates of anti-PF4/heparin Ab were lower in RA patients (10.4 %) than in OA patients (21.8 %) who received fondaparinux. The titers of anti-CCP Ab were significantly lower in RA patients with postoperative ant-PF4/heparin Ab compared with those without postoperative ant-PF4/heparin Ab There was no significant difference in preoperative PF4 levels between RA patients and OA patients. The heparin-binding affinity of the circulating PF4 was similar between RA patients and OA patients; however, the IgG fractions isolated from the sera of RA patients contained PF4 more frequently (69.2 %) than those from OA patients (10.2 %). CONCLUSIONS: Our results showed a reduced likelihood of postoperative anti-PF/heparin Ab production in RA patients compared with OA patients. This suggests that the mechanisms underlying the anti-PF4 immune response in RA patients differ from the mechanisms of the anti-PF4/heparin immune response seen in OA patients after joint replacement. TRIAL REGISTRATION: ISRCTN 18090286. Registered 8 July 2016.

Effects of a Foot Pump on the Incidence of Deep Vein Thrombosis After Total Knee Arthroplasty in Patients Given Edoxaban: A Randomized Controlled Study.

We conducted a randomized clinical trial to compare the effectiveness of the A-V Impulse System foot pump for reducing the incidence of deep-vein thrombosis (DVT) after total knee arthroplasty (TKA) in patients under edoxaban thromboprophylaxis. Patients undergoing primary TKA at our institution between September 2013 and March 2015 were enrolled after obtaining informed consent. The patients were randomized to use the foot pump (n = 58) and not to use the foot pump (n = 62). Both groups were given prophylactic edoxaban. Primary outcomes were any DVT as detected by bilateral ultrasonography up to postoperative day 10 (POD10) and pulmonary embolism (PE) up to POD28. The safety outcomes were bleeding and death of any cause up to POD28. Plasma D-dimer levels were measured before TKA and on POD10 after TKA. Immunoglobulin G (IgG)-class anti-PF4/heparin antibodies were measured using an IgG-specific enzyme-linked immunosorbent assay. The incidences of any DVT up to POD28 were 31.0% and 17.7% in patients with or without the foot pump, respectively. The incidences of major bleeding up to POD28 were 5.1% and 4.8% in patients with or without the foot pump, respectively. Foot pump use did not significantly reduce the incidence of DVTs in patients undergoing TKA under edoxaban thromboprophylaxis. Although seroconversion of anti-PF4/heparin antibodies was confirmed in one-fourth of patients, the seroconversion rates did not differ between patients with (20.7%) or without (25.8%) foot pump use. This study shows that the A-V Impulse system foot pump did not affect the incidence of DVT under edoxaban thromboprophylaxis in patients undergoing TKA. Seroconversion of anti-PF4/heparin antibodies was detected in a significant number of patients who underwent TKA under antithrombotic prophylaxis using edoxaban.

Risk of venous thromboembolism after total knee arthroplasty in patients with rheumatoid arthritis.

OBJECTIVE: To compare the incidence of venous thromboembolism (VTE) following total knee arthroplasty (TKA) between patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). METHODS: The subjects were composed of 1084 Japanese patients with OA and 204 with RA. Primary effectiveness outcomes were any deep vein thrombosis (DVT) as detected by bilateral ultrasonography up to postoperative Day 10 (POD10) and pulmonary embolism (PE) up to POD28. The main safety outcomes were bleeding and death from any cause up to POD28. Plasma D-dimer levels were measured before and at POD10 after TKA. RESULTS: The study cohort was composed of 1288 patients from 34 hospitals. There was no death up to POD28. PE occurred in 2 patients with OA and in no patients with RA. The incidence of primary effectiveness outcome was 24.3% and 24.0% in patients with OA and RA, respectively. The incidence of major bleeding up to POD28 was 1.3% and 0.5% in patients with OA and RA, respectively. No differences in the incidence of VTE (symptomatic/asymptomatic DVT plus PE) or bleeding were noted between patients with RA and OA. D-dimer levels on POD10 were significantly higher in patients with OA compared with those with RA. Also, D-dimer levels on POD10 were significantly lower in patients receiving fondaparinux than in patients without pharmacological prophylaxis. CONCLUSION: Despite some differences in demographic data, patients with RA and OA have equivalent risks of VTE and bleeding following TKA.

Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic disease.

The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction is immunomodulatory treatment, with drugs such as corticosteroid hormone and interferon-α, at present. However, there are many issues in long-term treatment with these drugs, such as insufficient effects and various side effects. We now urgently need to develop other therapeutic strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely used in Europe for the past 50 years as a thrombosis prophylaxis and for the treatment of phlebitis. We conducted a clinical trial to test the effect of subcutaneous administration of PPS in 12 patients with HAM/TSP in an open-labeled design. There was a marked improvement in lower extremity motor function, based on reduced spasticity, such as a reduced time required for walking 10 m and descending a flight of stairs. There were no significant changes in HTLV-I proviral copy numbers in peripheral blood contrary to the inhibitory effect of PPS in vitro for intercellular spread of HTLV-I. However, serum soluble vascular cell adhesion molecule (sVCAM)-1 was significantly increased without significant changes of serum level of chemokines (CXCL10 and CCL2). There was a positive correlation between increased sVCAM-1and reduced time required for walking 10 m. PPS might induce neurological improvement by inhibition of chronic inflammation in the spinal cord, through blocking the adhesion cascade by increasing serum sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has the potential to be a new therapeutic tool for HAM/TSP.

Antiviral effects of Psidium guajava Linn. (guava) tea on the growth of clinical isolated H1N1 viruses: its role in viral hemagglutination and neuraminidase inhibition.

Rapid evolution of influenza RNA virus has resulted in limitation of vaccine effectiveness, increased emergence of drug-resistant viruses and occurrence of pandemics. A new effective antiviral is therefore needed for control of the highly mutative influenza virus. Teas prepared by the infusion method were tested for their anti-influenza activity against clinical influenza A (H1N1) isolates by a 19-h influenza growth inhibition assay with ST6Gal I-expressing MDCK cells (AX4 cells) using fluorogenic quantification and chromogenic visualization. Guava tea markedly inhibited the growth of A/Narita/1/2009 (amantadine-resistant pandemic 2009 strain) at an IC(50) of 0.05% and the growth of A/Yamaguchi/20/06 (sensitive strain) and A/Kitakyushu/10/06 (oseltamivir-resistant strain) at similar IC(50) values ranging from 0.24% to 0.42% in AX4 cells, being 3.4- to 5.4-fold more potent than green tea (IC(50) values: 0.27% for the 2009 pandemic strain and 0.91% to 1.44% for the seasonal strains). In contrast to both teas, oseltamivir carboxylate (OC) demonstrated high potency against the growth of A/Narita/1/09 (IC(50) of 3.83nM) and A/Yamaguchi/20/06 (IC(50) of 11.57nM) but not against that of A/Kitakyushu/10/06 bearing a His274-to-Tyr substitution (IC(50) of 15.97µM). Immunofluorescence analysis under a confocal microscope indicated that both teas inhibited the most susceptible A/Narita/1/2009 virus at the initial stage of virus infection. This is consistent with results of direct inhibition assays showing that both teas inhibited viral hemagglutination at concentrations comparable to their growth inhibition concentrations but inhibited sialidase activity at about 8-times higher concentrations. Guava tea shows promise to be efficacious for control of epidemic and pandemic influenza viruses including oseltamivir-resistant strains, and its broad target blockage makes it less likely to lead to emergence of viral resistance.

Pravastatin reduces steroid-induced osteonecrosis of the femoral head in SHRSP rats.

BACKGROUND AND PURPOSE: Although the definite cause of steroid-induced osteonecrosis of the femoral head (ONFH) is unknown, peripheral circulatory failure, lipid metabolism disturbance, and increased oxidative stress are considered to be possible causes. We investigated whether pravastatin as a statin treatment reduces (1) the incidence of ONFH, (2) the adipocyte area, and (3) bone marrow changes in the femoral head. METHODS: We divided up 81 thirteen-week-old spontaneously hypertensive stroke-prone (SHRSP)/Izm male rats into 4 groups: a control group (group C), a group given pravastatin (group P), a group given steroid (group S), and a group given both pravastatin and steroid (Group PS). The steroid was administered at 15 weeks of age. Pravastatin, as a statin, was administered in the drinking water for 4 weeks. The rats were killed when 17 weeks old. Osteonecrosis was diagnosed based on histopathological examination. Oxidative stress was assessed from immunostaining. RESULTS: The incidence of histological osteonecrosis was lower in the groups given pravastatin. The percentage of adipocyte area in the bone marrow was lower in the PS group than in the S group. Immunohistochemical staining for oxidative stress showed that staining was less in the PS group than in the S group. Pravastatin had no effect on the blood-derived biochemical findings on lipid metabolism. However, it reduced the incidence of steroid-induced ONFH in these SHRSP rats. We presume that this occurred by reducing oxidative stress and by reducing the percentage of adipocyte area in the femoral heads. INTERPRETATION: Our data suggest that pravastatin may be effective in reducing steroid-induced ONFH.

Pentosan reduces osteonecrosis of femoral head in SHRSP.

Increased oxidative stress is considered one of the main causes of steroid-induced osteonecrosis of the femoral head (ONFH). The aim of this study was to evaluate the effects of a steroid hormone and pentosan polysulfate sodium (pentosan), a heparin analog, in stroke-prone spontaneously hypertensive rats (SHRSP) as a model of ONFH. One hundred twenty-three 13-week-old male SHRSP/Izm rats were divided into four groups: a control group (group C), pentosan-administered group (group P), steroid-administered group (group S), and group administered pentosan plus steroid (group PS). Methylprednisolone acetate, as the steroid hormone, at a dose of 4 mg (15 mg/kg) was administered at 15 weeks of age. Pentosan at a dose of 3 mg/day/kg was continuously administered intraperitoneally from 13 weeks of age for 4 weeks. Rats were sacrificed at 17 weeks of age, and heart blood and both femora were collected. Triglyceride levels were significantly lower in group PS than in group S, indicating that pentosan improves lipid metabolism. The incidence of histologic ONFH was significantly lower in group P, at 14.8% (10/71 femoral heads), than in group C, at 30.4% (17/56 femoral heads), and significantly lower in group PS, at 40.8% (29/71 femoral heads), than in group S, at 91.3% (42/46 femoral heads), indicating that pentosan markedly inhibits ONFH. Immunohistochemical staining for oxidative stress showed that the stainability was significantly lower in group PS than in group S. Pentosan seems to reduce the incidence of ONFH in SHRSP by improving lipid metabolism and decreasing oxidative stress.

Sodium pentosan polysulfate resulted in cartilage improvement in knee osteoarthritis--an open clinical trial.

BACKGROUND: Pentosan polysulfate sodium (pentosan) is a semi-synthetic drug manufactured from beech-wood hemicellulose by sulfate esterification of the xylopyranose hydroxyl groups. From in vitro and animal model studies, pentosan has been proposed as a disease modifying osteoarthritis drug (DMOAD). The objective of this study was to assess the efficacy, safety, and patient satisfaction in patients with mild radiographic knee osteoarthritis (OA) findings and OA-associated symptoms and signs. METHODS: Twenty patients were assessed clinically at Nagasaki University Hospital. The radiographic indications of OA were grade 1 to 3 using the Kellgren-Lawrence Grading System (K/L grade). Pentosan used in this study was manufactured and supplied in sterile injectable vials (100 mg/ml) by bene GmbH, Munich, Germany. The study was a single-center, open-label trial. Treatment consisted of 6 weekly subcutaneous injections (sc) of pentosan (2 mg/kg). Patients were clinically assessed at entry and 1 to 8, 11, 15, 24 & 52 weeks post treatment. The results were analyzed using one way ANOVA and Dunnett's method. RESULTS: Hydrarthroses were reduced quickly in all cases. The clinical assessments, i.e., knee flexion, pain while walking, pain after climbing up and down stairs, etc, were improved significantly and these clinical improvements continued for almost one year. The dose used in this study affected the blood coagulation test, but was within safe levels. Slightly abnormal findings were noted in serum triglycerides. CONCLUSIONS: Pentosan treatment in twenty patients with mild knee OA seemed to provide improvements in clinical assessments and C2C level of cartilage metabolism.

MRI findings of an inflammatory variant of well-differentiated liposarcoma.

The inflammatory variant of well-differentiated liposarcoma (WDLPS) is a rare subtype. We present a 75-year-old woman who had a tumor that was difficult to diagnose preoperatively. Magnetic resonance imaging of the tumor revealed a large, lobulated heterogeneous soft tissue mass with a distinctive pattern of intermingled well-differentiated fatty elements and nodular areas of high T2-intensity tissue.

Immunohistochemical analyses of beta-catenin and cyclin D1 expression in giant cell tumor of bone (GCTB): a possible role of Wnt pathway in GCTB tumorigenesis.

Giant cell tumor of bone (GCTB) is a benign neoplasm but occasionally shows local recurrence, and histologically consists of osteoclast-like giant cells (GC) and stromal mononuclear cells (SC), which are capable of proliferation and osteoblastic differentiation. Activation of Wnt signaling can induce osteoblast differentiation and osteoclastgenesis during bone resorption process. This study analyzed the profiles of beta-catenin and cyclin D1 expression in GCTB to elucidate an involvement of Wnt pathway in tumorigenesis. We performed immunohistochemistry for beta-catenin, cyclin D1, and Ki-67 in 16 GCTB tumors, including 5 recurrent cases that were surgically resected. All 16 cases of GCTB displayed beta-catenin, cyclin D1, and Ki-67 expression. Immunoreactivity for beta-catenin was observed in nuclei of SC and GC. Cyclin D1 immunoreactivity was found mainly in nuclei of GC, while Ki-67 immunoreactivity was restricted to nuclei of SC. The nuclear beta-catenin labeling index (LI) in both SC (60.6 vs. 41.8%, p=0.074) and GC (41.7 vs. 20.1%, p=0.095) was higher in recurrent tumors than in primary tumors in all the 4 cases. However, Ki-67 LI in SC (18.8 vs. 19.9%, p=0.851) and cyclin D1 LI in GC (55.4 vs. 70.1%, p=0.225) were not higher in recurrent tumors than in primary tumors. Our results suggested activation of Wnt/ beta-catenin pathway in GCTB tumorigenesis. Since cyclin D1 in GC was never associated with the expression of the well-known proliferative marker Ki-67, cyclin D1 expression might play a role in GC formation instead of promoting cell proliferation during GCTB tumorigenesis. Importantly, it was suggested that the nuclear beta-catenin staining level might be associated with tumor recurrence in GCTB.

Osteonecrosis of femoral head in the stroke-prone spontaneously hypertensive rats, especially old rats.

The average life span of stroke-prone spontaneously hypertensive rats (SHRSP) is about eight months. Male SHRSPs at 40 weeks old were used to study the idiopathic osteonecrosis of the femoral head (ION). The control group showed about 40% old necrosis and 20% early necrosis. The group administered with steroid hormone showed an increasing degeneration of adipocyte in the bone marrow, and 20% fresh necrosis was recognized. Furthermore, we observed the adipocyte change as well as early necrosis occurring among old necrosis sites. The study of aged rats may provide further understanding into the pathogenesis of ION.

A case of progressive osseous heteroplasia: a first case in Japan.

Progressive osseous heteroplasia (POH) is a rare, hereditary, disorder (number 166350 in Mendelian Inheritance in Man), which was first identified in 1994 and is characterized by dermal ossification beginning in infancy as a result of increasing and extensive bone formation in deep muscle and fascia. We describe a boy with typical clinical, radiographic, and genetic features of POH. A nonsense mutation in exon 7 of the GNAS1 gene was identified in genomic DNA from the patient. No such case has been reported in East Asia or Japan before this patient.

Hip rotationplasty with antibiotic-loaded bone cement spacer for severe infection following limb-sparing surgery.

Knee rotationplasty was initially proposed for the reconstruction of the knee joint in the congenital hypoplasia of the femur. Its application was extended to functional reconstruction of the knee joint after wide resection of malignant bone or soft tissue tumor around the knee. It has also been shown to salvage a failed knee-sparing surgery due to infection or the aseptic loosening of the prosthesis. Hip rotationplasty has been described as a method for the reconstuction of hip function, as well as in the knee joint, in the case of a primary malignant tumor of the proximal part of the femur in children. It has also been described as having a surgical application for the severe congenital deficiency of the proximal part of the femur to reconstruct hip and knee joints, as well as for the massive bone defect of the proximal part of the femur due to infection to mimic a functional femoral shaft. This article reports a case where the hip joint was secondarily reconstructed with hip rotationplasty after subtotal resection of the femur due to infection of the hip hemiarthroplastic prosthesis and osteomyelitis of the hip joint and femur.

Osteonecrosis in stroke-prone spontaneously hypertensive rats: effect of glucocorticoid.

BACKGROUND: High-dose administration of a steroid hormone has been associated with a major risk of osteonecrosis. In this study we investigated the effects of a steroid hormone on the incidence of osteonecrosis of the femoral head in stroke-prone spontaneously hypertensive rats/Nagasaki (SHRSP/Ngsks). METHODS: A total of 71 SHRSP/Ngsks were divided into two groups: a control group (C group, n = 40) and a steroid hormone group (S group, n = 31) given 5 mg (about 20 mg/kg) of methylprednisolone acetate during the 17th week of age. We compared the groups' laboratory data, histological appearance, incidence of osteonecrosis, and expression of oxidative stress on immunohistochemical analysis using the monoclonal antibodies anti-4HNE and anti-8OHdG. RESULTS: The S group showed an increase in total cholesterol, with the amounts of high-density lipoprotein, low-density lipoprotein, and triglycerides all significantly higher than in the C group. Histological examination showed that the frequency of necrosis of the femoral head was significantly higher in the S group (95.2%) than in the C group (51.2%). Most of the histological features of the osteonecrosis demonstrated typical features of a similar sort in the two groups. However, the S group showed bone marrow spaces in the femoral head that were occupied by an increased number of adipocytes and that were swollen, partially degenerative, and necrotic. On immunohistochemical analysis, the stains of anti-4HNE and anti-8OHdG antibody were stronger in the S group than in the C group. CONCLUSIONS: This study confirmed, to a remarkable degree, the suspicion that the administration of steroid hormone increases the number of adipocytes in marrow. Fat degeneration and necrosis, considered early signs of osteonecrosis, were also observed. It has been hypothesized that osteonecrosis is produced by the ischemic change accompanying compartment pressure load in marrow, where fat degeneration, necrosis, and endothelial cell injury might occur together with oxidative stress.

High-grade surface osteosarcoma of the hand.

A 32-year-old woman presented with a 1-year history of mild pain in the right ring finger. Radiographs and CT revealed a calcified lesion with cortical erosion on the surface of the proximal aspect of the right ring finger proximal phalanx. On magnetic resonance imaging (MRI), the lesion showed low signal intensity on T1- and T2-weighted images and slight enhancement with gadolinium. Clinically, it was diagnosed as a benign bone-forming lesion such as florid reactive periostitis, and excision was accordingly performed. However, histological examination revealed proliferation of atypical osteoblastic cells among irregularly arranged osteoid seams. Taking the imaging findings into account, a pathological diagnosis of high-grade surface osteosarcoma was established. In general, bone- and cartilage-forming lesions of the hands and feet are benign. Osteosarcoma of short tubular bones in the hands and feet is extremely rare; moreover, high-grade surface osteosarcoma is one of the rarest subtypes of osteosarcoma. Nonetheless, high-grade surface osteosarcoma should be included in the differential diagnosis, particularly if the radiological findings or clinical course are not entirely typical of a more common benign process, to avoid incorrect clinicoradiological and pathological diagnosis.