Effect of a Specific Questionnaire Sheet on Subclassification of Osteonecrosis of the Femoral Head.

BACKGROUND This study examined whether use of a specific questionnaire sheet for nontraumatic osteonecrosis of the femoral head (ONFH) could affect the subclassification of ONFH compared with a conventional medical interview. MATERIAL AND METHODS Study participants consisted of 400 patients with ONFH who visited our hospital between February 2011 and March 2015. Data on history of systemic steroid therapy and habitual alcohol intake were obtained during a conventional medical interview at the first visit and were re-evaluated using a specific questionnaire sheet at another visit. Patients were subclassified into 4 groups: steroid-associated, alcohol-associated, steroid/alcohol-associated, or idiopathic ONFH. RESULTS Use of the specific questionnaire sheet resulted in a 4.0% increase in the proportion of patients with a history of systemic steroid therapy, from 57.3% (n=229) to 61.3% (n=245), and a 14.3% increase for history of habitual alcohol intake, from 35.0% (n=140) to 49.3% (n=197). The proportion of patients with steroid/alcohol-associated ONFH increased from 2.5% (n=10) to 17.8% (n=71), while the proportion in the other 3 groups decreased: steroid-associated ONFH from 54.8% (n=219) to 43.5% (n=174); alcohol-associated ONFH from 32.5% (n=130) to 31.5% (n=126); and idiopathic ONFH from 10.2% (n=41) to 7.2% (n=29). Ninety-six patients (24.0%) were classified into a different subgroup based on the specific questionnaire sheet. CONCLUSIONS The use of a specific questionnaire sheet can change the distribution of ONFH subclassifications compared with use of a conventional medical history interview. Use of a specific questionnaire sheet can allow for more detailed self-reporting regarding potential causative factors for nontraumatic ONFH, especially habitual alcohol intake.

Is bone mineral density lower in the necrotic lesion in pre-collapse osteonecrosis of the femoral head?

The purpose of this study was to clarify whether bone mineral density (BMD) of the necrotic lesion in precollapse osteonecrosis of the femoral head (ONFH) is reduced according to Hounsfield unit (HU) values on computed tomography (CT). The superior one-third of the femoral head in the coronal section was set as the region of interest (ROI) for the measurement of HU values. First, HU values of 101 control participants were assessed to identify relevant confounding factors. Next, the relationship between HU values and BMD on dual-energy X-ray absorptiometry (DXA) was verified. Then the mean HU value of the ROI in patients with pre-collapse ONFH was compared with that in propensity score-matched control participants. Finally, the HU values of the lateral boundary in the patients with and without subsequent collapse were compared. Multivariable analysis showed that both age and BMI were significantly correlated with the HU value, which showed a strong correlation with the BMD of the femoral neck on DXA (r = 0.92). In 25 ONFH patients and 25 propensity-matched control participants, no significant difference was found in the HU value of the ROI (p = .54). The mean HU value of the lateral boundary in patients with subsequent collapse was found to be significantly higher than that in patients without subsequent collapse (p < .01). The assessment of HU values on CT was useful for the evaluation of BMD of the femoral head. The current assessment did not demonstrate reduced bone mineral density of the necrotic lesion in pre-collapse ONFH.

Quantitative evaluation of bone-resorptive lesion volume in osteonecrosis of the femoral head using micro-computed tomography.

Objectives To quantify the volume of bone-resorptive lesions in post-collapse osteonecrosis of the femoral head (ONFH) using micro-computed tomography (micro-CT) and assess their characteristics in post-collapse ONFH. Methods We investigated 35 femoral heads resected from 35 patients with ONFH (20 men and 15 women; mean age, 47.2 years). On each of seven coronal high-resolution micro-CT slices of the femoral head, the bone-resorptive areas were extracted using bone microstructure measurement software. Next, the total bone-resorptive volume ratio, defined as the ratio of all bone-resorptive cross-sectional areas to all femoral head cross-sectional areas in all seven slices, was calculated. Associations between total bone-resorptive volume ratio and sex, age, ONFH-associated factors, patient workload levels, ONFH stage, ONFH type, necrotic volume on magnetic resonance imaging, and duration from the onset of pain to surgery were analyzed. Lesion location and the association between bone-resorptive lesion and collapse were also evaluated. Results The mean total bone-resorptive volume ratio was 7.0±6.0%, which varied significantly by ONFH stage (ARCO collapse quantitation 3A, 3.5±2.1%; 3B, 6.8±3.0%; and 3C, 13.6±8.8%). ONFH stage was independently associated with total bone-resorptive volume ratio (P<0.05). Furthermore, high bone-resorptive volume ratios were found in the anterior femoral head and were associated with collapse. Conclusions This study demonstrated that bone-resorptive volume in post-collapse ONFH was significantly associated with the disease stage, which was more widespread in the anterior portion of the femoral head than in the posterior portion.

Effects of anterior boundary of the necrotic lesion on the progressive collapse after varus osteotomy for osteonecrosis of the femoral head.

BACKGROUND: Anterior localization of the necrotic lesion was recently proposed as an important factor for the occurrence of collapse even in medially located osteonecrosis of the femoral head (ONFH). We examined the effects of the anterior boundary of the necrotic lesion on progressive collapse after varus osteotomy for ONFH. METHODS: We reviewed the outcomes of 31 hips in 27 patients with ONFH treated by transtrochanteric curved varus osteotomy (CVO) from 2000 to 2012 with a mean follow-up of 10.5 years. The occurrence of progressive collapse of the anterior necrotic lesion was defined as the presence of ≥2 mm collapse using follow-up lateral radiographs. Postoperative osteoarthritic change was defined as ≥1 mm progression of joint space narrowing on follow-up radiographs. The location of the anterior boundary of the necrotic lesion was assessed using the anterior necrotic angle (the angle between the midline of the femoral neck shaft and the line passing from the femoral head center to the anterior boundary of the necrotic lesion on a mid-slice oblique magnetic resonance image). RESULTS: All hips had a postoperative intact ratio of ≥34% (percentage of the transposed intact articular surface of the femoral head to the weight-bearing area of the acetabulum after femoral osteotomy). Progressive collapse of the anterior necrotic lesion was seen in five hips (16%) during a mean of 2.2 years after CVO. Of these, four hips (80%) proceeded to develop osteoarthritic change at an average of 4.3 years after the collapse. Multivariate analysis revealed that the anterior necrotic angle was independently associated with progressive collapse of the anterior necrotic lesion as well as the postoperative intact ratio. CONCLUSIONS: This study suggests that hips with anterior localization of the necrotic lesion have a possible risk of progressive collapse of the anterior necrotic lesion after CVO, which can frequently lead to subsequent osteoarthritic change.

Differences in magnetic resonance findings between symptomatic and asymptomatic pre-collapse osteonecrosis of the femoral head.

PURPOSE: The purpose of this study was to assess the differences in magnetic resonance (MR) findings between the symptomatic and asymptomatic pre-collapse stage of osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: This study reviewed 123 consecutive hips in 91 patients in the pre-collapse stage of ONFH based on plain radiographic findings. These 123 hips were divided into symptomatic and asymptomatic groups according to the pain domain score in the Harris hip score system. Bone marrow edema (BME), synovial fluid effusion, and subchondral fracture were evaluated using MR imaging. Odds ratios (ORs) were calculated between these three parameters and symptoms. The subsequent clinical course after MR examination was also assessed for each hip that could be followed more than 1 year. RESULTS: Forty-six hips (37.4%) were categorized as symptomatic and 77 hips (62.6%) as asymptomatic. The prevalence of BME, synovial fluid effusion, and subchondral fracture were 87.0% (40/46), 80.4% (37/46), and 34.8% (16/46), respectively, in the symptomatic group, and 0%, 28.6% (22/77), and 0%, respectively, in the asymptomatic group, indicating significant differences between the two groups (p < 0.0001). Among these parameters, BME showed the highest OR with regard to the presence or absence of symptoms (BME, 965.8; joint effusion, 10.3; subchondral fracture, 83.9). Due to persistent pain and subsequent collapse, 30 of 35 (85.7%) symptomatic hips with BME subsequently underwent surgical treatment at a mean interval of 3.47 months after MR examination, while 25 of 66 (37.9%) asymptomatic hips without BME underwent surgical treatment at a mean interval of 20.7 months after MR examination. CONCLUSIONS: This study demonstrated that symptomatic pre-collapse ONFH diagnosed based on plain radiographic findings could be distinguished from asymptomatic pre-collapse ONFH by the presence of BME on MR imaging, and thus BME may be a sign of occult fracture.

Volume of hip synovitis detected on contrast-enhanced magnetic resonance imaging is associated with disease severity after collapse in osteonecrosis of the femoral head.

OBJECTIVE: To evaluate the relationship between the volume of hip synovitis detected on contrast-enhanced magnetic resonance imaging (MRI) and the disease stage of osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: Sixty-three consecutive hips in 40 ONFH patients were reviewed using contrast-enhanced MRI. Ten unaffected hips in 10 patients with unilateral ONFH were used as controls. Based on the Japanese Investigation Committee system, these hips were classified according to stage and type. The volume and location of hip synovitis were semi-quantitatively measured on contrast-enhanced MRI. Clinicoradiological factors were statistically analyzed to determine the relationship with the volume of hip synovitis. RESULTS: The mean synovial volume was significantly larger in ONFH hips (8,020 ± 6,900 mm3) than in controls (910 ± 1,320 mm3; p = 0.001). The area of synovitis in the anterior portion of the hip joint was double (mean: 2.17 ± 1.77) that in the posterior portion. The volume of synovitis was small in pre-collapse-stage hips (stage 1: 680 ± 690 mm3, stage 2: 1,460 ± 1,200 mm3), but significantly larger in post-collapse-stage hips (stage 3A: 7,820 ± 4,490 mm3, stage 3B: 13,850 ± 7,110 mm3; p < 0.001). Multiple regression analysis showed that disease stage was the only factor related to hip synovitis. CONCLUSIONS: Our study suggests that hip synovitis in ONFH might occur after femoral head collapse and worsen with collapse progression, mainly in the anterior portion.

Effects of sclerotic changes on stress concentration in early-stage osteonecrosis: A patient-specific, 3D finite element analysis.

Stress distribution remains unclear in early-stage osteonecrosis of the femoral head (ONFH). To clarify this issue, we generated patient-specific finite element models (FEMs) from 51 patients with ONFH. Patients' hips were classified into three groups: ONFH without a sclerotic boundary (Stage 1, n = 6), ONFH with a sclerotic boundary (Stage 2, n = 10), and ONFH with both a sclerotic boundary and <2 mm collapse (Stage 3, n = 35). Four hips without ONFH were used as controls. Stress distribution in each FEM was compared with magnetic resonance imaging (MRI) and computed tomography (CT) results. Fifteen wholly resected femoral heads in Stage 3 hips were assessed by micro-CT. Furthermore, we histologically examined three Stage 2 femoral heads that subsequently developed subchondral fractures after FEM analyses. In all FEMs of both control and Stage 1 hip, stress was equally distributed on the femoral head surface. However, in all FEMs of both Stages 2 and 3 hips, stress was concentrated at the lateral boundary of the femoral head surface, corresponding to both a low-intensity band on T1-weighted MRI images and sclerotic changes on CT. On micro-CT, subchondral fractures consistently began at the lateral boundary with sclerotic changes, in which bone volume fraction was increased. Histology showed breakage of subchondral plates at the junction between necrotic and reparative zones. In early-stage ONFH, sclerotic changes caused stress concentration, which can trigger subchondral fractures at the lateral boundary. Clinical Significance: Our results will clarify the pathogenic mechanism of collapse in ONFH. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3169-3177, 2018.

Osteoclast-related markers in the hip joint fluid with subchondral insufficiency fracture of the femoral head.

Similar to the radiological findings in rapidly destructive arthrosis of the hip joint (RDA), subchondral insufficiency fracture of the femoral head (SIF) can result in progressive femoral head collapse of unknown etiology. We thus examined the osteoclast activity of hip joint fluid in SIF with progressive collapse in comparison with that in RDA. Twenty-nine hip joint fluid samples were obtained intraoperatively with whole femoral heads from 12 SIF patients and 17 RDA patients. SIF cases were classified into subgroups based on the presence of ≥2 mm collapse on preoperative radiographs: SIF with progressive collapse (n = 5) and SIF without progressive collapse (n = 7). The levels of tartrate-resistant acid phosphatase (TRACP)-5b, interleukin-8, vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-9 were measured. The number of multinuclear giant cells at the subchondral region was histopathologically assessed using mid-coronal slice of each femoral head specimen. The median levels of all markers and the median number of multinuclear giant cells in SIF with progressive collapse were significantly higher than those in SIF without progressive collapse, while there were no significant differences in SIF with progressive collapse versus RDA. Regression analysis showed that the number of multinuclear giant cells was positively correlated with the level of TRACP-5b in joint fluid. The present study demonstrated the possible association of increased osteoclast activity with the existing condition of progressive collapse in SIF, which was quite similar to the findings in RDA, indicating that increased osteoclast activity may reflect the condition of progressive collapse in SIF as well as RDA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2987-2995, 2018.

The effect of the anterior boundary of necrotic lesion on the occurrence of collapse in osteonecrosis of the femoral head.

PURPOSE: The location of the necrotic lesion is one of the important factors for collapse in osteonecrosis of the femoral head (ONFH). The significance of anterior localization has been little studied. This study evaluated the effects of anterior boundary of a necrotic lesion on collapse. METHODS: We reviewed the outcomes of 113 consecutive non-collapsed asymptomatic hips in 98 ONFH patients with mean follow-up of 4.7 years (2.0-11.8) after the initial magnetic resonance (MR) imaging. The presence or absence of collapse was investigated using follow-up radiographs. The location of the anterior boundary of a necrotic lesion was assessed using the anterior necrotic angle between the midline of the femoral neck shaft and the line passing from the femoral head centre to the anterior boundary on mid-oblique MR imaging. Multivariate analysis was performed to identify risk factors for collapse, and further analyses were executed according to the lateral boundary of the necrotic lesion. RESULTS: During the follow-up period, collapse was confirmed in 61 hips (54.0%). Multivariate analysis revealed that the anterior necrotic angle was independently associated with collapse as well as the lateral boundary of the necrotic lesion. When the lateral boundary was located at the middle third of weight-bearing portion (32 hips), that was generally categorized as a low risk of collapse, all five cases with anterior necrotic angle ≥ 79° developed collapse, whereas only one of 27 cases (3.7%) with an anterior necrotic angle < 79° developed collapse (p < 0.0001). CONCLUSIONS: This study indicates that ONFH patients with anterior localization of a necrotic lesion can develop collapse even if the necrotic lesion is medially located.

Use of a long distally fixed intramedullary stem to treat a periprosthetic femoral fracture following total hip arthroplasty using a thrust plate hip prosthesis: A case report.

INTRODUCTION: The thrust plate hip prosthesis (TPP; Zimmer, Winterthur, Switzerland) is a hip prosthesis that is no longer in production. Few reports have focused on periprosthetic fractures following total hip arthroplasty (THA) with the use of a TPP. PRESENTATION OF CASE: We report a 57-year-old woman with a periprosthetic femoral fracture 13 years after THA with the use of a TPP. A plain radiograph showed a displaced subtrochanteric fracture of the right femur just below the distal tip of the lateral plate without implant loosening. She underwent revision surgery with a long distally fixed intramedullary stem in conjunction with a plate and cable system. Three months after surgery, bone union was confirmed using radiography and the patient was clinically asymptomatic. DISCUSSION: We encountered three major problems while planning surgical treatment, these being, discontinuation of the TPP system, loss of proximal femoral cancellous bone, and difficulties with the type of subtrochanteric fracture. After considering these problems, we planned revision surgery using a long distally fixed intramedullary stem in conjunction with a plate and cable system. CONCLUSION: This case shows that sufficient implant preparation based on precise preoperative planning is necessary to obtain good clinical results for the surgical treatment of periprosthetic femoral fractures following THA with the use of a TPP.

Osteonecrosis of the femoral head associated with pigmented villonodular synovitis.

A 23-year-old Japanese woman with no history of corticosteroid intake or alcohol abuse presented with a 10-month history of left hip pain without any antecedent trauma. An anteroposterior radiograph performed 10 months after the onset of pain showed slight joint space narrowing and bone erosions surrounded by sclerotic lesions in both the acetabular roof and femoral neck. Magnetic resonance images of the left hip showed a feature of osteonecrosis of the femoral head and a mass with villus proliferation extending from the posterior intertrochanteric area to the anteromedial aspect of the femoral neck. In addition, the left quadratus femoris muscle, which is generally located just above the nutrient vessels of the femoral head, was not detected. Based on these findings, the patient was diagnosed with osteonecrosis of the femoral head caused by impairment of the nutrient vessels from invasion of the pigmented villonodular synovitis. She underwent radical synovectomy of the left hip 16 months after the onset of pain, and her hip pain improved after the surgery.

The choice of locking plate in the treatment of peri-implant femoral fracture eight years after trans-trochanteric rotational osteotomy: A case report.

INTRODUCTION: Transtrochanteric anterior rotational osteotomy of the femoral head (TRO) was developed as a joint preserving surgery for osteonecrosis of the femoral head. To the best of our knowledge, peri-implant fractures after femoral osteotomy have rarely been reported. PRESENTATION OF CASE: We report a 58-year-old female who suffered a peri-implant femoral shaft fracture following a fall from a stepladder eight years after TRO. Fracture union was achieved six months after a preferred proximal femoral locking plate. DISCUSSION: The entry point of the ante-grade femoral nail would have been very close to the new position of the nutrient artery of the femoral head occasioned by the TRO and to avoid injury, we chose proximal femoral locking plate. CONCLUSION: It is important to consider the new position of the nutrient artery of the femoral head in the surgical planning of peri-implant fracture after TRO.

Histopathologic findings of spontaneous osteonecrosis of the knee at an early stage: a case report.

We histopathologically examined a surgically resected full specimen obtained from an early-stage spontaneous osteonecrosis of the knee (SPONK). On a mid-coronal cut section of the resected medial femoral condyle, a linear fracture line paralleling the subchondral bone endplate was found. Histopathologically, prominent callus formation was seen comprising of reactive woven bone and granulation tissue on both sides of the fracture. Fracture-related bone debris was focally observed at the osteochondral side of the fracture. Definitive features of antecedent bone infarction such as creeping substitution and bone marrow necrosis were not detected. These findings suggested that SPONK was the result of a subchondral fracture rather than primary osteonecrosis.

MRI-detected bone marrow changes within 3 weeks after initiation of high-dose corticosteroid therapy: a possible change preceding the subsequent appearance of low-intensity band in femoral head osteonecrosis.

Osteonecrosis of the femoral head is considered to occur early during the course of corticosteroid treatment. However, it remains unclear exactly how early it can develop after initiation of corticosteroid treatment. We report a case of osteonecrosis of the femoral head in which abnormal findings were observed on short-tau inversion recovery (STIR) sequence image performed 2 weeks and 4 days after initiation of high-dose corticosteroid therapy. A 45-year-old man with hemophagocytic syndrome was started on prednisolone, with a maximum dose of 40 mg/day. On day 13 after initiation of this corticosteroid therapy, he transiently experienced left hip pain with no apparent cause. STIR sequence image 5 days after the onset of pain revealed high-intensity bone marrow lesions at the femoral neck of both hips. At 3 months after initiation of corticosteroid therapy, T1-weighted magnetic resonance imaging revealed concave-shaped low-intensity bands, which corresponded to the preceding high-intensity lesions on both hips. Because of the subsequent progression to collapse of the left femoral head, he underwent prosthetic replacement surgery. The high-intensity lesions on STIR sequence image indicate the possibility that osteonecrosis can occur within 3 weeks after initiation of high-dose corticosteroid therapy.

Overexpression of the neuropilin 1 (NRP1) gene correlated with poor prognosis in human glioma.

We studied whether the expression of the Neuropilin (NRP) gene was correlated with clinicopathological features in glioma. We examined the gene expression of vascular endothelial growth factor (VEGF)-A, Flt-1, KDR, NRP1 and NRP2 in 37 gliomas by real time reverse transcriptase PCR (real time RT-PCR) as well as immunohistochemical analysis. The vascular counts of each tumor were evaluated by anti-CD34 antibody. NRP1 mRNA overexpression was significantly higher in neoplastic tissue compared to normal brain tissue samples. The higher grade of glioma overexpressed the NRP1 gene significantly (p=0.0015). The glioma patients with NRP1 overexpression showed a poorer prognosis (p=0.0202) than those without such overexpression. NRP1 was observed in the glioma cells by immunohistochemical analyses. VEGF-A and VEGFR overexpression did not show any correlation with the clinicopathological features, including NRP expression. These results suggest that NRP1 overexpression, rather than VEGF-A or VEGFR, contributes to tumor progression and has clinical significance for glioma.

Ribozyme mediated down-regulation of thrombospondin receptor CD36 inhibits the growth of the human osteosarcoma cell line.

Thrombospondin-1 (TSP1) is known to possess tumor suppressor functions. In contradiction, TSP1 enhances the stromal vascularization and growth of certain cancers. A cell adhesion receptor, CD36, has been shown to interact with a ligand TSP1. We studied how CD36 affects the growth of the osteosarcoma cell line (HOS) expressing TSP1. We used the anti-CD36 ribozyme to specifically suppress CD36 gene expression in the HOS. The expression of the CD36 mRNA was significantly suppressed in the ribozyme-introduced cell line (HOS/Rz). The transformant HOS/Rz markedly decreased its growth. The growth of the osteosarcoma cell line HOS may be regulated by autocrine or paracrine loop TSP1 and CD36.

Use of 11p15 mucins as prognostic factors in small adenocarcinoma of the lung.

PURPOSE: Patients with small adenocarcinoma of the lung (SACL) generally have a good prognosis. However, some SACL cases show lymph node metastasis, with poor prognosis. The expression pattern of 11p15 mucins (clustered on the p15 arm of the chromosome 11) is known to change during carcinogenesis in lung cancer. EXPERIMENTAL DESIGN: We evaluated the expression of the 11p15 mucins (MUC2, MUC5AC, and MUC6) in 79 surgical specimens of SACL cases by immunohistochemical analysis. Lymph node metastasis was estimated by pathological staging. RESULTS: Six (7.6%) and 11 (13.9%) of the 79 SACL cases showed MUC2 and MUC6 expression, respectively. Three SACL cases showed both MUC2 and MUC6 expression, and a significant correlation was found between MUC2 and MUC6 expression (Fisher's test, P = 0.033). Six (7.6%) SACL cases showed MUC5AC expression. Five of the 6 cases with MUC2 expression and 6 of the 11 cases with MUC6 expression were had lymph node metastasis. SACL cases with MUC2 or MUC6 expression showed a significantly higher incidence of nodal metastasis than those without expression (P < 0.001 and P = 0.006, chi(2) test, respectively). There was no significant correlation between MUC5AC expression and nodal involvement in SACL, whereas three of the six cases with MUC5AC expression showed lymph node metastasis. The SACL cases with MUC2 expression had a significantly poorer prognosis than those without MUC2 expression (P = 0.011, log-rank test). CONCLUSIONS: These results suggest that 11p15 mucins MUC2 and MUC6 are related to lymph node metastasis in SACL.